LETTER TO THE EDITOR
Reply
Franz H. Messerli, MD and
Albert Fournier, MD
Ochsner Clinic Foundation, 1514 Jefferson Highway, New Orleans, LA 70121
(Email: fmesserli{at}aol.com).
Dr. Ghali raises an interesting point about our study (1) that deserves to be scrutinized. In hypertension, beta-blockers as a class have never been shown to reduce heart attacks or strokes (2,3). This is true for atenolol in several prospective placebo-controlled randomized trials, but also for propranolol in the Medical Research Council (MRC) study (4) and for oxprenolol in the International Prospective Primary Prevention Study in Hypertension (IPPPSH) (5). In Cardiac Insufficiency Bisoprolol Study (CIBIS-II), the rate of hospitalization for a stroke was almost twice as high in the bisoprolol arm as in the placebo arm (6). Thus, there are several prospective randomized studies with atenolol, propranolol, oxprenolol, or bisoprolol documenting that beta-blockers are not efficacious in reducing strokes.
A notable exception that Dr. Ghali mentioned is the Carvedilol Or Metoprolol European Trial (COMET) in congestive heart failure patients (7). However, carvedilol is a drug that is distinctly different from traditional beta-blockers in that it does have some alpha-blocking properties and other features that exert a more favorable effect on systemic hemodynamic, metabolic endocrine findings, and target organ disease than do traditional beta-blockers (8). We also should emphasize that a stroke reduction in congestive heart failure without hypertension cannot necessarily be extrapolated to uncomplicated hypertension. Indeed, heart failure per se is a risk factor for stroke, but the pathogenesis is different from the one in hypertension and often involves emboli of cardiac origin. Because carvedilol was superior to metoprolol in preventing congestive heart failure and sudden death, it is likely that it decreased stroke risk, at least to some extent, by cardiac protection. Thus, there is little doubt that, for stroke prevention in essential hypertension, beta-blockers (with the possible exception of carvedilol) are not the drugs of choice.
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References
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- Fournier A, Messerli FH, Achard JM, Fernandez L. Cerebroprotection mediated by angiotensin II: a hypothesis supported by recent randomized clinical trials J Am Coll Cardiol 2004;43:1343-1347.[Abstract/Free Full Text]
- Messerli FH, Grossman E, Fournier A. Letter to the Editor JAMA 2003;289:700-701.[Free Full Text]
- Messerli FH, Beevers DG, Franklin SS, Pickering TG. ß-Blockers in hypertension—the emperor has no clothes: an open letter to present and prospective drafters of new guidelines for the treatment of hypertension Am J Hypertens 2003;16:870-873.[CrossRef][Medline]
- Medical Research Council Working Party MRC trial of treatment of mild hypertension: principal results Br Med J 1985;291:97-9104.[Medline]
- IPPPSH Collaborative Group. Cardiovascular risk and risk factors in a randomized trial of treatment based on the beta-blocker oxprenolol: the International Prospective Primary Prevention Study in Hypertension (IPPPSH) J Hypertens 1985;3:379-392.[Medline]
- Reduced costs with bisoprolol treatment for heart failure: an economic analysis of the second Cardiac Insufficiency Bisoprolol Study (CIBIS-II). Eur Heart J 2001;22:1021–31..
- Poole-Wilson PA, Swedberg K, Cleland JG, et al. Comparison of carvedilol and metoprolol on clinical outcomes in patients with chronic heart failure in the Carvedilol Or Metoprolol European Trial (COMET): randomised controlled trial Lancet 2003;362:7-13.[CrossRef][Medline]
- Messerli FH, Grossman E. Beta-blockers in hypertension: is carvedilol different? Am J Cardiol 2004;93:7-12.[CrossRef]
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References