Traditional beta-blockers may no longer be the best choice for initial treatment of hypertension but vasodilatory beta-blockers show promise.
Beta-blockers have long been a staple in the treatment of hypertension (HTN), but now that may be shifting as several clinical trials show they didn't fare as well in improving cardiovascular outcomes as other classes of drugs. Despite their proven benefit in certain clinical situations, when it comes to the treatment of uncomplicated hypertension, there may be better choices, the experts say. In addition, newer beta-blockers with vasodilatory effects may be more beneficial than their older counterparts.
One compelling reason for the emergence of questions surrounding the value of beta-blockers (BBs) is the data coming from two studies in particular, explained Michael A. Weber, M.D., professor of medicine at SUNY Downstate Medical Center in Brooklyn, N.Y. "The two most obvious are the Losartan Intervention for Endpoint Reduction (LIFE) study and the Angio-Scandinavian Cardiac Outcomes (ASCOT) trial in which beta-blockers were compared with other types of antihypertensives. The event rates- both fatal and non-fatal outcomes-seem to be higher in patients taking the beta-blocker," he told Drug Topics. "Particularly for endpoints like stroke and mortality, the BBs just didn't seem to be quite matching up."
In addition to study results, Weber explained that what has happened over the past few years with the advent of newer and safer drugs to treat HTN, such as angiotensin converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), and the newer calcium channel blockers (CCBs), is that physicians and patients alike don't want to use drugs with adverse effects. He explained that the BBs can cause lethargy and negatively affect both exercise performance and sexual function, in addition to negative effects on metabolic measurements, including the lipid profile and blood glucose levels. "There seems to be almost a list of reasons why we might want to be cautious with beta-blockers," he said.
Carvedilol, a non-selective BB with additional alpha-blocking properties, has already been shown to prolong survival and reduce cardiac events in patients with heart failure and those who develop left ventricular dysfunction following a myocardial infarction. Nebivolol is a highly selective B1-blocker that increases the availability of vascular nitric oxide which mediates key hemodynamic and vasoprotective properties of the vascular endothelium. Nebivolol has been shown to reduce peripheral resistance and increase stroke volume, allowing cardiac output to be maintained despite a modest decrease in heart rate.
Weber also noted that the vasodilatory BBs are better tolerated. "You don't get the sexual dysfunction, fatigue, diminished exercise tolerance, or unwanted metabolic effects," he said. They also have a lesser negative chronotropic effect than traditional BBs.
"What we don't have yet are outcome studies of these new drugs for hypertension," Weber warned. "We can't say for sure that they would perform better than, say, atenolol or metoprolol, but we can imagine they might." But even so, Weber said he expects study findings thus far will be reflected in future clinical guidelines, including the much-anticipated Eighth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-8), due out in 2009.
Already, Britain's HTN guidelines have relegated BBs to third-line status unless there are compelling reasons to use them sooner. In contrast, guidelines from the European Society of Cardiology/European Society of Hypertension continue to recommend BBs as a possible initial therapy. But "what the Europeans do say, though, is that they prefer the vasodilatory beta-blockers to the traditional ones," Weber pointed out.
The editorial, Beta-Blockers in the Treatment of Hypertension: New Data, New Directions, written by Weber and his colleagues, can be accessed online at the Web site of the Journal of Clinical Hypertension at http://www.lejacq.com/Journal_JCH.cfm.