Andrew J Lewin1, Matthew R Weir. 1. National Research Institute, 2010 Wilshire Boulevard, Suite 302, Los Angeles, CA 90057, USA. docL@sbcglobal.net
Abstract
OBJECTIVE: This was a post hoc subgroup analysis of efficacy and tolerability data from the Irbesartan/HCTZ Blood Pressure Reductions in Diverse Patient Populations (INCLUSIVE) trial stratified by baseline body mass index (BMI). The BMI subgroup data were also analyzed according to the presence or absence of type 2 diabetes mellitus (T2DM) at baseline. METHODS: The 18-week, prospective, multicenter, open-label, single-arm INCLUSIVE trial evaluated the efficacy and tolerability of a fixed-dose combination of irbesartan/hydrochlorothiazide (HCTZ) in adult hypertensive patients with systolic blood pressure (SBP) that was uncontrolled after >or=4 weeks of monotherapy. Patients received placebo for 4 to 5 weeks, HCTZ 12.5 mg for 2 weeks, irbesartan/HCTZ 150/12.5 mg for 8 weeks, and irbesartan/HCTZ 300/25 mg for 8 weeks. Patients were stratified into BMI subgroups based on values at screening. Normal weight was defined as a BMI <or=24.9 kg/m(2), overweight as a BMI of 25 to 29.9 kg/m(2), and obesity as a BMI >or=30 kg/m(2). The primary efficacy end point was the mean change in SBP from baseline (end of the placebo phase) to week 18 in the overall intent-to-treat (ITT) population. Secondary efficacy end points were the mean changes in SBP and diastolic blood pressure (DBP) from baseline to week 18 in each BMI subgroup, the proportions of patients in each BMI subgroup achieving their SBP target (<140 mm Hg [<130 mm Hg for patients with T2DM]) and DBP target (<90 mm Hg [<80 mm Hg for patients with T2DM]), and the mean SBP and DBP responses at the end of each treatment period. RESULTS: The ITT population included 736 patients, of whom 99 (13.5%) were normal weight, 243 (33.0%) were overweight, and 394 (53.5%) were obese. Mean baseline SBP and DBP values were similar across BMI subgroups. Obese patients were generally younger than normal-weight and overweight patients, and numerically more obese patients had T2DM and metabolic syndrome. The mean reductions in SBP and DBP at week 18 were statistically significant in all subgroups (all, P < 0.001); SBP and DBP goals were achieved by a respective 83.8% and 93.9% of normal-weight patients, 75.3% and 87.7% of overweight patients, and 76.9% and 77.2% of obese patients. Rates of SBP/DBP control to <140/90 mm Hg in normal weight, overweight, and obese patients without T2DM were 88.2%, 79.8%, and 80.9%, respectively; the corresponding rates of control to <130/80 mm Hg in patients with T2DM were 50.0%, 41.5%, and 38.5%. CONCLUSION: In this post hoc subgroup analysis of the INCLUSIVE trial, irbesartan/HCTZ combination therapy had comparable antihypertensive efficacy and tolerability regardless of BMI or diabetes status.
RCT Entities:
OBJECTIVE: This was a post hoc subgroup analysis of efficacy and tolerability data from the Irbesartan/HCTZ Blood Pressure Reductions in Diverse Patient Populations (INCLUSIVE) trial stratified by baseline body mass index (BMI). The BMI subgroup data were also analyzed according to the presence or absence of type 2 diabetes mellitus (T2DM) at baseline. METHODS: The 18-week, prospective, multicenter, open-label, single-arm INCLUSIVE trial evaluated the efficacy and tolerability of a fixed-dose combination of irbesartan/hydrochlorothiazide (HCTZ) in adult hypertensivepatients with systolic blood pressure (SBP) that was uncontrolled after >or=4 weeks of monotherapy. Patients received placebo for 4 to 5 weeks, HCTZ 12.5 mg for 2 weeks, irbesartan/HCTZ 150/12.5 mg for 8 weeks, and irbesartan/HCTZ 300/25 mg for 8 weeks. Patients were stratified into BMI subgroups based on values at screening. Normal weight was defined as a BMI <or=24.9 kg/m(2), overweight as a BMI of 25 to 29.9 kg/m(2), and obesity as a BMI >or=30 kg/m(2). The primary efficacy end point was the mean change in SBP from baseline (end of the placebo phase) to week 18 in the overall intent-to-treat (ITT) population. Secondary efficacy end points were the mean changes in SBP and diastolic blood pressure (DBP) from baseline to week 18 in each BMI subgroup, the proportions of patients in each BMI subgroup achieving their SBP target (<140 mm Hg [<130 mm Hg for patients with T2DM]) and DBP target (<90 mm Hg [<80 mm Hg for patients with T2DM]), and the mean SBP and DBP responses at the end of each treatment period. RESULTS: The ITT population included 736 patients, of whom 99 (13.5%) were normal weight, 243 (33.0%) were overweight, and 394 (53.5%) were obese. Mean baseline SBP and DBP values were similar across BMI subgroups. Obesepatients were generally younger than normal-weight and overweight patients, and numerically more obesepatients had T2DM and metabolic syndrome. The mean reductions in SBP and DBP at week 18 were statistically significant in all subgroups (all, P < 0.001); SBP and DBP goals were achieved by a respective 83.8% and 93.9% of normal-weight patients, 75.3% and 87.7% of overweight patients, and 76.9% and 77.2% of obesepatients. Rates of SBP/DBP control to <140/90 mm Hg in normal weight, overweight, and obesepatients without T2DM were 88.2%, 79.8%, and 80.9%, respectively; the corresponding rates of control to <130/80 mm Hg in patients with T2DM were 50.0%, 41.5%, and 38.5%. CONCLUSION: In this post hoc subgroup analysis of the INCLUSIVE trial, irbesartan/HCTZ combination therapy had comparable antihypertensive efficacy and tolerability regardless of BMI or diabetes status.