Beta-Blockers Not Good First-Line Hypertensive Medications: In a meta-analysis of the best 13 randomised controlled trials available (n=105 951) comparing beta blockers with other antihypertensive drugs or placebo or no treatment, the relative risk of stroke was 16% higher for beta blockers than for other drugs. There was no difference for myocardial infarction. When the effect of beta blockers was compared with that of placebo or no treatment, the relative risk of stroke was reduced by 19% for beta blockers, about half that expected from previous hypertension trials. There was no difference for myocardial infarction or mortality. Authors state that beta blockers should not remain a first choice in the treatment of primary hypertension and should not be used as reference drugs in future studies. Should beta blockers remain first choice in the treatment of primary hypertension? A meta-analysis. Lindholm LH, et al. Umea University Hospital , Umea , Sweden . . Lancet. 2005 Oct 29-Nov 4;366(9496):1545-53.

Beta-Blocker Reduced Endurance: Endurance time was reduced 35% by atenolol but not by transdermal clonidine or placebo. Neither active drug interfered with the progress of the conditioning program, Comparative effects of transdermal clonidine and oral atenolol on acute exercise performance and response to aerobic conditioning in subjects with hypertension. Arch Intern Med. 1989 Jul;149(7):1551-6 

Beta-Blockers Compared: Numerous beta-blockers are available. A mortality benefit after heart attacks has been shown for propranolol, timolol, metoprolol, and, in the presence of left ventricular dysfunction, carvedilol. In heart failure, the selective metoprolol and bisoprolol as well as the nonselective agent carvedilol (which possesses alpha-blocking properties) have a demonstrated mortality benefit. Not all tolerated beta-blockers are associated with a survival benefit and it is probably not advisable to extrapolate benefits to all drugs with similar (although probably not identical) properties. Carvedilol may have advantages over other beta-blockers and a possible survival advantage, suggested by the recent Carvedilol or Metoprolol European Trial (COMET). Cardiovascular drug class specificity: beta-blockers. Reiter MJ. University of Colorado . Prog Cardiovasc Dis. 2004 Jul-Aug;47(1):11-33  

Beta-Blockers, Diuretics Reduce Fractures: A case-control analysis using the UK General Practice Research Database included 30,601 adults ages 30-79 with a fracture vs. 120,819 controls. The most frequent fractures were of the hand/lower arm (42%) and of the foot (15.1%). Compared with patients who did not use either beta-blockers or thiazide diuretics, the OR for current use of beta-blockers only was 0.77; for current use of thiazides only, 0.80; and for combined current use of beta-blockers and thiazides, 0.71. Data were adjusted for smoking; body mass index; number of practice visits; and use of calcium channel blockers, angiotensin-converting enzyme inhibitors, antipsychotics, antidepressants, statins, antiepileptics, benzodiazepines, corticosteroids, and estrogens. Many elderly patients with hypertension who are at risk of developing osteoporosis may potentially benefit from combined therapy with beta-blockers and thiazides. Use of beta-blockers and risk of fractures. Schlienger RG, Kraenzlin ME, et al, University Hospital , Basel , Switzerland . JAMA. 2004 Sep 15;292(11):1326-32

Carvediol (Coreg) Appears Better than Metoprolol for Diabetes on ACE Inhibitor: RAS ) blockers (ACE inhibitors or angiotensin II receptor blockers), patients were given 6.25- to 25-mg dose of carvedilol (n = 498) or 50- to 200-mg dose of metoprolol tartrate (n = 737), each twice daily. Hydrochlorothiazide and a dihydropyridine calcium antagonist were added, if needed, to achieve blood pressure target. The mean HbA1c increased with metoprolol (0.15%; P<.001) but not carvedilol (0.02%; P = .65). Insulin sensitivity improved with carvedilol (-9.1%; P = .004) but not metoprolol (-2.0%; P = .48). Blood pressure was similar between groups. Progression to microalbuminuria was less frequent with carvedilol than with metoprolol (6.4% vs 10.3%; P = .04). Metabolic effects of carvedilol vs metoprolol in patients with type 2 diabetes mellitus and hypertension: a randomized controlled trial. Bakris GL, Fonseca V, et al.; GEMINI Investigators. Rush University , Chicago .. JAMA. 2004 Nov 10;292(18):2227-36. Ed: Carvediol is unfortunately very expensive at $121 per month or more vs. $15 for metoprolol at Walgreens 1/2/05.  The minor benefit on lab values of carvediol must be shown to have a significant long term health impact to merit such costs.

Nebivolol Good for Arterial Stiffness: The vasodilating beta-blocker nebivolol, but not atenolol, was found to increase arterial distensibility in sheep.  Nebivolol may be of benefit in conditions of increased large artery stiffness, such as isolated systolic hypertension. Nebivolol increases arterial distensibility in vivo. McEniery CM, Schmitt M, et al. University of Cambridge , UK Hypertension. 2004 Sep;44(3):305-10. Ed: Extensa is a new blood pressure medication available in England for about $36 per month.

  Nebivolol (Extensa) is a vasodilating β-blocker, combines β-adrenergic blocking activity with a vasodilating effect mediated by the endothelial L-arginine nitric oxide (NO) pathway. The blood pressure lowering effect of nebivolol is linked to a reduction in peripheral resistance and an increase in stroke volume and preservation of cardiac output. The effects of nebivolol have been compared with other β-blockers and also with other classes of antihypertensive agents. In general, response rates to treatment are higher and the frequency and severity of adverse events are either comparable or lower with nebivolol. Endothelium-derived NO is important in the regulation of large arterial stiffness, which in turn is a major risk factor for cardiovascular disease. Therefore, antihypertensive drugs, such as nebivolol, that also improve endothelial function and decrease arterial stiffness, may contribute to a reduction in cardiovascular risk.

Thomas E. Radecki, M.D., J.D.

modern-psychiatry.com