β-blocker Therapy is Not Associated with Reductions in Angina or Cardiovascular Events After Coronary Artery Bypass Graft Surgery: Insights from the IMAGINE Trial

Abstract

Purpose: To evaluate whether β-blockers were associated with a reduction in cardiovascular events or angina after Coronary Artery Bypass Graft (CABG) surgery, in otherwise stable low-risk patients during a mid-term follow-up.

Methods: We performed a post-hoc analysis of the IMAGINE (Ischemia Management with Accupril post-bypass Graft via Inhibition of angiotensin coNverting Enzyme) trial, which tested the effect of Quinapril in 2553 hemodynamically stable patients with left ventricular ejection fraction (LVEF) >40 %, after scheduled CABG. The association between β-blocker therapy and the incidence of cardiovascular events (death, cardiac arrest, myocardial infarction, revascularizations, angina requiring hospitalization, stroke or hospitalization for heart failure) or angina that was documented to be due to underlying ischemia was tested with Cox regression and propensity adjusted analyses.

Results: In total, 1709 patients (76.5 %) were using a β-blocker. Patients had excellent control of risk factors; with mean systolic blood pressure being 121 ± 14 mmHg, mean LDL cholesterol of 2.8 mmol/l, 59% of patients received statins and 92% of patients received antiplatelet therapy. During a median follow-up of 33 months, β-blocker therapy was not associated with a reduction in cardiovascular events (hazard ratio 0.97; 95 % confidence interval 0.74-1.27), documented angina (hazard ratio 0.85; 95 % confidence interval 0.61-1.19) or any of the individual components of the combined endpoint. There were no relevant interactions for demographics, comorbidities or surgical characteristics. Propensity matched and time-dependent analyses revealed similar results.

Conclusions: β-blocker therapy after CABG is not associated with reductions in angina or cardiovascular events in low-risk patients with preserved LVEF, and may not be systematically indicated in such patients.

Figures

Fig. 1

Outcome according to β-blocker therapy – Cumulative event rates for composite endpoints stratified for β-blocker therapy. Hazard ratios are adjusted for age, gender, ethnicity, history of myocardial infarction, revascularization, non-cardiac vascular event, hypertension, diabetes, hypercholesterolemia, days after CABG (coronary artery bypass grafting), beating heart surgery, nr of vessel disease, complete revascularization, left ventricular ejection fraction and concomitant medication. MACE, Major Adverse Cardiovascular Event

Fig. 2

Cox regression – Hazard ratios and 95 % confidence intervals for composite endpoints and individual components after adjustment for same variables as in Fig. 1. MACE, Major Adverse Cardiovascular Event

Fig. 3

Interaction analysis for β-blocker – Hazard ratios for β-blocker therapy in relevant subgroups

Fig. 4

Propensity matched analysis – (a) standardized differences between baseline characteristics before and after matching. (b) Cumulative event rate for the primary endpoint in the propensity matched population. CABG, Coronary Artery Bypass Grafting; PCI, Percutaneous Coronary Intervention

Fig. 5

Risk for primary endpoint with propensity score and time-dependent analysis of β-blocker therapy - Analysis performed with β-blocker therapy at randomization and β-blocker as a time-dependent covariate