Drug Topics - January 28, 2008 - (Page 15) 15 Cover Story since approval of the direct renin inhibitor aliskiren. Initially predicted to achieve blockbuster status, aliskiren has been given a somewhat mediocre review in a recent editorial published in the American Journal of Hypertension. Based on their analysis of six clinical trials, authors Jean E. Sealey and John H. Laragh indicated that aliskiren is no more effective in lowering BP than ACE inhibitors, ARBs, or diuretics. Although the combination of aliskiren and a diuretic appeared to lower BP more than an aliskiren-ARB combo, it still failed to control BP (<140/90 mm Hg) in 50% of the patients. In suggesting possible reasons for the agent’s modest efficacy, the authors state that although aliskiren suppresses plasma renin activity, it causes much greater reactive rises in plasma renin concentration than does any other antihypertensive. Because aliskiren, like ACE inhibitors and ARBs, only blocks 90% to 95% of plasma renin, the pressor consequences of its greater increases in plasma renin appear to offset its ability to lower BP “It seems safe . and simple to stick to the less expensive, equally effective, and widely available generic ACE inhibitors for treating the renin factor in HTN,” the authors concluded. In regard to AHA recommendations for first-line therapy for primary prevention, any of the tried and true agents will do (ACE inhibitors, ARBs, CCBs, or thiazide diuretics)—except beta-blockers. The class has been omitted from most of the recommendations, based on several discouraging studies. ASCOT-BPLA, for example, was stopped prematurely because atenolol-based therapy was inferior to amlodipine in reducing major cardiovascular events. A similar older study (Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension; LIFE) found losartan to be more effective than atenolol in preventing cardiovascular morbidity and death. The Conduit Artery Function Evaluation (CAFE) substudy of ASCOT found atenolol to be less effective than amlodipine in reducing central SBP and cardiac afterload, which might explain the less optimal benefits of this class. Beta-blockers—specifically carvedilol, metoprolol, and bisoprolol—remain the standard of care in patients with angina pectoris, past MI, or LV dysfunction with or without HF symptoms. But their cardio-, cerebro-, and renal-protection evidence is considered weak in patients who do not have symptomatic CAD, have not had an MI, or do not have HF. “I work with many patients who require a beta-blocker for conditions such as post MI or CAD, but I have never thought of a betablocker as a straightforward first-line therapy, since this class is usually reserved for use with other antihypertensives in patients with compelling indications,” commented Fang. For David Baran, M.D., FACC, who mostly treats patients with congestive heart failure, betablockers, along with ACE inhibitors, have literally been life savers. Baran is director of heart failure and transplant research at Newark Beth Israel Medical Center and a clinical assistant professor of medicine at Mt. Sinai School of Medicine. Both Baran and Weber pointed out that in practice, newer agents (e.g., carvedilol) are used more commonly and with more success, compared with the older beta-blocker atenolol. One of these new-generation beta-blockers is nebivolol, an agent that combines beta1 adrenoreceptor antagonist properties with nitric oxide-mediated vasodilatory actions. Nebivolol may be particularly beneficial in hypertensive patients with reduced endothelial function, such as African-Americans, diabetics, and those with vascular conditions. Nebivolol may also be an appealing option for obese patients, since the agent has been observed to have neutral effects on weight gain and lipids. These points seem to circle back to the question of which agent to use first in HTN—an issue that authors of the AHA guidelines consider “moot,” since combination therapy is usually required to achieve and Position statement: Antihypertensive treatment: Preferred drugs Subclinical organ damage LVH: ACEI, CA, ARB Asymptomatic atherosclerosis: CA, ACEI Microalbuminuria: ACEI, ARB Renal dysfunction: ACEI, ARB Clinical event Previous stroke: any BP lowering agent Previous MI: BB, ACEI, ARB Angina pectoris: BB, CA Heart failure: diuretics, BB, ACEI, ARB, antialdosterone agents Atrial fibrillation (recurrent): ARB, ACEI Atrial fibrillation (permanent): BB, non-dihydropyridine CA ESRD/proteinuria: ACEI, ARB, loop diuretics Peripheral artery disease: CA Condition ISH (elderly): diuretics, CA Metabolic syndrome: ACEI, ARB, CA Diabetes mellitus: ACEI, ARB Pregnancy: CA, methyldopa, BB Blacks: diuretics, CA Abbreviations: LVH: left ventricular hypertrophy; ISH: isolated systolic hypertension; ESRD: end-stage renal disease; ACEI: ACE inhibitors; ARB: angiotensin Source: 2007 Guidelines for the Management of Arterial Hypertension.The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC)
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