Publications by authors named "Hillary Mulder"

46 Publications

Clinical Outcome Predictions for the VerICiguaT Global Study in Subjects With Heart Failure With Reduced Ejection Fraction (VICTORIA) Trial.

J Card Fail 2021 Jun 24. Epub 2021 Jun 24.

Duke Clinical Research Institute, Duke University, Durham, North Carolina.

Background: The prediction of outcomes in patients with heart failure (HF) may inform prognosis, clinical decisions regarding treatment selection, and new trial planning. The VerICiguaT Global Study in Subjects With Heart Failure With Reduced Ejection Fraction included high-risk patients with HF with reduced ejection fraction and a recent worsening HF event. The study participants had a high event rate despite the use of contemporary guideline-based therapies. To provide generalizable predictive data for a broad population with a recent worsening HF event, we focused on risk prognostication in the placebo group.

Methods And Results: Data from 2524 participants randomized to placebo with chronic HF (New York Heart Association functional class II-IV) and an ejection fraction of less than 45% were studied and backward variable selection was used to create Cox proportional hazards models for clinical end points, selecting from 66 candidate predictors. Final model results were produced, accounting for missing data, and nonlinearities. Optimism-corrected c-indices were calculated using 200 bootstrap samples. Over a median follow-up of 10.4 months, the primary outcome of HF hospitalization or cardiovascular death occurred in 972 patients (38.5%). Independent predictors of increased risk for the primary end point included HF characteristics (longer HF duration and worse New York Heart Association functional class), medical history (prior myocardial infarction), and laboratory values (higher N-terminal pro-hormone B-type natriuretic peptide, bilirubin, urate; lower chloride and albumin). Optimism-corrected c-indices were 0.68 for the HF hospitalization/cardiovascular death model, 0.68 for HF hospitalization/all-cause death, 0.72 for cardiovascular death, and 0.73 for all-cause death.

Conclusions: Predictive models developed in a large diverse clinical trial with comprehensive clinical and laboratory baseline data-including novel measures-performed well in high-risk patients with HF who were receiving excellent guideline-based clinical care.

Clinical Trial Registration: Clinicaltrials.gov identifier, NCT02861534.Lay Summary: Patients with heart failure may benefit from tools that help clinicians to better understand a patient's risk for future events like hospitalization. Relatively few risk models have been created after the worsening of heart failure in a contemporary cohort. We provide insights on the risk factors for clinical events from a recent, large, global trial of patients with worsening heart failure to help clinicians better understand and communicate prognosis and select treatment options.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cardfail.2021.05.016DOI Listing
June 2021

Clinical Outcome Predictions for the VerICiguaT Global Study in Subjects With Heart Failure With Reduced Ejection Fraction (VICTORIA) Trial: VICTORIA Outcomes Model.

J Card Fail 2021 May 26. Epub 2021 May 26.

Duke Clinical Research Institute, Duke University, Durham, NC.

Background: Prediction of outcomes in patients with heart failure (HF) may inform prognosis, clinical decisions regarding treatment selection, and new trial planning. The VICTORIA trial included high-risk patients with HF and reduced ejection fraction and a recent worsening HF event. The study participants had an unusually high event rate despite usage of contemporary guideline-based therapies. To provide generalizable predictive data for a broad population with a recent worsening HF event, we focused on risk prognostication in the placebo group.

Methods: Data from 2524 participants randomized to placebo with chronic HF (New York Heart Association class [NYHA] II-IV) and ejection fraction <45% were studied and backward variable selection was used to create Cox proportional hazards models for clinical endpoints, selecting from 66 candidate predictors. Final model results were produced, accounting for missing data, non-linearities, and interactions with treatment. Optimism-corrected c-indices were calculated using 200 bootstrap samples.

Results: During a median follow-up of 10.4 months, the primary outcome of HF hospitalization or cardiovascular death occurred in 972 (38.5%) patients. Independent predictors of increased risk for the primary endpoint included HF characteristics (longer HF duration and worse NYHA class), medical history (prior myocardial infarction), and laboratory values (higher N-terminal pro-hormone B-type natriuretic peptide, bilirubin, urate; lower chloride and albumin). Optimism-corrected c-indices were 0.68 for the HF hospitalization/cardiovascular death model, 0.68 for HF hospitalization/all-cause death, 0.72 for cardiovascular death, and 0.73 for all-cause death.

Conclusions: Predictive models developed in a large diverse clinical trial with comprehensive clinical and laboratory baseline data-including novel measures-performed well in high-risk HF patients who were receiving excellent guideline-based clinical care.

Clinical Trial Registration: Clinicaltrials.gov identifier, NCT02861534.

Lay Summary: Patients with heart failure may benefit from tools that help clinicians better understand patient's risk for future events like hospitalization. Relatively few risk models have been created after worsening of heart failure in a contemporary cohort. We provide insights on risk factors for clinical events from a recent large, global trial of patients with worsening heart failure to help clinicians better understand and communicate prognosis and select treatment options.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cardfail.2021.05.016DOI Listing
May 2021

Comparative Effectiveness of Aspirin Dosing in Cardiovascular Disease.

N Engl J Med 2021 05 15;384(21):1981-1990. Epub 2021 May 15.

From Duke Clinical Research Institute, Duke University, Durham (W.S.J., H.M., L.M.W., M.J.P., M.T.R., H.R.R., L.H.C., A.G.S., L.G.B., B.G.H., D.F.H., L.G.Q., G.M.-G., A.F.H.), University of North Carolina at Chapel Hill, Chapel Hill (D.A.D.), and Wake Forest University School of Medicine, Winston-Salem (L.Z.) - all in North Carolina; Vanderbilt University Medical Center, Nashville (S.K., D.M., D.L.C., R.L.R.); Ochsner Health (M.B.E., R.N.R.) and Louisiana Public Health Institute (T.W.C., E.N.) - both in New Orleans; University of Kansas Medical Center, Kansas City (K.G.); University of Florida, Gainesville (R.D.A., C.J.P., E.M.H., B.R.M., E.A.S.); University of Pittsburgh Medical Center, Pittsburgh (S.K.J., K.M.M.), Penn State College of Medicine, Hershey (J.L.K.), and Temple University, Philadelphia (A.P.) - all in Pennsylvania; University of Iowa, Iowa City (S.G., D.R.); Medical College of Wisconsin, Milwaukee (J.W.), and Marshfield Clinic Research Institute, Marshfield (J.J.V.) - both in Wisconsin; Albert Einstein College of Medicine, Bronx (Y.H.G.), and Weill Cornell Medicine and New York-Presbyterian Hospital, New York (R.K.) - both in New York; Mayo Clinic, Rochester (V.L.R.), Essentia Health Heart and Vascular Center, Duluth (C.P.B.), and Allina Health and Minneapolis Heart Institute, Minneapolis (S.M.B.) - all in Minnesota; University of Utah School of Medicine (R.H.) and Intermountain Medical Center Heart Institute (K.U.K.) - both in Salt Lake City; University of Michigan, Ann Arbor (P.F.); Johns Hopkins University School of Medicine, Baltimore (D.E.F.); HealthCore, Wilmington, DE (K.H.); University of Chicago Medicine (T.S.P.) and Northwestern University Feinberg School of Medicine (D.J.F., F.S.A., A.M.K.) - both in Chicago; University of Nebraska Medical Center, Omaha (J.C.M., J.R.C.); University of California, Los Angeles, Los Angeles (D.S.B., G.C.F.), University of California, San Francisco, San Francisco (M.F.M., G.M.M.), and Stanford University School of Medicine, Stanford (R.A.H.) - all in California; University of Missouri School of Medicine, Columbia (L.R.W.); University of Colorado School of Medicine, Anschutz Medical Campus, Aurora (F.A.M.); Brigham and Women's Hospital, Harvard Medical School, Boston (E.M.A.); Chicago (D.R.D.); St. Joseph, MO (K.E.); Brighton, MI (J.G.M.); Columbia, TN (L.S.B.); Alachua, FL (D.N.Z.); Columbia, MD (T.E.M.); North Hills, CA (J.D.A.); and Metairie, LA (K.C.G.).

Background: The appropriate dose of aspirin to lower the risk of death, myocardial infarction, and stroke and to minimize major bleeding in patients with established atherosclerotic cardiovascular disease is a subject of controversy.

Methods: Using an open-label, pragmatic design, we randomly assigned patients with established atherosclerotic cardiovascular disease to a strategy of 81 mg or 325 mg of aspirin per day. The primary effectiveness outcome was a composite of death from any cause, hospitalization for myocardial infarction, or hospitalization for stroke, assessed in a time-to-event analysis. The primary safety outcome was hospitalization for major bleeding, also assessed in a time-to-event analysis.

Results: A total of 15,076 patients were followed for a median of 26.2 months (interquartile range [IQR], 19.0 to 34.9). Before randomization, 13,537 (96.0% of those with available information on previous aspirin use) were already taking aspirin, and 85.3% of these patients were previously taking 81 mg of daily aspirin. Death, hospitalization for myocardial infarction, or hospitalization for stroke occurred in 590 patients (estimated percentage, 7.28%) in the 81-mg group and 569 patients (estimated percentage, 7.51%) in the 325-mg group (hazard ratio, 1.02; 95% confidence interval [CI], 0.91 to 1.14). Hospitalization for major bleeding occurred in 53 patients (estimated percentage, 0.63%) in the 81-mg group and 44 patients (estimated percentage, 0.60%) in the 325-mg group (hazard ratio, 1.18; 95% CI, 0.79 to 1.77). Patients assigned to 325 mg had a higher incidence of dose switching than those assigned to 81 mg (41.6% vs. 7.1%) and fewer median days of exposure to the assigned dose (434 days [IQR, 139 to 737] vs. 650 days [IQR, 415 to 922]).

Conclusions: In this pragmatic trial involving patients with established cardiovascular disease, there was substantial dose switching to 81 mg of daily aspirin and no significant differences in cardiovascular events or major bleeding between patients assigned to 81 mg and those assigned to 325 mg of aspirin daily. (Funded by the Patient-Centered Outcomes Research Institute; ADAPTABLE ClinicalTrials.gov number, NCT02697916.).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1056/NEJMoa2102137DOI Listing
May 2021

Renal function and the effects of vericiguat in patients with worsening heart failure with reduced ejection fraction: insights from the VICTORIA (Vericiguat Global Study in Subjects with HFrEF) trial.

Eur J Heart Fail 2021 May 17. Epub 2021 May 17.

Canadian VIGOUR Centre, University of Alberta, Edmonton, Canada.

Aims: Vericiguat reduced the primary composite outcome of cardiovascular death or heart failure (HF) hospitalization in patients with worsening HF with reduced ejection fraction (HFrEF) and a lower limit of baseline estimated glomerular filtration rate (eGFR) of 15 mL/min/1.73 m . We evaluated the relationship between the efficacy of vericiguat and baseline and subsequent changes in renal function.

Methods And Results: In VICTORIA, core laboratory serum creatinine was measured at baseline (n = 4956) and weeks 16, 32, and 48. Worsening renal function (WRF), defined as an increase ≥0.3 mg/dL in creatinine from baseline to week 16, was assessed via a Cox model with respect to subsequent primary events. Mean age was 69 years, 24% were female, and mean baseline eGFR was 61 mL/min/1.73 m . During 48 weeks of treatment, the trajectories in eGFR and creatinine with vericiguat were similar to placebo (P = 0.50 and 0.18). The beneficial effects of vericiguat on the primary outcome were not influenced by baseline eGFR (interaction P = 0.48). WRF occurred in 15% of patients and was associated with worse outcomes (adjusted hazard ratio 1.28, 95% confidence interval 1.11-1.47; P < 0.001), but the beneficial effects of vericiguat on the primary outcome were similar in patients with or without WRF (interaction P = 0.76).

Conclusion: Renal function trajectories were similar between vericiguat- and placebo-treated patients and the beneficial effects of vericiguat on the primary outcome were consistent across the full range of eGFR and irrespective of WRF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ejhf.2221DOI Listing
May 2021

Association of Chronic Obstructive Pulmonary Disease with Morbidity and Mortality in Patients with Peripheral Artery Disease: Insights from the EUCLID Trial.

Int J Chron Obstruct Pulmon Dis 2021;16:841-851. Epub 2021 Mar 29.

Department of Medicine, Duke University Medical Center, Durham, NC, USA.

Background: Patients with chronic obstructive pulmonary disease (COPD) are at increased risk of developing lower extremity peripheral artery disease (PAD) and suffering PAD-related morbidity and mortality. However, the effect and burden of COPD on patients with PAD is less well defined. This post hoc analysis from EUCLID aimed to analyze the risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE) in patients with PAD and concomitant COPD compared with those without COPD, and to describe the adverse events specific to patients with COPD.

Methods: EUCLID randomized 13,885 patients with symptomatic PAD to monotherapy with either ticagrelor or clopidogrel for the prevention of MACE. In this analysis, MACE, MALE, mortality, and adverse events were compared between groups with and without COPD using unadjusted and adjusted Cox proportional hazards model.

Results: Of the 13,883 patients with COPD status available at baseline, 11% (n=1538) had COPD. Patients with COPD had a higher risk of MACE (6.02 vs 4.29 events/100 patient-years; p<0.001) due to a significantly higher risk of myocardial infarction (MI) (3.55 vs 1.85 events/100 patient-years; p<0.001) when compared with patients without COPD. These risks persisted after adjustment (MACE: adjusted hazard ratio (aHR) 1.30, 95% confidence interval [CI] 1.11-1.52; p<0.001; MI: aHR 1.45, 95% CI 1.18-1.77; p<0.001). However, patients with COPD did not have an increased risk of MALE or major bleeding. Patients with COPD were more frequently hospitalized for dyspnea and pneumonia (2.66 vs 0.9 events/100 patient-years; aHR 2.77, 95% CI 2.12-3.63; p<0.001) and more frequently discontinued study drug prematurely (19.36 vs 12.54 events/100 patient-years; p<0.001; aHR 1.34, 95% CI 1.22-1.47; p<0.001).

Conclusion: In patients with comorbid PAD and COPD, the risks of MACE, respiratory-related adverse events, and premature study drug discontinuation were higher when compared with patients without COPD.

Registration: ClinicalTrials.gov: NCT01732822.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/COPD.S292978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018572PMC
June 2021

Apixaban Versus Warfarin in Patients With Atrial Fibrillation and Left Ventricular Hypertrophy: Insights From the ARISTOTLE Trial.

Circ Arrhythm Electrophysiol 2021 Mar 4;14(3):e009614. Epub 2021 Mar 4.

Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (S.M.A.-K., H.M., D.W., R.D.L., J.H.A., C.B.G.).

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCEP.120.009614DOI Listing
March 2021

The Dose-Response Relationship Between Physical Activity and Cardiometabolic Health in Adolescents.

Am J Prev Med 2021 01;60(1):95-103

Duke Clinical Research Institute, Durham, North Carolina; Duke Center for Childhood Obesity Research, Duke University School of Medicine, Durham, North Carolina; Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina; Duke Children's Health and Discovery Initiative, Duke University School of Medicine, Durham, North Carolina.

Introduction: This study examines the dose-response relationship between moderate-to-vigorous physical activity and cardiometabolic measures in adolescents.

Methods: Cross-sectional spline analyses were performed using 2003-2016 National Health and Nutrition Examination Survey data among adolescents (aged 12-19 years, N=9,195) on objectively measured (2003-2006) and self-reported (2007-2016) weekly mean minutes of moderate-to-vigorous physical activity and cardiometabolic measures (systolic and diastolic blood pressure, total cholesterol, high-density lipoprotein, BMI, and cardiorespiratory fitness). Inflection points were determined for nonlinear relationships.

Results: For objective moderate-to-vigorous physical activity, female adolescents had significant nonlinear associations with inflection points at 90 minutes/week for BMI percentile and systolic blood pressure. Male adolescents had inflection points at 150 weekly minutes of objective activity for BMI percentile and cardiorespiratory fitness. BMI percentile was about 7% lower for female and male adolescents at 150 weekly minutes of objectively measured moderate-to-vigorous physical activity than at 0 minutes. For self-reported moderate-to-vigorous physical activity, inflection points were at 375 minutes/week (diastolic blood pressure for female adolescents) and 500 minutes/week (systolic blood pressure for male adolescents).

Conclusions: Among several significant dose-response relationships between physical activity and cardiometabolic health in adolescents, consistent and often nonlinear relationships were identified for BMI, with inflection points at 90-150 minutes of objective moderate-to-vigorous physical activity. Notable differences in associations and linearity were identified by sex and physical activity measure (objective or self-reported). These results support calls for any increase in physical activity among adolescents and suggest that recommendations closer to the adult guidelines of 150 weekly minutes of physical activity may be health promoting and more attainable for youth than the current recommendation of 420 weekly minutes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.amepre.2020.06.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7769140PMC
January 2021

Cause of Death Among Patients With Peripheral Artery Disease: Insights From the EUCLID Trial.

Circ Cardiovasc Qual Outcomes 2020 11 12;13(11):e006550. Epub 2020 Nov 12.

Duke Heart Center, Division of Cardiology, School of Medicine (R.D.L., M.R.P., W.S.J.), Duke University, Durham, NC.

Background: Peripheral artery disease is common and associated with high mortality. There are limited data detailing causes of death among patients with peripheral artery disease.

Methods: EUCLID (Examining Use of Ticagrelor in Peripheral Artery Disease) was a randomized clinical trial that assigned patients with peripheral artery disease to clopidogrel or ticagrelor. We describe the causes of death in EUCLID using mortality end points adjudicated through a clinical events classification process. The association between baseline factors and cardiovascular death was evaluated by Cox proportional hazards modeling. The competing risk of noncardiovascular death was assessed by the cumulative incidence function for cardiovascular death and the Fine and Gray method to ascertain the association between baseline characteristics and cardiovascular mortality.

Results: A total of 1263 out of 13 885 (9.1%) patients died (median follow-up: 30 months). There were 706 patients (55.9%) with a cardiovascular cause of death and 522 (41.3%) with a noncardiovascular cause of death. The most common cause of cardiovascular death was sudden cardiac death (20.1%); while myocardial infarction (5.2%) and ischemic stroke (3.2%) were uncommon. The most common causes of noncardiovascular death were malignancies (17.9%) and infections (11.9%). The factor most associated with a higher risk of cardiovascular death was age per 5 year increase (HR, 1.26 [95% CI, 1.20-1.32]). Female sex was associated with a lower risk of cardiovascular death (HR, 0.68 [95% CI, 0.56-0.82]). To evaluate the effect of noncardiovascular death as a competing risk, we superimposed the cumulative incidence function curve with the Kaplan-Meier curve. These curves closely approximated each other. After accounting for the competing risk of noncardiovascular death, the magnitude and direction of the factors associated with cardiovascular death were minimally changed.

Conclusions: Among patients with symptomatic peripheral artery disease, noncardiovascular causes of death reflected a high proportion (40%) of deaths. Accounting for noncardiovascular deaths as a competing risk, there was not a significant change in the risk estimation for cardiovascular death. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01732822.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCOUTCOMES.120.006550DOI Listing
November 2020

Association of Disease Progression With Cardiovascular and Limb Outcomes in Patients With Peripheral Artery Disease: Insights From the EUCLID Trial.

Circ Cardiovasc Interv 2020 10 12;13(10):e009326. Epub 2020 Oct 12.

Division of Cardiology, Duke University Medical Center, Durham, NC (J.A.R., D.I.N., W.S.J., M.R.P.).

Background: Patients with peripheral artery disease have a high risk of future cardiovascular disease events and mortality. Little is known about the changes in symptom classification over time in patients with peripheral artery disease and the association of changes in symptom classification with subsequent cardiovascular disease events.

Methods: In this analysis of the EUCLID trial (Examining Use of Ticagrelor in Peripheral Artery Disease), we examined the changes in Rutherford classification (RC) of patients over 12 months. We examined the baseline characteristics of patients by change in symptom classification at 12 months (improved=decreased RC, no change, or worsened=increased RC), and the association between changes in symptom classification (RC) at 12 months and subsequent cardiovascular disease events.

Results: Among 12 759 patients, 3240 (25%) were classified as improved by RC at 12 months, 8132 (64%) as no change, and 1387 (11%) as worsened. At 12 months, many patients who were asymptomatic or had mild/moderate claudication at enrollment had no change in symptom classification over 12 months (73.7% and 70.9%). Patients who worsened over 12 months were more likely to have comorbidities (diabetes mellitus and prior myocardial infarction) and more events (myocardial infarction, amputation, and major bleeding) by 12 months postrandomization, all <0.001. Worsened symptom classification over 12 months was associated with increased risk of all-cause death (adjusted hazard ratio, 1.29 [95% CI, 1.03-1.62]), major amputation (adjusted hazard ratio, 4.12 [95% CI, 2.46-6.88]), and a composite of cardiovascular death, myocardial infarction, or stroke (adjusted hazard ratio, 1.30 [95% CI, 1.05-1.62]), all <0.05 after 12 months postrandomization.

Conclusions: Patients with comorbidities and prior history of cardiovascular disease events at baseline and within the first 12 months of the trial were more likely to have worsened symptom classification at 12 months. Worsening symptom classification over 12 months was associated subsequently with an increased risk of all-cause death, amputation, and a composite of cardiovascular death, myocardial infarction, or stroke. Graphic Abstract: A graphic abstract is available for this article.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCINTERVENTIONS.120.009326DOI Listing
October 2020

Association of Health Status Scores With Cardiovascular and Limb Outcomes in Patients With Symptomatic Peripheral Artery Disease: Insights From the EUCLID (Examining Use of Ticagrelor in Symptomatic Peripheral Artery Disease) Trial.

J Am Heart Assoc 2020 10 13;9(19):e016573. Epub 2020 Sep 13.

Division of Cardiology Duke University Medical Center Durham NC.

Background There are limited data on health status instruments in patients with peripheral artery disease and cardiovascular and limb events. We evaluated the relationship between health status changes and cardiovascular and limb events. Methods and Results In an analysis of the EUCLID (Examining Use of Ticagrelor in Symptomatic Peripheral Artery Disease) trial, we examined the characteristics of 13 801 patients by tertile of health status instrument scores collected in the trial (EuroQol 5-Dimensions [EQ-5D], EQ visual analog scale [VAS], and peripheral artery questionnaire). We assessed the association between the baseline health status measurements and major adverse cardiovascular events, major adverse limb events, and lower-extremity revascularization procedures during trial follow-up and the association between 12-month health status change scores and subsequent end points during follow-up. There were 13 217 (95%) patients with EQ-5D scores, 13 533 (98%) with VAS scores, and 4431 (32%) with peripheral artery questionnaire scores. Patients in the lowest baseline EQ-5D tertile (0 to <0.69) were more likely to be female with severe claudication compared with the highest tertile (0.79-1.0; <0.01). Patients in the lowest VAS (0-60) and peripheral artery questionnaire (0-49) tertiles had lower ankle-brachial indices compared with the highest tertiles (80-100 and 76-108, respectively; <0.01). There was a significant association between baseline EQ-5D, VAS, and peripheral artery questionnaire scores and adjusted major adverse cardiovascular events, major adverse limb events, and lower-extremity revascularization (<0.05). Improved EQ-5D and VAS scores over 12 months were associated with reduced risk of subsequent major adverse cardiovascular events or lower-extremity revascularization (all <0.01). Conclusions Although health status instruments are rarely used in clinical practice, these measures are associated with outcomes, including major adverse cardiovascular events, major adverse limb events, and lower-extremity revascularization. Further research is needed to determine the relationship between changes in these instruments, revascularization, and outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/JAHA.120.016573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792388PMC
October 2020

Angiotensin-Neprilysin Inhibition in Black Americans: Data From the PIONEER-HF Trial.

JACC Heart Fail 2020 10 9;8(10):859-866. Epub 2020 Sep 9.

Thrombolysis in Myocardial Infarction Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; Duke Clinical Research Institute and Department of Medicine, Duke University School of Medicine, Durham, North Carolina. Electronic address:

Objectives: This study compared the efficacy and safety of sacubitril/valsartan to enalapril in Black and non-Black Americans with acute decompensated heart failure (ADHF).

Background: Black patients have a different response to treatment with angiotensin-converting enzyme inhibitors compared with other racial and ethnic groups. How Black patients with ADHF respond to sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor, is unclear. PIONEER-HF was a double-blind randomized clinical trial of sacubitril/valsartan versus enalapril in hospitalized patients with ADHF following hemodynamic stabilization.

Methods: In a pre-specified subgroup analysis, we examined changes in N-terminal pro-B-type natriuretic peptide, clinical outcomes, and safety according to race.

Results: The study population, all enrolled in the United States, included 316 (36%) Black participants, 515 (58%) White participants, and 50 (5.7%) participants of other racial groups. The reduction in N-terminal pro-B-type natriuretic peptide concentration at weeks 4 and 8 was significantly greater with sacubitril/valsartan than enalapril in both Black (ratio of change with sacubitril/valsartan vs. enalapril: 0.71; 95% confidence interval [CI]: 0.58 to 0.88) and non-Black patients (ratio of change: 0.71; 95% CI: 0.61 to 0.83; interaction p = 1.00). Compared with enalapril, sacubitril/valsartan also reduced the pre-specified exploratory composite of cardiovascular death or HF rehospitalization in both Black (hazard ratio: 0.47; 95% CI: 0.24 to 0.93) and non-Black patients (hazard ratio: 0.65; 95% CI: 0.40 to 1.06; interaction p = 0.44).

Conclusions: Among Black patients admitted with ADHF in the United States, the in-hospital initiation of sacubitril/valsartan was more effective than enalapril in reducing natriuretic peptide levels and the composite of cardiovascular death or HF rehospitalization. The effect of sacubitril/valsartan did not differ by race. (Comparison of Sacubitril/Valsartan Versus Enalapril on Effect on NT-proBNP in Patients Stabilized From an Acute Heart Failure Episode [PIONEER-HF]; NCT02554890).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jchf.2020.06.019DOI Listing
October 2020

Outcomes following revascularization with radial artery bypass grafts: Insights from the PREVENT-IV trial.

Am Heart J 2020 10 8;228:91-97. Epub 2020 Aug 8.

Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA.

Background: The optimal role of radial artery grafts in coronary artery bypass grafting (CABG) remains uncertain. The purpose of this study was to examine angiographic and clinical outcomes following CABG among patients who received a radial artery graft.

Methods: Patients in the angiographic cohort of the PREVENT-IV trial were stratified based upon having received a radial artery graft or not during CABG. Baseline characteristics and 1-year angiographic and 5-year clinical outcomes were compared between patients.

Results: Of 1,923 patients in the angiographic cohort of PREVENT-IV, 117 received a radial artery graft. These patients had longer surgical procedures (median 253 vs 228 minutes, P < .001) and had a greater number of grafts placed (P < .0001). Radial artery grafts had a graft-level failure rate of 23.0%, which was similar to vein grafts (25.2%) and higher than left internal mammary artery grafts (8.3%). The hazard of the composite clinical outcome of death, myocardial infarction, or repeat revascularization was similar for both cohorts (adjusted hazard ratio 0.896, 95% CI 0.609-1.319, P = .58). Radial graft failure rates were higher when used to bypass moderately stenotic lesions (<75% stenosis, 37% failure) compared with severely stenotic lesions (≥75% stenosis, 15% failure).

Conclusions: Radial artery grafts had early failure rates comparable to saphenous vein and higher than left internal mammary artery grafts. Use of a radial graft was not associated with a different rate of death, myocardial infarction, or postoperative revascularization. Despite the significant potential for residual confounding associated with post hoc observational analyses of clinical trial data, these findings suggest that when clinical circumstances permit, the radial artery is an acceptable alternative to saphenous vein and should be used to bypass severely stenotic target vessels.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ahj.2020.08.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7508822PMC
October 2020

Association Between Triglycerides and Residual Cardiovascular Risk in Patients With Type 2 Diabetes Mellitus and Established Cardiovascular Disease (From the Bypass Angioplasty Revascularization Investigation 2 Diabetes [BARI 2D] Trial).

Am J Cardiol 2020 10 12;132:36-43. Epub 2020 Jul 12.

Duke Clinical Research Institute, Duke University, Durham, North Carolina. Electronic address:

Triglyceride (TG) levels encompass several lipoproteins that have been implicated in atherogenic pathways. Whether TG levels independently associate with cardiovascular disease both overall and, in particular among patients with established coronary artery disease (CAD) and type 2 diabetes (T2DM), remains controversial. Data from the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial was used to evaluate patients with T2DM and CAD. Cox proportional hazards models were used to determine the association between TG levels and outcomes. Stepwise adjustment was performed for demographics, clinical factors, lipid profile and statin treatment. The primary composite outcome was time to CV death, myocardial infarction (MI), or stroke and secondary outcome was CV death. Among 2,307 patients with T2DM and CAD, the mean (±SD) TG levels were 181 (±136) with a median (Q1-Q3) 148mg/dL (104-219). Overall, 51% of patients had TG <150 mg/dL, 18% 150-199 mg/dL, 28% 200-499 mg/dL and 3% ≥500 mg/dL. Participants with elevated TG levels (≥150 mg/dL) were younger (61 vs 63 years, p <0.001), had higher BMI (32 vs 30 kg/m, p <0.001), more likely to have had prior MI (34.2 vs 30.1%, p = 0.033) and revascularization (25.8 vs 21.4%, p = 0.013), had lower HDL-C (34 vs 39 mg/dL, p <0.001) and higher HbA1c (8 vs 7%, p <0.001). In unadjusted analyses, baseline TG levels were linearly associated with both the primary composite and secondary outcomes. In fully adjusted analyses, every 50 mg/dL increase in TG level was associated with a 3.8% (HR 1.038, 95%CI 1.004-1.072, p <0.001) increase in the primary composite outcome and a 6.4% (HR 1.064 95%CI 1.018-1.113, p <0.001) increase in the secondary outcome. There was no interaction between TG and outcomes within key subgroups including female sex, additional non-coronary atherosclerotic disease, CKD or low LDL (<100 mg/dL). In conclusion, among patients with T2DM and CAD, elevated TG were independently associated with adverse cardiovascular outcomes, even after adjustment for clinical and simple biochemical covariates.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.amjcard.2020.07.005DOI Listing
October 2020

Incidence and Factors Associated With Major Amputation in Patients With Peripheral Artery Disease: Insights From the EUCLID Trial.

Circ Cardiovasc Qual Outcomes 2020 07 3;13(7):e006399. Epub 2020 Jul 3.

Department of Medicine, Division of Cardiology (M.R.P., W.S.J.), Duke University Health System, Durham, NC.

Background: Peripheral artery disease (PAD) is associated with increased risk of mortality, cardiovascular morbidity, and major amputation. Data on major amputation from a large randomized trial that included a substantial cohort of patients without critical limb ischemia (CLI) have not been described. The objective was to describe the incidence and types of amputations in the EUCLID trial (Examining Use of Ticagrelor in Peripheral Artery Disease) population, subcategorize amputations in the CLI versus no CLI cohorts, and describe the events surrounding major amputation.

Methods And Results: Postrandomization major amputation was analyzed in the EUCLID trial. Patients were stratified by baseline CLI status. The occurrence of major amputation was ascertained and defined as the highest level. Perioperative events surrounding major amputation were obtained including acute limb ischemia, revascularization, and all-cause mortality. All variables were assessed for significance in univariable and multivariable models. The rate of major amputation during the course of the trial was 1.6% overall, 8.4% in the CLI at baseline group, and 1.2% in the no CLI at baseline group. The annualized rate of major amputation was 0.6% in PAD overall, 3.9% in the CLI at baseline group, and 0.5% in the no CLI at baseline group. Several factors were associated with increased risk of major amputation, including history of amputation, the presence of diabetes mellitus, baseline Rutherford category 4 to 6, and an ankle-brachial index <0.8. Factors associated with a lower risk for major amputation included prior statin use. The 30-day mortality rate after major amputation was 6.5% overall, 5.6% in the CLI at baseline group, and 6.8% in the no CLI at baseline group. The annual mortality rate following major amputation was 22.8% in the CLI at baseline group and 16.0% in the no CLI at baseline group.

Conclusions: The risk factors for major amputation in EUCLID patients are similar to previous large registries' reports except for diabetes mellitus in patients with CLI. The mortality following major amputation is lower in the EUCLID trial compared with registry data. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01732822.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCOUTCOMES.119.006399DOI Listing
July 2020

The Dose-Response Relationship Between Physical Activity and Cardiometabolic Health in Young Adults.

J Adolesc Health 2020 08 19;67(2):201-208. Epub 2020 Jun 19.

Duke Clinical Research Institute, Durham, North Carolina; Duke Center for Childhood Obesity Research, Duke University School of Medicine, Durham, North Carolina; Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina; Children's Health and Discovery Institute, Duke University School of Medicine, Durham, North Carolina. Electronic address:

Purpose: Guidelines recommend 150 minutes of weekly moderate-to-vigorous physical activity (MVPA) for all adults, although physical activity level correlation with cardiometabolic health is not well characterized for young adults. We determined the dose-response relationship of MVPA on measures of cardiometabolic health in young adults.

Methods: We examined young adults (aged 20-29 years; N = 5,395, 47.9% female) in the 2003-2016 National Health and Nutrition Examination Survey. Exposures were objective (accelerometer based) and self-reported weekly mean minutes of MVPA. Cardiometabolic outcome measures were body mass index (BMI), high-density lipoprotein (HDL), total cholesterol, systolic blood pressure, and diastolic blood pressure. The dose-response relationships were assessed with unadjusted spline analyses. Sex-stratified outcomes were modeled using multivariable linear regression with mean estimated change presented for 150-minute dose increases of MVPA.

Results: Among females, associations between objective activity and cardiometabolic measures were all linear. Compared with no activity, 150 minutes of objective activity was associated with a lower BMI (-1.37 kg/m) and total cholesterol (-4.89 mg/dL), whereas 150 minutes of self-reported activity was associated with a higher HDL (1 mg/dL) and lower diastolic blood pressure (-.42 mm Hg). Among males, an inflection point was identified in the dose-response curves for objective activity with BMI around 100 minutes. Compared with no activity, 150 self-reported minutes was associated with lower BMI (-.26 kg/m), higher HDL (.52 mg/dL), and lower total cholesterol (-1.35 mg/dL).

Conclusions: The dose-response relationships between physical activity and cardiometabolic markers in young adults were predominantly linear, supporting public health calls for any increase in physical activity in this population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jadohealth.2020.04.021DOI Listing
August 2020

The association between triglycerides and incident cardiovascular disease: What is "optimal"?

J Clin Lipidol 2020 Jul - Aug;14(4):438-447.e3. Epub 2020 May 6.

Duke Clinical Research Institute, Durham, NC, USA. Electronic address:

Background: Elevated triglycerides (TGs) are associated with increased risk of cardiovascular disease (CVD), but the best way to both measure TGs and assess TG-related risk remains unknown.

Objective: The objective of the study was to evaluate the association between TGs and CVD and determine whether the average of a series of TG measurements is more predictive of CVD risk than a single TG measurement.

Methods: We examined 15,792 study participants, aged 40-65 years, free of CVD from the Atherosclerosis Risk in Communities and Framingham Offspring studies, using fasting TG measurements across multiple examinations over time. With up to 10 years of follow-up, we assessed time-to-first CVD event, as well as a composite of myocardial infarction, stroke, or cardiovascular death.

Results: Compared with a single TG measurement, average TGs over time had greater discrimination for CVD risk (C-statistic, 0.60 vs 0.57). Risk for CVD increased as average TGs rose until an inflection point of ~100 mg/dL in men and ~200 mg/dL in women, above which this risk association plateaued. The relationship between average TGs and CVD remained statistically significant in multivariable modeling adjusting for low-density lipoprotein cholesterol, and interactions were found by sex and high-density lipoprotein cholesterol level.

Conclusions: The average of several TG readings provides incremental improvements for the prediction of CVD relative to a single TG measurement. Regardless of the method of measurement, higher TGs were associated with increased CVD risk, even at levels previously considered "optimal" (<150 mg/dL).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jacl.2020.04.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7492406PMC
May 2020

Utilization of Invasive Procedures for Adult Eustachian Tube Dysfunction.

Otolaryngol Head Neck Surg 2020 Nov 11;163(5):963-970. Epub 2020 Jun 11.

Department of Otolaryngology, Harvard Medical School, Boston, Massachusetts, USA.

Objective: Eustachian tube dysfunction (ETD) is a common diagnosis among adults presenting for outpatient care. We sought to determine national utilization and the associated cost of invasive procedures for adult ETD.

Study Design: Cross-sectional study.

Setting: National health care database.

Subjects And Methods: The Truven Health MarketScan Databases (2010-2014) analytic cohort included health care encounters of patients ≥18 years of age with a diagnosis of ETD or related conditions of otitis media with effusion (OME) or tympanic membrane retraction (TMR). Visits associated with recent diagnoses of acute upper respiratory infection, head and neck cancer, or radiation therapy were excluded. Invasive procedure usage was subdivided into nasal and otologic procedures.

Results: ETD, OME, or TMR was diagnosed in 1,298,987 patients, 11.1% of which were chronic. The most common procedure was diagnostic endoscopy (including nasal endoscopy and laryngopharyngoscopy), which was used most frequently in the first 3 months after diagnosis, during which it was performed in 120,971 (9.3%) patients. The most frequent therapeutic nasal procedure was eustachian tube inflation without catheterization, performed in 11,412 patients over 5 years at a total cost of $1,210,939 ($106 per person annually). The most common therapeutic otologic procedure was myringotomy with tympanostomy, performed on 56,137 patients over 5 years at a total cost of $47,713,708 ($810 per person annually).

Conclusion: Several nasal and otologic procedures are associated with a diagnosis of adult ETD at substantial cost. Development of therapeutic alternatives should be sought to mitigate the need for invasive procedures to treat this condition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0194599820931467DOI Listing
November 2020

The effect of lateral neck dissection on complication rate for total thyroidectomy.

Am J Otolaryngol 2020 May - Jun;41(3):102421. Epub 2020 Feb 13.

Duke University Medical Center, Department of Surgery, Division of Head and Neck Surgery & Communication Sciences, Durham, NC, United States of America.

Purpose: To determine the complication profile for total thyroidectomy with and without concomitant lateral neck dissection using a large administrative database.

Materials And Methods: The IBM MarketScan® Commercial Database (2010-2014) analytic cohort was queried for patients ≥18 years or older undergoing total thyroidectomy (or equivalent procedures) from January 1, 2010 to June 30, 2014. Subgroup analysis was performed for patients undergoing concomitant unilateral and bilateral lateral neck dissection. The complication profiles were described.

Results: 55,204 patients underwent total thyroidectomy or equivalent procedures. Hypoparathyroidism or hypocalcemia was coded in 20.3% overall, with 4.7% having permanent hypoparathyroidism. Vocal cord paralysis was coded in 3.3% overall with permanent rate of 0.7%. Tracheotomy was performed in 0.3% of patients. 2743 underwent total thyroidectomy with concomitant unilateral lateral neck dissection, and 560 of these patients underwent bilateral lateral neck dissection. In patients undergoing unilateral lateral neck dissection, 30.5% of patients have hypoparathyroidism/hypocalcemia coded, with a permanent rate of 8.8%. Vocal cord paralysis was coded in 8.3% of patients, with a permanent rate of 1.9%. Tracheotomy was performed in 1.2% of patients. In patients undergoing bilateral lateral neck dissection, 39.6% had hypoparathyroidism/hypocalcemia coded, with a permanent rate of 10.9%. These patients had vocal cord paralysis coded in 10.2% of cases, with a permanent rate of 2.1%. Tracheotomy was performed in 2.5% of patients.

Conclusion: The addition of unilateral and especially bilateral lateral neck dissection increases both overall and permanent complication rates for total thyroidectomy. These data may help to inform preoperative discussions with patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.amjoto.2020.102421DOI Listing
September 2020

Regional variation in clinical characteristics and outcomes in patients with atrial fibrillation: Findings from the ARISTOTLE trial.

Int J Cardiol 2020 03 30;302:53-58. Epub 2019 Dec 30.

Duke Clinical Research Institute, Durham, NC, United States of America. Electronic address:

Background: Variation in patient characteristics and practice patterns may influence outcomes at a regional level.

Methods: We assessed differences in demographics, practice patterns, outcomes, and the effect of apixaban compared with warfarin in ARISTOTLE (n = 18,201) by prespecified regions: North America, Latin America, Europe, and Asia Pacific. The primary outcomes were stroke/systemic embolism and major bleeding.

Results: Compared with other regions, patients from Asia Pacific were younger, more women were enrolled in Latin America. Coronary artery disease was more prevalent in Europe and Asia Pacific had the highest rate of prior stroke and renal impairment. Over 50% of patients in North America were taking ≥9 drugs at randomization, compared with 10% in Latin America. North America had the highest rates of temporary study drug discontinuation and procedures. Time in therapeutic range (INR 2.0-3.0) on warfarin was highest in North America and lowest in Asia Pacific. After adjustment and compared with Europe, patients in Asia Pacific had 2-fold higher risk of stroke/systemic embolism and 3-fold higher risk of intracranial hemorrhage. Patients in Latin America had 2-fold increased risk of all-cause death compared with Europe. The benefits of apixaban compared with warfarin were consistent across regions; there was a pronounced reduction in major bleeding in patients from Asia Pacific compared with other regions (p-interaction = 0.03).

Conclusions: Patients with AF enrolled in prespecified regions in ARISTOTLE had differences in clinical baseline characteristics and practice patterns. After adjustment, patients in Asia Pacific and Latin America had worse outcomes than patients from other regions. The relative benefits of apixaban compared with warfarin were consistent across regions with an even greater treatment effect in the reduction of bleeding in patients from Asia Pacific.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijcard.2019.12.060DOI Listing
March 2020

Have the Major Cardiovascular Outcomes Trials Impacted Payer Approval Rates for PCSK9 Inhibitors?

Circ Cardiovasc Qual Outcomes 2020 01 10;13(1):e006019. Epub 2020 Jan 10.

Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCOUTCOMES.119.006019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7039320PMC
January 2020

Gastrointestinal bleeding in patients with atrial fibrillation treated with Apixaban or warfarin: Insights from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial.

Am Heart J 2020 03 31;221:1-8. Epub 2019 Oct 31.

Duke Clinical Research Institute, Durham, NC; Division of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, NC. Electronic address:

Objectives: A history of gastrointestinal bleeding (GIB) in patients with atrial fibrillation (AF) may impact decisions about anticoagulation treatment. We sought to determine whether prior GIB in patients with AF taking anticoagulants was associated with an increased risk of stroke or major hemorrhage.

Methods: We analyzed key efficacy and safety outcomes in patients with prior GIB in ARISTOTLE. Centrally adjudicated outcomes according to GIB history were analyzed using Cox proportional hazards models adjusted for randomized treatment and established risk factors.

Results: A total of 784 (4.3%) patients had prior GIB events (321 [41%] lower, 463 [59%] upper); 215 (27%) occurred <1 year before study enrollment. Patients with prior GIB were older, had more comorbidities, and higher CHADS and HAS-BLED scores than those with no GIB. Major GIB occurred more frequently in those with prior GIB (lower: aHR 1.72, 95% CI 0.86-3.42; upper: aHR 3.13, 95% CI 1.97-4.96). This association with major GIB was more pronounced in patients with GIB <1 year before randomization versus no recent GIB (recent lower: aHR 2.58, 95% CI 0.95-7.01; recent upper: aHR 5.16, 95% CI 2.66-10.0). There was no association between prior GIB and risk of stroke/systemic embolism or all-cause death. In those with prior GIB, the apixaban versus warfarin relative risks for stroke/systemic embolism, hemorrhagic stroke, death, or major bleeding were consistent with the results of the overall trial.

Conclusions: In patients with AF on oral anticoagulants, prior GIB was associated with an increased risk of subsequent major GIB but not stroke, intracranial bleeding, or all-cause mortality. For the key outcomes of stroke, hemorrhagic stroke, death, and major bleeding, we found no evidence that the treatment effect (apixaban vs. warfarin) was modified by a history of GIB.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ahj.2019.10.013DOI Listing
March 2020

Clinical Implications of the New York Heart Association Classification.

J Am Heart Assoc 2019 12 27;8(23):e014240. Epub 2019 Nov 27.

Section of Cardiovascular Medicine Center for Outcomes Research Evaluation (CORE) Yale University School of Medicine New Haven CT.

Background The New York Heart Association (NYHA) classification has served as a fundamental tool for risk stratification of heart failure (HF) and determines clinical trial eligibility and candidacy for drugs and devices. However, its ability to adequately stratify risk is unclear. Methods and Results To compare NYHA class with objective assessments and survival in patients with HF, we performed secondary analyses of 4 multicenter National Institutes of Health-funded HF clinical trials that included patients classified as NYHA class II or III: TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist), DIG (The Effect of Digoxin on Mortality and Morbidity in Patients With Heart Failure), HF-ACTION (Efficacy and Safety of Exercise Training in Patients With Chronic Heart Failure), and GUIDE-IT (Guiding Evidence-Based Therapy Using Biomarker Intensified Treatment in Heart Failure). Twenty-month cumulative survival was compared between classes using Kaplan-Meier curves and the log rank test. NT-proBNP (N-terminal pro-B-type natriuretic peptide), Kansas City Cardiomyopathy Questionnaire (KCCQ) scores, 6-minute walk distances, left ventricular ejection fraction, and cardiopulmonary test parameters were compared using Wilcoxon rank sum tests and percentage overlap using kernel density estimations. Cumulative mortality varied significantly across NYHA classes and HF clinical trials (likelihood ratio, <0.001). Mortality at 20 months for NYHA class II ranged from 7% for patients in HF-ACTION to 15% in GUIDE-IT, whereas mortality for NYHA class III ranged from 12% in TOPCAT to 26% in GUIDE-IT. There was substantial percentage overlap in values for NT-proBNP levels (79% and 69%), KCCQ scores (63% and 54%), 6-minute walk distances (63% and 54%), and left ventricular ejection fraction (88% and 83%). Similarly, there was substantial overall in values for minute ventilation-carbon dioxide production relationship (71%), maximal oxygen uptake (54%), and exercise duration (53%). Conclusions The NYHA system poorly discriminates HF patients across the spectrum of functional impairment. These findings raise important questions about the need for improved phenotyping of these patients to facilitate risk stratification and response to interventions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/JAHA.119.014240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6912957PMC
December 2019

Patients With Atrial Fibrillation Taking Nonsteroidal Anti-Inflammatory Drugs and Oral Anticoagulants in the ARISTOTLE Trial.

Circulation 2020 01 21;141(1):10-20. Epub 2019 Nov 21.

Duke Clinical Research Institute, Duke University, Durham, NC (F.D., H.M., D.M.W., R.D.L., J.H.A., J.B.W., C.B.G., S.M.A-K.).

Background: The use of nonsteroidal anti-inflammatory drugs (NSAIDs) with oral anticoagulants has been associated with an increased risk of bleeding. We investigated the risk of bleeding and major cardiovascular outcomes in patients with atrial fibrillation taking NSAIDs and apixaban or warfarin.

Methods: The ARISTOTLE trial (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation; n=18 201) compared apixaban with warfarin in patients with atrial fibrillation at an increased risk of stroke. Patients in ARISTOTLE without severe renal (creatine clearance ≤30 mL/min) or liver disease were included in this analysis (n=17 423). NSAID use at baseline, NSAID use during the trial (incident NSAID use), and never users were described. The primary outcome was major bleeding. Secondary outcomes included clinically relevant nonmajor bleeding, gastrointestinal bleeding, heart failure hospitalization, stroke or systemic embolism, and all-cause mortality. NSAID use during the trial, and the interaction between randomized treatment, was analyzed using time-dependent Cox proportional hazards models.

Results: Those with baseline NSAID use (n=832 [4.8%]), incident NSAID use (n=2185 [13.2%]), and never users were similar in median age (age [25th, 75th]; 70 [64, 77] versus 70 [63, 75] versus 70 [62, 76]). Those with NSAID use at baseline and incident NSAID use were more likely to have a history of bleeding than never users (24.5% versus 21.0% versus 15.6%, respectively). During a median follow-up (25th, 75th) of 1.8 (1.4, 2.3) years and when excluding those taking NSAID at baseline, we found that incident NSAID use was associated with an increased risk of major bleeding (hazard ratio [HR], 1.61 [95% CI, 1.11-2.33]) and clinically relevant nonmajor bleeding (HR, 1.70 [95% CI, 1.16-2.48]), but not gastrointestinal bleeding. No significant interaction was observed between NSAID use and randomized treatment for any outcome.

Conclusions: A substantial number of patients in the ARISTOTLE trial took NSAIDs. Incident NSAID use was associated with major and clinically relevant nonmajor bleeding, but not with gastrointestinal bleeding. The safety and efficacy of apixaban versus warfarin appeared not significantly to be altered by NSAID use. This study warrants more investigation of the effect of NSAIDs on the outcomes of patients treated with apixaban.

Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00412984.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCULATIONAHA.119.041296DOI Listing
January 2020

Natriuretic Peptide Response and Outcomes in Chronic Heart Failure With Reduced Ejection Fraction.

J Am Coll Cardiol 2019 09;74(9):1205-1217

Inova Heart and Vascular Center, Fairfax, Virginia.

Background: The GUIDE-IT (GUIDing Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure) trial demonstrated that a strategy to "guide" application of guideline-directed medical therapy (GDMT) by reducing amino-terminal pro-B-type natriuretic peptide (NT-proBNP) was not superior to GDMT alone.

Objectives: The purpose of this study was to examine the prognostic meaning of NT-proBNP changes following heart failure (HF) therapy intensification relative to the goal NT-proBNP value of 1,000 pg/ml explored in the GUIDE-IT trial.

Methods: A total of 638 study participants were included who were alive and had available NT-proBNP results 90 days after randomization. Rates of subsequent cardiovascular (CV) death/HF hospitalization or all-cause mortality during follow-up and Kansas City Cardiomyopathy Questionnaire (KCCQ) overall scores were analyzed.

Results: A total of 198 (31.0%) subjects had an NT-proBNP ≤1,000 pg/ml at 90 days with no difference in achievement of NT-proBNP goal between the biomarker-guided and usual care arms. NT-proBNP ≤1,000 pg/ml by 90 days was associated with longer freedom from CV/HF hospitalization or all-cause mortality (p < 0.001 for both) and lower adjusted hazard of subsequent HF hospitalization/CV death (hazard ratio: 0.26; 95% confidence interval: 0.15 to 0.46; p < 0.001) and all-cause mortality (hazard ratio: 0.34; 95% confidence interval: 0.15 to 0.77; p = 0.009). Regardless of elevated baseline concentration, an NT-proBNP ≤1,000 pg/ml at 90 days was associated with better outcomes and significantly better KCCQ overall scores (p = 0.02).

Conclusions: Patients with heart failure with reduced ejection fraction whose NT-proBNP levels decreased to ≤1,000 pg/ml during GDMT had better outcomes. These findings may help to understand the results of the GUIDE-IT trial. (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment [GUIDE-IT]; NCT01685840).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jacc.2019.06.055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6719723PMC
September 2019

Racial differences in long-term outcomes among black and white patients with drug-eluting stents.

Am Heart J 2019 08 15;214:46-53. Epub 2019 Apr 15.

Duke University Medical Center, Durham, NC; Duke Clinical Research Institute, Durham, NC. Electronic address:

Background: Some studies suggest that black patients may have worse outcomes after drug-eluting stent (DES) placement. There are limited data characterizing long-term outcomes by race. The objective was to compare long-term outcomes between black and white patients after percutaneous coronary intervention (PCI) with DES implantation.

Methods: We analyzed 915 black and 3,559 white (n = 4,474) consecutive patients who underwent DES placement at Duke University Medical Center from 2005 through 2013. Over 6-year follow up, we compared rates of myocardial infarction (MI), all-cause mortality, revascularization, and major bleeding between black and white patients. A multivariable Cox regression model was fit to adjust for potentially confounding variables. Dual-antiplatelet therapy use over time was determined by patient follow-up surveys and compared by race.

Results: Black patients were younger; were more often female; had higher body mass indexes; had more diabetes mellitus, hypertension, and renal disease; and had lower median household incomes than white patients (P < .001). At 6 years after DES placement, black relative to white patients had higher unadjusted rates of MI (12.1% vs 10.1%, hazard ratio 1.25, 95% CI 1.00-1.57, P = .05) and major bleeding (17.8% vs 14.3%, hazard ratio 1.28, 95% CI 1.07-1.54, P = .01), but there were no significant differences in other outcomes. After multivariable adjustment, there were no statistically significant racial differences in any of these outcomes at 6 years. Similarly, dual-antiplatelet therapy use was comparable between racial groups.

Conclusions: Unadjusted rates of MI and major bleeding over long-term follow up were higher among black patients compared to white patients, but these differences may be explained by racial differences in comorbid disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ahj.2019.04.005DOI Listing
August 2019

Clinical factors related to morbidity and mortality in high-risk heart failure patients: the GUIDE-IT predictive model and risk score.

Eur J Heart Fail 2019 06 27;21(6):770-778. Epub 2019 Mar 27.

Duke Clinical Research Institute, Durham, NC, USA.

Background: Most heart failure (HF) risk scores have been derived from cohorts of stable HF patients and may not incorporate up to date treatment regimens or deep phenotype characterization that change baseline risk over the short- and long-term follow-up period. We undertook the current analysis of participants in the GUIDE-IT (Guiding Evidence-Based Therapy Using Biomarker Intensified Treatment) trial to address these limitations.

Methods And Results: The GUIDE-IT study randomized 894 high-risk patients with HF and reduced ejection fraction (≤ 40%) to biomarker-guided treatment strategy vs. usual care. We performed risk modelling using Cox proportional hazards models and analysed the relationship between 35 baseline clinical factors and the primary composite endpoint of cardiovascular (CV) death or HF hospitalization, the secondary endpoint of all-cause mortality, and the exploratory endpoint of 90-day HF hospitalization or death. Prognostic relationships for continuous variables were examined and key predictors were identified using a backward variable selection process. Predictive models and risk scores were developed. Over a median follow-up of 15 months, the cumulative number of HF hospitalizations and CV deaths was 328 out of 894 patients (Kaplan-Meier event rate 34.5% at 12 months). Frequency of all-cause deaths was 143 out of 894 patients (Kaplan-Meier event rate 12.2% at 12 months). Outcomes for the primary and secondary endpoints between strategy arms of the study were similar. The most important predictor that was present in all three models was the baseline natriuretic peptide level. Hispanic ethnicity, low sodium and high heart rate were present in two of the three models. Other important predictors included the presence or absence of a device, New York Heart Association class, HF duration, black race, co-morbidities (sleep apnoea, elevated creatinine, ischaemic heart disease), low blood pressure, and a high congestion score.

Conclusion: Risk models using readily available clinical information are able to accurately predict short- and long-term CV events and may be useful in optimizing care and enriching patients for clinical trials.

Clinical Trial Registration: ClinicalTrials.gov ID number NCT01685840.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ejhf.1450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6830509PMC
June 2019

Influence of Weight Reduction and Enhanced Protein Intake on Biomarkers of Inflammation in Older Adults with Obesity.

J Nutr Gerontol Geriatr 2019 Jan-Mar;38(1):33-49. Epub 2019 Feb 27.

a Center for the Study of Aging , Duke University Medical Center , Durham , NC , USA.

Both aging and obesity are associated with increased levels of pro-inflammatory metabolites, while weight reduction is associated with improvements in inflammatory status. However, few studies have explored the response of key inflammatory markers to the combined settings of weight reduction in an aging population. There are also few studies that have investigated the potential impact of diet composition on inflammatory marker responses. In the MEASUR-UP trial, we evaluated changes in baseline levels of inflammatory markers with post-study levels for a traditional weight loss control group versus a group with generous, balanced protein intake. In this 6-month randomized controlled trial (RCT), older (≥60 years) adults with obesity (BMI ≥30 kg/m) and Short Physical Performance Battery (SPPB) score of 4-10 were randomly assigned to either a traditional weight loss regimen, (Control, n = 14) or one with higher protein intake (≥30 g) at each meal (Protein, n = 25). All participants were prescribed a hypo-caloric diet and attended weekly support and education groups and weigh-ins. Protein participants consumed ≥30 g of high-quality protein/meal, including lean and extra lean beef provided to them for two of the three meals per day. Protein intakes were 0.8 and 1.2 g/kg/day for Control and Protein, respectively. Adiponectin, leptin, C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), IL-6, IL-8, serum amyloid A (SAA), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and glycated serum protein (GSP) levels were measured at 0 and 6-month time points. At the 6-month endpoint, there was significant weight loss and decrease in BMI in both the Control (-4.8 ± 8.2 kg; -2.3 ± 2.4 kg/m; p = 0.05) and Protein (-8.7 ± 7.4 kg; -2.9 ± 2.3 kg/m; p < 0.0001) groups. SPPB scores improved in both arms, with a superior functional response in Protein (p < 0.05). Body fat (%) at baseline was positively correlated with leptin, hs-CRP, VCAM-1, ICAM-1, and GSP. Several markers of inflammation responded to the Protein group: leptin (p < 0.001), hs-CRP (p < 0.01), and ICAM-1 (p < 0.01) were decreased and adiponectin increased (p < 0.01). There were no significant changes in any inflammatory markers in the Control arm. In the between group comparison, only adiponectin trended towards a group difference (more improvement in Protein; p < 0.07). Our findings in the MEASUR-UP trial show that a weight loss diet with enhanced protein intake is comparable to an adequate protein diet in terms of weight loss success and that it can lead to improvements in inflammatory status, specifically for adiponectin, leptin, hs-CRP, and ICAM-1. These findings are important given current recommendations for higher protein intakes in older adults and justify the additional study of the inflammatory impact of an enhanced protein diet. (ClinicalTrials.gov identifier: NCT01715753).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/21551197.2018.1564200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6447442PMC
May 2020

Health Care Utilization and Prescribing Patterns for Adult Eustachian Tube Dysfunction.

Otolaryngol Head Neck Surg 2019 06 5;160(6):1071-1080. Epub 2019 Feb 5.

6 Department of Otolaryngology, Harvard Medical School, Boston, Massachusetts, USA.

Objective: Eustachian tube dysfunction (ETD) prompts >2 million adult visits in the United States annually. While disease prevalence and health care utilization are established for children, practice patterns for adults remain unknown. Our objective was to determine national resource utilization for adult ETD.

Study Design: Cross-sectional study.

Setting: National database sample.

Subjects And Methods: The Truven Health MarketScan Databases (2010-2014) analytic cohort included health care encounters of patients ≥18 years of age with a diagnosis of ETD, otitis media with effusion, or tympanic membrane retraction. Visits associated with recent diagnoses of acute upper respiratory infection, head and neck cancer, or radiation therapy were excluded. Acute ETD (<3 months) and chronic ETD (≥3 months) were subgroups. Medication usage was quantified by class.

Results: ETD was diagnosed for 1,298,987 patients, 11% of which was chronic. Over 92% of patients were seen in outpatient clinics, most often by otolaryngology (57%) for chronic ETD and by general medicine (49%) for acute ETD. Medications were frequently utilized, as 530,146 (53.7%) patients received ≥1 prescription. Top prescriptions for chronic ETD included intranasal corticosteroids (22%), antibiotics (22%), oral corticosteroids (13%), and analgesics (6%). The overall annual cost of prescribed medications associated with visits in which either acute or chronic ETD was diagnosed exceeded $8.5 million for a mean of $80.78 per patient who filled a prescription.

Conclusion: Adult ETD is frequently treated with several medication classes by a variety of provider types. Understanding the potential adverse effects and cost associated with these practices should be a priority.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0194599819826959DOI Listing
June 2019

Polyvascular Disease and Risk of Major Adverse Cardiovascular Events in Peripheral Artery Disease: A Secondary Analysis of the EUCLID Trial.

JAMA Netw Open 2018 11 2;1(7):e185239. Epub 2018 Nov 2.

Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina.

Importance: The effect of polyvascular disease on cardiovascular outcomes in the background of peripheral artery disease (PAD) is unclear.

Objective: To determine the risk of ischemic events (both cardiac and limb) among patients with PAD and polyvascular disease.

Design, Setting, And Participants: In this post hoc secondary analysis of the international Examining Use of Ticagrelor in Peripheral Artery Disease (EUCLID) trial, outcomes were compared among 13 885 enrolled patients with PAD alone, PAD + coronary artery disease (CAD), PAD + cerebrovascular disease (CVD), and PAD + CAD + CVD. Adjusted Cox proportional hazards regression models were implemented to determine the risk associated with polyvascular disease and outcomes, and intention-to-treat analysis was performed. The EUCLID trial was conducted from December 31, 2012, to March 7, 2014; the present post hoc analysis was performed from June 1, 2017, to February 5, 2018.

Interventions: EUCLID evaluated ticagrelor vs clopidogrel in preventing major adverse cardiac events (cardiovascular death, myocardial infarction [MI], or ischemic stroke) and major bleeding in patients with PAD.

Main Outcomes And Measures: The primary end point was a composite of cardiovascular death, MI, or ischemic stroke. Key secondary end points included the individual components of the primary end point and acute limb ischemia leading to hospitalization, major amputation, and lower-extremity revascularization. The primary end point of Thrombolysis in Myocardial Infarction (TIMI) major bleeding was also evaluated.

Results: The EUCLID trial randomized 13 885 patients with a median age of 66 years (interquartile range, 60-73 years), of whom 3888 (28.0%) were women. At baseline, 7804 patients (56.2%) had PAD alone; 2639 (19.0%) had PAD + CAD; 2049 (14.8%) had PAD + CVD; and 1393 (10.0%) had PAD + CAD + CVD. Compared with patients with isolated PAD, the adjusted hazard ratios (aHRs) for major adverse cardiac events were 1.34 (95% CI, 1.15-1.57; P < .001) for PAD + CVD, 1.65 (95% CI, 1.43-1.91; P < .001) for PAD + CAD, and 1.99 (95% CI, 1.69-2.34; P < .001) for PAD + CAD + CVD. The aHRs for lower-extremity revascularization were 1.17 (95% CI, 1.03-1.34; P = .01) for PAD + CAD, 1.17 (95% CI, 1.02-1.35; P = .02) for PAD + CVD, and 1.34 (95% CI, 1.15-1.57; P < .001) for PAD + CAD + CVD. Polyvascular disease was not associated with an increased risk of acute limb ischemia (aHR for PAD + CVD, 0.91; 95% CI, 0.62-1.34, P = .63; PAD + CAD, 0.93; 95% CI, 0.64-1.34, P = .69; and PAD + CAD + CVD, 0.98; 95% CI, 0.63-1.53, P = .93), major amputation (aHR for PAD + CVD, 0.83; 95% CI, 0.54-1.27, P = .40; PAD + CAD, 0.74; 95% CI, 0.47-1.16, P = .19; and PAD + CAD + CVD, 1.12; 95% CI, 0.69-1.80, P = .65), or TIMI major bleeding (PAD + CVD, 0.98; 0.66-1.44, P = .91; PAD + CAD, 1.04; 0.74-1.48, P = .81; and PAD + CAD + CVD, 0.96; 95% CI, 0.62-1.51, P = .88).

Conclusions And Relevance: Compared with patients with PAD alone, the risk of major adverse cardiac events and lower-extremity revascularization increased with multiple vascular bed involvement. There was no clear increased risk of bleeding associated with polyvascular disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamanetworkopen.2018.5239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6324381PMC
November 2018

Outcomes of apixaban versus warfarin in patients with atrial fibrillation and multi-morbidity: Insights from the ARISTOTLE trial.

Am Heart J 2019 02 22;208:123-131. Epub 2018 Nov 22.

Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC.

Background: Patients with atrial fibrillation (AF) often have multi-morbidity, defined as ≥3 comorbid conditions. Multi-morbidity is associated with polypharmacy, adverse events, and frailty potentially altering response to anticoagulation. We sought to describe the prevalence of multi-morbidity among older patients with AF and determine the association between multi-morbidity, clinical outcomes, and the efficacy and safety of apixaban compared with warfarin.

Methods: In this post-hoc subgroup analysis of the ARISTOTLE trial, we studied enrolled patients age ≥ 55 years (n = 16,800). Patients were categorized by the number of comorbid conditions at baseline: no multi-morbidity (0-2 comorbid conditions), moderate multi-morbidity (3-5 comorbid conditions), and high multi-morbidity (≥6 comorbid conditions). Association between multi-morbidity and clinical outcomes were analyzed by treatment with a median follow-up of 1.8 (1.3-2.3) years.

Results: Multi-morbidity was present in 64% (n = 10,713) of patients; 51% (n = 8491) had moderate multi-morbidity, 13% (n = 2222) had high multi-morbidity, and 36% (n = 6087) had no multi-morbidity. Compared with the no multi-morbidity group, the high multi-morbidity group was older (74 vs 69 years), took twice as many medications (10 vs 5), and had higher CHADS-VASc scores (4.9 vs 2.7) (all P < .001). Adjusted rates per 100 patient-years for stroke/systemic embolism, death, and major bleeding increased with multi-morbidity (Reference no multi-morbidity; moderate multi-morbidity 1.42 [1.24-1.64] and high multi-morbidity 1.92 [1.59-2.31]), with no interaction in relation to efficacy or safety of apixaban.

Conclusions: Multi-morbidity is prevalent among the population with AF; efficacy and safety of apixaban is preserved in this subgroup supporting extension of trial results to the most complex AF patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ahj.2018.09.017DOI Listing
February 2019