Optimal control of myocardial ischaemia: the benefit of a fixed combination of atenolol and nifedipine in patients with chronic stable angina

Abstract

Objective-To study the effects on myocardial ischaemia of 50 mg of atenolol, 20 mg of slow release nifedipine, and their fixed combination given 12 hourly.Design-A treadmill exercise test and 24 hour ambulatory electrocardiographic monitoring were carried out after a period of five days off treatment (control) and at the end of three weeks of each treatment period.Patients-23 patients with stable angina pectoris, documented coronary artery disease, and a positive exercise test were randomised in a double blind, three way, cross over study.Results-Compared with the control, nifedipine significantly induced an increase in resting heart rate of (mean (SEM)) 14 (2) beats/min whereas atenolol and the combination significantly reduced it by 24 (2) and 20 (1) beats/min respectively. The number of exercise tests rendered negative after each intervention was five for nifedipine, nine for atenolol, and 11 for the combination. Compared with the control the time to the start of myocardial ischaemia (1 mm ST segment depression) during exercise significantly increased by 3-2 (0-6) min after nifedipine, by 4-6 (0 4) min after atenolol, and by 4-6 (0 5) min after the combination; rate-pressure product (beats/min. mm Hg) at 1 mm ST segment depression increased by 2824 (970) after nifedipine but fell by 4436 (900) and 4501 (719) after atenolol and the combination. The weekly frequency of angina was reduced from a mean of five while taking nifedipine, to three while taking atenolol, and to two while taking the combination. The total ischaemic time during ambulatory monitoring was significantly reduced from 69 (17) min during control to 37-5 (9-8) min during nifedipine, to 15-6 (5-5) min during atenolol, and to 6-5 (2-7) min during the combination.Conclusion-The undesirable effect ofa high basal heart rate induced by nifedipine was neutralised by its combination with atenolol. Whereas atenolol and the combination were equally efficacious in controiling exercise induced ischaemia, the combination was more effective in reducing total ischaemic burden. (Br Heart J 1992;68:291-5) In most patients with chronic stable angina, both an increase in myocardial oxygen consumption and a decrease in myocardial blood flow contribute to the development of ischaemia, whether symptoms occur at rest or during exercise.' 2 3 Blockers relieve ischaemia primarily by decreasing myocardial oxygen demand, and calcium channel blockers do so by improving myocardial oxygen supply. By acting on these different determinants of myocardial ischaemia, the combination of both drugs could provide better control of myocardial ischaemia.We have investigated the anti-ischaemic effects of a calcium antagonist (nifedipine) and a ,B blocker (atenolol) singly and in a fixed combination on symptoms, and exercise induced and ambulatory ischaemia.Patients and methods Thirty patients were enrolled, but only 23 completed the study: 19 men and four women, aged 40 to 72 (mean 56-2) years, who had stable exertional angina of eight to 156 months duration (mean 56.2). T...

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

“…The combination is better than felodipine monotherapy el-Tamimi and Davies [18] Atenolol 50 mg/day + nifedipine SR 20 mg/day vs atenolol vs nifedipine SR Suboptimal β-blockade (n = 23) Combination better than metoprolol for time to 1mm STD, STD at highest comparable workload, and maximal STD.…”

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

“…However, differences in patient selection, study design, and drug dosages all prevent critical comparisons. Specific comparisons were β blockers and dihydropyridines,67 68 69 70 71 β blockers and diltiazem or verapamil,72 73 74 and studies with three drugs 75 76. Within the time frame of our search there was no compelling evidence to choose one β blocker over another (I) 77 78 79.…”

“…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.…”