SAFETY AND TOLERABILITY OF COMBINATION OLMESARTAN MEDOXOMIL (OM)+AMLODIPINE BESYLATE (AML)+HYDROCHLOROTHIAZIDE (HCTZ) IN PATIENTS WITH HYPERTENSION: THE TRINITY STUDY: PP.5.166

Abstract

Since hypertension is an asymptomatic disease, patient adherence to therapy is often influenced by a treatment's tolerability and adverse-event (AE) profile. The efficacy and safety of OM 40 mg+AML 10 mg+HCTZ 25 mg compared with its corresponding dual components (OM/AML, OM/HCTZ, or AML+HCTZ) was evaluated in 2492 moderate to severe HTN patients in a phase 3, multicenter, parallel-group study consisting of a 12-wk double-blind treatment period followed by a 40-wk open-label treatment period. Patients were stratified by age, race, and diabetic status and received dual-combination therapy for 2 wks. A subset of treatment-naive patients received placebo (n=36) prior to switching to dual-combination therapy, which continued for all patients from wks 2 to 4. OM+AML+HCTZ was initiated in a subset of patients from each of the 3 dual-combination groups at wk 4 and continued until wk 12.The primary safety cohort (n=2302) for the assessment of AEs was defined as patients who took at least 1 dose of study medication at or beyond wk 4. At baseline for all randomized patients, mean age was 55.1 y, with 52.9% male, 66.8% Caucasian, 19% >/=65 y, and 15.5% diabetic; mean SeBP was 168.5/100.9 mmHg. Across all groups, treatment-emergent AEs (TEAEs) (>/=3%) included dizziness (7.0%), headache (6.5%), peripheral edema (6.0%), fatigue (5.4%), and upper respiratory tract infection (3.2%). Similar TEAE incidences were seen across all 4 treatment groups, and most TEAEs and drug-related TEAEs were mild or moderate in severity. Slightly more discontinuations due to TEAEs occurred in the OM+AML+HCTZ group due to the greater pharmacodynamic effects. Overall, OM+AML+HCTZ was safe and well tolerated by most patients.