Adherence to triple‐component antihypertensive regimens is higher with single‐pill than equivalent two‐pill regimens: A randomized controlled trial

ABSTRACT: Using a single‐pill combination (SPC) for hypertension (HTN) treatment resulted in better adherence and persistence than a free‐equivalent combination in previous observational studies. The aim of this study is to confirm superior adherence with a triple‐component SPC compared with an equivalent two‐pill regimen in a randomized controlled trial (RCT) using a medication event monitoring system (MEMS). This is a multicenter, open‐label, RCT. Subjects were persons with HTN whose clinic blood pressure was not adequately controlled (systolic >140 mmHg or diastolic >90 mmHg) with a dual combination. Eligible patients were randomized to either the triple‐component SPC (olmesartan/amlodipine/hydrochlorothiazide 20/5/12.5 mg) group or the equivalent two‐pill (olmesartan/hydrochlorothiazide 20/12.5 mg + amlodipine 5 mg) group and maintained for 12 weeks. Primary outcomes were the difference in percentage of doses taken (PDT) and percentage of days with the prescribed dose taken correctly (PDTc) between the single‐ and two‐pill therapy groups, calculated from MEMS data. From 8 hospitals, 145 patients with HTN were randomized. The single‐pill group had significantly higher PDT and PDTc than the two‐pill group: median (25–75 percentile) PDT 95.1 (86.7–100.0) versus 92.1 (73.0–97.3); and PDTc 91.0 (79.4–96.5) versus 88.6 (69.2–96.3%), P = 0.04 for both by the Wilcoxon rank sum test. The single‐pill combination of the triple‐component antihypertensive regimen showed better adherence than the equivalent two‐pill therapy. Reducing pill burden by means of a single‐pill combination is an effective strategy for enhancing adherence to multiple‐agent antihypertensive therapy. STUDY HIGHLIGHTS: WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? WHAT QUESTION DID THIS STUDY ADDRESS? WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? This finding strongly supports the current HTN treatment guideline to prefer SPC with a higher level of evidence.