Beta-blocker treatment beyond 1 year after myocardial infarction (MI) for patients without heart failure or left ventricular systolic dysfunction was not associated with improved cardiovascular outcomes in a new analysis of a nationwide cohort of more than 40,000 patients.

“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 left ventricular systolic dysfunction who may have longer survival compared with those who develop such complications after an MI,” state the authors, led by Divan Ishak, MD, Uppsala University, Sweden.

The study was published online in Heart on May 2.  

The researchers explain that clinical outcomes following MI have improved in recent years, partly because of the use of evidence-based therapies including timely reperfusion and secondary prevention medications. As such, more patients are surviving MI with no heart failure or left ventricular systolic dysfunction.

Beta-blockers are an established therapy for patients with heart failure and/or left ventricular systolic dysfunction because they reduce morbidity and mortality. For those without heart failure or left ventricular systolic dysfunction, evidence supports the use of beta-blockers in the early phase after MI, but there is uncertainty as to whether they should be continued beyond the first year in the absence of other clinical indications.

In historical randomized trials, longer-term beta-blocker therapy has been shown to reduce mortality rates, but these trials were conducted before the introduction of invasive reperfusion strategies and antithrombotic agents into routine MI care. More recent studies have been limited by the inclusion of only a subset of MI patients, relatively small sample size, or short follow-up, the authors note.

While more comprehensive randomized trials are in progress, the benefit of beta-blockers in the chronic phase beyond the first year might remain unknown and the long follow-up required to draw firm conclusions may be challenging to achieve.

The current study therefore aimed to investigate the association between beta-blocker therapy and cardiovascular outcomes beyond the first year after MI in patients without heart failure or left ventricular systolic dysfunction using real-world data from the SWEDEHEART registry of patients with coronary heart disease in Sweden.  

The study included all 43,618 patients aged 18 years or over with MI, including ST-elevation (STEMI) and non-STEMI, who had been hospitalized at one of the 74 cardiac care units in Sweden between 2005 and 2016.

Follow-up started 1 year after hospitalization (index date). Patients with heart failure or left ventricular systolic dysfunction up until the index date were excluded. Patients were allocated into two groups according to beta-blocker treatment. The primary outcome was a composite of all-cause mortality, MI, unscheduled revascularization, and hospitalization for heart failure.

Results showed that, overall, 78.5% of patients received a beta-blocker and 21.5% did not take a beta-blocker at the index date 1 year following MI. The median age was 64 years, and 25.5% were female. The median follow-up was 4.5 years.

In the intention-to-treat analysis, the unadjusted rate of primary outcome was lower among patients who received a beta-blocker versus those who did not (3.8 versus 4.9 events/100 person-years; hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.73 to 1.04).

However, following inverse propensity score weighting and multivariable adjustment, the risk of the primary outcome was not different according to beta-blocker treatment (HR, 0.99; 95% CI, 0.93 to 1.04). These findings were consistent across individual secondary endpoints and across patient subgroups.

The authors say that this is the largest study to have evaluated beta-blocker therapy in patients without heart failure or left ventricular systolic dysfunction following MI. Although the design is observational, it includes a large sample of patients, has a median follow-up of 4.5 years, and implements causal inference techniques, they state.

They also point out that the results align with those of a recent meta-analysis of contemporary trials looking at this question.

They note that the potential mechanism of beta-blockers in improving cardiovascular outcomes following MI is attributed to the inhibition of the sympathetic overdrive, lowering heart rate, and thus reducing myocardial oxygen consumption.

However, routine and timely coronary reperfusion, as well as usage of potent antiplatelet therapy, reduces infarct size, minimizing the upregulation of sympathetic activity, particularly in those individuals who do not sustain substantial myocardial damage.

In addition, beta-blockers have been associated with several side effects, including depression and fatigue, so determining whether they are indicated beyond the first year after MI may have an impact on patient health-related quality of life, the authors suggest.

In an accompanying editorial, Tom Evans, MD, and Ralph Stewart, MD, Green Lane Cardiovascular Service, Auckland City Hospital, New Zealand, say the current study raises an important question directly relevant to the quality of care: Do patients with a normal left ventricular ejection fraction benefit from long-term beta-blocker therapy after myocardial infarction?

They note that the study had a number of strengths including a large sample size, a representative study population, detailed information on risk markers used for the propensity adjusted analysis, and unbiased evaluation of outcomes from administrative datasets up to 12 years after the index MI.

But they caution that the potential for unrecognized confounding is a limitation, and therefore more evidence from large randomized clinical trials is needed to answer this question.

This work was supported by grants from the Swedish Government.

Heart. Published online May 2, 2023. Full text, Editorial

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