In the placebo arm of Metoprolol controlled release/Extended Release randomized Intervention Trial in Heart Failure (MERIT-HF) 26 , RHR was a highly significant independent risk factor for all-cause mortality ( P = 0.003), CV mortality ( P = 0.006), and worsening heart failure ( P < 0.0001).
Post hoc analysis was thus undertaken in those with limiting angina (n = 1507; 13.8%) 47 which reported ivabradine to be associated with a borderline significant 24% reduction in the primary endpoint (hazard ratio, 0.76 [95% CI, 0.58–1.00]; P = 0.05) and a 42% reduction in hospitalization for MI (hazard ratio, 0.58 [95% CI, 0.37–0.92]).
Compared with placebo, verapamil, which reduced mean pulse by 6 bpm and blood pressure by 5/4 mmHg, showed a trend to reduce mortality at 18 months (hazard ratio, 0.80; P = 0.11), and a significant reduction in the composite of cardiac death/MI (hazard ratio, 0.80; P = 0.03) 42 .