Publications by authors named "Tine L De Backer"

19 Publications

  • Page 1 of 1

Non-vitamin K Antagonist Oral Anticoagulants (NOACs) Versus Warfarin in Patients with Atrial Fibrillation Using P-gp and/or CYP450-Interacting Drugs: a Systematic Review and Meta-analysis.

Cardiovasc Drugs Ther 2021 Oct 12. Epub 2021 Oct 12.

Department of Bioanalysis, Pharmaceutical Care Unit, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium.

Purpose: Non-vitamin K antagonist oral anticoagulants (NOACs) are excreted by P-glycoprotein (P-gp) and some are metabolized by CYP450 enzymes such as CYP3A4. Although fewer drug interactions are present with NOACs, it is unclear whether NOACs should also be preferred over vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) using pharmacokinetically interacting drugs. Therefore, the benefit-risk profile of NOACs versus VKAs was investigated in AF patients treated with P-gp and/or CYP450-interacting drugs.

Methods: Using PubMed and Embase, randomized controlled trials and observational studies on the effectiveness and safety of NOACs versus VKAs in AF patients using P-gp and/or CYP450-interacting drugs were included. A meta-analysis was performed, calculating relative risks (RR) and 95% confidence intervals (CI) with the Mantel-Haenszel method.

Results: Twelve studies were included, investigating 10,793 NOAC and 10,096 VKA users treated with P-gp/CYP3A4 inhibitors, whereas no studies on P-gp and/or CYP450-inducing drugs were identified. Compared to VKAs, NOACs were associated with a borderline non-significantly lower stroke or systemic embolism (stroke/SE) risk (RR 0.85, 95%CI (0.72-1.01)), significantly lower intracranial bleeding (RR 0.47, 95%CI (0.34-0.65)) and all-cause mortality risks (RR 0.87, 95%CI (0.79-0.95), but significantly higher gastrointestinal bleeding risk (RR 1.74, 95%CI (1.06-2.86)). Among AF patients using amiodarone, NOACs were associated with significantly lower stroke/SE (RR 0.71, 95%CI (0.54-0.93)) and intracranial bleeding risks (RR 0.51, 95%CI (0.29-0.88)), but significantly higher gastrointestinal bleeding risk (RR 2.15, 95%CI (1.24-3.72)) than VKAs.

Conclusion: The benefit-risk profile of NOACs compared to VKAs was preserved in AF patients using P-gp/CYP3A4 inhibitors, including amiodarone.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10557-021-07279-8DOI Listing
October 2021

The impact of underweight and obesity on outcomes in anticoagulated patients with atrial fibrillation: A systematic review and meta-analysis on the obesity paradox.

Clin Cardiol 2021 May 26;44(5):599-608. Epub 2021 Mar 26.

Department of Bioanalysis, Pharmaceutical Care Unit, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.

Although obesity is associated with the development and progression of atrial fibrillation (AF), an obesity paradox may be present, illustrated by seemingly protective effects of obesity on AF-related outcomes. Body mass index (BMI) has an impact on outcomes in AF patients using oral anticoagulants. After searching Medline and Embase, meta-analysis of results of four randomized and five observational studies demonstrated significantly lower risks of stroke or systemic embolism (RR 0.80, 95%CI [0.73-0.87]; RR 0.63, 95%CI [0.57-0.70]; and RR 0.42, 95%CI [0.31-0.57], respectively) and all-cause mortality (RR 0.73, 95%CI [0.64-0.83]; RR 0.61, 95%CI [0.52-0.71]; and RR 0.56, 95%CI [0.47-0.66], respectively) in overweight, obese and morbidly obese anticoagulated AF patients (BMI 25 to <30, ≥30 and ≥40 kg/m , respectively) compared to normal BMI anticoagulated AF patients (BMI 18.5 to <25 kg/m ). In contrast, thromboembolic (RR 1.92, 95%CI [1.28-2.90]) and mortality (RR 3.57, 95%CI [2.50-5.11]) risks were significantly increased in underweight anticoagulated AF patients (BMI <18.5 kg/m ). In overweight and obese anticoagulated AF patients, the risks of major bleeding (RR 0.86, 95%CI [0.76-0.99]; and RR 0.88, 95%CI [0.79-0.98], respectively) and intracranial bleeding (RR 0.75, 95%CI [0.58-0.97]; and RR 0.57, 95%CI [0.40-0.80], respectively) were also significantly lower compared to normal BMI patients, while similar risks were observed in underweight and morbidly obese patients. This meta-analysis demonstrated lower thromboembolic and mortality risks with increasing BMI. However, as this paradox was driven by results from randomized studies, while observational studies rendered more conflicting results, these seemingly protective effects should still be interpreted with caution.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/clc.23593DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8119828PMC
May 2021

Non-Vitamin K Antagonist Oral Anticoagulants (NOACs) Versus Warfarin in Patients with Atrial Fibrillation and (Morbid) Obesity or Low Body Weight: a Systematic Review and Meta-Analysis.

Cardiovasc Drugs Ther 2021 Jan 11. Epub 2021 Jan 11.

Department of Bioanalysis, Pharmaceutical Care Unit, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium.

Purpose: Oral anticoagulants are crucial for preventing systemic thromboembolism in atrial fibrillation (AF), with guidelines preferring non-vitamin K antagonist oral anticoagulants (NOACs) over vitamin K antagonists (VKAs) in the general AF population. However, as NOACs are administered in fixed doses, concerns of unintentional underdosing in morbidly obese patients and unintentional overdosing in underweight patients have emerged. Therefore, a critical appraisal of the benefit-risk profile of NOACs in AF patients across the body weight spectrum is needed.

Methods And Results: After searching Medline, this systematic review discusses the impact of body weight on the risk-benefit profile of NOACs versus VKAs. The meta-analysis demonstrated that NOAC use in obese and class III obese AF patients (body mass index (BMI) ≥ 30 and ≥ 40 kg/m, respectively) was associated with significantly lower stroke/systemic embolism (stroke/SE) risks (RR 0.82, 95%CI [0.71-0.96] and RR 0.75, 95%CI [0.64-0.87], respectively), similar to lower major bleeding risks (RR 0.83, 95%CI [0.69-1.00] and RR 0.74, 95%CI [0.57-0.95], respectively) and similar mortality risks (RR 0.92, 95%CI [0.73-1.15] and RR 1.17, 95%CI [0.83-1.64], respectively) compared to VKAs. In AF patients ≤ 60 kg, significantly lower stroke/SE (RR 0.63, 95%CI [0.56-0.71]) and major bleeding risks (RR 0.71, 95%CI [0.62-0.80]), but similar mortality risks (RR 0.68, 95%CI [0.42-1.10]), were observed for NOAC- versus VKA-treated patients.

Conclusion: The benefit-risk profile of NOACs seems preserved in (morbidly) obese AF patients and patients with low body weight. However, more data are needed on underweight AF patients (BMI < 18.5 kg/m) and on differences between NOACs in these patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10557-020-07122-6DOI Listing
January 2021

Effectiveness and Safety of Oral Anticoagulants in Older Patients With Atrial Fibrillation: A Systematic Review and Meta-Analysis.

Front Pharmacol 2020 9;11:583311. Epub 2020 Sep 9.

Pharmaceutical Care Unit, Department of Bioanalysis, Ghent University, Ghent, Belgium.

Background And Objective: Atrial fibrillation (AF), the most common cardiac arrhythmia, typically increases with age. Oral anticoagulants (OACs) are the cornerstone of treatment to reduce the associated risk for systemic thromboembolism. Four large randomized controlled trials (RCTs) have shown that non-vitamin K antagonist oral anticoagulants (NOACs) are non-inferior to vitamin K antagonists (VKAs) in preventing stroke and systemic embolism, as well as regarding their risk for major bleeding. However, as vulnerable geriatric patients with AF were largely underrepresented in these trials, physicians are faced with the challenge of choosing the right anticoagulant for geriatric patients in real-life clinical practice. In this vulnerable patient group, NOACs tend to be underused or underdosed due to concerns of excessive fall-related intracranial bleeding, cognitive impairment, multiple drug-drug interactions, low body weight or impaired renal function. As life expectancy continues to rise worldwide, the number of geriatric patients substantially increases. Therefore, there is an urgent need for a critical appraisal of the added value of NOACs in geriatric patients with AF at high thromboembolic and bleeding risk.

Methods And Results: This systematic review provides an overview of the literature on the impact of increased age (≥75 years), multimorbidity, polypharmacy, increased falling risk, frailty and dementia on the effectiveness and safety of NOACs as compared to VKAs, after searching the Medline database. Moreover, a meta-analysis on the impact of increased age ≥75 years old was performed after pooling results from 6 analyses of RCTs and 6 longitudinal observational cohort studies, highlighting the superior effectiveness (hazard ratio (HR) 0.83, 95% confidence interval (CI) [0.74-0.94] for stroke/SE; HR 0.77, 95%CI [0.65-0.92] for mortality) and non-inferior safety (HR 0.93, 95%CI [0.86-1.01] for major bleeding; HR 0.58, 95%CI [0.50-0.67] for intracranial bleeding; HR 1.17, 95%CI [0.99-1.38] for gastrointestinal bleeding) of NOACs versus VKAs in older AF patients.

Conclusion: Across geriatric subgroups, apixaban was consistently associated with the most favourable benefit-risk profile and should therefore be preferred in geriatric patients with AF. However, research gaps on the impact of increased falling risk, frailty and baseline dementia were identified, requiring careful consideration while awaiting more results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2020.583311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509201PMC
September 2020

Community pharmacy-based study of adherence to non-vitamin K antagonist oral anticoagulants.

Heart 2020 11 23;106(22):1740-1746. Epub 2020 Jun 23.

Pharmaceutical Care Unit, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.

Objective: This study aimed to assess implementation adherence (how well the patient's actual intake matches the prescribed dosing regimen) to non-vitamin K antagonist oral anticoagulants (NOACs) and to explore experiences with and beliefs about NOACs in a real-world sample of long-term NOAC users.

Methods: A cross-sectional observational study was conducted in home-dwelling adults who started taking a NOAC at least 1 year prior to inclusion. Pharmacy dispensing data were used to calculate the Medication Possession Ratio (MPR). Patients were recruited in 158 community pharmacies in Flanders, Belgium. They completed a questionnaire collecting basic characteristics and exploring self-reported adherence to NOACs (using the Medication Adherence Report Scale, MARS) and experiences with and beliefs about NOACs (using the Beliefs about Medicines Questionnaire, BMQ).

Results: A total of 766 patients (mean age 76.2±8.8 years, median CHADS-VASc score 4 (IQR=3-4)) were included. The majority (93.5%) used NOAC for stroke prevention in atrial fibrillation. The median MPR was 95.2% (IQR=87.8-99.7) which corresponds with half of the study population not taking their NOAC on at least 17 cumulative days per year. Almost 21% of participants reported non-adherence on the MARS (score <25), with unintentional non-adherence (forgetfulness) most frequently reported (15.4%). Although two-thirds of NOAC users indicated to experience adverse drug reactions, the BMQ demonstrated a positive attitude towards NOAC therapy, where necessity beliefs outweigh the concerns.

Conclusions: Our data indicate that long-term NOAC users have high implementation adherence and a positive attitude towards NOAC therapy. However, taking into account patients' thromboembolic risk and NOACs' short half-lives, further optimisation of NOAC use seems warranted in this population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/heartjnl-2020-316781DOI Listing
November 2020

Average pixel intensity method for prediction of outcome in secondary mitral regurgitation.

Heart 2020 06 22;106(12):904-909. Epub 2020 Mar 22.

Heart Center, Universitair Ziekenhuis Ghent, Ghent, Belgium.

Background: Echocardiographic grading of secondary mitral regurgitation (SMR) severity is challenging and involves multiple guideline-recommended parameters. We previously introduced the average pixel intensity (API) method for grading SMR. In this study, the clinical outcome in SMR based on the API method for grading MR was compared with conventional grading methods.

Methods: 231 patients with systolic heart failure and reduced ejection fraction (ischaemic/non-ischaemic) and SMR were prospectively enrolled. MR was graded using all guideline-recommended parameters and the API method, which is based on the pixel intensity of the continuous wave Doppler signal. The primary outcome was MACE (major adverse cardiac event).

Results: The API method was applicable in 98% of patients with SMR (n=227). During a median follow-up of 24 months, 98 patients (43%) had a MACE (cardiovascular mortality (n=50, 22%), heart failure hospitalisation (n=44, 19%), mitral valve surgery (n=11, 5%), percutaneous mitral intervention (n=12, 5%), heart transplantation (n=5, 2%)). On log-rank test, the API method was highly significant in predicting clinical outcome. On multivariable Cox proportional hazard analysis, SMR grading with the API method was an independent predictor of clinical outcome (along with NYHA class and right ventricular systolic pressure; p<0.001), increasing the event risk by 9% per 10 au API rise (p=0.001). In the same multivariable analysis, proximal isovelocity surface area (PISA)-effective regurgitant orifice area or PISA-regurgitant volume were not independent predictors of events (p=0.18 and 0.26, respectively).

Conclusion: SMR grading with the API method is an independent predictor of clinical outcome and provides prognostic information in addition to clinical and other echocardiographic variables.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/heartjnl-2019-316157DOI Listing
June 2020

The sEROtonergic pathway: a hERO for the brain, a zERO for the valves?

Heart 2019 08 25;105(15):1134-1135. Epub 2019 May 25.

Cardiovascular Diseases, University Hospital Ghent, Ghent, Belgium.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/heartjnl-2018-314551DOI Listing
August 2019

A Long and Winding Road from Tortuous Arteries to a Straightforward Diagnosis of FMD.

Am J Hypertens 2017 08;30(8):765-766

Department of Cardiovascular Diseases and Clinical Pharmacology, Ghent University Hospital, Ghent, Belgium.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ajh/hpx082DOI Listing
August 2017

Vascular dysregulation in normal-tension glaucoma is not affected by structure and function of the microcirculation or macrocirculation at rest: a case-control study.

Medicine (Baltimore) 2015 Jan;94(2):e425

From the Heymans Institute of Pharmacology (JB, TLMDB, SVV, MA, LMVB), Clinical Pharmacology, Ghent University; Department of Ophthalmology (GV, A-MS, PK, TR), Ghent University Hospital; Institute of Biomedical Technology (IBiTech) (PS), Ghent University, Ghent, Belgium; and Department of Internal Medicine (FV), Maastricht University Medical Centre, Maastricht, The Netherlands.

In normal-tension glaucoma (NTG), optic nerve damage occurs despite a normal intraocular pressure. Studies implicating systemic blood pressure or, more recently, arterial stiffness in the pathophysiology of NTG have produced conflicting results. Our aim was to investigate whether NTG is associated with alterations in the macrocirculation or microcirculation, cardiac function, and peripheral and central hemodynamics. Thirty patients with NTG (mean age 65 years, range 46-79) and 33 healthy subjects (mean age 67 years, range 42-79) matched for age and sex were included in the study. Exclusion criteria (for both cases and controls) were history of cardiovascular disease, diabetes mellitus, severe hypertension, and hypercholesterolemia. Aortic stiffness was measured using carotid-femoral pulse wave velocity (PWV), central hemodynamics using carotid artery applanation tonometry, and diameter, stiffness, and intima-media thickness (IMT) of the carotid and femoral artery using echo-tracking. Total peripheral resistance index (TPRI) was derived from mean arterial pressure and cardiac index, measured using ultrasound. There were no statistically significant differences in arterial structure nor function between NTG patients and age and sex-matched controls. NTG versus controls, respectively: brachial blood pressure 126 ± 15/77 ± 8 versus 127 ± 16/76 ± 7 mm Hg, P = 0.81; carotid-femoral PWV 9.8 ± 2.1 versus 10.1 ± 1.9 m/s, P = 0.60; TPRI 1833 ± 609 versus 1779 ± 602 dyne.s/cm5/m2, P = 0.79; and carotid IMT 0.65 ± 0.14 versus 0.68 ± 0.13 mm, P = 0.39. This study could not show an association of NTG with altered IMT, arterial stiffness, total peripheral resistance, cardiac output, and peripheral or central hemodynamics at rest. Although the majority of these NTG patients do exhibit symptoms of vascular dysregulation, in the present study this was not translated into alterations in the microcirculation or macrocirculation at rest.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000000425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4602537PMC
January 2015

Asymmetry in prevalence of femoral but not carotid atherosclerosis.

J Hypertens 2014 Jul;32(7):1429-34

aHeymans Institute of Pharmacology, Clinical Pharmacology bInstitute Biomedical Technology (IBiTech), Ghent University cDepartment of Internal Medicine (Cardiovascular Diseases), Ghent University and Ghent University Hospital dDepartment of Public Health, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.

Objective(s): Atherosclerotic disease is caused by a combination of systemic and local factors (e.g. geometry) affecting local flow conditions. In contrast to the carotid artery, at the iliac-femoral artery region, a large degree of bilateral asymmetry exists. Therefore, we aimed to determine the influence of body side on the prevalence of atherosclerosis (i.e. plaque and intima-media thickness; IMT) at the carotid and femoral arteries.

Methods: Data were used from the ASKLEPIOS study, including 2524 apparently healthy individuals with a mean age of 46 years (range 35-55 years). Echographic images were obtained bilaterally of the carotid and femoral arteries. A single observer approach was used for the acquisition and quantification of plaques and IMT.

Results: The carotid artery displays no significant left-right difference in IMT values nor plaque prevalence (right: 12.0 vs. left 13.3%; P = 0.18). In contrast, for the femoral artery, the IMT distribution at the right common femoral artery is more skewed (P90 right: 1.11 mm, left 1.01 mm; P < 0.001), which is mirrored by a significantly higher plaque prevalence (right: 21.9 vs. left: 15.7%; P < 0.001).

Conclusion: In the present study, atherosclerotic lesions are more prevalent at the right than at the left femoral artery. This finding highlights the possible role of local arterial geometry in the development of atherosclerosis and underscores the importance of the choice of body side when assessing vascular health.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/HJH.0000000000000205DOI Listing
July 2014

Buflomedil for intermittent claudication.

Cochrane Database Syst Rev 2013 Mar 28(3):CD000988. Epub 2013 Mar 28.

Heart Center, Ghent University Hospital, Ghent, Belgium.

Background: Intermittent claudication (IC) is pain caused by chronic occlusive arterial disease, that develops in a limb during exercise and is relieved with rest. Buflomedil is a vasoactive agent used to treat peripheral vascular disease. However, its clinical efficacy for IC has not yet been critically examined. This is an update of a Cochrane review first published in 2000, and previously updated in 2007 and 2008.

Objectives: To evaluate the available evidence on the efficacy of buflomedil for IC.

Search Methods: For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched January 2013) and CENTRAL (2012, Issue 12).

Selection Criteria: Double-blinded, randomized controlled trials (RCTs) in patients with IC (Fontaine stage II) receiving oral buflomedil compared with placebo. Pain-free walking distance (PFWD) and maximum walking distance (MWD) were analysed by standardized exercise test.

Data Collection And Analysis: Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information.

Main Results: We included two RCTs with 127 participants. Both RCTs showed moderate improvements in PFWD for patients on buflomedil. This improvement was statistically significant for both trials (WMD 75.1 m, 95% confidence interval (CI) 20.6 to 129.6; WMD 80.6 m, 95% CI 3.0 to 158.2), the latter being a wholly diabetic population. For both RCTs, MWD gains were statistically significant with wide confidence intervals (WMD 80.7 m, 95% CI 9.4 to 152; WMD 171.4 m, 95% CI 51.3 to 291.5), respectively.

Authors' Conclusions: There is little evidence available to evaluate the efficacy of buflomedil for IC. Most trials were excluded due to poor quality. The two included trials showed moderately positive results; these are undermined by publication bias since we know of at least another four unpublished, irretrievable, and inconclusive studies.Buflomedil's benefit is small in relation to safety issues and its narrow therapeutic range.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/14651858.CD000988.pub4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7047040PMC
March 2013

Noninvasive assessment of carotid-femoral pulse wave velocity: the influence of body side and body contours.

J Hypertens 2013 May;31(5):946-51

Heymans Institute of Pharmacology, Ghent University, Ghent, Belgium.

Background: Recently, an expert group advised to measure carotid-femoral (cf) pulse wave velocity (PWV) on the right side of the body, and to use a sliding caliper when tape measure distance cannot be obtained in a straight line. The present study investigates the evidence for this advice by comparing the real travelled cf path lengths (RTPLs) at both body sides and comparing the straight distance (as can be obtained with a sliding caliper) with the tape measure distance.

Methods: RTPLs were measured with MRI in 98 individuals (49 men, age 21-76 years). Path lengths from the aortic arch to the carotid (AA-CA) and femoral (AA-FA) sites were determined. RTPL was calculated as (AA-FA) - (AA-CA) and compared between both sides. RTPLs were compared with 80% of the direct cf distance using a tape measure and the straight cf distance obtained from MRI images.

Results: RTPL was slightly longer [11 mm (12), P < 0.001] at the right side. The 80%-rule overestimated RTPLs with 0.5% at the right and 2.7% at the left side. Straight MRI distance tended (P = 0.09) to perform slightly better than tape measure distance.

Conclusion: The travelled cf path is slightly longer at the right than at the left body side and the straight MRI distance tends to perform better than tape measure distance. The present study supports the advice of the expert consensus group to measure cf-PWV at the right body side using a sliding caliper when tape measure distance cannot be obtained in a straight line.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/HJH.0b013e328360275dDOI Listing
May 2013

Naftidrofuryl for intermittent claudication.

Cochrane Database Syst Rev 2012 Dec 12;12:CD001368. Epub 2012 Dec 12.

Heart Center, Ghent University Hospital, Ghent, Belgium.

Background: Lifestyle changes and cardiovascular prevention measures are a primary treatment for intermittent claudication (IC). Symptomatic treatment with vasoactive agents (Anatomic Therapeutic Chemical Classification (ATC) for medicines from the World Health Organisation class CO4A) is controversial.

Objectives: To evaluate evidence on the efficacy and safety of oral naftidrofuryl (ATC CO4 21) versus placebo on the pain-free walking distance (PFWD) of people with IC by using a meta-analysis based on individual patient data (IPD).

Search Methods: For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched October 2012) and CENTRAL (2012, Issue 9).For the original review the authors handsearched the European Journal of Vascular and Endovascular Surgery (1984 to 1994) and checked relevant bibliographies. They contacted the registration holder of naftidrofuryl and the authors of identified trials for any unpublished data.

Selection Criteria: We included only randomized controlled trials (RCTs) with low or moderate risk of bias for which the IPD were available.

Data Collection And Analysis: We collected data from the electronic data file or from the case report form and checked the data by a statistical quality control procedure. All randomized patients were analyzed following the intention-to-treat (ITT) principle. The geometric mean of the relative improvement in PFWD was calculated for both treatment groups in all identified studies.The effect of the drug was assessed compared with placebo on final walking distance (WDf) using multilevel and random-effect models and adjusting for baseline walking distance (WD0). For the responder analysis, therapeutic success was defined as an improvement of walking distance of at least 50%.

Main Results: We included seven studies in the IPD (n = 1266 patients). One of these studies (n = 183) was only used in the sensitivity analysis so that the main analysis included 1083 patients. The ratio of the relative improvement in PFWD (naftidrofuryl compared with placebo) was 1.37 (95% confidence interval (CI) 1.27 to 1.49, P < 0.001). The absolute difference in responder rate, or proportion successfully treated, was 22.3% (95% CI 17.1% to 27.6%). The calculated number needed to treat was 4.5 (95% CI 3.6 to 5.8).

Authors' Conclusions: Oral naftidrofuryl has a statistically significant and clinically meaningful, although moderate, effect of improving walking distance in the six months after initiation of therapy for people with intermittent claudication. Access by researchers to data from RCTs that are suitable for IPD analysis should be possible through repositories of data from pharmacological trials. Regular formal appraisal of the balance of risk and benefit is needed for older pharmaceutical products.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/14651858.CD001368.pub4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7075104PMC
December 2012

Left ventricular hypertrophy by electrocardiography and echocardiography in the African American Study of Kidney Disease Cohort Study.

J Am Soc Hypertens 2012 May-Jun;6(3):193-200. Epub 2012 Feb 16.

Beth Israel Deaconess Medical Center, Boston, MA, USA.

Although electrocardiographic criteria for diagnosing left ventricular hypertrophy have a low sensitivity in the general population, their test characteristics have not been evaluated in the high-prevalence group of American Americans with chronic kidney disease. The purpose of the current study was to evaluate these test characteristics among African Americans (n = 645) with hypertensive kidney disease as part of the African-American Study of Kidney Disease and Hypertension cohort. Electrocardiograms were read by 2 cardiologists at an independent core laboratory using the 2 Sokolow-Lyon criteria and the Cornell criteria. Left ventricular hypertrophy on echocardiography was defined as left ventricular mass index greater than 49.2 and greater than 46.7 g/m(2.7) in men and women, respectively. Sixty-nine percent of the population had left ventricular hypertrophy on echo, whereas 34% had left ventricular hypertrophy by any of the electrocardiographic criteria. Sensitivity by individual electrocardiographic criteria was 16.5% by Sokolow-Lyon-1, 19.3% by Sokolow-Lyon-2, and 24.7% by Cornell criteria, with specificity ranging from 89% to 92%. When using any of the 3 criteria, sensitivity increased to 40.4% with a decrease in specificity to 78.0%. Consistent with findings in a general population, left ventricular hypertrophy by electrocardiography had low sensitivity and high specificity in this cohort of African Americans with hypertensive kidney disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jash.2012.01.004DOI Listing
September 2012

Carotid to femoral pulse wave velocity: a comparison of real travelled aortic path lengths determined by MRI and superficial measurements.

J Hypertens 2011 Aug;29(8):1577-82

Heymans Institute of Pharmacology, Ghent University Hospital Ghent, Belgium.

Objectives: Carotid-femoral pulse wave velocity (PWV) is the gold standard method for determination of arterial stiffness. PWV is assessed by dividing travelled distance by travel time. Standardization and validation of the methodology for travelled distance measurement is of crucial importance. The aim of the current investigation was to standardize and validate the methodology for travelled distance measurement.

Methods: Real travelled carotid-femoral path lengths were measured with MRI in 98 healthy men/women (50% men, age 21-76 years) and are used as reference distance. This reference distance was compared with 11 estimates of aortic path length from body surface distances commonly used in PWV measurement, nine of them based on tape measures and two based on body height. Determinants of the difference between reference distance and the best body surface distance were determined. Additionally, the influence of body contours was identified.

Results: The tape measure distance from carotid to femoral artery (CA-FA), multiplied by 0.8, yielded the best agreement with the reference aortic path length [difference 0.26 cm (SD 3.8), not statistically significant]. Thirty percent of the variation in difference between the reference distance and tape measure distance (CA-FA × 0.8) was explained by age. Adding BMI increased this number to 34%.

Conclusion: The tape measure distance from CA-FA, multiplied by 0.8, corresponds best with the real travelled aortic path length. This distance is moderately (yet statistically significantly) influenced by age and minimally by BMI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/HJH.0b013e3283487841DOI Listing
August 2011

Bias in benefit-risk appraisal in older products: the case of buflomedil for intermittent claudication.

Drug Saf 2009 ;32(4):283-91

Heymans Institute of Pharmacology, Ghent University, Department of Cardiovascular Diseases, University Hospital Ghent, Ghent, Belgium.

Benefit-risk assessment should be ongoing during the life cycle of a pharmaceutical agent. New products are subjected to rigorous registration laws and rules, which attempt to assure the availability and validity of evidence. For older products, bias in benefit-risk assessment is more likely, as a number of safeguards were not in place at the time these products were registered. This issue of bias in benefit-risk assessment of older products is illustrated here with an example: buflomedil in intermittent claudication. Data on efficacy were retrieved from a Cochrane systematic review. Data on safety were obtained by comparing the number of reports of serious adverse events and fatalities published in the literature with those reported in postmarketing surveillance databases. In the case of efficacy, the slim basis of evidence for the benefit of buflomedil is undermined by documented publication bias. In the case of safety, bias in reporting to international safety databases is illustrated by the discrepancy between the number of drug-related deaths published in the literature (20), the potentially drug-related deaths in the WHO database (20) and deaths attributed to buflomedil in the database of the international marketing authorization holder (11). In older products, efficacy cannot be evaluated without a thorough search for publication bias. For safety, case reporting of drug-related serious events and deaths in the literature remains a necessary instrument for risk appraisal of older medicines, despite the existence of postmarketing safety databases. The enforcement of efficient communication between healthcare workers, drug companies, national centres of pharmacovigilance, national poison centers and the WHO is necessary to ensure the validity of postmarketing surveillance reporting systems. Drugs considered obsolete because of unfavourable benefit-risk assessment should not be allowed to stay on the market.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2165/00002018-200932040-00003DOI Listing
July 2009

The role of whole blood viscosity in premature coronary artery disease in women.

Atherosclerosis 2002 Dec;165(2):367-73

Cardiovascular Center, Onze-Lieve-Vrouw Hospital, Moorselbaan 164, 9300, Aalst, Belgium.

Background: Impaired hemorheology has been demonstrated in atherosclerotic disease and has shown a relationship with classical risk factors. Blood viscosity (eta), being the ratio of shear stress over shear rate, is an important parameter of hemorheology. In women with premature coronary artery disease (CAD), the underlying risk factors are a matter of debate and the role of whole blood viscosity in its pathogenesis has not been documented.

Aim: To investigate the association of whole blood viscosity with premature CAD in women, with complaints suggestive of angina pectoris.

Methods: Eighty-eight women (mean age 53 years) were divided into two groups, those with a high likelihood of CAD (LIKELI+) and those with a low likelihood of CAD (LIKELI-), based on medical history and technical investigations. Assessment of risk factors comprised smoking, diabetes mellitus, arterial hypertension, left ventricular hypertrophy (LVH), systolic and diastolic blood pressures, total low-density lipoprotein (LDL)- and high-density lipoprotein (HDL)-cholesterol, triglycerides, body mass index, menopause, hormone replacement therapy, uric acid and creatinine, and predicted 10-year cardiovascular risk according to the Framingham study was calculated. Whole blood viscosity was determined at 37 degrees C using a rotational cone-and-plate viscosimeter.

Results: Baseline characteristics did not differ significantly between the groups except for antiplatelet therapy (P=0.001), prevalence of diabetes mellitus (P=0.002), predicted 10-year cardiovascular risk (P=0.007), essential hypertension (P=0.02), LVH (P=0.03) and smoking habits (P=0.04). LIKELI+ women had a significantly higher whole blood viscosity at all shear rates compared with LIKELI- women (P<0.05). All blood viscosities measured from 25 to 125 s(-1) were highly significantly (P<0.0001) correlated with eta(250s(-1)). Univariate correlates with eta(250s(-1)) comprised triglycerides (P=0.006) and haematocrit (P=0.026). Binary logistic multivariate regression analysis for high likelihood of CAD revealed that only presence of arterial hypertension (P<0.0001) was predictive. Multiple regression analysis demonstrated that haematocrit (P=0.001) and likelihood of CAD (P=0.01) were the only significant determinants of eta(250s(-1)).

Conclusion: In this study, blood viscosity did not appear as an independent risk factor for the prediction of premature CAD in women. Viscosity may act as a marker of CAD or of classical risk factors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/s0021-9150(02)00281-2DOI Listing
December 2002
-->