PATTERNS OF COMPLIANCE WITH ONCE VERSUS TWICE-DAILY ANTIHYPERTENSIVE DRUG-THERAPY IN PRIMARY-CARE - A RANDOMIZED CLINICAL-TRIAL USING ELECTRONIC MONITORING

OBJECTIVE: To evaluate patterns of compliance with once versus twice d aily administration of antihypertensive therapy (primary outcome measu re) and relevance oi partial compliance for blood pressure control (se condary outcome measure). DESIGN: Multicentre, nonblinded, parallel gr oup randomized design. SETTING: Nonacademic primary care practices acr oss Canada. STUDY POPULATION: Patients with mild essential hypertensio n (diastolic blood pressure 95 to 110 mmHg) of either sex (40% women), age 18 to 80 years (average 55 years). One hundred and ninety-eight p atients were randomized to active treatment; 14 patients discontinued the study because of side effects. INTERVENTIONS: After a four-week pl acebo run-in period, patients were randomized to amlodipine 5 mg once- a-day or diltiazem slow release formulation (SR) 90 mg twice daily. Do ses were increased to 10 mg and 180 mg to achieve sitting diastolic bl ood pressure of 90 mmHg or less. OUTCOME MEASURE: During 20 weeks on a ctive treatment, compliance was assessed by pill counts and medication event monitoring system (MEMS), assessing percentage of prescribed do ses taken, percentage days correct doses taken, percentage prescribed doses taken on time and blood pressure central as determined by office blood pressure measurement. RESULTS: The percentage prescribed doses taken (by either pill count or MEMS) showed a high degree of complianc e, similar for the two treatments. However, other parameters of compli ance were significantly better with once versus twice dairy therapy. P artial compliance (less than 80% by pill count) led to less blood pres sure control with the short acting diltiazem, but did not affect brood pressure control for the long acting amlodipine. Side effects profile s did not differ between the two treatments. CONCLUSIONS: Within the c onstraints of a clinical trial, hypertensive patients in primary care show a high degree of overall compliance with once or twice daily pill -taking, but patterns of pill-taking are more erratic with twice versu s once daily medication, particularly in men. The results suggest that the negative consequences of partial compliance for blood pressure co ntrol can be offset by choosing agents with a duration of action well beyond the dosing interval.