Amlodipine combined with beta blockade for chronic angina: Results of a multicenter, placebo‐controlled, randomized double‐blind study

Abstract

Summary: Amlodipine, a potent long-acting dihydropyridine calcium antagonist, was compared with placebo in a parallel, randomized, double-blind study in 134 patients with chronic stable angina pectoris maintained on betaadrenergic blocking agents. After a single-blind, two-week placebo period, patients were randomized to receive either amlodipine (2.5, 5, and 10 mg) or placebo once daily for four weeks. The effects of amlodipine on maximal exercise time, work, time to angina onset, and subjective indices including angina frequency, nitroglycerin tablet consumption, and patient and investigator ratings were assessed. Each dose of amlodipine produced increases in exercise time and calculated total work accomplished compared to baseline. Improvements at 5 and 10 mg were significantly greater than placebo which produced no significant change (p < 0.05). Qualitative improvements in the severity of angina were produced by amlodipine at 5 and 10 mg daily assessed by patient-rating questionnaires (pc0.05). Reductions in angina frequency attacks per week and weekly nitroglycerin tablet consumption occurred but were not statistically significant when cornpared with placebo. Adverse effects observed during amlodipine treatment prompted discontinuation of treatment in only 2 out of 100 patients. Three patients discontinued treatment for reported lack of efficacy. No laboratory abnormalities prompted treatment discontinuation and minor side effects of dizziness, nausea, headache, and fatigue were observed infrequently. The results of this controlled, large-scale multicenter trial suggest that amlodipine significantly increased exercise capacity and was well tolerated when added to the antianginal regimen of patients remaining symptomatic while receiving beta-blocking agents.

Combination Therapy With Beta‐adrenergic Blockade and Amlodipine as Second Line Treatment in Essential Hypertension

“…Among these drugs, amlodipine seems to be particularly indicated for combination therapy with atenolol: the reciprocal reduction of side‐effects of each of the two drugs confirms the rationality of this combination 17 . In addition, both short‐ and long‐term studies show that this combination therapy is effective in patients with ischaemic heart disease, regardless of blood pressure values 18–20 …”

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

“…The anti-ischaemic complementary effects of dihydropyridines and beta blockers have been studied extensively' 4 " 612 " 14 ', but the results are conflicting and inconclusive. When considering patients already on a single agent, the sample size to demonstrate benefit of a second agent has to be very large and many of the earlier studies on the use of dihydropyridines in patients on beta-blockers could not, based on their sample size, exclude a type II statistical error' 41 .…”

“…This increase was caused by an increase in heart rate, from 60 (7) at rest/baseline to 85 (14) at rest/after treatment, and from 120 (16) at highest comparable workload/baseline to 143 (16) at highest comparable workload/after treatment (both / ) <001). Systolic blood pressure remained unchanged at the different exercise stages after the switch to felodipine.…”

North of England evidence based guidelines development project: summary version of evidence based guideline for the primary care management of stable angina

“…Adding dihydropyridines to β blockers produces a dose dependent improvement in exercise tolerance (I)71 111 112 113 114 115 116 117 and adding diltiazem to β blockers produces a dose dependent improvement in symptom control and exercise tolerance (I) 74 117 118. If this second combination is used the cautions in the British National Formulary should be observed 47.…”