Efficacy and safety of the selective 11¦Â-HSD-1 inhibitors MK-0736 and MK-0916 in overweight and obese patients with hypertension

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• 作者：Sukrut Shah ; PhD ; RPh ; ^{sukrut_shah@merck.com} ; Anne Hermanowski-Vosatka ; MD ; PhD ; Kendra Gibson ; RN ; MSN ; MBA ; Rae Ann Ruck ; RN ; BSN ; Gang Jia ; PhD ; John Zhang ; PhD ; Peggy M.T. Hwang ; PhD ; Nicholas W. Ryan ; PharmD ; Ronald B. Langdon ; PhD ; Peter U. Feig ; MD
• 关键词：Metabolic syndrome ; dyslipidemia ; low-density lipoprotein cholesterol ; ambulatory blood pressure monitoring
• 刊名：Journal of the American Society of Hypertension
• 出版年：2011
• 出版时间：May-June 2011
• 年：2011
• 卷：5
• 期：3
• 页码：166-176
• 全文大小：394 K

文摘

11¦Â-hydroxysteroid dehydrogenase type 1 (11¦Â-HSD1) may be involved in several abnormalities associated with the metabolic syndrome. This study evaluated the antihypertensive efficacy and safety of two 11¦Â-HSD1 inhibitors, MK-0736 and MK-0916, in overweight-to-obese hypertensive patients. Patients aged 18?5 years with sitting diastolic blood pressure (SiDBP) 90?04 mm Hg, systolic BP <160 mm Hg (after washout of prior antihypertensive medications), and BMI ?7 to <41 kg/m² were randomized to receive 2 or 7 mg/d MK-0736, 6 mg/d MK-0916, or placebo for 12 weeks (n = 51?4/group). Patients with BMI ?0 to <27 kg/m² received 6 mg/d MK-0916 or placebo for 24 weeks (n = 19/group). The primary endpoint was placebo-adjusted change from baseline in trough SiDBP in patients treated for 12 weeks with 7 mg/d MK-0736. The primary endpoint was not met (placebo-adjusted reduction = 2.2 mm Hg; P = .157). With 7 mg/d MK-0736, placebo-adjusted LDL-C decreased by 12.3 % , high-density lipoprotein cholesterol by 6.3 % , and body weight by 1.4 kg. Both 11¦Â-HSD1 inhibitors were generally well tolerated. In overweight-to-obese patients with hypertension, reduction in SiDBP with MK-0736 was not statistically significant. Nonetheless, MK-0736 was well tolerated and did appear to modestly improve other BP endpoints, LDL-C, and body weight.