Antithrombotic Medications: Is More Better?
During Scientific Sessions 2018, I was able to remotely attend several great and informative lectures pertaining to the management of cardiovascular diseases. I was especially interested in the sessions related to antithrombotic therapy as this directly applies to my daily practice of Vascular Neurology. One of those sessions focused on management of tricky situations in post PCI patients. Dr. Roxana Mehran discussed the management of patients with atrial fibrillation and a recent PCI.
Antiplatelet medications are used for secondary prophylaxis in patients with coronary artery disease and ischemic stroke. Patients are routinely prescribed dual antiplatelet therapy (DAPT), usually a combination of aspirin with a P2Y12 inhibitor such as clopidogrel, ticagrelor or prasugrel. This is usually continued for six to 12 months after a PCI.
Results from the recently published POINT (1) trial showed reduced risk of recurrent ischemic stroke in the short term but an increased risk of hemorrhage with long term use of DAPT for patients with a recent TIA or minor stroke. Data from the SPS-3 (2) trial showed increased risk of hemorrhage with no clear benefit of using DAPT when compared to monotherapy in secondary stroke prevention for patients with a history of lacunar stroke. Therefore, patients who have experienced a recent transient ischemic attack or minor stroke are prescribed a short course of DAPT for 21-30 days.
DAPT has been shown to be inferior to warfarin for embolic stroke prophylaxis, with similar bleeding risk in atrial fibrillation(3). Therefore oral anticoagulants are the treatment of choice for atrial fibrillation. The AHA/ASA guidelines recommend against using DAPT in place of warfarin for atrial fibrillation in high bleeding risk patients.
About 5-10% of patients who undergo PCI are also taking an oral anticoagulant for atrial fibrillation. This creates a tricky situation where they need to be on triple therapy with DAPT and an oral anticoagulant. The triple therapy regimen has been associated with a significantly elevated risk of hemorrhage. WOEST (4) study data showed that using the combination of clopidogrel and an oral anticoagulant after PCI can reduce this risk as compared to the triple therapy regimen. The triple therapy arm 44.4% patients experienced a bleeding episode as compared to 19.4% in the double therapy arm (p<0.001). Moreover there was a higher rate of recurrent bleeding in the triple therapy group at 12% vs. 2.2% in the double therapy cohort. Most importantly, the double therapy did not cause an increase in the incidence of stent thrombosis or recurrent myocardial infarction. These data are encouraging and there are ongoing trials comparing various combination regimens of direct anticoagulants with antiplatelets in this difficult clinical scenario. These much awaited trials will hopefully provide some clarity regarding the optimal combination and duration of treatment. For now, we do have some evidence supporting the use of these triple therapy regimens for the shortest durations possible and periodically assessing the indications for continuing these combination regimens for our patients. When it comes to antithrombotic medications, more may not always be better.
- Clopidogrel and Aspirin in Acute Ischemic Stroke and High-Risk TIA. N Engl J Med 2018; 379:215-225
- Effects of Clopidogrel Added to Aspirin in Patients with Recent Lacunar Stroke. N Engl J Med 2012; 367:817-825
- Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial. Lancet. 2006 Jun 10;367(9526):1903-12
- 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 Mar 30;381(9872):1107-15