Managing Antiplatelet Therapy

Dual Antiplatelet Therapy In 1955, President Dwight Eisenhower, recovering from an acute myocardial infarction (MI), was treated with warfarin (Coumadin®) to prevent a repeat MI (Figures 1 and 2).¹ Coumadin, FDA-cleared in 1954, had become an essential part of acute coronary syndrome treatment; it was intended to reduce the risk of a secondary MI, peripheral artery disease, ischemic stroke, and venous thromboembolic disease subsequent to an MI. Coumadin continues today as the most-prescribed anticoagulant in North America, though now its most frequent indication is prophylaxis to reduce the risk of ischemic stroke in non-valvular atrial fibrillation. Because of its narrow therapeutic and safety range, Coumadin requires monthly laboratory monitoring using the prothrombin time assay, which, beginning in 1987, was enhanced through computation of the international normalized ratio (PT/INR).² The accepted therapeutic range worldwide is an INR of 2–3. An INR below 2 signals increased risk of thrombosis, above 3, risk of hemorrhage.³

In 1992, thienopyridine, a nucleic acid derivative distributed as ticlopidine (Ticlid®), was added to post-MI Coumadin therapy (Figure 3).⁴ Ticlopidine is an antiplatelet drug that reversibly occupies the platelet membrane ADP receptor, P2Y₁₂ (Figure 3). Ticlopidine competes with ADP for P2Y₁₂ receptor sites, suppressing ADP's platelet activation property. From 1992 to 2000, Coumadin and Ticlid administered together were the most commonly used post-MI antithrombotic regimen. This regimen was typically discontinued six months to two years after the event. Regrettably, 1 in 3–5000 ticlopidine patients developed life-threatening thrombotic thrombocytopenic purpura or aplastic anemia, creating a negative public perception.⁵ This…

ABBRVIATIONS: AA-arachidonic acid, ACS-acute coronary syndrome, ADP-adenosine diphosphate, ALR-aspirin low responder, AMI-acute myocardial infarction, ARU-aspirin reaction (or resistance) units, ASA-acetylsalicylic acid, CABG-coronary artery bypass graft, CLR-clopidogrel low responder, COX-cyclooxygenase, CT-closure time, DAPT-dual antiplatelet therapy, CLIA-clinical laboratory improvements amendment, FDA-US Food and Drug Administration, LTA-light transmittance aggregometry, MI-myocardial infarction, NSAID-non-steroidal anti-inflammatory drug, CYP-cytochrome oxidase pathway, PCI-percutaneous intervention, PGE₁-prostaglandin E1, PGG₂-prostaglandin G₂, PGH₂-prostaglandin H₂, POC-point of care, PRU-P2Y₁₂ reaction units, PT/INR-prothrombin time with international normalized ratio, TEG-thromboelastography, TEM-thromboelastometry, TXA₂-thromboxane A2, WBA-whole blood aggregometry, VASP-vasodilator-stimulated phosphoprotein