Clinical Research
Coronary Artery Disease
Rivaroxaban in Patients Stabilized After a ST-Segment Elevation Myocardial Infarction: Results From the ATLAS ACS-2–TIMI-51 Trial (Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Standard Therapy in Subjects with Acute Coronary Syndrome–Thrombolysis In Myocardial Infarction-51)

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Objectives

The present analysis reports on the pre-specified subgroup of ST-elevation myocardial infarction (STEMI) patients, in whom anticoagulant therapy has been of particular interest.

Background

In ATLAS ACS-2–TIMI-51 (Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Standard Therapy in Subjects with Acute Coronary Syndrome–Thrombolysis In Myocardial Infarction-51), rivaroxaban reduced cardiovascular events across the spectrum of acute coronary syndrome (ACS).

Methods

Seven thousand eight hundred seventeen patients in ATLAS ACS-2-TIMI 51 presented with a STEMI. After being stabilized (1 to 7 days), they underwent randomization to twice daily rivaroxaban 2.5 mg, rivaroxaban 5 mg, or placebo. Data are presented as 2-year Kaplan-Meier rates, and for intention-to-treat (ITT) and modified ITT (mITT) analyses.

Results

Among STEMI patients, rivaroxaban reduced the primary efficacy endpoint of cardiovascular death, myocardial infarction, or stroke, compared with placebo (ITT: 8.4% vs. 10.6%, hazards ratio [HR]: 0.81, 95% confidence interval [CI]: 0.67 to 0.97, p = 0.019; mITT: 8.3% vs. 9.7%, HR: 0.85, 95% CI: 0.70 to 1.03, p = 0.09). This reduction emerged by 30 days (ITT and mITT: 1.7% vs. 2.3%, p = 0.042) and was evident in analyses that included events while patients received background dual antiplatelet therapies (ITT: 7.9% vs. 11.9%, p = 0.010; mITT: 7.7% vs. 10.1%, p = 0.061). In terms of the individual doses, rivaroxaban 2.5 mg reduced cardiovascular death (ITT: 2.5% vs. 4.2%, p = 0.006; mITT: 2.2% vs. 3.9%, p = 0.006), which was not seen with 5 mg of rivaroxaban. Rivaroxaban versus placebo increased non-coronary artery bypass grafting Thrombolysis In Myocardial Infarction major bleeding (2.2% vs. 0.6%, p < 0.001) and intracranial hemorrhage (0.6% vs. 0.1%, p = 0.015) without a significant increase in fatal bleeding (0.2% vs. 0.1%, p = 0.51).

Conclusions

In patients with a recent STEMI, rivaroxaban reduced cardiovascular events. This benefit emerged early and persisted during continued treatment with background antiplatelet therapies. Rivaroxaban compared with placebo increased the rate of major bleeding, but there was no significant increase in fatal bleeding. (An Efficacy and Safety Study for Rivaroxaban in Patients With Acute Coronary Syndrome; NCT00809965)

Key Words

anticoagulant
ST-segment elevation myocardial infarction
therapy

Abbreviations and Acronyms

ACS
acute coronary syndrome
CABG
coronary artery bypass grafting
CI
confidence interval
HR
hazard ratio
ITT
intention-to-treat
MI
myocardial infarction
mITT
modified intention-to-treat
NSTEMI
non–ST-elevation MI
STEMI
ST-segment elevation myocardial infarction
TIMI
Thrombolysis In Myocardial Infarction

Cited by (0)

This study was supported by research grants from Johnson & Johnson Pharmaceutical Research and Development and Bayer Healthcare. Dr. Mega has received research grant support from Johnson & Johnson, Bayer Healthcare, Bristol-Myers Squibb/sanofi-aventis, Daiichi Sankyo, Eli Lilly; research supplies from Accumetrics and Nanosphere; and honoraria for consulting from American Genomics, Boehringer Ingelheim, Janssen, and Merck. Dr. Braunwald has received research grant support from Abbott, AstraZeneca, Amgen, Bayer Healthcare, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Merck (SPRI), Pfizer, Roche (Diagnostics), sanofi-aventis, Johnson & Johnson; and has been a consultant for Merck (no compensation), Amorcyte, Daiichi Sankyo, The Medicines Co., Ikaria, CardioRentis, sanofi-aventis, and CVRx (no compensation). Ms. Murphy has received research grant support from Bayer Healthcare, Johnson & Johnson; and honoraria for consulting from Amarin Pharmaceuticals, and Eli Lilly and Company. Drs. Kiss, Parkhomenko, Tendera, and Widimsky have received research grant support from Johnson & Johnson and Bayer Healthcare. Drs. Burton and Plotnikov are employed by and own stock in Johnson & Johnson. Dr. Gibson has received research grant support from Johnson & Johnson, Bayer Healthcare, Bristol-Myers Squibb; honoraria for consulting from Portola Pharmaceuticals, sanofi-aventis, The Medicines Co., Daiichi Sankyo Company, Eli Lilly and Company, Biogen IDEC, Bristol-Myers Squibb, Ischemix, Inc., Johnson & Johnson, Bayer Healthcare, GlaxoSmithKline, Merck Schering Plough, Ortho McNeil, Medicure, Inc., Archemix, Inc., Genentech, Inc., and Boeringer Ingelheim; payment for lectures from Daiichi Sankyo Company, Eli Lilly and Company, Medicines Co.; and payment for development of educational presentations from Daiichi Sankyo Company and Eli Lilly and Company.