Dr Franz Messerli, from St. Luke’s Roosevelt Hospital, stated that, "Slowing heart rate is known to prolong life expectancy, and with beta blockers post-MI [myocardial infarction] and in heart failure, the slower you can make the heart rate, the better. But this new paper goes against the grain. What we show is that in hypertension, when you slow down the heart rate with a beta blocker, it actually shortens your life expectancy, it causes more heart attacks, more heart failure, and more strokes." Messerli says he and his team believe the likely explanation for this is "that slowing the heart rate with beta blockers increases the central pressure, and obviously the latter is one of the determinants of stroke and heart attack."
sees things slightly differently, however. Dr John Cockcroft (Another hypertension expert from Wales Heart Institute, Cardiff, UK), argues that in this review, the studies included almost exclusively used atenolol — something the authors do point out — and that it is this drug per se that is likely the culprit here.
What is vitally important to determine in this setting, he adds, "is whether it's atenolol that's bad or whether it's reduction of heart rate that's bad." This is crucial because there are other drugs that aren't beta blockers that lower heart rate, he explained, such as the new agent ivabradine (Procoralan, Servier). "This issue needs resolving because if it's heart-rate reduction [that is the cause], then that's bad news, and we need to know about it."
In the new review, Bangalore et al included nine randomized controlled trials evaluating beta blockers for hypertension that also reported heart-rate data, including 34,096 patients taking beta blockers, 30,139 taking other antihypertensives, and 3987 receiving placebo. Of the patients in the beta-blocker arms, 78% received atenolol, 9% took oxprenolol, 1% propranolol, and 12% received atenolol/metoprolol/pindolol or hydrochlorothiazide.
Paradoxically, a lower heart rate (as attained in the beta-blocker group at study end) was associated with a greater risk for the end points of all-cause mortality (r = –0.51; p < 0.0001), cardiovascular mortality (r = –0.61; p < 0.0001), MI (r = –0.85; p < 0.0001), stroke (r = –0.20; p = 0.06), or heart failure (r = –0.64; p < 0.0001).
"In contrast to patients with MI and heart failure, beta-blocker-associated reduction in heart rate increased the risk of cardiovascular events and death for hypertensive patients," the researchers conclude.
Messerli stated that, "In the past, the term cardioprotection was synonymous with bradycardia. The more you had bradycardia, the better the heart was protected. This is not the case in hypertension. This may be okay post-MI and in heart failure, but it's not okay in hypertension."
Dr Norman M Kaplan (University of Texas Southwestern Medical Center, Dallas), in an editorial accompanying the review, agrees: "With this addition to the evidence, beta blockers will surely remain as indicated for heart failure, for after MI, and for tachyarrhythmias, but no longer for hypertension in the absence of these compelling indications."
Messerli and his colleagues do state in their discussion, however: "Further studies are needed to establish causation. It should also be noted that the beta blocker used in the studies was mainly atenolol, and hence, any meaningful extrapolation of these results to other beta blockers, including the newer vasodilating beta blockers, should be done with caution."
Cockcroft contends that because this new review contains studies almost exclusively using atenolol, "this doesn't move the argument forward very much." Atenolol, he says, "has been tried and found guilty, and yet around 40% of prescriptions for beta blockers in the UK and in the US are still for atenolol. Atenolol should not be given to anybody. Nobody disagrees that atenolol is guilty, and yet we are still using it."
He says that people think lowering heart rate is good, "because it reduces the amount of cyclical stress on the aorta, but if at the same time you are putting the central aortic pressure up, these things may cancel each other out." Atenolol has been compared in this respect with one of the newer vasodilating beta blockers, nebivolol (Bystolic, Forest/Mylan), and it was found that atenolol increases the central aortic pressure but nebivolol does not, he notes.
"The newer vasodilating beta blockers may well not have any of these detrimental effects. Because they are vasodilatory, they may well offset the slowing of heart rate by decreasing wave reflection from the periphery and, in the case of nebivolol, by releasing nitric oxide, an endogenous vasodilator with antiatherogenic activity," he adds.
Regarding the role now of beta blockers in hypertension, Messerli commented that, "Beta blockers in hypertension are not very useful, and you probably should use any other single drug first before you add a beta blocker, and if you want to add a beta blocker, please use a vasodilating one such as carvedilol or nebivolol."
Cockcroft agrees with much of this, but maintains that beta blockade is still very important. "Beta blockade is vital. A large number of patients with hypertension have angina as well, so they've got to have a beta blocker. Furthermore, there is now evidence that younger subjects with hypertension (< 50 years of age) may well be better treated with a beta blocker than older hypertensives, as they have a different hemodynamic form of hypertension. It's what beta blocker you give them that counts, and it shouldn't be atenolol."
He believes the continued obsession with atenolol is "partly due to cheapness and habit, but also due to the failure of the people with good beta blockers to disseminate information on the deleterious effects of atenolol."
- Heart rate lowering with beta-blockers in patients with hypertension is associated with a greater risk for cardiovascular and all-cause mortality.
- Heart rate lowering with beta-blockers is associated with an increased risk for heart failure, nonfatal MI, and stroke, with a linear inverse relationship.
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.
Kaplan NM. Beta-blockers in hypertension. Adding insult to injury. J Am Coll Cardiol. 2008;52:1490-1491.
Dhakam Z, Yasmin, McEniery CM, et al. A comparison of atenolol and nebivolol in isolated systolic hypertension. J Hypertens. 2008;26:351-356.
Reducing Heart Rate in Hypertension Can Be Harmful: Slowing the heart rate with beta blockers in people with hypertension is associated with an increased risk of cardiovascular events and death, a new systematic review shows. Furthermore, the slower the heart rate, the greater the risk. See This Weeks’ Item #13