Clinical Edge

Summaries of Must-Read Clinical Literature, Guidelines, and FDA Actions

Rivaroxaban + Aspirin for CV Prevention

N Engl J Med; 2017 Oct 5; Eikelboom, et al

Patients with stable atherosclerotic vascular disease assigned to rivaroxaban plus aspirin had better cardiovascular (CV) outcomes and more major bleeding events than those taking aspirin alone; however, rivaroxaban alone did not result in better CV outcomes than aspirin alone and resulted in more major bleeding events. This according to a double-blind clinical trial that randomly assigned 27,395 participants with stable atherosclerotic vascular disease to receive rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg once daily). Primary outcome was a composite of CV death, stroke, or myocardial infarction. The study was stopped for superiority of the rivaroxaban-plus-aspirin group after a mean follow-up of 23 months. Researchers found:

  • The primary outcome occurred in fewer patients in the rivaroxaban-plus-aspirin group than in the aspirin-alone group (379 vs 496 patients; HR, 0.76), but major bleeding events occurred in more patients in the rivaroxaban-plus-aspirin groups (288 vs 170 patients; HR, 1.70).
  • There was no significant difference in intracranial or fatal bleeding between the 2 groups.
  • There were 313 deaths (3.4%) in the rivaroxaban-plus-aspirin group as compared with 378 (4.1%) in the aspirin-alone group (HR, 0.82).
  • The primary outcome did not occur in significantly fewer patients in the rivaroxaban-alone group, but major bleeding events occurred in more patients in the rivaroxaban-alone group.

Citation:

Eikelboom JW, Connolly SJ, Bosch J, et al. Rivaroxaban with or without aspirin in stable cardiovascular disease. N Engl J Med. 2017;377:1319-1330. doi:10.1056/NEJMoa1709118.

Commentary:

We know that the sudden development of a clot (thrombosis) on top of an existent atherosclerotic plaque is the most common cause of MI. For this reason, aspirin has been a standard addition to therapy in patients with coronary artery disease to decrease the risk of recurrent MI. Many additions to aspirin have been studied, including dual antiplatelet therapy and the use of anticoagulant therapy. For the most part, these additions have yielded no clear benefit, with some trials showing decreases in some of the thrombotic endpoints which were often offset by an increase in major bleeding, yielding no overall benefit above that of aspirin alone. This trial was stopped early by the safety monitoring board due to clear overall benefit of a combination of aspirin and low-dose of rivaroxaban, 2.5 mg bid. It should be noted that the dose where benefit was seen was one-quarter of the dose recommended for stroke prophylaxis for atrial fibrillation. While there was increased bleeding risk, there was no increase in intracranial bleeds or fatal bleeding. There was a net benefit and lower mortality in the low-dose rivaroxaban plus aspirin group compared to the aspirin group alone. The accompanying editorial for this study is worth a read.1 This study will certainly be discussed among guideline committee members and we await clear recommendations about its place in the treatment of patients with coronary artery disease. —Neil Skolnik, MD

  1. Braunwald E. An important step for thrombocardiology. N Engl J Med. 2017;377(14):1387-1388. doi:10.1056/NEJMe1710241.

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