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Stable angina pectoris: The medical management of symptomatic myocardial ischemia Parker, J.D, Parker, J.O, Canadian Journal of Cardiology 2012, 28(25), S70-80. Prevalence of stable angina and summary: In Canada, 500,000 (2% of the population) people over the age of 12 report 1 2 exertional angina. Globally, stable angina is more prevalent in women and varies broadly country to country. Cumulative 3 post intervention studies confirm that many patients develop or continue to have angina following revascularization. Exertional angina continues to be a problem, in particular. Although dramatic advances in the prevention and treatment of CAD have been attributed to the development of effective surgical and percutaneous revascularization techniques, skilled individualized medical management of symptomatic stable angina remains critical. Patients with stable angina have an excellent prognosis; those who obtain relief from symptomatic myocardial ischemia may do well without invasive intervention. Medical Management: The pharmacological prevention of exertional symptoms of angina has involved the use of agents which reduce myocardial oxygen demand and/or increase myocardial oxygen supply in response to exercise. Currently, the classes of anti-anginal agents available in Canada are organic nitrates, β-adrenergic blocking agents, and calcium channel antagonists. Organic Nitrates are potent vasodilators that reduce preload, thereby reducing myocardial oxygen consumption and left 4 ventricular chamber size. In addition, when using dosing regimens that avoid tolerance, nitrates decrease myocardial oxygen 4 consumption by reducing blood pressure and increasing conduit artery distensibility. Table 1 presents pharmacologic characteristics of commonly available organic nitrates, all of which have evidence of effectiveness in the therapy of exertional angina. Table 1. Pharmacologic characteristics of common organic nitrates Half-life Elimination Heart rate Vascular resistance Usual dosage SL NTG 6-9 min Hepatic ↑ ↓↓ 0.4-0.6 mg TD GTN 6-9 min Hepatic ↔ ↔ 0.2-0.6mg/h (intermittent) ISDN 1-2 (4-5) hrs* Hepatic ↑ ↓ 5†-30mg TID (eccentric) IS-5-MN (phasic release) 4-5hrs Hepatic ↔ ↔ 60-240mg OD GTN, glyceryl trinitrate; IS-5-MN, isosorbide-5-mononitrate; ISDN, isosorbide dinitrate; OD, once daily; SL, sublingual; TD, transdermal; TID, three times daily. *Half-life of active metabolite isosorbide-5-mononitrate. †ISDN (5 mg) may be administered sublingually for prevention of angina. Tolerance has been shown to develop with all types of organic nitrates when they are administered using dosing patterns or 5 preparations that lead to continuous nitrate concentrations in plasma over a 24-hour period. Tolerance is manifested by loss of the hemodynamic and symptomatic effects of nitrates. To date, the only approach that has been applied clinically is the use of ‘intermittent therapy’ where dosing regimens or nitrate formulations that yield low or nitrate-free concentrations in plasma for 10-12 hours per day are employed. Isosorbide dindrate is also available in 5 mg tablets that can be used sublingually; although not regularly used for the treatment of acute episodes of angina it can be effective when taken prior to activity for those with refractory effort angina. Sublingual nitroglycerin is prescribed for acute attacks of angina or pre-exertional activities. It is important to remember that sublingual nitroglycerin can also be used prophylactically when patients with exertional symptoms embark on patterns of activity that generally lead to the development of angina. β-Adrenergic Blockers reduce myocardial oxygen demand in response to exercise by decreasing heart rate, blood pressure, 6-10 and myocardial inotropic responses. Via negative chronotropic effects, they can improve coronary blood flow by increasing diastole time. Table 2 presents the pharmacologic characteristics of common β-1 selective β adrenergic blockers and nonselective β-Adrenergic Blockers. Pharmacodynamic and pharmokinetic effects of these agents are based on the half-life, β-1 receptor selectivity, sympathomimetic activity, lipophilicity and elimination to determine individual use. Agents with β-1 receptor selectivity can be used in patients with either chronic obstructive lung disease or diabetes. Clinically effective doses are determined by resting heart rate, blood pressure, and side effect profile. The effect of β-adrenergic blockers on resting heart rate can be a poor predictor of their effect on the heart rate response to exercise; it is strongly recommended that this response be assessed with either a hallway walk or formal exercise testing for patients who exhibit poor responses to initial dosing. Stable angina pectoris: The medical management of symptomatic myocardial ischemia Parker, J.D, Parker, J.O, Canadian Journal of Cardiology 2012, 28(25), S70-80. Table 2. Pharmacologic characteristics of common β-1 selective β adrenergic blockers and nonselective β-Adrenergic Blockers organic nitrates A. β-1 selective β-adrenergic blockers Atenolol Half-life (hrs) 6-9 β-1 selectivity + Sympathomimetic activity No Lipophilicity Low Elimination Renal Usual dosage (mg) 50-100 OD B. Nonselective β-adrenergic blockers Propanolol Half-life (hrs) 2-5 β-1 selectivity 0 Sympathomimetic No activity Lipophilicity High Elimination Hepatic Usual dosage (mg) 40-60 BID Metropolol 3-4 + No Moderate Hepatic 50-100 BID Bisoprolol 10-12 + No Moderate Hepatic and renal 2.5-10 OD Acebutalol 3-4* + Yes Moderate Hepatic and renal 200-600BID Timolol 3-5 0 No Nadolol 14-25 0 No Pindolol 3-4 0 Yes Moderate Hepatic 10-20 BID Low Renal 40-160 OD Moderate Hepatic and renal 5-20 BID BID, twice daily; hrs, hours, OD, once daily *Active metabolite of acebutalol (diacetolol) has half-life of 8-12 hrs. 11-22 Calcium channel Blocking Agents are also effective anti-anginal agents and antihypertensive agents. While their basic mechanism of action is similar (i.e., blockade of the L-type calcium channel and reduction of intracellular calcium concentrations), the three classes of calcium channel antagonists each have quite different chronotropic, hemodynamic and inotropic effects. The dihydropyridines (the prototype is nifedipine) have little effect on heart rate or atrioventricular conduction while having the most prominent effect on peripheral resistance. Although nifedipine was the first of this class to be introduced, another effective dihydropyridine is amlodipine, a drug that has become very widely used in the therapy of angina and hypertension. The benzothiazepines (the prototype is diltiazem) and the phenylalkylamines (the prototype is verapamil) also reduce peripheral vascular resistance, although both these classes have prominent negative chronotropic effects and impair atrioventricular conduction. All 4 calcium channel antagonists approved for angina in Canada are available in once per day formulations (amlodipine, nifedipine GITS, diltiazem CD, and verapamil sustained release [SR]) (see Table 3). Table 3. Pharmacologic characteristics of common calcium channel antagonists Half-life (hrs) Elimination Heart rate Vascular resistance Usual dosage (mg) Nifedipine (GITS) 2-5 Hepatic ↑ ↓↓ 20-90 OD Amlodipine Diltiazem (CD) Verapamil (SR) 30-50 Hepatic ↔ ↓↓ 2.5-10 OD 4-6 Hepatic ↓ ↓ 120-360 OD 5-12 Hepatic ↓ ↓ 180-360 BID BID, twice daily; CD, controlled delivery; GITS, gastrointestinal therapeutic system; OD, once daily; SR, slow release. Combination therapy: Combination therapy should be used with caution and consideration should be given to ensuring maximally-tolerated doses single-drug therapy before the addition of another class of anti-anginal. Consistent benefit has been demonstrated from the addition of a second agent when patients remain symptomatic on maximal monotherapy. Choice of therapy: There remains no clear ‘first choice’ in the therapy of angina. β-adrenergic blockers currently are the main stay for treatment of angina, particularly in the presence of prior infarction. Choice of therapy is often based on the presence of associated clinical conditions such as concomitant hypertension (dihydropyridine calcium channel antagonist). Some may prefer calcium channel antagonists as first line therapy, based on the assumption of a favourable side-effect profile. In the absence of left ventricular systolic dysfunction or prior infarction there is no clear guidance to choose a β-adrenergic blocker versus a calcium channel antagonist, although β-adrenergic blockade seems logical in the absence of contraindication or striking hypertension. Stable angina pectoris: The medical management of symptomatic myocardial ischemia Parker, J.D, Parker, J.O, Canadian Journal of Cardiology 2012, 28(25), S70-80. Errata: Correction to Parker, J.D, Parker, J.O. Stable angina pectoris: The medical management of symptomatic myocardial ischemia. Can JCardiol 2012;28(25): S70-80. The suggested dose ranges for nonselective β-adrenergic blockers, Table 2-B, should read as per this fact sheet. These suggested dose ranges are incorrect in the published paper. References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. C.M. Chow, L. Donovan, D. Manuel, H. Johansen, J.V. Tu. Regional variation in self-reported heart disease prevalence in Canada. Can J Cardiol, 21 (2005), pp. 1265–1271 N. Payne, C. Saul. Variations in use of cardiology services in a health authority: comparison of coronary artery revascularisation rates with prevalence of angina and coronary mortality. BMJ, 314 (1997), pp. 257–261 P.W. Serruys, F. Unger, J.E. Sousa et al. Comparison of coronary-artery bypass surgery and stenting for the treatment of multivessel disease. N Engl J Med, 344 (2001), pp. 1117–1124 J.D. Parker, J.O. Parker. Nitrate therapy for stable angina pectoris. N Engl J Med, 338 (1998), pp. 520–531 T. Munzel, A. Daiber, A. Mulsch. Explaining the phenomenon of nitrate tolerance. Circ Res, 97 (2005), pp. 618–628 J.O. Parker, A. Porter, J.D. Parker. Propranolol in angina pectorisComparison of long-acting and standard-formulation propranolol. Circulation, 65 (1982), pp. 1351–1355 J.C. Tardif, I. Ford, M. Tendera, M.G. Bourassa, K. Fox. Efficacy of ivabradine, a new selective I(f) inhibitor, compared with atenolol in patients with chronic stable angina. Eur Heart J, 26 (2005), pp. 2529–2536 S. Savonitto, D. Ardissiono, K. Egstrup et al. Combination therapy with metoprolol and nifedipine versus monotherapy in patients with stable angina pectorisResults of the International Multicenter Angina Exercise (IMAGE) Study. J Am Coll Cardiol, 27 (1996), pp. 311–316 K.M. Fox, D. Mulcahy, I. Findlay, I. Ford, H.J. Dargie, The Total Ischaemic Burden European Trial (TIBET) Effects of atenolol, nifedipine SR and their combination on the exercise test and the total ischaemic burden in 608 patients with stable anginaThe TIBET Study Group. Eur Heart J, 17 (1996), pp. 96–103 D.T. Kawanishi, C.L. Reid, E.C. Morrison, S.H. Rahimtoola. Response of angina and ischemia to long-term treatment in patients with chronic stable angina: a double-blind randomized individualized dosing trial of nifedipine, propranolol and their combination. J Am Coll Cardiol, 19 (1992), pp. 409–417 S. Savonitto, D. Ardissiono, K. Egstrup et al. Combination therapy with metoprolol and nifedipine versus monotherapy in patients with stable angina pectorisResults of the International Multicenter Angina Exercise (IMAGE) Study. J Am Coll Cardiol, 27 (1996), pp. 311–316 K.M. Fox, D. Mulcahy, I. Findlay, I. Ford, H.J. Dargie, The Total Ischaemic Burden European Trial (TIBET). Effects of atenolol, nifedipine SR and their combination on the exercise test and the total ischaemic burden in 608 patients with stable anginaThe TIBET Study Group. Eur Heart J, 17 (1996), pp. 96–103 D.T. Kawanishi, C.L. Reid, E.C. Morrison, S.H. Rahimtoola. Response of angina and ischemia to long-term treatment in patients with chronic stable angina: a double-blind randomized individualized dosing trial of nifedipine, propranolol and their combination. J Am Coll Cardiol, 19 (1992), pp. 409–417 S.P. Glasser, T.J. Gana, L.G. Pascual, K.S. Albert. Efficacy and safety of a once-daily graded-release diltiazem formulation dosed at bedtime compared to placebo and to morning dosing in chronic stable angina pectoris. Am Heart J, 149 (2005), pp. e1–e9 R.B. van Dijk, K.I. Lie, H.J. Crijns. Diltiazem in comparison with metoprolol in stable angina pectoris. Eur Heart J, 9 (1988), pp. 1194–1199 O. De Divitiis, V. Liguori, S. Di Somma et al. Bisoprolol in the treatment of angina pectoris: a double blind comparison with verapamil. Eur Heart J, 8 (suppl M) (1987), pp. 43–54 W.H. Frishman, S. Glasser, P. Stone et al. Comparison of controlled-onset, extended-release verapamil with amlodipine and amlodipine plus atenolol on exercise performance and ambulatory ischemia in patients with chronic stable angina pectoris. Am J Cardiol, 83 (1999), pp. 507–514 W. Schneider, F.D. Maul, W.D. Bussmann et al. Comparison of the antianginal efficacy of isosorbide dinitrate (ISDN) 40 mg and verapamil 120 mg three times daily in the acute trial and following two-week treatment. Eur Heart J, 9 (1988), pp. 149–158 R.S. Kohli, E.A. Rodrigues, L.O. Hughes, A. Lahiri, E.B. Raftery. Sustained release verapamil, a once daily preparation: objective evaluation using exercise testing, ambulatory monitoring and blood levels in patients with stable angina. J Am Coll Cardiol, 9 (1987), pp. 615–621 G. Cocco, R. Alfiero. A double-blind dose-response study of amlodipine in patients with stable angina pectoris. Eur Heart J, 12 (1991), pp. 169–174 D.R. Kinnard, M. Harris, K.F. Hossack. Endurance testing for evaluation of antianginal therapy with amlodipine, a calcium channel blocking agent. J Am Coll Cardiol, 12 (1988), pp. 791–796