A 64-year-old man comes to the office due to exertional chest pain over the last 6 months. He is a lifelong 1 pack per day cigarette smoker and has a history of type 2 diabetes mellitus and peripheral artery disease. The patient undergoes treadmill exercise stress testing and develops substernal chest pain on moderate exertion accompanied by ECG changes that resolve immediately upon rest. He refuses invasive cardiac testing. The patient is started on low-dose aspirin therapy for secondary prevention of cardiovascular disease but experiences shortness of breath and wheezing with the medication. Which of the following is the best alternate therapy for this patient?
This patient's clinical history is consistent with stable angina (angina pectoris) due to underlying coronary heart disease (CHD). Patients with stable angina should be started on aspirin to decrease the risk of adverse cardiovascular events. Aspirin impairs prostaglandin synthesis by irreversibly inhibiting cyclooxygenase (COX). Inhibition of COX-1 in platelets prevents synthesis of thromboxane A2, a potent stimulator of platelet aggregation and vasoconstriction. This helps reduce the risk of occlusive thrombus formation and subsequent myocardial infarction.
Some patients are unable to tolerate aspirin due to exacerbation of preexisting respiratory symptoms (eg, rhinitis, asthma) or development of allergic reactions (eg, urticaria, angioedema, anaphylaxis). In these patients, alternate antiplatelet agents should be used for prevention of cardiovascular events. Clopidogrel irreversibly blocks the P2Y12 component of ADP receptors on the platelet surface and prevents platelet aggregation. Clopidogrel is as effective as aspirin for prevention of cardiovascular events and should be used in patients with aspirin allergy.
(Choices A and G) Apixaban is a direct factor Xa inhibitor that prevents platelet activation and fibrin clot formation. Warfarin inhibits an enzyme required for synthesis of active vitamin K, resulting in decreased synthesis of vitamin K-dependent clotting factors (II, VII, IX, and X). Both apixaban and warfarin are typically used for prevention and/or treatment of thromboembolic events, not coronary artery disease.
(Choice B) Cilostazol is a phosphodiesterase inhibitor that is occasionally used in patients with symptomatic peripheral vascular disease (ie, claudication).
(Choice D) Low molecular weight heparins (LMWHs; enoxaparin, dalteparin) are indirect thrombin inhibitors that bind with antithrombin and convert it from a slow to a rapid inactivator of thrombin and factor Xa. They are used in patients with acute coronary syndrome (unstable angina or myocardial infarction) but have no role in the management of patients with stable angina.
(Choice E) Eptifibatide is a platelet glycoprotein IIb/IIIa inhibitor that inhibits the final common pathway of platelet aggregation. Eptifibatide is occasionally used in some patients with acute coronary syndrome, but it is not used for patients with stable CHD.
(Choice F) Naproxen is a nonsteroidal anti-inflammatory drug (NSAID) that is used for pain management in patients with osteoarthritis. Use of both nonselective and selective COX-2 NSAIDs increases the risk of adverse cardiovascular events.
Educational objective:
Clopidogrel irreversibly blocks the P2Y12 component of ADP receptors on the platelet surface and prevents platelet aggregation. Clopidogrel is as effective as aspirin in the prevention of cardiovascular events in patients with coronary heart disease.