Triple Antithrombotic Therapy in Cardiac Patients: More Questions Than Answers

Perspective:

The following are 10 key points from a review article on triple antithrombotic therapy in cardiac patients:

1. Vitamin K antagonism (VKA) alone is not an alternative to dual antiplatelet therapy (DAPT) in patients with acute coronary syndrome and stent implantation.

2. Available retrospective and randomized data, overall, suggest that triple therapy (TT) is more effective than DAPT or VKA combined with one antiplatelet drug, but at the expense of increased bleeding rates. When compared with DAPT, the bleeding risk is increased by about two- to five-fold by TT.

3. The shortest possible duration of TT is recommended. European Society of Cardiology (ESC) guidelines recommend TT for 1 month after bare-metal stent implantation; this should be prolonged to 3 months in the case of implantation of a drug-eluting stent (or to 6 months in the case of a paclitaxel-eluting stent).

4. ESC guidelines recommend a lower target international normalized ratio (INR) range of 2.0-2.5 (instead of 2.0-3.0) during the period of TT. This is in contrast to the 2012 American College of Chest Physicians guidelines, in which an INR range of 2.0-3.0 is suggested.

5. The WOEST multicenter trial is the first randomized prospective trial to address the issue of an optimal antithrombotic strategy for patients with atrial fibrillation after coronary stenting. Patients were randomized to TT or 75 mg clopidogrel daily and VKA (Dewilde WJ, et al. Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial. Lancet 2013;381:1107-15.) The primary endpoint of all types of Thrombosis in Myocardial Infarction (TIMI) bleeding was reduced in the dual-therapy arm; the trial was not powered for the analysis of ischemic events (but MI, stroke, and stent thrombosis were numerically lower in the dual-therapy arm). In providing their own recommendations, the authors wrote, ‘We are not convinced from the WOEST data that aspirin should be abandoned completely. Instead, we believe that the duration of aspirin and thus TT should be shortened to 1 month.’

6. Most bleeding events in patients on TT occur in the gastrointestinal tract. Use of a proton-pump inhibitor during times of TT seems reasonable to reduce the risk of gastrointestinal bleeding.

7. If TT is necessary, dosing of antithrombotic drugs should be kept as low as possible. Low doses of aspirin are effective, and, if aspirin is given at all, it should be dosed ≤100 mg daily.

8. TT using novel direct oral anticoagulants (NOACs) is not currently recommended. In providing their own opinion, the authors wrote, ‘In the case that the patient and the treating physician nonetheless decide to use NOACs in TT rivaroxaban in a reduced dose may be preferred.’

9. Third-generation P2Y12 antagonists (i.e., prasugrel or ticagrelor) should be avoided when TT is necessary.

10. Drawing from a subgroup of ACTIVE W trial patients (in which atrial fibrillation patients with low thromboembolic risk had similar ischemic event rates during the first 6 months of treatment with DAPT vs. VKA), the authors suggested that DAPT may be a reasonable alternative to TT in patients with a low CHA2DS2-VASc score (i.e., 0-1).

Clinical Topics: Acute Coronary Syndromes, Invasive Cardiovascular Angiography and Intervention, Stable Ischemic Heart Disease, Interventions and ACS, Chronic Angina

Keywords: Vitamin K, Risk, Platelet Aggregation Inhibitors, Morpholines, Thiophenes, Ticlopidine, Fibrinolytic Agents, Purinergic P2Y Receptor Antagonists, International Normalized Ratio, Paclitaxel, Thromboembolism, Prothrombin Time, Thrombosis, United States, Myocardial Infarction, Stroke, Acute Coronary Syndrome, Coronary Restenosis, Drug-Eluting Stents, Piperazines, Proton Pump Inhibitors, Gastrointestinal Hemorrhage, Percutaneous Coronary Intervention, Dinucleoside Phosphates, Hemorrhage


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