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J Am Coll Cardiol, 2008; 51:516-517, doi:10.1016/j.jacc.2007.09.050 © 2008 by the American College of Cardiology Foundation |
* Tulane University School of Medicine, 109 Holly Drive, Metairie, Louisiana 70005 (Email: tgiles4{at}cox.net).
Bangalore et al. (1) cited a lack of benefit with beta-blockers in reducing all-cause or cardiovascular mortality and myocardial infarction from a meta-analysis by Lindholm et al. (2); in fact, no difference was observed for these end points versus other anti-hypertensives. Some of the early assessments of beta-blockers, including the STOP-1 and -2 (Swedish Trial in Old Patients with Hypertension-1 and -2), showed that beta-blockers reduced total and cardiovascular morbidity compared with placebo and that the results were similar to angiotensin-converting enzyme (ACE) inhibitors and calcium channel blockers (3,4).
Most of the evidence summarized by Bangalore et al. (1) concern studies of atenolol. However, the authors neglected to point out that the less favorable clinical outcomes seen with atenolol versus other therapies might be due to an absence of 24-h efficacy when it is used once daily at a dose of 50 mg. In fact, the INVEST (International Verapamil-Trandolapril Study) demonstrated no difference in outcomes between a beta-blocker– and calcium-antagonist–based regimen (5). Notably, in this trial atenolol was dosed twice daily. Similarly, data from the UKPDS (United Kingdom Prospective Diabetes Study) also showed atenolol to have efficacy similar to an ACE inhibitor regimen in preventing macrovascular complications in hypertensive diabetic patients (6).
We also believe that the term, "pseudo antihypertensive" efficacy, is misleading, because the authors probably refer to relative blood pressure reductions as distinct from the efficacy of treating the disease, hypertension. As the authors point out, beta-blockers are important for treating a wide range of high-risk cardiovascular conditions.
We agree with the authors that, historically, use of traditional beta-blockers has been constrained by associated side effects, in particular, fatigue and sexual dysfunction. However, there is mounting evidence showing that the side effect profile of vasodilatory beta-blockers is markedly different and comparable to placebo (7,8). Vasodilating beta-blockers also demonstrate neutral or beneficial metabolic profiles. As cited by the authors, the GEMINI (Glycemic Effects in Diabetes Mellitus: Carvedilol-Metoprolol Comparison in Hypertensives) study in diabetic hypertensives showed maintained glycemic control and improved insulin resistance with carvedilol versus metoprolol (8). Similarly, nebivolol demonstrated improved insulin sensitivity when compared with metoprolol in hypertensive patients (9).
The authors incorrectly state that the European Society for Hypertension/European Society of Cardiology (ESH/ESC) is no longer endorsing beta-blockers as first-line therapy for hypertension. In actuality, ESH/ESC guidelines, published this year, maintain beta-blockers among the classes of drugs suitable for initiation and maintenance of blood pressure treatment (10). Furthermore, ESH/ESC and the American College of Clinical Endocrinologists recognize the differences that exist between agents in this class, distinguishing the vasodilatory beta-blockers from traditional ones in patients with metabolic risk factors.
We are not sure what the phenotype of an "uncomplicated" patient with hypertension is. Clearly, many with increased blood pressures have non-obstructive coronary and carotid plaques.
The use of beta-blockers in the treatment of patients with hypertension is deeply rooted in the knowledge of the role of the sympathetic nervous system in the pathophysiology of complications. We believe that recommendations for the use of beta-blockers in an individual with hypertension should be made after reviewing the totality of the data. Beta-blockers will continue to play a critical role in treatment of hypertension, and dismissing the entire class without fully examining the evidence might indeed amount to "throwing the baby out with the bath water."
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