The FDA has approved cangrelor (Kengreal – The Medicines Company), an IV P2Y12 platelet inhibitor, as an adjunct to percutaneous coronary intervention (PCI) in patients who have not been pretreated with a P2Y12 inhibitor and are not being given a glycoprotein IIb/IIIa inhibitor.

Recent guidelines from the American Heart Association and American Stroke Association reviewed antithrombotic therapy options for secondary prevention of stroke in patients who have had a stroke or transient ischemic attack (TIA).

Antiplatelet drugs are the drugs of choice for prevention and treatment of arterial thrombosis. Anticoagulants are the drugs of choice for prevention and treatment of venous thromboembolism and for prevention of cardioembolic events in patients with atrial fibrillation.

The FDA has approved vorapaxar (Zontivity – Merck), an oral protease-activated receptor-1 (PAR-1) antagonist, for use with aspirin and/or clopidogrel to reduce the risk of thrombotic cardiovascular events in patients with peripheral arterial disease or a history of myocardial infarction (MI). It is the first PAR-1 antagonist to be approved by the FDA.

The treatment of atrial fibrillation includes anticoagulation, rate control, and rhythm control. New US guidelines for the management of atrial fibrillation have recently been published.

One of our readers has suggested that more attention should have been paid to a study comparing the antiplatelet effects of immediate-release and enteric-coated aspirin that appeared in Circulation last year.1 The safety benefits of enteric-coated aspirin are unclear. It may protect against dyspepsia, but not against major gastrointestinal bleeding, which is thought to be mainly a systemic effect of prostaglandin inhibition.

ANTIPLATELET EFFECTS OF ASPIRIN — Aspirin irreversibly acetylates cyclooxygenase-1, blocking thromboxane synthesis and inhibiting platelet activation and aggregation for the life of the platelet (5-7 days). Aspirin prophylaxis reduces the incidence of myocardial infarction and/or death by 15-25% in patients with coronary heart disease or ischemic stroke, and in those undergoing angioplasty or a coronary artery bypass graft. Aspirin can also prevent myocardial infarction in asymptomatic men and ischemic stroke in asymptomatic women, but the risk-benefit ratio is less favorable because the thrombotic risk is lower and the benefit in preventing thrombosis is offset by a small risk of gastrointestinal bleeding or hemorrhagic stroke.2

THE STUDY — The effects of a single 325-mg dose of immediate-release or enteric-coated aspirin on platelet aggregation were assessed 4 or 8 hours post-dose in 400 healthy volunteers. The rate of platelet nonresponse (<60% inhibition of platelet aggregation) to enteric-coated aspirin was 49% at 4 hours and 17% at 8 hours; ex vivo addition of aspirin to the samples reduced the rates of nonresponse to 12% and 0%, respectively. The rate of nonresponse to immediate-release aspirin was 0%.1

CONCLUSION — A study in healthy volunteers (not patients with atherosclerosis) of the effect of a single 325-mg dose of immediate-release or enteric-coated aspirin (not the usual recommended maintenance dose of 81 mg) on platelet response (not cardiovascular events) has limited applicability to clinical practice. Nevertheless, most patients who take aspirin for prophylaxis might be well advised to take regular aspirin.

1. T Grosser et al. Drug resistance and pseudoresistance: an unintended consequence of enteric coating aspirin. Circulation 2013; 127:377.

2. Antithrombotic drugs. Treat Guidel Med Lett 2011; 9:61.

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Anticoagulants are the drugs of choice for treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), collectively referred to as venous thromboembolism (VTE).

The FDA has approved use of Kcentra (CSL Behring), a human-derived 4-factor prothrombin complex concentrate (PCC), for urgent reversal of warfarin anticoagulation in adults with acute major bleeding. It is the only 4-factor PCC available in the US.

The FDA has approved apixaban (Eliquis – Bristol-Myers Squibb/Pfizer), an oral direct factor Xa inhibitor, for prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. It is the third new oral anticoagulant to be approved for this indication as an alternative to warfarin.

Atrial fibrillation increases the risk of thromboembolic stroke. Anticoagulant therapy can reduce this risk and is recommended for patients with atrial fibrillation and one or more of the following: congestive heart failure, hypertension, age ≥75 years, diabetes, or prior stroke or transient ischemic attack (CHADS₂ score ≥1).

A reader has asked us to review the choice of drugs for heparin-induced thrombocytopenia (HIT), a prothrombotic state with high morbidity and mortality. Three recent publications have made somewhat different recommendations on its treatment.

The standard antithrombotic therapy for treatment of patients with acute coronary syndrome (ACS) is dual antiplatelet therapy with aspirin and clopidogrel (Plavix) or another thienopyridine, plus a parenteral anticoagulant while the patient is hospitalized, followed by antiplatelet therapy alone after discharge. The addition of the oral anticoagulant warfarin (Coumadin, and others) to dual antiplatelet therapy is generally not recommended for this indication because of fluctuations in its anticoagulant effect and the risk of bleeding. A recently published trial found that addition of a low dose of the oral anticoagulant rivaroxaban (Xarelto) to antiplatelet therapy after discharge reduced the risk of major cardiovascular events without increasing the incidence of fatal bleeding.

The labeling of dabigatran etexilate (Pradaxa – Boehringer Ingelheim), an oral direct thrombin inhibitor, has recently been updated to include new dosing and monitoring recommendations and a warning on the risk of bleeding. Dabigatran etexilate was approved in the US in 2010 for the prevention of thromboembolic stroke in patients with non-valvular atrial fibrillation. It has been shown to be more effective than warfarin (Coumadin, and others) for this indication.

The FDA has approved Duexis (Horizon), a fixed-dose combination of the nonsteroidal anti-inflammatory drug (NSAID) ibuprofen and the H2-receptor antagonist (H2RA) famotidine, for symptomatic relief of osteoarthritis and rheumatoid arthritis and to decrease the risk of developing gastric and duodenal ulcers in patients at risk for NSAID-associated ulcers. Vimovo, a combination of the NSAID naproxen and the proton pump inhibitor (PPI) esomeprazole, is also approved by the FDA for prevention of NSAID-associated gastric ulcers.

Arterial thrombi are composed mainly of platelet aggregates held together by small amounts of fibrin. Antiplatelet drugs are the drugs of choice for prevention and treatment of arterial thrombosis, but anticoagulants are also effective, and their effects can add to those of antiplatelet drugs. Venous thrombi are composed mainly of fibrin and trapped red blood cells, with relatively few platelets. Anticoagulants are the agents of choice for prevention and treatment of venous thromboembolism and for prevention of cardioembolic events in patients with atrial fibrillation.

The FDA has approved ticagrelor (Brilinta – AstraZeneca), an oral antiplatelet drug, for use with low-dose aspirin to reduce the rate of thrombotic cardiovascular events in patients with acute coronary syndrome (ACS). It will compete with clopidogrel (Plavix) and prasugrel (Effient) for such use. Clopidogrel is expected to become available generically in the US within the next few months.

The FDA has approved rivaroxaban (Xarelto – Janssen), an oral direct factor Xa inhibitor, for prevention of deep vein thrombosis (DVT) in patients undergoing knee or hip replacement surgery.

The FDA has approved the oral direct thrombin inhibitor dabigatran (da big’ a tran) etexilate (Pradaxa – Boehringer Ingelheim) for prevention of thromboembolic stroke in patients with non-valvular atrial fibrillation. It has been available in Canada (Pradax) since 2008 for prevention of thromboembolism in patients undergoing knee or hip replacement surgery and was recently approved there for use in atrial fibrillation.