Long-term use of carvedilol in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention

Abstract

BackgroundDespite its recommendation by the current guidelines, the role of long-term oral beta-blocker therapy has never been evaluated by randomized trials in uncomplicated ST-segment elevation myocardial infarction (STEMI) patients without heart failure, left ventricular dysfunction or ventricular arrhythmia who underwent primary percutaneous coronary intervention (PCI).Methods and resultsIn a multi-center, open-label, randomized controlled trial, STEMI patients with successful primary PCI within 24 hours from the onset and with left ventricular ejection fraction (LVEF) ≥40% were randomly assigned in a 1-to-1 fashion either to the carvedilol group or to the no beta-blocker group within 7 days after primary PCI. The primary endpoint is a composite of all-cause death, myocardial infarction, hospitalization for heart failure, and hospitalization for acute coronary syndrome. Between August 2010 and May 2014, 801 patients were randomly assigned to the carvedilol group (N = 399) or the no beta-blocker group (N = 402) at 67 centers in Japan. The carvedilol dose was up-titrated from 3.4±2.1 mg at baseline to 6.3±4.3 mg at 1-year. During median follow-up of 3.9 years with 96.4% follow-up, the cumulative 3-year incidences of both the primary endpoint and any coronary revascularization were not significantly different between the carvedilol and no beta-blocker groups (6.8% and 7.9%, P = 0.20, and 20.3% and 17.7%, P = 0.65, respectively). There also was no significant difference in LVEF at 1-year between the 2 groups (60.9±8.4% and 59.6±8.8%, P = 0.06)ConclusionLong-term carvedilol therapy added on the contemporary evidence-based medications did not seem beneficial in selected STEMI patients treated with primary PCI.Trial registrationCAPITAL-RCT (Carvedilol Post-Intervention Long-Term Administration in Large-scale Randomized Controlled Trial) ClinicalTrials.gov.number, NCT 01155635.

Oral β-Blocker Therapy in Acute Myocardial Infarction

“…Indeed, in the CAPITAL-RCT trial, which is the only RCT exploring the effectiveness of an oral β-blocker in uncomplicated STEMI patients, the event rate for a composite of all-cause death, myocardial infarction, hospitalization for heart failure, and hospitalization for acute coronary syndrome at median 4-year follow-up was very low, and the event rate did not differ with regard to β-blocker use. 15 The lack of a dose-response relationship for β-blockers in the present study might be explained very well, if β-blockers are not at all effective in preventing cardiovascular events in patients with uncomplicated AMI. A large RCT (REDUCE-SWEDEHEART: ClinicalTrials.gov NCT 03278509) is ongoing to evaluate the role of β-blocker after AMI in contemporary practice.…”

Eurasian Clinical Guidelines on Diagnosis and Treatment of Acute Coronary Syndrome With St Segment Elevation (Stemi)

“…Убедительные данные об улучшении прогноза при назначении БАБ у больных с ОКСпST были получены, в основном, в дореперфузионную эру [156]. Польза рутинного назначе-ния БАБ у больных, которые подверглись первичной ЧКВ, на основании РКИ и системных мета-анализов, не показана [157,158,159,160]. Вместе с тем, результаты некоторых регистров говорят о том, что назначение БАБ приводит к улучшению прогноза [161,162].…”

Design and rationale of the Danish trial of beta-blocker treatment after myocardial infarction without reduced ejection fraction: study protocol for a randomized controlled trial

“…In the reperfusion era only one randomized controlled trial (CAPITAL-RCT) [12] has investigated the longterm efficacy of beta-blockers in patients with LVEF ≥ 40% after MI and successful PCI. The trial included patients with ST-elevation MI (STEMI) and suggested no benefit of carvedilol on a composite outcome (all-cause mortality, MI, hospitalization for HF and acute coronary syndrome) after a median follow up time of 3.9 years.…”

“…A metaanalysis of beta-blockers for HF with reduced, midrange, and preserved ejection fraction demonstrated no evidence of benefit of beta-blockers for all-cause mortality when LVEF was > 40% in sinus rhythm [48]. The ongoing trials DANBLOCK, BETAMI, and REBOOT and the published CAPITAL-RCT [12] all include patients with midrange LVEF. Hopefully, these trials will resolve whether beta-blockers are beneficial in this group of patients.…”