Antihypertensive and metabolic effects of Angiotensin receptor blocker/diuretic combination therapy in obese, hypertensive African American and white patients

Abstract

A clinical trial showed comparable blood pressure (BP) lowering by valsartan/hydrochlorothiazide and amlodipine/hydrochlorothiazide in obese hypertensive patients. Relative to amlodipine/hydrochlorothiazide, valsartan/hydrochlorothiazide reduced the hyperglycemic response to glucose challenge. An objective of this post hoc analysis was to determine whether this benefit extended to African Americans and whites. Treatments (160/12.5 mg of valsartan/hydrochlorothiazide force titrated to 320/25 mg of valsartan/hydrochlorothiazide at week 4 or 12.5 mg of hydrochlorothiazide force titrated to 25 mg of hydrochlorothiazide at week 4 with 5 and 10 mg of amlodipine added at weeks 8 and 12, respectively) were administered once daily. Both treatments reduced clinic BP from baseline to all visits (P < 0.0001), regardless of race/ethnicity (126 African Americans, 212 whites). In African Americans, there were no significant between-treatment differences in clinic or ambulatory BP lowering at weeks 8 or 16. Whites responded better to valsartan/hydrochlorothiazide. In both racial/ethnic subgroups, the addition of valsartan but not amlodipine mitigated the hyperglycemic response to hydrochlorothiazide through enhanced insulin secretion. Valsartan/hydrochlorothiazide was as effective as amlodipine/hydrochlorothiazide was in reducing BP in obese, hypertensive African Americans and better than amlodipine/hydrochlorothiazide in whites. In both racial/ethnic subgroups, the addition of valsartan to hydrochlorothiazide reduced the negative metabolic effects associated with thiazide therapy.

Trial registration: ClinicalTrials.gov NCT00439738.

Conflict of interest statement

Conflicts of Interest: Author disclosures: Dr. Ofili has served as a consultant for Novartis Pharmaceuticals Corporation. Dr Ofili is also supported in part by the following research awards from the National Institutes of Health: PHS Grant UL1 RR025008, U54 RR026137, and 2R25RR017694-06A1 from the National Center for Research Resources (NCRR); and PHS Grant U01HL084891from the National Heart Lung and Blood Institute. The contents of this manuscript are solely the responsibility of the authors and do not necessarily represent the official views of NCRR, NHLBI, or NIH. Drs. Zappe, Purkayastha, and Samuel are employees of Novartis Pharmaceuticals Corporation.

Figures

Figure 1

Clinic mean sitting systolic blood pressure (MSSBP) and mean sitting diastolic blood pressure (MSDBP) values throughout the study (last observation carried forward) by racial/ethnic and treatment group. Error bars represent standard error. HCTZ=hydrochlorothiazide; V=valsartan.

Figure 2

Mean change from baseline to Week 16 (last observation carried forward) in 24-hour ambulatory blood pressure by racial/ethnic and treatment group. Error bars represent standard error. HCTZ=hydrochlorothiazide; MADBP=mean ambulatory diastolic blood pressure; MASBP=mean ambulatory systolic blood pressure; V=valsartan.

Figure 3

Mean postprandial glucose (A) and insulin (B) at baseline and end of study after a 2-hour oral glucose tolerance test by racial/ethnic and treatment group. HCTZ=hydrochlorothiazide; V=valsartan.

Figure 3

Mean postprandial glucose (A) and insulin (B) at baseline and end of study after a 2-hour oral glucose tolerance test by racial/ethnic and treatment group. HCTZ=hydrochlorothiazide; V=valsartan.