Medication adherence affecting cardiovascular outcomes even in clinical trials

Two new analyses of recent cardiology trials highlighted the prevalence and potential adverse effects of nonadherence to medications.

Two recent studies highlighted the importance of medication adherence in patients with cardiovascular disease.

The first study used data from the ISCHEMIA trial (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches), which randomized patients with chronic coronary disease to guideline-directed medical therapy with or without angiography and revascularization. Researchers compared 12-month health status outcomes by medication adherence with an a priori hypothesis that nonadherent patients would have better health status if randomized to invasive management.

Self-reported medication-taking was assessed at randomization with a modified Morisky Green-Levine Adherence Scale. Twelve-month health status was assessed with the 7-item Seattle Angina Questionnaire summary score (SAQ-7SS), which ranges from 0 to 100, with higher scores being better. The association of adherence with outcomes was evaluated and outcomes were published on Aug. 15 by the Journal of the American College of Cardiology (JACC).

Of 4,480 randomized participants, 1,245 (27.8%) were nonadherent at baseline. This group scored worse than adherent patients on their baseline SAQ-7SS in the conservative (72.9 vs. 75.6) and invasive (71.0 vs. 74.2) arms. Adjusted analyses found that adherence was associated with higher 12-month SAQ-7SS in both treatment groups (mean difference in SAQ-7SS with conservative treatment vs. invasive management, 1.6 [95% credible interval, 0.3 to 2.9] vs. 1.9 [95% credible interval, 0.8 to 3.1]), with no interaction by treatment. The study authors noted that strategies to improve medication adherence are needed to improve health status outcomes in patients with chronic coronary disease, regardless of whether they receive invasive or medical therapy.

A second study showed that nonadherence to antiplatelet therapy after percutaneous coronary intervention (PCI) was common, even in a clinical trial. The purpose of this study was to investigate the impact of nonadherence to study protocol regimens in the MASTERDAPT (Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation with an Abbreviated Versus Prolonged DAPT Regimen) trial.

One month after PCI, 4,579 patients at high risk for bleeding were randomized to either abbreviated treatment, which was single antiplatelet therapy (SAPT) for 11 months (five months in patients on oral anticoagulation) or standard treatment—dual antiplatelet therapy (DAPT) for at least two additional months followed by SAPT. Results were also published by JACC on Aug. 15.

Nonadherence was observed in 464 (20.2%) patients in the abbreviated treatment group and 214 (9.4%) in the standard treatment group. In inverse probability-of-censoring weights analyses, adverse events did not differ significantly between groups, and major bleeding was lower with abbreviated treatment. Among patients on oral anticoagulants, SAPT discontinuation six months after PCI was associated with similar rates of cardiovascular events and less bleeding compared with continuing SAPT.

“The findings reinforce the importance of accounting and correcting for nonadherence in clinical trials in order to derive more unbiased treatment effects,” the authors said.

An editorial accompanying the two studies agreed that both reinforce the high prevalence of medication nonadherence and its potential impact on both estimates of treatment effect and health outcomes.

“While effective tools that enhance medication adherence are already available to us, we must do a better job of implementing these strategies if patients are to fully realize the benefits of medications that lower cardiac risk and improve quality of life,” the editorial concluded.