Study: Beta-Blockers Effective in HF for Seniors, Women

Meta-analysis included more than 13,000 patients from 11 clinical trials

A meta-analysis designed to address clinician concerns about the efficacy and tolerability of beta-blockers in older patients and women with heart failure (HF) yielded reassuring results.

The study, published online in BMJ, found that beta-blockers reduced all-cause mortality and hospital admissions for HF regardless of age or sex, and that tolerability was the same as placebo, reported Dipak Kotecha, PhD, of the University of Birmingham, England, and colleagues.

Under-representation of older patients and women in clinical trials, along with concerns about altered pharmacokinetics and side effects, has led to the under-use of beta-blockers in these patient groups, Kotecha and colleagues said.

"Using the near totality of available data from randomized controlled trials of beta-blockers in patients with heart failure with reduced ejection fraction (HFrEF) and sinus rhythm, our analysis shows that there is no evidence of a clinically significant interaction with age or sex with respect to all-cause mortality," the investigators said.

"We observed a significant benefit from beta-blockers in each quarter of the age distribution, with absolute reductions in mortality of about 4% in the youngest and oldest patients. Results for hospital admission related to heart failure were similar, with significant reductions in each age quarter, albeit with minor attenuation of treatment effect in older patients," they said.

"Discontinuation of treatment was similar in patients randomized to beta-blockers or placebo, even in older patients, suggesting that 'intolerance' of beta-blockers in clinical practice could reflect false attribution to intercurrent events or preconceptions about side effects," Kotecha and colleagues suggested.

The meta-analysis was conducted by the Beta-blockers in Heart Failure Collaborative Group, which included investigators from the original clinical trials. The group is supported by pharmaceutical companies that manufacture beta-blockers.

However, an independent expert, not affiliated with the study and with no ties to pharmaceutical companies, agreed with the study authors' conclusions.

"These findings reinforce the recommendations of current clinical guidelines. In daily clinical practice, however, prescription rates of beta-blockers and the doses taken are lower than might be expected based on the available evidence. Beta-blockers seem to be underused, especially in women and older adults of both sexes," said Arno Hoes, MD, PhD, of the University Medical Center Utrecht, The Netherlands, in an editorial.

The prospectively-designed meta-analysis gathered individual patient data from 13,833 patients ages 40 to 85 involved in 11 clinical trials, including trials such as the CAPRICORN and the SENIORS study. The median age was 64, and 24% of the patients were women.

Compared with placebo, beta-blockers reduced mortality across all age groups:

• First quartile (median age 50): hazard ratio 0.66, 95% confidence interval 0.53-0.83
• Second quartile (median age 60): HR 0.71, 95% CI 0.58-0.87
• Third quartile (median age 68): HR 0.65, 95% CI 0.53-0.78
• Fourth quartile (median age 75): HR 0.77, 95% CI 0.64-0.92

The investigators found no significant interaction when age was modeled continuously (P=0.1), and the absolute mortality reduction was 4.3% over a median follow-up of 1.3 years (number needed to treat, 23).

Hospital admission for heart failure was significantly reduced by beta-blockers, although the effect was attenuated at older ages (interaction P=0.05). There was no evidence of an interaction between treatment effect and sex in any age group. Drug discontinuation was similar regardless of treatment allocation, age, or sex (14.4% in patients receiving beta-blockers, 15.6% in those receiving placebo).

"This analysis confirms that treatment with beta-blockers reduces mortality and hospital admissions related to heart failure in patients with HFrEF with sinus rhythm, irrespective of age or sex," Kotecha and colleagues concluded. "In addition, the tolerability of beta-blockers was similar to placebo, reinforcing the use of beta-blockers in all patients with HFrEF in sinus rhythm and discouraging the practice of withholding such treatment in women or elderly patients."

Hoes agreed. "This individual patient data meta-analysis reports important information for patients and clinicians. Clinicians should offer beta-blockers to all men and women with HFrEF and in sinus rhythm, irrespective of their age. Patients should expect this equity of approach," he said.

"When typical side effects occur, both prescribers and patients should realize that adults given placebos in trials of beta-blockers report side effects at comparable rates," he advised.

Reviewed by F. Perry Wilson, MD, MSCE Assistant Professor, Section of Nephrology, Yale School of Medicine and Dorothy Caputo, MA, BSN, RN, Nurse Planner.

last updated 04.22.2016

This article was first published on MedPage Today and reprinted with permission from UBM Medica. Free registration is required.

Disclosures:

The study was supported by AstraZeneca, GlaxoSmithKline, Merck Serono, and Menarini.

Kotecha received grants from Menarini and nonfinancial support from Daiichi-Sankyo.

Hoes reported no financial relationships with industry.

References:

Primary Source:BMJ

Kotecha D, et al "Effect of age and sex on efficacy and tolerability of beta-blockers in patients with heart failure with reduced ejection fraction: individual patient data meta-analysis" BMJ 2016; DOI: 10.1136/bmj.i1855.

Secondary Source:BMJ

Source Reference: Hoes AW "Beta-blockers for heart failure" BMJ 2016; DOI: 10.1136/bmj.i2074.