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

Abstract

Background: Despite 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 results: In 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).

Conclusion: Long-term carvedilol therapy added on the contemporary evidence-based medications did not seem beneficial in selected STEMI patients treated with primary PCI.

Trial registration: CAPITAL-RCT (Carvedilol Post-Intervention Long-Term Administration in Large-scale Randomized Controlled Trial) ClinicalTrials.gov.number, NCT 01155635.

Trial registration: ClinicalTrials.gov NCT01155635.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. Study flow chart.

ITT = intention-to-treat; IQR = interquartile range.

Fig 2. Dose of carvedilol at each follow-up.

Among 394 patients in the carvedilol group, 12 patients did not receive the assigned carvedilol treatment; prescription of bisoprolol in 7 patients and no prescription of beta-blocker in 5 patients (protocol violation).

Fig 3. Comparison of LVEF between the carvedilol group and the no beta-blocker group at baseline, at 3-month follow-up, and at 1-year follow-up.

LVEF data was missing in 6 patients (4 patients in the carvedilol group and 2 patients in the no beta-blocker group). IQR = interquartile range; SD = standard deviation, LVEF = left ventricular ejection fraction.

Fig 4

Kaplan-Meier curves for the primary endpoint (a composite of death, MI, hospitalization for ACS, or hospitalization for HF) (A), for all-cause death (B).

Fig 5. Kaplan-Meier curves for any coronary revascularization (A), and for a secondary composite endpoint (a composite of death, MI, stroke, hospitalization for ACS, hospitalization for HF or any coronary revascularization) (B).

MI = myocardial infarction; ACS = acute coronary syndrome; HF = heart failure.