Publications by authors named "Antonio Fagundes"

5 Publications

  • Page 1 of 1

Effect of Evolocumab in Patients With Prior Percutaneous Coronary Intervention.

Circ Cardiovasc Interv 2022 Mar 25;15(3):e011382. Epub 2022 Feb 25.

Thrombolysis in Myocardial Infarction (TIMI) Study Group, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (R.H.M.F., A.A.F., K.O., T.A.Z., M.T., J.F.K., S.AM., R.P.G., M.S.S., B.A.B.).

Background: Patients with prior percutaneous coronary intervention (PCI) are at high residual risk for multiple types of coronary events within and beyond the stented lesion. This risk might be mitigated by more intensive LDL-C (low-density lipoprotein cholesterol)-lowering beyond just with statin therapy.

Methods: FOURIER (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk) randomized 27 564 patients with stable atherosclerotic disease on statin to the PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitor evolocumab or placebo with a median follow-up of 2.2 years. The end points of interest were major adverse cardiovascular events (MACE; a composite of cardiovascular death, myocardial infarction, stroke, unstable angina or coronary revascularization), and major coronary events (a composite of coronary heart death, myocardial infarction, or coronary revascularization). We compared the risk of MACE and the magnitude of relative and absolute risk reductions with evolocumab in patients with and without prior PCI.

Results: Seventeen thousand seventy-three patients had prior PCI. In the placebo arm, those with prior PCI had higher rates of MACE (13.2% versus 8.3%; hazard ratio [HR] 1.61 [95% CI, 1.42-1.84]; <0.0001) and major coronary events (11.5% versus 6.0%; HR, 1.72 [95% CI, 1.49-1.99]; <0.0001). Relative risk reductions with evolocumab were similar in patients with and without prior PCI (MACE: HR, 0.84 [0.77-0.91] versus HR, 0.88 [0.77-1.01]; 0.51; major coronary events: HR, 0.82 [0.75-0.90] versus HR, 0.88 [0.75-1.04]; 0.42). Absolute risk reductions for MACE were 2.0% versus 0.9% ( 0.14) and for major coronary events 2.0% versus 0.7% ( 0.045). In those with prior PCI, the effect of evolocumab on coronary revascularization (HR, 0.76 [0.69-0.85]) was directionally consistent across types of revascularization procedures: coronary artery bypass grafting (HR, 0.71 [0.54-0.94]); any PCI (HR, 0.77 [0.69-0.86]); PCI for de novo lesions (HR, 0.76 [0.66-0.88]); and PCI for stent failure or graft lesions (HR, 0.76 [0.63-0.91]).

Conclusions: Evolocumab reduces the risk of MACE in patients with prior PCI including the risk of coronary revascularization, with directionally consistent effects across several types of revascularization procedures, including coronary artery bypass grafting and PCI for stent or graft failure.

Registration: URL: https://www.

Clinicaltrials: gov; Unique identifier: NCT01764633.
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March 2022

Epidemiology of Acute Heart Failure in Critically Ill Patients With COVID-19: An Analysis From the Critical Care Cardiology Trials Network.

J Card Fail 2022 Apr 17;28(4):675-681. Epub 2022 Jan 17.

Levine Cardiac Intensive Care Unit, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

Background: Acute heart failure (HF) is an important complication of coronavirus disease 2019 (COVID-19) and has been hypothesized to relate to inflammatory activation.

Methods: We evaluated consecutive intensive care unit (ICU) admissions for COVID-19 across 6 centers in the Critical Care Cardiology Trials Network, identifying patients with vs without acute HF. Acute HF was subclassified as de novo vs acute-on-chronic, based on the absence or presence of prior HF. Clinical features, biomarker profiles and outcomes were compared.

Results: Of 901 admissions to an ICU due to COVID-19, 80 (8.9%) had acute HF, including 18 (2.0%) with classic cardiogenic shock (CS) and 37 (4.1%) with vasodilatory CS. The majority (n = 45) were de novo HF presentations. Compared to patients without acute HF, those with acute HF had higher cardiac troponin and natriuretic peptide levels and similar inflammatory biomarkers; patients with de novo HF had the highest cardiac troponin levels. Notably, among patients critically ill with COVID-19, illness severity (median Sequential Organ Failure Assessment, 8 [IQR, 5-10] vs 6 [4-9]; P = 0.025) and mortality rates (43.8% vs 32.4%; P = 0.040) were modestly higher in patients with vs those without acute HF.

Conclusions: Among patients critically ill with COVID-19, acute HF is distinguished more by biomarkers of myocardial injury and hemodynamic stress than by biomarkers of inflammation.
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April 2022

End-of-life care in the cardiac intensive care unit: a contemporary view from the Critical Care Cardiology Trials Network (CCCTN) Registry.

Eur Heart J Acute Cardiovasc Care 2022 Mar;11(3):190-197

Divison of Cardiology, Duke University School of Medicine, Durham, NC, USA.

Aims: Increases in life expectancy, comorbidities, and survival with complex cardiovascular conditions have changed the clinical profile of the patients in cardiac intensive care units (CICUs). In this environment, palliative care (PC) services are increasingly important. However, scarce information is available about the delivery of PC in CICUs.

Methods And Results: The Critical Care Cardiology Trials Network (CCCTN) Registry is a network of tertiary care CICUs in North America. Between 2017 and 2020, up to 26 centres contributed an annual 2-month snapshot of all consecutive medical CICU admissions. We captured code status at admission and the decision for comfort measures only (CMO) before all deaths in the CICU. Of 13 422 patients, 10% died in the CICU and 2.6% were discharged to palliative hospice. Of patients who died in the CICU, 68% were CMO at death. In the CMO group, only 13% were do not resuscitate/do not intubate at admission. The median time from CICU admission to CMO decision was 3.4 days (25th-75th percentiles: 1.2-7.7) and ≥7 days in 27%. Time from CMO decision to death was <24 h in 88%, with a median of 3.8 h (25th-75th 1.0-10.3). Before a CMO decision, 78% received mechanical ventilation and 26% mechanical circulatory support. A PC provider team participated in the care of 41% of patients who died.

Conclusions: In a contemporary CICU registry, comfort measures preceded death in two-thirds of cases, frequently without PC involvement. The high utilization of advanced intensive care unit therapies and lengthy times to a CMO decision highlight a potential opportunity for early engagement of PC teams in CICU.
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March 2022

Effect of Evolocumab on Complex Coronary Disease Requiring Revascularization.

J Am Coll Cardiol 2021 01 13;77(3):259-267. Epub 2020 Nov 13.

TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. Electronic address:

Objectives: This study sought to evaluate the ability of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolocumab to reduce the risk of complex coronary atherosclerosis requiring revascularization.

Background: PCSK9 inhibitors induce plaque regression and reduce the risk of coronary revascularization overall.

Methods: FOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) was a randomized trial of the PCSK9 inhibitor evolocumab versus placebo in 27,564 patients with stable atherosclerotic cardiovascular disease on statin therapy followed for a median of 2.2 years. Clinical documentation of revascularization events was blindly reviewed to assess coronary anatomy and procedural characteristics. Complex revascularization was the composite of complex percutaneous coronary intervention (PCI) (as per previous analyses, ≥1 of: multivessel PCI, ≥3 stents, ≥3 lesions treated, bifurcation PCI, or total stent length >60 mm) or coronary artery bypass grafting surgery (CABG).

Results: In this study, 1,724 patients underwent coronary revascularization, including 1,482 who underwent PCI, 296 who underwent CABG, and 54 who underwent both. Complex revascularization was performed in 632 (37%) patients. Evolocumab reduced the risk of any coronary revascularization by 22% (hazard ratio [HR]: 0.78; 95% CI: 0.71 to 0.86; p < 0.001), simple PCI by 22% (HR: 0.78; 95% CI: 0.70 to 0.88; p < 0.001), complex PCI by 33% (HR: 0.67; 95% CI: 0.54 to 0.84; p < 0.001), CABG by 24% (HR: 0.76; 95% CI: 0.60 to 0.96; p = 0.019), and complex revascularization by 29% (HR: 0.71; 95% CI: 0.61 to 0.84; p < 0.001). The magnitude of the risk reduction with evolocumab in complex revascularization tended to increase over time (20%, 36%, and 41% risk reductions in the first, second, and beyond second years).

Conclusions: Adding evolocumab to statin therapy significantly reduced the risk of developing complex coronary disease requiring revascularization, including complex PCI and CABG individually. (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER); NCT01764633.).
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January 2021

Clevidipine for hypertensive emergency.

Rev Bras Ter Intensiva 2010 Mar;22(1):92-5

Hospital do Coração do Brasil, Brasília, DF, Brasil.

Hypertensive emergency, is the most severe presentation of arterial hypertension, having high morbidity-mortality. Clevidipine is a calcium channel blocker. Its pharmacokinetics is favorable to use for hypertensive emergencies, rendering this drug a promising alternative to the restricted therapeutic armamentarium available both in the emergency room and intensive care unit. In this review we describe the pharmacodynamics, pharmacokinetics and clinical trials evaluating Clevidipine in emergency situations, comparing this drug to other traditionally used drugs in this condition.
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March 2010