Bidirectional adherence changes and associated factors in patients switched from free combinations to equivalent single-pill combinations of antihypertensive drugs.

There are no reported studies assessing the effects of fixed-dose single-pill combinations (SPCs) of antihypertensive drugs on adherence in real-world patients with hypertension switched from free combinations to the corresponding SPCs. In this retrospective cohort study with a 1-year mirror-image design, a total of 896 patients who had been prescribed with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker and a thiazide-type diuretic within the preceding 12 months of the index (switching) date and the corresponding SPC within 12 months after the index date were included by using the Taiwan National Health Insurance database from January 2001 to December 2007. Adherence was measured by medication possession ratio (MPR). For patients switched to SPCs, the MPR increased significantly from 42% in the preindex period to 69% in the postindex period (relative difference, 75%; 95% confidence interval, 58%-100%; P<0.001). However, for switched patients with high adherence (MPR ≥0.8) in the preindex period, the MPR unexpectedly decreased in the postindex period (absolute difference, -13%; 95% confidence interval, -17% to -9%; P<0.001). In multivariate analysis, MPR difference was inversely related to the preindex MPR, the number of other antihypertensive drugs, and congestive heart failure. In summary, despite of the dramatic effect of SPCs on improving adherence, this strategy is not effective or even worse in patients adequately adhering to their free-combined antihypertensive regimens. The inverse association between adherence improvement and number of concurrent antihypertensive drugs suggests early use of SPCs to curtail the nonadherence gap.