Long-term efficacy, tolerability, and safety of the combination of enalapril and felodipine ER in the treatment of hypertension. Enalapril-Felodipine ER Factorial Study Group

Abstract

A recent 8-week, double-masked, placebo-controlled, 3 x 4 factorial-design study demonstrated that enalapril-felodipine extended-release (ER) combinations had statistically significant additive effects for reducing both sitting systolic blood pressure (SiSBP) and sitting diastolic blood pressure (SiDBP) and were generally well tolerated in hypertensive patients with SiDBPs ranging from 95 to 115 mm Hg. The present open-label study was undertaken to assess the long-term efficacy, tolerability, and safety of such combinations. Patients from the factorial study were eligible for the 1-year, open-label extension. Initially, all patients received enalapril 5 mg-felodipine ER 2.5 mg once daily; if SiDBP was not controlled (< 90 mm Hg) after 4 weeks of treatment, the dose was titrated upward at 2- to 4-week intervals to a maximum of enalapril 10 mg-felodipine ER 10 mg. Hydrochlorothiazide (HCTZ) 12.5 mg was added to the regimen of patients whose hypertension was not controlled at the highest enalapril-felodipine ER dose. A total of 507 patients were enrolled, of whom 502 were assessable. At their last study visit, 391 (78%) of the assessable patients were receiving only an enalapril-felodipine ER combination. The enalapril-felodipine ER combinations resulted in mean trough SiDBPs of 85 to 89 mm Hg (decreases of 13 to 16 mm Hg from baseline) and SiSBPs of 137 to 140 mm Hg (decreases of 13 to 21 mm Hg). Overall, 407 (81%) of the 502 assessable patients achieved an SiDBP < 90 mm Hg or a reduction from baseline > or = 10 mm Hg (responders); such a response was recorded in 331 patients (66%) taking a combination of enalapril-felodipine ER alone and 76 patients (15%) taking the combination with the addition of HCTZ 12.5 mg. Blood pressure reductions were maintained throughout the treatment period. Drug-related adverse events were relatively infrequent, often transient, usually mild, and apparently not dose related. The most frequently reported drug-related adverse events were edema/swelling, asthenia/fatigue, dizziness, cough, and headache. These results suggest that combination therapy with enalapril-felodipine ER is effective for long-term blood pressure reduction, has an excellent safety profile, and is generally well tolerated. Addition of low-dose HCTZ to the enalapril-felodipine ER combination appears to provide further blood pressure control without increasing drug-related adverse events.