Rivaroxaban when used to treat patients with atrial fibrillation who have had a previous MI is associated with higher risk for adverse events.
The question of whether the efficacy and safety of rivaroxaban to treat nonvalvular atrial fibrillation (AF) differed in patients with and without a history of prior myocardial infarction (MI) was recently posed and studied by investigators from the Duke Clinical Research Institute. Their study,1 just published in the European Heart Journal, was a pre-specified subgroup analysis of the ROCKET-AF trial,2 which randomized 14,262 patients with nonvalvular AF to either rivaroxaban or warfarin and studied the pre-specified endpoint of stroke and systemic embolism. All patients from the parent trial were stratified by whether they had a history of prior MI (n = 2468, 17%) or not (n = 11,794, 83%). The endpoint of interest was cardiovascular (CV) death, MI, and unstable angina, and patients were analyzed in an on-treatment fashion.
In the prior MI group, there were more men (75% vs 57%) and more patients with atherosclerotic and heart failure risk factors (congestive heart failure, diabetes, hypertension, aspirin use at baseline, and higher mean CHADS2 score [3.64 vs 3.43]). Interestingly, there were fewer patients with a history of prior stroke or transient ischemic attacks (46% vs 54%) in the group with prior MI.
Overall, rivaroxaban had a lower rate of CV death, MI, unstable angina compared with warfarin, although statistical significance was not achieved (HR = 0.86; 95% CI, 0.73 to 1.00; P = .05). Not surprisingly, the rates of the composite endpoint occurred 3 times more frequently in those with prior MI than in those with no prior MI (95% CI, 2.59 to 3.56). However, there was no significant interaction for CV death, MI, and unstable angina based on history of prior MI (P-int = .10), suggesting that there is no difference in the efficacy profile of rivaroxaban in patients with and without prior MI. With respect to safety, those with prior MI had increased major bleeding, which was likely a result of increased aspirin use at baseline. This was not, however, associated with increases in intracranial hemorrhage or fatal bleeding and the rate of these bleeding endpoints was actually lower with rivaroxaban compared with warfarin.
Although a history of MI in patients with AF in ROCKET-AF was relatively common (about 1 in 5 patients) and these patients had a 3-fold higher rate of CV death, MI, and unstable angina, there did not seem to be a difference in efficacy outcomes of rivaroxaban based on the presence of prior MI. Additional prospective data is needed to confirm this observational study. The clinical ramifications of this study suggest that patients with previous MI are at higher risk for subsequent adverse events. And, although there does not appear to be a significant difference in the efficacy of rirvaroxaban based on this subgroup analysis, there may be some differences with respect to bleeding.
1. Patel MR, Hellkamp AS, Lokhnygina Y, et al. Outcomes of discontinuing rivaroxaban compared with warfarin in patients with nonvalvular atrial fibrllation: analysis from the ROCKET-AF Trial (Rivaroxaban Once-Daily, Oral, Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation). J Am Coll Cardiol. 2013;61:651-658. (Abstract)
2. Mahaffey KW, Stevens SR, White HD, et al; ROCKET-AF Investigators. Ischaemic cardiac outcomes in patients with atrial fibrillation treated with vitamin K antagonism or factor Xa inhibition: results from the ROCKET-AF trial. Eur Heart J. 2013 Oct 15; [Epub ahead of print]. (Abstract)