Low Dose Combination Therapy vs. High Dose Monotherapy in the Management of Hypertension.

Author(s): Neutel JM, Smith DH, Weber MA

Affiliation(s): Orange County Research Center, Orange, CA.

Publication date & source: 1999-11, J Clin Hypertens (Greenwich)., 1(3):79-86.

Publication type:

A common approach to the management of hypertension suggests the use of an initial drug and the addition of a second agent if goal blood pressures (BPs) are not achieved. The Sixth Report of the Joint National Committee (JNC VI) suggests that the use of low dose combination therapy may be an appropriate alternative to initial treatment. In this prospective, randomized, open label, blinded end point (PROBE) study, following a 2 week single blind placebo washout period, qualified patients were started on a calcium channel blocker, felodipine 5 mg for 2 weeks. Patients who were nonresponders (DBP equals 90 mm Hg) were randomized to either felodipine 10 mg (n equals 17, mean age 52.4, 12 males), an ACE inhibitor, enalapril 5 mg/felodipine 5 mg (n equals 20 mean, mean age 52.1, 13 males), or another ACE inhibitor, benazepril 10 mg/amlodipine 5 mg (n equals 18, mean age 53.9, 15 males) for an additional 6 weeks. Ambulatory BP monitoring was performed at the end of the single blind placebo washout period and again at the end of the study. All three treatment groups had significant reductions in mean 24 hour systolic and diastolic BP compared to baseline. The reduction in mean 24 hour systolic and diastolic BPs in the benazepril/amlodipine treated patients (-17.2/-9.7 mm Hg) was significantly greater (p equals 0.05) than in the felodipine 10 mg treated patients (-11.9/-6.4 mm Hg) and was also numerically but not statistically significantly greater than in the enalapril/felodipine treated patients (-14.2/-8.2 mm Hg). Similar differences were seen when assessing daytime BP (06:00-21:59) and nighttime BP (10:00-05:59). The reductions in morning systolic and diastolic BP (6 am-noon) in the benazepril/amlodipine treated patients (-18.6/-10.7 mm Hg) were numerically but not statistically significantly greater than the enalapril/felodipine treated patients (-13.6/-7.5 mm Hg) and the felodipine 10 mg treated patients (-14.9/-8.3 mm Hg). The data from this study suggests that using low dose combination therapy in patients who are nonresponders to first line monotherapy with a calcium channel blocker provides greater blood pressure control than up titration to higher dose monotherapy. Low dose combination therapy may therefore be an important early alternative to up titration of monotherapy in patients who are nonresponders. These data confirm other observations with combination therapy with A -blockers/ diuretics, ACE inhibitors/diuretics, and angiotensin II (AII) receptor blockers/diuretics. (c)1999 by Le Jacq Communications, Inc.