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Beta-Blockers Lose Luster for Hypertension Therapy

      SNOWMASS, CO – Beta-blockers have lost their decades-long status as first-line therapy for hypertension. “Generally, I think there is a consensus that beta-blockers are a poor choice for uncomplicated hypertension,” Clive Rosendorff, MD, PhD, observed at the Annual Cardiovascular Conference at Snowmass.
      Abundant evidence indicates that beta-blockers provide less protection against stroke, myocardial infarction (MI), and overall mortality than other classes of antihypertensive agents. They offer less renal protection than ramipril and achieve less regression of left ventricular hypertrophy than other anti­hypertensive drugs.
      Moreover, as was shown in the Conduit Artery Function Evaluation (CAFE) study, beta-blockers have what has been termed “pseudo-antihypertensive efficacy.” That is, they fail to reduce central aortic blood pressure to the same extent they lower systolic blood pressure, which may explain why they are less cardioprotective than other antihypertensive drugs. They also are associated with an increase in insulin resistance, reduced exercise tolerance, weight gain, and a high rate of withdrawal because of side-effects, said Dr. Rosendorff, professor of medicine at Mount Sinai School of Medicine, New York.
      Editor's Note
      Old standby beta-blockers were one of the first types of antihypertensive classes available, with propranolol coming to market almost 50 years ago. Since then, many variations of these adrenergic blocking agents have been developed, some of which cross the blood-brain barrier, some of which are relatively cardioselective, and some of which can be used in once-daily ­dosing: by all accounts, very useful medications.
      Beta-blockers have been considered acceptable first-line treatments for hypertension for decades, but now with the JNC-8 and additional information in this piece, it seems that we have better agents for run-of-the-mill, uncomplicated hypertension.
      But before we discard our beta-blockers outright, we need to be mindful that many patients have good reasons beyond hypertension to be taking them. Recall that beta-blockers are very useful for a variety of other conditions: congestive heart failure, angina, tachycardias, migraine, essential tremor, performance anxiety, hyperthyroidism, and many others that are off label.
      As with any medication we prescribe, we want to practice person-centered medicine and individualize (while we minimize) medication regimens.
      — Karl Steinberg, MD, CMD
      Editor in Chief
      Dr. Rosdendorff chaired the joint American College of Cardiology/American Heart Association/American Society for Hypertension committee that wrote the recently released revised scientific statement on the treatment of hypertension in the prevention and management of ischemic heart disease. He also chaired the 2007 AHA scientific statement on the subject (Circulation 2007;115:2761–88).
      One of the most persuasive pieces of evidence of the shortcomings of beta-blockers as first-line agents for uncomplicated hypertension to appear since the release of the 2007 AHA scientific statement was a meta-analysis of six meta-analyses. The six meta-analyses incorporated a total of 26 randomized trials of beta-blockers versus placebo. The conclusion: Beta-blockers were no better than placebo in preventing MI or mortality, although they did result in a 16%-22% relative reduction in stroke risk (J. Am. Coll. Cardiol. 2007;50:563–72).
      This meta-meta-analysis also included three meta-analyses of comparative trials of beta-blockers versus diuretics and three meta-analyses of beta-blockers compared with other drugs. Beta-blockers turned out to be significantly worse than the other antihypertensive agents in terms of the three endpoints of MI, stroke, and mortality.
      A caveat: These clinical trials and meta-analyses were nearly all restricted to atenolol and short-acting metoprolol.
      “We don't have any comparable data for newer beta-blockers. Carvedilol has never been looked at from the point of view of outcomes in hypertension. Bisoprolol likewise, and nabivolol, too. It's possible that the paradigm might be changed quite considerably when we have data to support the use of these newer beta-blockers in the treatment of hypertension,” the cardiologist said.
      Dr. Rosendorff stressed that his comments on the drawbacks of beta-blockers for uncomplicated hypertension represented his own views and not necessarily those of the joint American College of Cardiology/American Heart Association/American Society for Hypertension panel.
      Of note, the recently published report of the Eighth Joint National Committee (JNC-8) doesn't list beta-blockers among the four classes of antihypertensive medications recommended for the initial treatment of hypertension (JAMA 2014;311:507–20).
      Dr. Rosendorff reported having no financial conflict of interest.