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October 28th, 2014

Is the Role of Beta-Blockers in Coronary Artery Disease Treatment Changing?

Is the Role of Beta-Blockers in Coronary Artery Disease Treatment Changing?

October 27, 2014

Beta-blockers have been a universal treatment throughout the Cardiovascular Continuum1 for decades. They are a mainstay in the treatment of hypertension, stable ischemic heart disease, post-myocardial infarction (MI), heart failure, and in sympathetic-mediated tachyarrhythmias. A recent post-hoc analysis of the CHARISMA (Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance) trial2 shows that we have need to stop and ponder the use of these agents in patients with stable ischemic heart disease.

The CHARISMA trial was a prospective, randomized trial to evaluate the efficacy and safety of clopidogrel plus aspirin as compared to aspirin alone in patients at high risk for cardiovascular events. In the post-hoc analysis patients were divided into 3 cohorts: 1) patients with prior MI; 2) patients with known atherothrombotic disease (cardiovascular, cerebrovascular, or symptomatic peripheral vascular) but without MI; and 3) patients without known atherothrombotic disease but with risk factors alone. Heart failure patients were excluded from the analysis due to known beneficial effects. Cox proportional hazard modeling was used to assess the effect of prior beta-blocker usage and the primary outcome (composite of nonfatal MI, stroke or cardiovascular mortality). After 28 months, beta-blocker use was associated with 31% lower risk of the primary outcome (69%, 95% CI: 0.50-0.94) primarily driven by the lower risk of recurrent MI. However, in patients in groups 2 and 3, beta-blocker use not associated with lower ischemic outcomes but was associated with a higher risk of stroke (16%; 95% CI: 0.92-4.92 [p=0.079]).

What should we take away from this retrospective analysis? First, it is hypothesis generating, needs to be prospectively studied to confirm the reported outcomes, and should not drive us away from the use of beta-blockers in stable ischemic heart disease. But a cautionary note towards the use of older generation beta-blockers such as atenolol and metoprolol may be offered especially in light of similar results from the REACH registry.3 Beta-blocker efficacy appears to be associated with a heart rate reduction-sympathetic stimulation model-thereby reducing myocardial demand. Should we be closely monitoring heart rate response when using a beta-blocker and looking for a clinically important reduction such as 60 bpm or less or is this too low to maintain central aortic pressure? Another observation is to use beta-blockers with vasodilating properties such as carvedilol over the older generation beta-blockers that have shown to have less weight gain, a lower rate of new onset diabetes mellitus and central hemodynamic pressure increases. Lastly, what is the proper timeframe for treatment with beta-blockers in stable ischemic heart disease: a few years, lifetime, or an evidence-driven timeline from monitored biologic markers?

Born in the late 1600s, Voltaire echoed the sentiment of our ancient elders: “Doctors are men who prescribe medicines of which they know little to cure diseases of which they know less in human beings of which they know nothing.”

 I agree that there is a place for the beta blockers but many factors make it not a universal cure for all cardiac patients.  By far, most patients with cardiovascular disease are older patients.  Additionally this older group of course have less liver and kidney function.  The lack of specific isozymes in the liver to break down the beta blockers in turn slows the eliminitation of the drug thus drastically increasing Adverse Drug Events.  In all studies the use of Calcium Channel Blockers and Chlorthalidone provide more positive outcomes hands down.  Since the geriatric's liver continues to make the CYP3A4 elimination of the drug remains consistent and risk of Adverse Drug Events are minor.  Looks like Voltaire's statement continues to resonate throughout healthcare.


1. Dzau V, Braunwald E. Resolved and unresolved issues in the prevention and treatment of coronary artery disease: a workshop consensus statement. Am Heart J. 1991;121(4 Part 1):1244-1263.

2. Bangalore S, Bhatt DL, Steg PG, Weber MA, Boden WE, Mann CW, Montalescot G, Hsu A, Fox KA, Lincoff AM. Β-blockers and cardiovascular events in patients with and without myocardial infarction: post hoc analysis from the CHARISMA Trial. Circ Cardiovasc Qual Outcomes. 2014 Sep 30. [Epub ahead of print]

3. Bangalore S, Steg G, Deedwania P, et al.; REACH Registry. Β-blocker use and clinical outcomes in stable outpatients with and without coronary artery disease. JAMA. 2012;308(13):1340-1349.

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