Low-dose quadruple antihypertensive combination: more efficacious than individual agents--a preliminary report

Increasingly combined antihypertensive agents are being used in practice to enhance control and improve compliance. To determine whether a capsule containing a quarter of the standard dose of 4 antihypertensive agents has greater efficacy than the standard dose of each individually, we prospectively randomized 108 untreated white hypertensive patients (55% male) aged 50+/-1 years (mean+/-SEM), with mean blood pressure 160+/-1/96+/-1 mm Hg. Patients received amlodipine (5 mg; n=22), atenolol (50 mg; n=20), bendroflumethiazide (2.5 mg; n=22), captopril (50 mg twice daily; n=22) or a capsule containing each of the 4 above at one-quarter dosage (n=22) in a parallel group design for 4 weeks. Blood pressure was measured using a semiautomated device (Omron 705), and the reduction in mean arterial pressure with the combined preparation was compared with that of the individual components. Statistical analysis used ANOVA and Tukey-Kramer honestly significant difference for multiple comparisons. The reduction in mean arterial pressure with the combination (19+/-2 mm Hg) was significantly greater than that with individual agents amlodipine (10+/-2 mm Hg; P<0.005), atenolol (10+/-2 mm Hg; P<0.005), bendroflumethiazide (6+/-1 mm Hg; P<0.005), and captopril (11+/-1 mm Hg; P<0.01). In addition, the percentage reduction in systolic (18+/-1 mm Hg; P<0.005) and diastolic (17+/-2 mm Hg; P=0.06) blood pressure was greater with the combination. More patients achieved a blood pressure of <140/90 mm Hg with the combination (60%) than any individual drug (15% to 45%; P<0.05). A low-dose combination of 4 agents representing 4 classes of standard antihypertensive agents was more efficacious than a standard single dose of each agent individually.