Efficacy and safety of fixed combinations of irbesartan/HCTZ in patients with uncontrolled SBP on monotherapy, according to previous antihypertensive drug class, in the inclusive trial

To determine the efficacy and safety of irbesartan/HCTZ fixed combinations in diverse patient populations with uncontrolled SBP on monotherapy who were enrolled in the Irbesartan/HCTZ Blood Pressure Reductions In Diverse Patient Populations (INCLUSIVE) trial, analyzed by previous antihypertensive drug class. This subgroup analysis of a multicenter, prospective, open-label, single-arm study with forced titration to SBP response included patients, ≥18 years of age, with hypertension and uncontrolled SBP (140–179 mmHg; 130–179 mmHg for patients with diabetes) after ≥4 weeks of antihypertensive monotherapy. Treatment was sequential, with placebo (4 weeks), HCTZ 12.5 mg (2 weeks), irbesartan/HCTZ 150/12.5 mg (8 weeks), and irbesartan/HCTZ 300/25 mg (8 weeks). Mean changes in SBP and DBP from baseline to study end, SBP and DBP control rates, and safety were evaluated. A total of 844 subjects completed the placebo wash-out phase and were enrolled in the study. Patients had previously failed to achieve SBP control on monotherapy with ACE inhibitors (34%), angiotensin receptor blockers (ARBs; 20%), calcium channel blockers (CCBs; 20%), diuretics (14%), and beta-blockers (11%). Few patients were previously on alpha-blockers (1%) and other antihypertensives (1%), and were excluded from further analysis. Mean change in SBP/DBP from baseline for the ITT population (n=736) was −21.5±14.3/−10.4±8.7 mmHg (P<0.001). Mean SBP changes by previous monotherapy ranged from −24.2±16.0 mmHg (P<0.001) in patients uncontrolled on beta-blockers to −20.1±14.8 mmHg (P<0.001) in those uncontrolled on ACE inhibitors. Mean DBP changes ranged from −12.9±9.2 mmHg (P<0.001; beta-blockers) to −9.3±8.3 mmHg (P<0.001; CCBs). SBP control (<140 mmHg; <130 mmHg for patients with diabetes) rates ranged from 72% (ACE inhibitors) to 84% (beta-blockers). DBP control (<90 mmHg; <80 mmHg for patients with diabetes) rates ranged from 80% (ACE inhibitors; diuretics) to 91% (beta-blockers). Treatments were well tolerated. Titration from HCTZ monotherapy to low- and high-dose irbesartan/HCTZ fixed combinations allows SBP control to be attained in over 70% of patients previously uncontrolled on any antihypertensive monotherapy.