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Prior beta-blockers predict extra burden of heart failure in women with ACS


Beta-blockers taken for hypertension may predispose women to worse outcomes, compared with men, when they later present with acute coronary syndromes (ACS), a registry study suggests.

In the analysis of more than 13,000 patients with ACS and no history of cardiovascular (CV) disease, the women who had taken beta-blockers for hypertension showed about a one-third increased risk for heart failure (HF) at the time of their ACS presentation.

The difference between women and men was especially pronounced among patients with ST-segment elevation MI, compared with those with non-STEMI.

No such relationship between sex and risk for HF with ACS was observed among the larger portion of the cohort that had not previously been treated with beta-blockers, according to a report published July 13 in Hypertension, with lead author Raffaele Bugiardini, MD, University of Bologna (Italy).

Mortality at 30 days was sharply higher for patients with than without HF at their ACS presentation, by more than 600% for women and more than 800% for men.

“Our study provides robust evidence of an interaction between sex and beta-blocker therapy and suggests an increased risk of HF among women presenting with incident myocardial infarction,” Dr. Bugiardini said in an interview.

Given their novelty, “our findings raise strong concern about the appropriate role of beta-blockers in the therapy of hypertension in women with no prior history of cardiovascular diseases. Beta-blocker use may be an acute precipitant of heart failure in women presenting with incident ACS as first manifestation of coronary heart disease.” Dr. Bugiardini and colleagues wrote.

“There is one main implication for clinical practice. Discontinuing a beta-blocker in an otherwise healthy woman with hypertension and no prior CV disease is not harmful and could be wise,” Dr. Bugiardini said. “Blood pressure in women may be regulated in a safer way, such as using other medications and, of course, through diet and exercise.”

Rationale for the study

Men and women “differ with respect to the risk, causes, and prognosis of HF,” Dr. Bugiardini and colleagues wrote, and current guidelines “do not differentiate between the use of beta-blockers in men and in women.”

However, they proposed, “because prior trials and meta-analyses enrolled nearly five men for every woman, any differences in the effect of beta-blockers among women would have been concealed by the effect of beta-blocker therapy among men.”

The current study looked at data from October 2010 to July 2018 in the ISACS ARCHIVES, ISACS-TC, and the EMMACE-3X registries, covering 13,764 patients from 12 European countries who had a history of hypertension and presented with confirmed ACS.

Of the combined cohort, 2,590 (19%) had been treated with beta-blockers prior to their ACS presentation. They were similar to those without a history of beta-blocker use with respect to baseline features and use of other medications in an adjusted analysis.

In the group with prior beta-blocker use, 21.3% of the women and 16.7% of the men had HF of Killip class 2 or higher, a 4.6% absolute difference that worked out to a relative risk of 1.35 (95% confidence interval, 1.10-1.65).

The corresponding rates for women and men without prior beta-blocker use were 17.2% and 16.1%, respectively, for an absolute difference of only 1.1% and an RR of1.09 (95% CI, 0.97-1.21).

The interaction between sex and beta-blocker therapy for the HF outcome was significant (P < .034). An analysis that excluded patients in cardiogenic shock at their ACS presentation produced similar results.

In an analysis only of patients with STEMI, the RR for HF in women versus men was 1.44 (95% CI, 1.12-1.84) among those with a history of beta-blocker use, and 1.11 (95% CI, 0.98-1.26) among those who hadn’t used the drugs. The interaction between sex and beta-blocker use was significant (P = .033).

No such significant interaction was seen for the subgroup with non-STEMI as their index ACS (P = .14).

Heart failure at ACS was the most powerful observed predictor of 30-day mortality in women and in men in multivariate analysis; the odds ratios were 7.54 (95% CI, 5.78-9.83) and 9.62 (95% CI, 7.67-12.07), respectively.

“Our study underscores the importance of sex analyses in clinical research studies, which may provide further actionable data,” Dr. Bugiardini stated. “Failure to include both sexes in therapeutic studies is a missed opportunity to uncover underlying sex-specific risks. The adverse effect of beta-blocker therapy in women with hypertension is a sex-specific risk.”


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