Verma AA, et al. - Researchers compared the clinical outcomes and medication adherence with fixed-dose combination (FDC) therapy vs multipill combination therapy in a real-world setting using linked clinical and administrative databases. Among older adults, they noted an association of initiating combination antihypertensive treatment, FDC therapy with a significantly lower risk of composite clinical outcomes, which may be related to better medication adherence.

Methods

• Experts conducted a population-based retrospective cohort study of 13,350 individuals 66 years and older in Ontario, Canada with up to 5 years of follow-up.
• The individuals who were newly initiated on one angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II-receptor blocker (ARB) plus one thiazide diuretic were included.
• To compare individuals receiving FDC vs multipill therapy, high-dimensional propensity score matching was used.
• For acute myocardial infarction (AMI), heart failure, or stroke, the primary outcome was a composite of death or hospitalization.
• Two analyses were conducted to examine the relationship between adherence and patient outcomes.
• First, an on-treatment analysis was conducted to ascertain if outcomes differed between groups while patients were on treatment, censoring patients when they first discontinued treatment, defined as not receiving medications within 150% of the previous days’ supply.
• Second, an intention-to-treat analysis was conducted that followed individuals allowing for breaks in treatment to quantify the difference in drug adherence between groups and assess its impact on clinical outcomes.

Results

• Findings suggested that as expected, no significant difference in the primary outcome between groups in the on-treatment analysis was noted (HR 1.06, 95% CI 0.86–1.31, P=0.60).
• Results demonstrated that, the proportion of total follow-up days covered with medications in the intention-to-treat analysis was significantly greater in the FDC group (70%; IQR 19–98) than in the multipill group (42%, IQR 11–91, P < 0.01), and the primary outcome was less frequent in FDC recipients (3.4 vs 3.9 events per 100 person-years; HR 0.89, 95% CI 0.81–0.97, P < 0.01).
• The lack of data regarding cause of death and blood pressure measurements and the possibility of residual confounding were the main limitations of this study.