Three main groups of drugs are used in the symptomatic treatment of chronic stable angina: beta-blockers, nitrates, and calcium channel blockers. Aspirin is used as an antiplatelet drug for the secondary prophylaxis of vascular events in patients with angina. The range of agents, their dosages, contra-indications and side-effects are described in the British National Formulary (BNF).
All recommendations for treatment apply only in the absence of recognised contra-indications, side-effects or interactions as documented in the BNF.
British Medication Associations R.P. (1995). British National Formulary. Bath: BMA, The Pharmaceutical Press.
Recommendations:
Secondary prophylactic treatment
Recommendation:
The Antiplatelet Trialists Collaboration's meta-analysis (1994) demonstrated benefits for patients with angina being treated with aspirin. They analysed data on patients with suspected or definite acute myocardial infarction from nine trials. The rates of myocardial infarction, stroke and vascular death in the antiplatelet group were 992/9388 (10.6%) compared with 1348/9385 (14.4%) in the controls, a 29% odds reduction (4% s.d.). This produced a reduction of 38/1000 in the risk of a subsequent vascular event. There was a similar picture from the other three high risk groups: prior myocardial infarction; prior stroke or transient ischaemic attack; other high risk groups (unstable angina, stable angina, post coronary artery bypass graft).
Recommendations:
Parker et al. (1986) studied the dose response effect of prophylactic sublingual glyceryl trinitrate spray on treadmill walking. Sublingual spray was better than placebo with an up to 50% increase of walking time before the onset of angina.
Comment: We identified no trial of glyceryl trinitrate tablets; this is presumably because of the time frame of the literature search.
Ryden and Schaffrath (1987) studied 126 patients taking sublingual or buccal glyceryl trinitrate in an open randomised crossover study. There were significantly fewer angina attacks during the buccal treatment period. Buccal treatment was used prophylactically significantly more often and when used was successful significantly more often.
Recommendation
Beevers et al. (1983) studied patients in a hypertension clinic; those on
beta-blockers had fewer cardiovascular events than those taking other antihypertensive drugs (diuretics, methyl dopa).
Nidorf et al. (1990) looked at the effect of beta-blockers taken for any reason in patients who subsequently had a myocardial infarction. The
28-day survival post myocardial infarct was 50% higher in beta-blocker treated patients.
Nidorf, S.M., Thompson, P.L., Jamrozik, K.D. and Hobbs, M.S.T. (1990). Reduced risk of death at 28 days in patients taking beta-blocker before admission to hospital with myocardial infarction. British Medical Journal 300:71-74.
beta-blockers have a subsequently lower mortality rate ( I).
Yusuf et al. (1985) carried out a meta-analysis (65 studies) of beta-blocker use during and after myocardial infarction. There was a 25% lower mortality over one year in those receiving beta-blockers.
In a meta-analysis of nine post myocardial infarction beta-blocker trials (The
Beta-Blocker Pooling Project Research Group, 1988), in terms of mortality, high risk patients benefit more (30% lower mortality) than lower risk patients (20% lower mortality).
-Blocker Pooling Project Research Group. European Heart Journal 9:8-16.
Yusuf, S., Peto, L., Collins, R. and Sleight, P. (1985) blockade during and after myocardial infarction. An overview of the randomised trials. Progress in Cardiovascular Diseases, 27:335-371.
beta-blocker compared with dihydropyridines: McGill et al. (1986) studied 25 patients taking either nicardipine 30 mg three times daily or propranolol 40 mg three times daily in a double blind randomised crossover trial. Symptoms and exercise tolerance were both significantly improved compared to placebo.
Egstrup (1988) studied 42 patients taking metoprolol up to 100 mg twice daily, nifedipine up to 20 mg three times daily and their combination in a randomised double blind study. They studied ischaemia measured on ambulatory monitoring. On this end point nifedipine was no better than
placebo; metoprolol was significantly better than placebo; the combination was no better than metoprolol alone.
Ardissino et al. (1991) compared metoprolol CR 200 mg once daily and nifedipine 20 mg twice daily. Metoprolol decreased the number and duration of ischaemic episodes only slightly better on Holter monitoring and clinically, whether patients had episodes on effort and at rest i.e. "mixed angina", made no difference. Nifedipine was ineffective at this dose.
van der Does et al. (1991) studied 163 patients in a double blind randomised controlled trial. Following a placebo period patients were randomised to receive carvedilol 25 mg twice daily or nifedipine SR 20 mg twice daily. There was no dose titration. While both drugs were significantly better than placebo there was no difference in angina attacks, glyceryl trinitrate use or exercise test workload. There were less side effects on carvedilol.
el-Tamimi and Davies (1992) compared atenolol versus nifedipine versus the combination. Atenolol was slightly better than nifedipine in terms of effect on exercise time; the combination was slightly better for decreasing the number of attacks.
Egstrup, K. (1988) Randomised double blind comparison of metoprolol, nifedipine, and their combination in chronic stable angina. Effects on total ischaemic activity and heart rate at onset of ischaemia. American Heart Journal 116:971-978.
el-Tamimi, H. and Davies, G.J. (1992) Optimal control of myocardial ischaemia: the benefit of a fixed combination of atenolol and nifedipine in patients with chronic stable angina. British Heart Journal 68:291-295.
McGill, D., McKenzie, W. and McCreadie, M. (1986) Comparison of nicardipine and propranolol for chronic stable angina pectoris. American Journal of Cardiology 57:39-43.
van der Does, R., Eberhardt, R., Derr, I., Ehmer, B., Rudorf, J. and Uberbacher, H.J. (1991) Treatment of chronic stable angina with carvedilol in comparison with nifedipine s.r. European Heart Journal 12:60-64.
beta-blocker compared with diltiazem or verapamil: Levantesi et al. (1989) compared verapamil 80 mg four times daily and propranolol 60 mg four times daily. Using the end point of exercise performance on a bicycle exercise test the two drugs were equivalent.
Vliegen et al. (1991) compared diltiazem CR 240 mg once daily and metoprolol 100 mg twice daily. They had an equal effect on angina attacks and exercise duration. Diltiazem was perhaps slightly better over the whole eight months.
Steffensen et al. (1993) compared atenolol 100 mg once daily, diltiazem 120 mg SR twice daily and the combination (single blind). The end points were: exercise duration, number of angina attacks and glyceryl trinitrate use. The combination halved number of attacks (4-5 to 2.9) and glyceryl trinitrate use (3-4 to 1.8). Overall, atenolol alone was slightly better than diltiazem; the combination was better again.
Steffensen, R., Grande, P., Pedersen, F. and Haunso, S. (1993) Effects of atenolol and diltiazem on exercise tolerance and ambulatory ischaemia. International Journal of Cardiology 40:143-153.
Vliegen, H.W., van der Wall, E.E., Niemeyer, M.G., Holwerda, N.J., Bernink, P.J., de Weerd, P., Bosma, A.H., van der Wieken, L.R., Timmermans, A.J., Molhoek, G.P. et al. (1991) Long-term efficacy of diltiazem controlled release versus metoprolol in patients with stable angina pectoris. Journal of Cardiovascular Pharmacology 18 Suppl 9:S55-S60.
Other comparisons: Stone et al. (1990) compared the effect of titrated dosages of propranolol LA, diltiazem SR or nifedipine on exercise tolerance, tapes and symptoms. Propranolol improved ambulatory ischaemia; diltiazem prolonged exercise time (by 30 seconds in 600); propranolol and diltiazem both reduced angina; nifedipine had no effect.
Humen and Kostuk (1991) studied the effect of adding isosorbide dinitrate, in a dose of up to 180 mg per day, to diltiazem or propranolol. While diltiazem and propranolol were both better than placebo and diltiazem was slightly better than propranolol there was no extra effect from adding isosorbide dinitrate.
Stone, P.H., Gibson, R.S., Glasser, S.P., DeWood, M.A., Parker, J.D., Kawanishi, D.T., Crawford, M.H., Messineo, F.C., Shook, T.L., Raby, K. et al. (1990) Comparison of propranolol, diltiazem, and nifedipine in the treatment of ambulatory ischaemia in patients with stable angina. Differential effects on ambulatory ischaemia, exercise performance, and anginal symptoms. The ASIS Study Group. Circulation 82:1962-1972.