Effects of combination drugs on antihypertensive medication adherence in a real-world setting: a Korean Nationwide Study

Objectives We tried to clarify, by using representative national data in a real-world setting, whether single-pill combinations (SPCs) of antihypertensives actually improve medication adherence. Design A nationwide population-based study. Setting We used a 2.2% cohort (n=1 048 061) of the total population (n=46 605 433) that was randomly extracted by National Health Insurance of Korea from 2008 to 2013. Participants We included patients (n=116677) who were prescribed with the same antihypertensive drugs for at least 1 year and divided them into groups of angiotensin II receptor blocker (ARB)-only, calcium channel blocker (CCB)-only, multiple-pill combinations (MPCs) and SPCs of ARB/CCB. Primary outcome measures Medication possession ratio (MPR), a frequently used indirect measurement method of medication adherence. Results Adjusted MPR was higher in combination therapy (89.7% in SPC, 87.2% in MPC) than monotherapy (81.6% in ARB, 79.7% in CCB), and MPR of SPC (89.7%, 95% CI 89.3 to 90.0) was higher than MPR of MPC (87.2%, 95% CI 86.7 to 87.7) (p<0.05). In subgroup analysis, adherence of SPC and MPC was 92.3% (95% CI 91.5 to 93.0) vs 88.1% (95% CI 87.1 to 89.0) in those aged 65-74 years and 89.3% (95% CI 88.0 to 90.7) vs 84.8% (95% CI 83.3 to 92.0) in those >= 75 years (p<0.05). According to total pill numbers, adherence of SPC and MPC was 90.9% (CI 89.8 to 92.0) vs 85.3% (95% CI 84.1 to 86.5) in seven to eight pills and 91.2% (95% CI 89.3 to 93.1) vs 82.5% (95% CI 80.6 to 84.4) in nine or more (p<0.05). The adherence difference between SPC and MPC started to increase at five to six pills and at age 50-64 years (p<0.05). When analysed according to elderly status, the adherence difference started to increase at three to four pills in the elderly (>= 65 years) and at five to six in the non elderly group (20-64 years) (p<0.05). These differences all widened further with increasing age and the total medications. Conclusion SPC regimens demonstrated higher adherence than MPC, and this tendency is more pronounced with increasing age and the total number of medications.