Multicenter Cluster-Randomized Trial of a Multifactorial Intervention to Improve Antihypertensive Medication Adherence and Blood Pressure Control Among Patients at High Cardiovascular Risk (The COM99 Study)

BACKGROUND: Medication nonadherence is common and results in preventable disease complications. This study assessed the effectiveness of a multifactorial intervention to improve both medication adherence and blood pressure control and to reduce cardiovascular events. METHODS AND RESULTS: In this multicenter, cluster-randomized trial, physicians from hospital-based hypertension clinics and primary care centers across Spain were randomized to receive and provide the intervention to their high-risk patients. Eligible patients were ≥ 50 years of age, had uncontrolled hypertension, and had an estimated 10-year cardiovascular risk greater than 30%. Physicians randomized to the intervention group counted patients' pills, designated a family member to support adherence behavior, and provided educational information to patients. The primary outcome was blood pressure control at 6 months. Secondary outcomes included both medication adherence and a composite end point of all-cause mortality and cardiovascular-related hospitalizations. Seventy-nine physicians and 877 patients participated in the trial. The mean duration of follow-up was 39 months. Intervention patients were less likely to have an uncontrolled systolic blood pressure (odds ratio 0.62, 95% confidence interval 0.50 to 0.78) and were more likely to be adherent (odds ratio 1.91, 95% confidence interval 1.19 to 3.05) than control group patients at 6 months. After 5 years, 16% of the patients in the intervention group and 19% in the control group met the composite end point (hazard ratio 0.97, 95% confidence interval 0.67 to 1.39). CONCLUSIONS: A multifactorial intervention to improve adherence to antihypertensive medication was effective in improving both adherence and blood pressure control, but it did not appear to improve long-term cardiovascular events.