Author + information
- John R. Cockcroft, MD⁎ ()
- ↵⁎Department of Cardiology, Cardiff University, Wales Heart Research Institute, University Hospital of Wales, Cardiff, Wales CF14 4XN, United Kingdom
Bangalore et al. (1) recently reported that a lower heart rate was associated with a greater risk for all-cause mortality (r = −0.51; p < 0.0001), cardiovascular mortality (r = −0.61; p < 0.0001), myocardial infarction (MI) (r = −0.85; p < 0.0001), stroke (r = −0.20; p = 0.06), or heart failure (r = −0.64; p < 0.0001). They concluded that beta-blocker–associated reduction in heart rate increased the risk of cardiovascular events and death in hypertensive patients, in contrast to patients with MI and heart failure. In an accompanying editorial, Kaplan (2) stated that beta-blockers will continue to be indicated for heart failure, tachyarrhythmias, and secondary prevention post-MI, but not for treatment of hypertension in patients without these compelling indications. However, as the authors wrote, care should be taken in extrapolating these findings to newer beta-blockers, especially the vasodilating agents (e.g., nebivolol and carvedilol) (3). It should be emphasized that the studies included in this review used atenolol almost exclusively: 78% of patients received atenolol; 12%, atenolol/metoprolol/pindolol or hydrochlorothiazide; 9%, oxprenolol; and 1%, propranolol. Thus, it is difficult to extrapolate the findings to newer vasodilating beta-blockers. Future studies should strive to determine whether atenolol per se or the reduction of heart rate is responsible for increased cardiovascular risk. This issue needs to be resolved, because the findings would have major clinical implications (3).
Another important issue to resolve is the effect of drugs on central pressure. The benefits of heart rate reduction may be negated by a drug that lowers heart rate while simultaneously increasing central pressure (4). Different drugs, especially beta-blockers, have differential effects on peripheral and central pressure, and a number of studies have now shown that central pressure is a better predictor of outcome than pressure in the arm (5,6). As demonstrated in the CAFE (Conduit Artery Function Evaluation) study, antihypertensive medications can have substantially different effects on central aortic pressure and hemodynamics, despite a similar impact on brachial blood pressure (7). Vasodilatory beta-blockers may well offset any deleterious hemodynamic effects of heart rate reduction by decreasing wave reflection from the periphery. In a study by Dhakam et al. (8), the central hemodynamic effects of nebivolol and atenolol were compared in patients with systolic hypertension. Despite similar reductions in peripheral blood pressure, nebivolol reduced central pulse pressure more than atenolol. Both drugs reduced aortic stiffness, but nebivolol had less impact on the aortic augmentation index. These findings suggest that important differences may exist among drugs in the beta-blocker class.
Finally, beta-blockade remains very important in the treatment of cardiovascular disease, and in hypertensive patients with coexisting angina. Further, hypertensive patients younger than 50 years old may benefit more from beta-blockade than older patients, as they have a different hemodynamic form of hypertension (9). However, all evidence to date (4) suggests that a beta-blocker other than atenolol should be chosen when beta-blockade is required.
It is premature to sound the death knell for all beta-blockers in the treatment of hypertension based upon the Bangalore et al. (1) review, but it is high time to stop prescribing atenolol.
Please note: Prof. Cockcroft is on the advisory board of Forest Laboratories and has received lecture fees and grant support for scientific studies on nebivolol.
- American College of Cardiology Foundation
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