RESUMEN
OBJECTIVES: The purpose of this study was to evaluate the efficacy and tolerability of monotherapy with the selective aldosterone blocker eplerenone in both black and white patients with hypertension. BACKGROUND: Essential hypertension and cardiovascular-renal-target organ damage is more prevalent in black than white adults in the U.S. METHODS: Black (n = 348) and white (n = 203) patients with mild-to-moderate hypertension were randomized to double-blind treatment with eplerenone 50 mg, the angiotensin II receptor antagonist losartan 50 mg, or placebo once daily. Doses were increased if blood pressure remained uncontrolled. The primary end point was change in mean diastolic blood pressure (DBP) after 16 weeks of therapy. RESULTS: Adjusted mean changes from baseline in DBP were -5.3 +/- 0.7, -10.3 +/- 0.7, and -6.9 +/- 0.6 mm Hg in the placebo, eplerenone-treated, and losartan-treated groups, respectively (mean +/- SE, p < 0.001 eplerenone vs. placebo, p < 0.001 eplerenone vs. losartan). In black patients, DBP decreased by -4.8 +/- 1.0, -10.2 +/- 0.9, and -6.0 +/- 0.9 mm Hg for the placebo, eplerenone-treated, and losartan-treated groups, respectively (mean +/- SE, p < 0.001 eplerenone vs. placebo, p < 0.001 eplerenone vs. losartan), whereas in white patients, DBP decreased by -6.4 +/- 1.0, -11.1 +/- 1.1, and -8.4 +/- 1.0 mm Hg, respectively (p = 0.001 eplerenone vs. placebo, p = 0.068 for eplerenone vs. losartan). For reduction of systolic blood pressure (SBP), eplerenone was superior to placebo and losartan in all patients combined and in black patients, and was superior to placebo in white patients. Eplerenone was as effective as losartan in reducing SBP and DBP in the high renin patient, but more effective than losartan in the low renin patient. Similarly, eplerenone was at least as effective as losartan in patients with differing baseline levels of aldosterone. Both eplerenone and losartan were well tolerated. CONCLUSIONS: The antihypertensive effect of eplerenone was equal in black and white patients and was superior to losartan in black patients.
Asunto(s)
Antihipertensivos/uso terapéutico , Población Negra , Hipertensión/tratamiento farmacológico , Losartán/uso terapéutico , Antagonistas de Receptores de Mineralocorticoides/uso terapéutico , Espironolactona/análogos & derivados , Espironolactona/uso terapéutico , Población Blanca , Adulto , Aldosterona/sangre , Análisis de Varianza , Antagonistas de Receptores de Angiotensina , Antihipertensivos/efectos adversos , Presión Sanguínea/efectos de los fármacos , Método Doble Ciego , Eplerenona , Femenino , Humanos , Hipertensión/etnología , Losartán/efectos adversos , Masculino , Persona de Mediana Edad , Antagonistas de Receptores de Mineralocorticoides/efectos adversos , Renina/sangre , Renina/efectos de los fármacos , Sistema Renina-Angiotensina/efectos de los fármacos , Espironolactona/efectos adversos , Resultado del TratamientoRESUMEN
Since the isolation and purification of aldosterone from adrenal extracts 50 years ago (Experientia 9 (1953) 33), scientists have learned a great deal about how and where aldosterone acts, the factors that control its release, what is its role in the pathophysiology of cardiovascular disease, how to make and study aldosterone antagonists, and for what medical purposes these agents are useful. In this paper, we will discuss the evolution of aldosterone antagonists from the relatively nonselective spironolactone (Aldactone), to the highly selective eplerenone (Inspra). Eplerenone represents a molecule with improved steroid receptor selectivity and pharmacokinetic properties in man compared to spironolactone. Recent clinical results have demonstrated that these improvements translate into tolerability and efficacy in patients with cardiovascular disease.
Asunto(s)
Antagonistas de Receptores de Mineralocorticoides , Espironolactona/análogos & derivados , Aldosterona/historia , Aldosterona/metabolismo , Animales , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/metabolismo , Ensayos Clínicos como Asunto , Eplerenona , Ginecomastia/tratamiento farmacológico , Ginecomastia/metabolismo , Historia del Siglo XX , Humanos , Antagonistas de Receptores de Mineralocorticoides/síntesis química , Antagonistas de Receptores de Mineralocorticoides/historia , Antagonistas de Receptores de Mineralocorticoides/farmacocinética , Antagonistas de Receptores de Mineralocorticoides/uso terapéutico , Espironolactona/síntesis química , Espironolactona/historia , Espironolactona/farmacocinética , Espironolactona/uso terapéuticoRESUMEN
Approximately 40% of Japanese patients with essential hypertension, including low-renin hypertension, are inadequately managed. Low-renin hypertension generally responds poorly to angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers, but may respond more optimally to diuretics, calcium channel blockers, and aldosterone blockers. This multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study evaluated the efficacy and safety of the selective aldosterone blocker eplerenone in 193 Japanese patients with essential hypertension. Although not a study inclusion criterion, baseline active plasma renin levels were consistently low (5.7-10.1 mU/L); most patients met the criteria for low-renin hypertension (< or =42.5 mU/L; normal range, 7-76 mU/L). Patients received placebo or eplerenone 50, 100, or 200 mg once daily for 8 weeks. Systolic blood pressure decreased significantly (-6.8 to -10.6 mm Hg vs. -2.1 mm Hg; p< or =0.0022 vs. placebo). Eplerenone offers significant blood pressure reduction with good tolerability in Japanese patients with hypertension, including those with low-renin hypertension.