Felodipine, metoprolol and their combination compared with placebo in isolated systolic hypertension in the elderly

This study compared with placebo the efficacy and tolerability of optimised doses of felodipine 5-20 mg daily, metoprolol 50-200 mg daily and their combination in subjects 60 years or over with isolated systolic hypertension. The study employed a randomised double-blind crossover design with allocation of treatment order within subjects by Latin squares. For each subject, after a single-blind run-in placebo phase, there were four randomised treatment phases each of six weeks duration, with a dose titration step at three weeks if necessary. Twenty-eight subjects entered the randomised phases of the study and twenty-one completed all four phases-13 male, 8 female (ages: median 71, range 59-85 years). At the end of both the felodipine and metoprolol phases systolic and diastolic pressure were reduced at 2 hours postdose compared with the placebo phase (p < 0 001), the blood pressure reduction with felodipine (-40/-20 mmHg) being greater than that with metoprolol (-15/ -9 mmHg) (p <0.01). Immediately predose (12 hours postdose) there was a persisting reduction of supine systolic blood pressure (- 17 mmHg) with felodipine (p < 0.001), but there was no significant effect of metoprolol. At both measurement times the two drugs when in combination had an additive effect on blood pressure. There was a 20% increase in reported symptoms during each of the active treatment phases. Four subjects withdrew during the randomised phases because of probable drug-related adverse events and six subjects required dosage reductions during the felodipine or combination phases. Thus in elderly subjects with isolated systolic hypertension, felodipine is an effective blood pressure reducing agent with expected adverse vasodilator effects, whereas metoprolol although well tolerated is less effective than felodipine. In combination the effects of the drugs on blood pressure are additive without any increase in adverse effects.