Addition of felodipine to metoprolol vs replacement of metoprolol by felodipine in patients with angina pectoris despite adequate beta-blockade: Results of the Felodipine ER and Metoprolol CR in Angina (FEMINA) Study

Abstract

AimsThe study aimed to compare the addition of felodipine to metoprolol, and of the replacement of metoprolol by felodipine, with continuation of metoprolol, in patients with angina pectoris despite optimal betablockade. Methods and resultsThe study was double-blind, parallel, randomized and controlled, and comprised 363 patients from 27 outpatient cardiology clinics in the Netherlands. The patients had angina and positive bicycle exercise tests despite optimal beta-blockade (resting heart rate <65 beats . min~ '). Randomization was to three treatment groups: continuation of metoprolol (control), addition of felodipine to metoprolol, and replacement of metoprolol by felodipine. Exercise tests were repeated after 2 and 5 weeks. The main outcome measure was: exercise result after 5 weeks, compared with baseline, betweengroup comparison of changes vs control. There were no significant differences in exercise duration and onset of chest pain vs control. The addition of felodipine increased time until 1 mm ST depression (43 s, 95% confidence interval 20-65 s), and decreased both ST depression at highest comparable work load (0-46 mm, 95% confidence interval 0-19-0-72), and maximal ST depression (0-49 mm, 95% confidence interval 0-23-0-74). Exercise results after replacement of metoprolol by felodipine were not different from control, apart from a significant increase in rate pressure product. Significantly more patients experienced adverse events in the felodipine monotherapy group. ConclusionCombination of metoprolol and felodipine is to be preferred to felodipine monotherapy in patients who have signs and symptoms of myocardial ischaemia despite optimal beta-blockade.

Relative efficacy of antianginal drugs used as add-on therapy in patients with stable angina: A systematic review and meta-analysis

“…There were 28 studies (37 comparisons) of a CCB added to a BB ( n = 2468); 7–35 12 studies (12 comparisons) of a BB added to a CCB ( n = 1489); 9,11,12,14–16,19,20,24,25,29,34 7 studies (8 comparisons) of a LAN added to a BB or CCB ( n = 329); 7,36–40 3 studies (4 comparisons) of ranolazine added to a BB or CCB ( n = 1388); 41–43 8 studies (9 comparisons) of trimetazidine added to a BB or CCB ( n = 2875); 44–51 1 study of ivabradine added to a BB ( n = 889). 52 No studies were found that evaluated the impact of nicorandil in an add-in role on either ETT or clinical measures of anti-anginal efficacy.…”

A Metabolic Approach to the Management of Ischemic Heart Disease

“…Double-blind, parallel, randomized, controlled Combination was not more effective than monotherapy but may lead to improvement in symptomatic patients who have a rapid onset of exercise-induced ischemia Dunselman et al [17] Metoprolol 100 or 200 mg/day + felodipine 5 then 10 mg/day vs felodipine vs metoprolol (control)…”

Combination Therapy in Angina: A Review of Combined Haemodynamic Treatment and the Role for Combined Haemodynamic and Cardiac Metabolic Agents

“…Although research has continued into the effects of combined haemodynamic treatment, much of this research has produced conflicting and inconclusive results 12 . Few trials have been adequate in design, and many studies, on the basis of their sample size, could not exclude a type II statistical error.…”