Ever since beta-blockers were pharmaceutically introduced, there loomed a cloud of doubt over their therapeutic safety. Whether beta-blockers can be used liberally for a range of cardiovascular diseases or not has been a persistent question for physicians and cardiologists across the globe.
Though research supports the use of beta-blockers in patients with a history of myocardial infarction (MI) and decreased ejection fraction, the question remains: is there sufficient evidence to endorse liberal use of beta-blockers in conditions like coronary artery disease (CAD) or its risk equivalents?
Fortunately, these are the times of evidence based medicine where everything is put into question before use. It is therefore reasonable to question the continuance of beta-blockers without sufficient supporting data from clinical trials. And had it not been for the findings of the CHARISMA trial, the answer to the question above would have remained a mystery.
The CHARISMA trial
Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (popularly known as CHARISMA) is one of the most important clinical trials in cardiology, and arguably one of the most comprehensive ones in the field of medicine. It was led by Dr. Deepak L. Bhatt, MD, from Cleveland Clinic and conducted across 32 countries over a course of more than 2 years. The study was aimed at investigating the possible benefits of dual antiplatelet (aspirin plus clopidogrel) therapy in patients with prior MI, stroke or symptomatic peripheral arterial disease. However, Bangalore et al. interestingly extracted some astounding results relating to the use of beta blockers, by carrying out a post hoc analysis of the results from the trial. In this article we discuss results related to the use of beta blockers.
Read more: An overview of the CHARISMA trial
A brief history
Beta blockers have been known to scientists for more than 50 years now. However, their potential benefits were largely unknown until Black et al. hypothesized that beta blockers, through their adrenergic receptors blocking effect, could improve angina by decreasing myocardial oxygen demand. The whole outlook on beta blockers has changed since a study revealed its drastic impact in reducing morbidity and mortality in patients with congestive heart failure. Note that these findings, however, do not justify the liberal use of beta blockers in CAD and equivalent conditions.
Answers to most of these queries come from the post hoc analysis of CHARISMA trial. Bangalore et al. looked at the hard outcomes, in terms of non-fatal MI, stroke or cardiovascular mortality, in three subsets of patients segregated on the basis of prior MI, CAD or risk factors only, without established CAD. None of the groups had had heart failure at baseline, and all groups were assessed for the outcomes on the basis of whether or not they were subjected to beta-blockers at baseline or not.
Here are two key findings from this study:
Q1. Should beta blockers be prescribed to every patient with CAD?
Answer to this question is quite obvious from the results: the study revealed that beta-blocker use in patient group with prior MI was tied to 31% reduction in overall end points and 40% reduction in new onset MI. Results did not approve of any mortality benefit among the patients with beta-blocker and without beta-blockers. As opposed to that, the other two groups, with established CAD and CAD risk factors, failed to exhibit any morbidity or mortality benefit with or without the use of beta-blockers.
The conclusion: Bangalore et al. concluded that the use of beta-blockers should be highly individualized, rather than generic for every CAD case.
Q2. Is there any harm associated with the use of beta blockers in other two cases?
Second question that comes to mind is, if beta-blockers do not confer any tangible benefit in terms of morbidity or mortality, both in the established CAD and the risk factor groups, should there be any concern regarding increased harm?
Results were suggestive that use of beta-blockers increased the risk of stroke in the risk factor group without CAD, similar to what the POISE study also mentioned. Therefore, it is safe to deduce that lesser the burden of CAD, greater is the risk associated with the use of beta-blockers.
The conclusion: Findings from other studies reinforce findings of CHARISMA trial that beta-blockers increase the risk of stroke.
What this study is not about
Unquestionably, this study is not about the use of beta-blockers in patients with acute MI or heart failure. There is a growing body of evidence in support of beta-blocker use in such subset of patients.
Conclusively, this study highlights some important learning points:
- Beta-blockers have been shown to be beneficial in patients with prior MI.
- There is no morbidity or mortality advantage of beta-blockers use at baseline in the subset of patients with established but stable CAD.
- Beta-blockers confer a negative impact in patients having only CAD risk factors and no prior MI.
– Contributed by Dr. Haseeb Ashraf
- Bangalore S, Bhatt DL, Steg PG, et al. ß-blockers and cardiovascular events in patients with and without myocardial infarction: Post hoc analysis from the CHARISMA trial. Circ Cardiovasc Qual Outcomes 2014; OI:10.1161/CIRCOUTCOMES.114.001073.
- Bhatt DL, Topol EJ, for the CHARISMA Study Group. The Main Results of the CHARISMA trial. Program and abstracts from the American College of Cardiology 55th Annual Scientific Session. Late Breaking Clinical Trials I. Abstract 402-10.
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