CORRESPONDENCE: LETTER TO THE EDITOR
Beta-Blocker–Induced Heart Rate Lowering, Cardioprotection, and Hypertension
Steven S. Khan, MD*
* Kaiser-Permanente Hospital, UCLA School of Medicine, Cardiology, 1526 North Edgemont, 2nd Floor, Los Angeles, California 90027 (Email: steven.s.khan{at}kp.org).
Bangalore et al. (1) have provided an intriguing observation that cardiovascular (CV) events, including CV death, myocardial infarction, heart failure, stroke, and all-cause death, may be increased in hypertensive patients placed on beta-blockers and that this may be related to the degree of heart rate reduction. They have done this by performing meta-regression analyses to demonstrate the relationship between heart rate and cardiovascular outcomes.
However, the data in their graphs show that the regression lines cross the line of unity. The 1 study that is consistently at or below unity in their graphs is the IPPSH (International Prospective Primary Prevention Study in Hypertension), which compared a beta-blocker with placebo. Similarly, the only other placebo-controlled trial analyzed, STOP (Swedish Trial in Old Patients with Hypertension) (2), shows a relative risk of about 0.9 in Figure 4 of Bangalore et al. (1). This suggests that beta-blockers are not increasing CV events because there is no increase in events in beta-blocker patients compared with placebo patients. The major differences in outcome rates are in the studies comparing beta-blockers with active controls.
These findings suggest that beta-blockers were less effective at preventing CV events than other antihypertensive agents. The mechanism for this may be evident in Table 2 of Bangalore et al. (1), which shows that beta-blockers resulted in less blood pressure reduction in 5 of 7 active control trials analyzed by the authors, with up to a 9.2-mm Hg difference in systolic blood pressure. This suggests that beta-blockers were simply less effective antihypertensive agents in general. Thus, an alternative interpretation of the authors' findings is not that beta-blockers increase mortality, as has been widely reported in the press, but that beta-blockers are simply less effective antihypertensive agents than diuretics or dihydropyridine calcium-channel blockers. As a result, they are also less effective at preventing hypertension-related cardiovascular events than other medications. The clinical message I would take from this study is that we must remember that the primary goal of antihypertensive treatment is to lower blood pressure and not to lower heart rate.
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1. Bangalore S, Sawhney S, Messerli FH. Relation of beta-blocker–induced heart rate lowering and cardioprotection in hypertension J Am Coll Cardiol 2008;52:1482-1489.[Abstract/Free Full Text]2. Dahlof B, Lindholm LH, Hansson L, Schersten B, Ekbom T, Wester PO. Morbidity and mortality in the Swedish Trial in Old Patients with Hypertension (STOP-Hypertension) Lancet 1991;338:1281-1285.[CrossRef][Web of Science][Medline]
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