CHAPTER 23 Myocardial Ischemia and Acute Coronary Syndromes

Kevin M. Sowinski

Myocardial ischemia occurs as a result of increased The specific mechanisms by which drugs may facil- myocardial demand, decreased myocardial oxygen itate or cause MIs will be discussed. supply, or both, and most commonly occurs in An acute coronary syndrome is associated with patients with atherosclerotic coronary artery disease. three clinical manifestations: ST-segment elevation This chapter discusses the specific mechanisms by MI, non-ST-segment elevation MI, and unstable which drug therapy may cause increased myocardial .1,2 For the purposes of this chapter, it is dif- oxygen demand or decreased supply. ficult to separate the acute coronary syndromes Angina pectoris is a clinical syndrome of chest because, for the most part, the individual case data discomfort caused by reversible myocardial isch- in the literature do not provide sufficient detail. emia that produces disturbances in myocardial Therefore, in most cases, the specific acute coro- function but no myocardial necrosis. Myocardial nary syndromes will not be discussed separately. ischemia can also occur without any symptoms of Furthermore, based on the available literature, it is angina and is typically referred to as silent myocar- difficult to distinguish drugs based on whether they dial ischemia. Acute myocardial infarction (MI) is a cause myocardial ischemia or infarction. clinical syndrome associated with the development of a prolonged occlusion of a coronary artery lead- CAUSATIVE AGENTS ing to decreased oxygen supply, myocardial isch- emia, and irreversible damage to myocardial tissue. Drugs reported to cause angina pectoris, myocar- MI in patients with coronary artery disease is usu- dial ischemia, an acute coronary syndrome, or all ally associated with a coronary artery thrombosis three are listed in Table 23-1.3-462 Drug- induced superimposed on a ruptured atherosclerotic plaque. myocardial ischemia or acute coronary syndrome

471 472 DRUG-INDUCED DISEASES: Prevention, Detection, and Management

Table 23-1 Agents Implicated in Drug-Induced Myocardial Ischemia and/or Acute Coronary Syndromes Level of Therapeutic Area (drug class, drugs) Incidence/Index of Risk Evidencea Drug Discontinuation3-16 NK C Argatroban, aspirin, β-­blockers, , clopidogrel, heparin, nitroglycerin Analgesics7,17-28 NSAIDs Highly variable, dependent on drug A, B, C and drug dose Selective COX-2 inhibitors (rofecoxib, , valdecoxib) Celecoxib: RR 1.86, 95% CI 1.33–2.54 Nonselective NSAIDs (diclofenac, ibuprofen) Ibuprofen: RR 1.51, 95% CI 0.96–2.37 Diclofenac: RR 1.63, 95% CI 1.12–2.37

Opioids (, dihydrocodeine, morphine) NK C Others (, gold sodium thiomalate, , penicillamine) NK C Anesthetics29-32 NK C Benzocaine, enflurane, isoflurane, mepivacaine, sevoflurane, propofol Anticancer/-­Associated Agents33-112 NK C 5-, , , , , , , , , , hydroxyurea, floxuridine, flutamide, L-­, lapatinib, , , , sorafenib, , , Antidepressants17,113-123 NK C Selective serotonin reuptake inhibitors (, , , ) Tricyclic Others (, , , , phenelzine) Anti-HIV124-131 Abacavir, didanosine Abacavir: RR 1.89, 95% CI 1.47–2.45 B Didanosine: RR 1.49, 95% CI 1.14–1.95 B Protease inhibitors Protease inhibitors: RR 1.16, 95% CI B 1.10–1.23 Anti-­Infectives17,132-139 NK C , amphotericin, azithromycin, cinoxacin, clarithromycin, co-­trimoxazole, fluconazole, ketoconazole, mefloquine, mesalamine, metronidazole, nitrofurantoin, norfloxacin, penicillin G, roxithromycin Antipsychotics17,120,140,141 NK C Antimigraine17,142-176 NK C , ergonovine, , methylergonovine, , , sumatriptan, zolmitriptan Blood Modifiers17,177-181 NK C Coagulation factor VIIA, darbepoetin, erythropoietin, factor VIII inhibitor/prothrombin complex concentrates, tranexamic acid Cardiovascular Drugs Calcium-­channel blockers17,182-207 (diltiazem, lacidipine, felodipine, NK C isradipine, nifedipine, nisoldipine, ) ACE inhibitors17,208,209 (captopril, enalapril, lisinopril, perindopril) NK C β-­ blockers17,198,201,210-213 (ophthalmic and systemic) NK C Stress testing agents/β-­ agonists214-237 (adenosine, NK C , atropine, dipyridamole, dopexamine, , ) Other cardiovascular drugs17,238-244 (, diazoxide, disopyramide, NK C diuretics, encainide, , hydralazine, , minoxidil, nitroprusside, , , sublingual isosorbide dinitrate)