Consistency of the beneficial effect of metoprolol succinate extended release across a wide range dose of angiotensin-converting enzyme inhibitors and digitalis.

BACKGROUND: The effects of beta-blockade with different extent of angiotensin-converting enzyme inhibitors (ACEI) and digitalization are unknown. To assess the effect of metoprolol succinate controlled release/extended release (CR/XL) combined with high versus low doses of ACEI and digitalis, we analyzed data from The Metoprolol CR/XL Randomized Intervention Trial in Chronic Heart Failure (MERIT-HF) in which patients with heart failure and left ventricular ejection fraction < or =40% were randomized to metoprolol CR/XL versus placebo. METHODS AND RESULTS: Outcome was analyzed separately for those on a low dose (< or =median) of the ACEI or digitalis versus high dose (> median). The mean dose of ACEI in the high-dose group (n = 1457) was 3 times higher than that in the low-dose group (n = 2094). Mortality was reduced to a similar extent in the high- and low-dose ACEI subgroups (RR = .69 versus .64, respectively). Corresponding figures for combined mortality/all hospitalization and for mortality/hospitalization for heart failure were .85 versus .83, and .70 versus .68, respectively. Likewise, reduction in total mortality with metoprolol CR/XL was similar in patients receiving no digitalis (n = 1447; RR = .56), low dose (n = 1122; RR = .71), or high dose (n = 1421; RR = .71). CONCLUSION: This analysis of MERIT-HF demonstrates consistent and similar improvement in outcome of patients receiving metoprolol CR/XL when combined with either a high or low dose of an ACEI or digitalis, or no digitalis at all. Thus regardless of ACEI and digitalis dose and whether patients are treated with digitalis or not, it is very important to add a beta-blocker to the existing heart failure therapy. beta-blockers should not be withheld until target doses of ACEI have been achieved.

Efficacy, safety and tolerability of beta-adrenergic blockade with metoprolol CR/XL in elderly patients with heart failure.

AIM: To study the efficacy and tolerability of beta-blockade in elderly patients with heart failure in the MERIT-HF study. METHODS AND RESULTS: Cox proportional hazards model was used to calculate hazard ratios (HR) with 95% confidence intervals (CI). Risk reduction was defined as (1-HR). In patients > or = 65 years total mortality was reduced by 37% (95% CI 17% to 52%; p=0.0008), sudden death by 43% (95% CI 17% to 61%; p=0.0032), and death from worsening heart failure by 61% (95% CI 32% to 77%; p=0.0005). Hospitalisations for worsening heart failure was reduced by 36% (p=0.0006). Elderly patients with severe heart failure (NYHA class III/IV with ejection fraction < 0.25; n=425, and patients above 75 years (n=490) showed similar risk reductions. Metoprolol CR/XL was safe and well tolerated both during initiating therapy and during long-term follow-up. CONCLUSIONS: Metoprolol CR/XL was easily instituted, safe and well tolerated in elderly patients with systolic heart failure. The data suggest that these are the patients in whom treatment will have the greatest impact as shown by number of lives saved and number of hospitalisations avoided. The time has come to overcome the barriers that physicians perceive to beta-blocker treatment, and to provide it to the large number of elderly patients with heart failure in need of this therapy.

Metoprolol CR/XL in female patients with heart failure: analysis of the experience in Metoprolol Extended-Release Randomized Intervention Trial in Heart Failure (MERIT-HF).

BACKGROUND: Underrepresentation of women in heart failure clinical trials has limited conclusions regarding the effect of various management strategies on survival in women with heart failure and decreased left ventricular ejection fraction (LVEF). METHODS AND RESULTS: MERIT-HF (Metoprolol Extended-Release Randomized Intervention Trial in Heart Failure) was a randomized, placebo-controlled study, the purpose of which was to evaluate the effect of metoprolol controlled-release/extended-release (CR/XL) in 3991 patients with New York Heart Association class II to IV heart failure and LVEF < or =0.40. We performed a post hoc analysis to evaluate the effect of metoprolol CR/XL on outcome in women (n=898), including the outcome in 183 women with severe heart failure (New York Heart Association class III/IV and LVEF < 0.25). Treatment with metoprolol CR/XL in women resulted in a 21% reduction in the primary combined end point of all-cause mortality/all-cause hospitalizations (164 versus 137 patients; P=0.044). The number of cardiovascular hospitalizations was reduced by 29% (164 versus 120; P=0.013), and hospitalization for worsening heart failure was reduced by 42% (95 versus 56; P=0.021). Similar results were noted in the subgroup of women with severe heart failure, with a 57% reduction in cardiovascular hospitalizations (63 versus 30; P=0.005) and a 72% reduction in hospitalization due to worsening heart failure (46 versus 14; P=0.0004). A pooling of mortality results from MERIT-HF, the Cardiac Insufficiency Bisoprolol Study (CIBIS II), and the Carvedilol Prospective Randomized Cumulative Survival Study (COPERNICUS) showed very similar survival benefits in women and men. CONCLUSIONS: The beneficial effects of metoprolol CR/XL extend to women with heart failure, including women with clinically stable severe heart failure.