Recommendation:
Egstrup et al. (1988) studied CR metoprolol 200 mg once daily versus standard metoprolol in the same dose. There was a minor difference in adverse reactions but no difference in any outcome measures at 100 mg once daily; at 200 mg once daily there was a slight improvement in exercise tolerance.
Antaloczy and Kekes (1989) studied atenolol versus pindolol. Both drugs worked; atenolol increased exercise tolerance more at the doses used.
Floris et al. (1991) studied metoprolol OROS 200 mg and found it equivalent to atenolol 100 mg.
Egstrup, K., Gundersen, T., Harkonen, R., Karlsson, E. and Lundgren, B. (1988) The antianginal efficacy and tolerability of controlled-release metoprolol once daily: a comparison with conventional metoprolol tablets twice daily. European Journal of Clinical Pharmacology 33 Suppl:S45-S49.
Floris, B., Paoletti, G., Pelizza, L., Bertulla, A. and Motolese, M. (1991) A comparison of metoprolol OROS with atenolol in the treatment of effort angina pectoris: a randomised double-blind study. International Journal of Clinical Pharmacology, Therapy and Toxicology 29:139-143.
Recommendations:
Psaty et al. (1990) studying hypertensive patients found that acute
beta-blocker withdrawal caused a four fold increase (CI 1.2-16) in coronary events in the month after stopping.
Recommendation:
The DAVIT II trial (1990) studied the effect of verapamil 360 mg daily versus placebo started in the second week post-myocardial infarction. There were fewer major events in the verapamil group. In patients who did not get heart failure there was also a lower mortality rate.
Rodrigues et al. (1988) compared nicardipine 30 mg three times daily with verapamil 120 mg three times daily in patients undergoing a modified Chung protocol exercise test. Exercise time was 1.5 minutes longer on verapamil than nicardipine. Eleven out of 20 patients preferred verapamil. There was no difference in angina attacks or glyceryl trinitrate use (there is the possibility of a Type II error).
Gibbs et al. (1991) studied the effect of verapamil SR 240-480 mg versus placebo. Angina frequency and symptoms improved at all doses. Only the high dose produced an (11%) increase in exercise time.
Friedensohn et al. (1991) found no difference in walking time between isosorbide dinitrate SR 120 mg, verapamil SR or combination; all were better than placebo (60-80 sec increase over 520 sec).
Subramanian et al. (1992) compared the effect of verapamil 120 mg three times daily or nifedipine 20 mg three times daily on exercise tolerance. No statistics are given on the comparison but verapamil seems a bit better. Adreactions were worse with nifedipine.
Friedensohn, A., Meshulam, R. and Schlesinger, Z. (1991) Randomised double-blind comparison of the effects of isosorbide dinitrate retard, verapamil sustained-release, and their combination on myocardial ischaemic episodes. Cardiology 79 Suppl 2:31-40.
Gibbs, J.S., McAlpine, H.M., Wright, C., McLenachan, J.M., Sparrow, J., Sutton, G., Dargie, H.J. and Fox, K.M. (1991) Double-blind randomised placebo-controlled dose-efficacy study of sustained release verapamil in chronic stable angina. International Journal of Cardiology 31:281-286.
Rodrigues, E.A., Kohli, R.S., Hains, A.D.B., Lahiri, A. and Raftery, E.B. (1988) Comparison of nicardipine and verapamil in the management of chronic stable angina. International Journal of Cardiology 18:357-369.
Subramanian, V.B., Bowles, M.J., Khurmi, N.S., Davies, A.B. and Raftery, E.B. (1992) Randomised double blind comparison of verapamil and nifedipine in chronic stable angina. American Journal of Cardiology 50:696-703.
Recommendation:
Scheidt et al. (1985) compared nicardipine 30 mg three times daily with placebo. There was no significant effect on angina attacks, glyceryl trinitrate use (there is the possibility of a Type II error) but exercise tolerance improved by 0.6 minutes on a modified Bruce protocol.
Bowles et al. (1986) studied nifedipine and nicardipine compared with placebo as monotherapy. Both were effective in increasing exercise duration and were themselves equivalent.
Parker et al. (1988) compared isradipine 7.5 mg three times daily against placebo. There was a 25% increase in exercise tolerance (267 seconds to 312 seconds) three hours after a dose but not nine hours after. There was no significant reduction in angina attacks or glyceryl trinitrate use (there is the possibility of a Type II error).
Deedwania et al. (1993) compared amlodipine 2.5 mg, 5 mg, or 10 mg against placebo. On a modified Bruce protocol there was a 15% improvement in exercise duration (535 seconds increasing to 610 seconds). There was no difference in adreactions and no dose response detected (there is the possibility of a Type II error).
Klinke et al. (1989) studied diltiazem SR in dosages of 120 mg twice daily and 180 mg twice daily versus placebo. There was no significant difference between the dosages.
Theroux et al. (1991) studied diltiazem SR 180 mg twice daily versus placebo. There were: reductions in ST segment depression on stress testing and on Holter monitoring; and a 30 second (of 447) increase in exercise tolerance.
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 twice daily or nifedipine SR 20 mg twice daily. There was no dose titration. Both drugs were significantly better than placebo.
Thadani et al. (1994) studied diltiazem SR 60 mg - 480 mg daily versus placebo in patients with angina. There was a dose related increase in exercise time reaching 68 seconds in the highest dose group and a dose related reduction in angina attacks.
Deedwania, P.C., Cheitlin, M.D., Das, S.K., Pool, P.E., Singh, J.B. and Pasternak, R.C. (1993) Amlodipine once a day in stable angina: double-blind crossover comparison with placebo. Clinical Cardiology 16:599-602.
Klinke, W.P., Juneau, M., Grace, M., Kostuk, W.J., Pflugfelder, P., Maranda, C.R., Warnica, W., Chin, C., Annable, L. and Dempsey, E.E. (1989) Usefulness of sustained-release diltiazem for stable angina pectoris. American Journal of Cardiology 64:1249-1252.
Parker, J.O., Enjalbert, M. and Bernstein, V. (1988) Efficacy of the calcium antagonist isradipine in angina pectoris. Cardiovascular Drugs and Therapy 1:661-664.
Scheidt, S., LeWinter, M.M., Hermanovich, J., Venkataraman, K. and Freedman, D. (1985) Nicardipine for stable angina pectoris. British Journal of Clinical Pharmacology 20 Suppl 1:178S-186S.
Thadani, U., Glasser, S., Bittar, N. and Beach, C.L. (1994) Dose-response evaluation of once-daily therapy with a new formulation of diltiazem for stable angina pectoris. Diltiazem CD Study Group. American Journal of Cardiology 74:9-17.
Theroux, P., Baird, M., Juneau, M., Warnica, W., Klinke, P., Kostuk, W., Pflugfelder, P., Lavallee, E., Chin, C., Dempsey, E., et al. (1991) Effect of diltiazem on symptomatic and asymptomatic episodes of ST segment depression occurring during daily life and during exercise. Circulation 84:15-22.
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.
Frishman et al. (1988) compared the effect of diltiazem (maximum dose 360 mg) against nifedipine (maximum dose 120 mg) on exercise tolerance, angina, glyceryl trinitrate use and haemodynamics. The only difference was that nifedipine was worse than diltiazem in terms of adreactions.
Wallace et al. (1989) studied nifedipine 40 mg to 120 mg versus diltiazem 120 mg to 360 mg. Both had same effect on improving exercise tests: increased exercise tolerance from 480-550 seconds.
DeWood and Wolbach (1990) compared nicardipine 30 three times daily and nifedipine 20 three times daily (caps) with respect to side-effects. Patients were stratified by prior symptoms with nifedipine. No difference on angina. Only difference was in dizziness, which was more common with nifedipine. No other differences reached significance although 250 patients randomised.
Frishman, W., Charlap, S., Kimmel, B., Teicher, M., Cinnamon, J., Allen, L. and Strom, J. (1988) Diltiazem, nifedipine, and their combination in patients with stable angina pectoris: effects on angina, exercise tolerance, and the ambulatory electrocardiographic ST segment. Circulation 77:774-786.
Wallace, W.A., Wellington, K.L., Murphy, G.W. and Liang, C.S. (1989) Comparison of antianginal efficacies and exercise hemodynamic effects of nifedipine and diltiazem in stable angina pectoris. American Journal of Cardiology 63:414-418.
Recommendations:
Feng et al. (1990) found that isosorbide mononitrate 20 mg three times daily as monotherapy over a four week period reduced angina from 50 attacks of ischaemia per week, demonstrated on Holter monitoring, to ten.
Friedensohn et al. (1991) found no difference in walking time between isosorbide dinitrate SR 120 mg, verapamil SR or their combination; all were better than placebo (60-80 sec increase over 520 sec).
Parker (1993) studied asymmetric isosorbide mononitrate 20 mg twice daily (08.00 hours, 15.00 hours) and found that it led to decreased angina and increased exercise tolerance. There was no rebound or tolerance effect over three weeks.
Chrysant et al. (1993) showed that isosorbide mononitrate SR (once daily dose) worked better than placebo. It prolonged exercise tolerance compared to placebo with no tolerance at 4 or 12 hours post dose. There was no rebound in the morning before the dose. There was however little evidence of increased efficacy beyond 120 mg.
Thadani et al. (1994) looked at the effect of asymmetrical isosorbide mononitrate 20 mg twice daily (08.00 hours, 15.00 hours) in a group of patients 55-60% of whom were on beta-blockers. There was a 15-20% increase in exercise time and no rebound or early morning angina. They concluded that asymmetrical isosorbide mononitrate 20 mg twice daily was better than placebo in patients both on or off beta-blockers.
Feng, J.Z., Feng, X.H. and Schneeweiss, A. (1990) Efficacy of isosorbide-5-mononitrate on painful and silent myocardial ischaemia after myocardial infarction. American Journal of Cardiology 65:32J-35J.
Friedensohn, A., Meshulam, R. and Schlesinger, Z. (1991) Randomised double-blind comparison of the effects of isosorbide dinitrate retard, verapamil sustained-release, and their combination on myocardial ischaemic episodes. Cardiology 79 Suppl 2:31-40.
Parker, J.O. (1993) Eccentric dosing with isosorbide-5-mononitrate in angina pectoris. American Journal of Cardiology 72:871-876.
Thadani, U., Maranda, C.R., Amsterdam, E., Spaccavento, L., Friedman, R.G., Chernoff, R., Zellner, S., Gorwit, J. and Hinderaker, P.H. (1994) Lack of pharmacologic tolerance and rebound angina pectoris during twice-daily therapy with isosorbide-5-mononitrate. Annals of Internal Medicine 120:353-359.
Recommendations:
Thompson (1986) compared multiple 5 mg patches (mean number 3.5) used continuously against placebo. There was a small increase in treadmill time even after 19 days.
Karlson and Henning (1987) found no difference between the effect of 5 mg patches and 10 mg long-acting tablets; both were the same as placebo.
Rezakovic et al. (1988) looked at the use of a 5 mg patch with no other therapy and no nitrate free interval. The number of angina attacks and glyceryl trinitrate use were reduced by the patches. They concluded that continuous 5 mg patch alone was effective.
Colditz et al. (1988) from a meta-analysis concluded that transdermal glyceryl trinitrate was effective at 4 hours with exercise tolerance increased by 76 seconds. There was no effect at 24 hours because of tolerance.
Fletcher et al. (1988) looked at the effect of continuous 5 mg glyceryl trinitrate patches on quality of life using the Sickness Impact Profile. There was no effect on angina rate or glyceryl trinitrate use. Quality of life was worse on glyceryl trinitrate and headache was more common (causing 5% of patients to be withdrawn).
In a study of continuous cutaneous glyceryl trinitrate patches at any dose they were shown to be ineffective after 4 hours or 24 hours within one week (Steering Committee, Transdermal Nitroglycerin Co-operative Study, 1991). Higher doses failed to overcome tolerance.
Fletcher, A., McLoone, P. and Bulpitt, C. (1988) Quality of life on angina therapy: a randomised controlled trial of transdermal glyceryl trinitrate against placebo. Lancet 2:4-8.
Karlson, B.W. and Henning, R. (1987) Comparison of nitroglycerin-TTS and long-acting nitroglycerin tablets in the treatment of angina pectoris: a double-blind controlled study. Clinical Cardiology 10:573-577.
Rezakovic, D.E., Jr., Pavicic, L. and Majacic, M. (1988) A randomised placebo controlled, double-blind, crossover trial of transdermal nitroglycerin in stable angina pectoris. European Heart Journal 11:1011-1017.
Steering Committee, Transdermal Nitroglycerin Co-operative Study (1991) Acute and chronic anitanginal efficacy of continuous twenty four hour application of transdermal nitroglycerin. American Journal of Cardiology 68:1263-1273.
Thompson, R. (1986) Influence of transdermal nitrates on exercise capacity in patients with stable angina. Angiology 37:448-454.
Scardi et al. (1991) studied intermittent patch use in a dose of 20 mg per 24 hours (12 hours on, 12 hours off). This was found to be better than the continuous patch. Fifty per cent of patients developed tolerance. At ten hours, continuous use produced a 30 second increase in exercise time over placebo; intermittent use was 30 seconds better again.
Krepp and Turpe (1989) looked at a special glyceryl trinitrate patch which delivered 7.5 mg of glyceryl trinitrate in a biphasic pattern with little nitrate in last 6 hours. Exercise time on a bicycle ergometer increased from 3.6 to 5 minutes, angina attacks decreased from 7.3 per week to 2.3 per week, glyceryl trinitrate use decreased from 8.7 to 2.5. Effect present at 2 hours, 10 hours, 1 day and 7 days.
DeMots and Glasser (1989) studied placebo, low (10 mg/20 mg) or high (30 mg/40 mg) dose patches in patients with stable exercise tests and an acute response to sublingual glyceryl trinitrate. Patches were used 12 hours on, 12 hours off. Active treatment was better than placebo, producing about a one minute increase in exercise tolerance at 29 days. There was no effect on glyceryl trinitrate use or number of episodes of angina. High dose patches were better than low dose patches which were better than placebo.
Paciaroni and Luca (1991) studied transdermal glyceryl trinitrate with an eight hour nitrate free interval. Angina attacks were reduced from 2.6 to 1.0 attacks per week (placebo 2.6 to 1.8). Glyceryl trinitrate use decreased.
Krepp, H.P. and Turpe, F. (1989) Anti-ischaemic effects of phasic release nitroglycerin system during acute and sustained therapy. European Heart Journal 10 Suppl A:36-42.
Paciaroni, E. and Luca, C. (1991) Discontinuous transdermal nitroglycerin as treatment for stable angina in the elderly: a double-blind multicentre study. The Transdermal TNG Trial Group of Instituto Nazionale Ricovero e Cura Anziani (I.N.R.C.A.). European Heart Journal 12:1076-1080.
Ulvenstam et al. (1992) compared nicorandil 10 mg - 20 mg twice daily against nifedipine 20 mg twice daily. They had equal effects on exercise tolerance, workload, angina rate (there is the possibility of a Type II error).