A multicenter trial of low dose captopril administered twice daily in patients with essential hypertension unresponsive to beta blocker-diuretic treatment.

Two hundred and one patients with essential hypertension, whose supine diastolic blood pressure (SDBP) was greater than or equal to 95 mmHg following 2 weeks of treatment with the optimal dose of a beta blocker-diuretic combination (Phase 1), were randomly assigned to the addition of either 25 or 50 mg captopril BID for 6 weeks (Phase 2). At the end of Phase 2, the dose of captopril was doubled in the patients not normalized (SDBP greater than or equal to 95 mmHg) and maintained in the others (SDBP less than 95) for an additional 4 weeks (Phase 3). At the end of Phase 3, the beta blocker was withdrawn in the normalized (SDBP less than 95 mmHg) patients, and captopril plus diuretic was given for 4 weeks (Phase 4). The addition of captopril at either dose level led to a significant fall (p less than 0.01) in standing and supine diastolic and systolic blood pressure after the first 2 weeks of treatment. There was no significant difference in response between the two dose levels of captopril. At the end of Phase 2, 59.4% and 55.8% of patients, respectively, assigned to 25 and 50 mg captopril BID, were normalized. Doubling the dose of captopril (Phase 3) led to approximately an additional 30% of patients being normalized. At the end of Phase 4 (captopril plus diuretic) the SDBP was still less than 95 mmHg in 63% of patients, whereas it was increased in the others. Side effects were noted in 10 patients (5%). The incidence was similar in each treatment group, and a total of four patients (2%) were withdrawn due to side effects.