Case Builds Against Beta-Blockers Beyond First Year After Heart Attack

The conventional wisdom of giving long-term beta-blockers for secondary prevention after myocardial infarction (MI), in the absence of another clinical indication, was questioned by a large cohort study from Sweden.

For survivors who were still on beta-blocker therapy 1 year after heart attack hospitalization and had a normal left ventricular (LV) ejection fraction, the next few years did not bring a significantly lower risk of combined all-cause mortality, MI, unscheduled revascularization and hospitalization for heart failure following inverse propensity score weighting and multivariable adjustment (18.9% vs 21.7% for peers without beta-blockers; adjusted HR 0.99, 95% CI 0.93-1.04).

This finding persisted after accounting for beta-blocker discontinuation or treatment switch during the median 4.5 years of follow-up for this cohort of consecutive patients in the national SWEDEHEART registry, according to Gorav Batra, MD, PhD, cardiologist of Uppsala University, Sweden, and colleagues. Their report was published in Heart.

For many years, American and European guidelines alike have given blanket endorsements to beta-blockers after ST elevation MI (STEMI) and non-ST elevation MI (NSTEMI), regardless of left ventricular function, and without specifying duration of therapy.

However, this class of drugs is now in decline, as their supporting evidence base is judged to be outdated, coming from an era preceding early reperfusion, early coronary revascularization, statins, antithrombotics, and other contemporary heart attack treatments.

Any perceived benefits of beta-blockers are also to be weighed against the risk of side effects such as depression and fatigue.

“The results of our study address an existing gap in the current evidence and provide an insight into long-term optimal secondary prevention strategies for a large proportion of MI survivors, namely patients with no heart failure or LVSD [left ventricular systolic dysfunction] who may have longer survival compared with those who develop such complications after an MI,” Batra’s group wrote.

The nationwide cohort study included individuals who had an MI in 2005-2016 recorded in the SWEDEHEART registry.

People deemed eligible and included in propensity-score weighting were 43,618 individuals without heart failure or asthma at the 1-year mark after heart attack hospitalization. All were adults who had been hospitalized with STEMI and NSTEMI at one of the 74 cardiac care units in Sweden.

Median age of the cohort was 64, with 25.5% of participants being women.

According to Sweden’s drug dispensing records, 78.5% still received beta-blockers a year after their MI. Some baseline characteristics were well-matched between beta-blocker and non-beta-blocker groups, though the latter had approximately twice as many patients with a prior history of MI or coronary revascularization but was less likely to have STEMI, undergo in-hospital revascularization, and to be on statins.

Attempts to adjust for between-group differences still left room for residual confounding in this observational study. What’s more, the investigators could not ascertain true adherence to beta-blocker therapy among study participants.

“Substantial differences in treatment effects between propensity adjusted case-control studies compared with randomised clinical trials of the same treatment are well described. This knowledge supports the view that large randomised clinical trials are essential to reliably evaluate treatment effects,” commented Tom Evans, MBChB, and Ralph Stewart, MBChB, both of Te Whatu Ora Health New Zealand Te Toka Tumai Auckland.

“Despite strong evidence that long-term beta-blockers can improve outcomes after myocardial infarction, it has been uncertain whether this benefit applies to lower risk patients who are taking other evidence-based therapies and who have a normal LV ejection fraction. It is therefore important to understand gaps in the information provided by historical trials,” Evans and Stewart wrote in an accompanying editorial.

Ongoing trials — such as BETAMI, REDUCE-SWEDEHEART, and DANBLOCK — are expected to fill some of the evidence gap.