Clinical Outcomes in Hypertensive Patients Treated with a Single-pill Fixed-dose Combination of Renin-angiotensin System Inhibitor and Thiazide Diuretic

Two or more antihypertensive agents are required to achieve blood pressure control for the most hypertensive patients. However, comparison of clinical outcomes between fixed-dose combinations (FDC) and free-equivalent combinations of renin-angiotensin system (RAS) inhibitor and thiazide diuretic is lacking nowadays. Patients who were newly diagnosed with hypertension between July 1st, 2008 and December 31st, 2011 and prescribed with FDC (n = 13 176) or free combinations of RAS inhibitors and thiazide diuretic (n = 4392) were identified from the National Health Insurance Research Database of Taiwan and matched in 3:1 ratio using the propensity score method. The primary end point was major adverse cardiovascular events (MACE). The secondary end points were hospitalization of heart failure, new diagnosis of chronic kidney disease, and the initiation of dialysis. Compared with he FDC group was associated with better medication adherence compared with the free combination group. FDC of RAS inhibitor and thiazide diuretic reduced MACE (hazard ratio [HR]: 0.85; 95% confidence interval [CI]: 0.74-0.97; P = 0.017), hospitalization for heart failure and initiation of dialysis compared with the free combination regimens. The outcome benefits of FDC was mainly driven by reduced cardiovascular and renal events in the patients with proportion of days covered <80%. In this retrospective claims database analysis, compared with the free combination regimens, the use of FDC of RAS inhibitor and thiazide diuretic was associated with improved medication compliance and clinical outcomes in the management of hypertension, particularly in the patients with poor medication adherence.