Which of the following drugs has been linked with increased cardiac moality:

Answer is A (Rofecoxib) Rofecoxib (selective COX-2 inhibitor) induces a Prothrombotic state and has been linked to increased incidence of thrombotic events including myocardial infarction, stroke and venous thrombosis. `Selective COX-2 inhibitor Rofecoxib increases the risk of myocardial infarctions' - `Placebo controlled trials with three structurally distinct COX-2 inhibitors - Celecoxib, valdecoxib (withdrawn) and rofecoxib (withdrawn) revealed an increase in the incidence of myocardial infarction, stroke and thrombosis'. Rofecoxib and Valdecoxib were withdrawn from the market in 2004 and 2005 respectively due to increased risk of thrombogenic cardiovascular events (myocardial infarction, stroke and thrombosis) Mechanisms of Drug-Induced Myocardial lschemia and Acute Coronary Syndrome Mechanism Examples Increased Myocardial Oxygen Demand * Increased hea rate Directly: Cocaine, adrenergic adrenergic I3-agonists, sympathomimetics, withdrawal of J3-antagonists Indirectly: potent vasodilators (Nifedipine, minoxidil, hydralazine) * Increased myocardial contractility Directly: Cocaine, adrenergic n-agonist, sympathomimetics, withdrawal of (3-antagonists Indirectly: potent vasodilators (Nifedipine, minoxidil, hydralazine) * Increased left ventricular systolic wall tension Cocaine, phenylephrine Decreased Myocardial Oxygen Supply (temporary, non-total occlusion) * Increased coronary vascular resistance (vasospasm, thrombosis) Cocaine, anti-migraine agents (ergot alkaloids, triptans) * Decreased coronary diastolic perfusion pressure Enalapril, nifedipine, minoxidil, hydralazine, nitroprusside, adenosine, dipyridamole Drug-Induced Acute Coronary Syndromes * Acute coronary syndrome associated with acute drug therapy - Coronary aery thrombosis, superimposed on a damaged atherosclerotic plaque - Coronary aery vasospasm (with or without a superimposed coronary aery thrombosis) * Acute coronary syndrome associated with chronic drug therapy (Increased cardiovascular risk) Cocaine, oral contraceptives, estrogens, COX-2 inhibitors, NSAIDs Cocaine, anti-migraine agent (ergot alkaloids, triptans) Cocaine, estrogens, COX-2 inhibitors, NSAIDs, HIV agents/protease inhibitors, oral contraceptives, rosiglitazone