ST-Elevation Myocardial Infarction

Transcription

1 in Patients following a ST-Elevation Myocardial Infarction Jessica L. Mega, Eugene Braunwald, Sabina A. Murphy, Alexei Plotnikov, Paul Burton, Robert Gabor Kiss, Alexandr Parkhomenko, Michal Tendera, Petr Widimsky, & C. Michael Gibson on behalf of the ATLAS ACS 2-TIMI 51 Investigators

2 Disclosures ATLAS ACS 2-TIMI 51 was supported by research grants from Johnson & Johnson and Bayer Healthcare. Received grants for clinical research or research supplies via the TIMI Study Group and Brigham and Women's Hospital from: Bayer Healthcare, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, Johnson & Johnson, Sanofi-Aventis, Accumetrics, Nanosphere, NIH/NHLBI Served as a consultant for: Merck, Janssen

3 ACS AND THROMBIN GENERATION Acute Coronary Syndromes n=28 nm) hrombin (n Th Coronary Artery Disease n=25 Control Time (seconds) Adapted from Brummel-Ziedins, et al. J Thromb Haem 2008;6:

4 THROMBIN INDUCES THROMBOSIS AND HEMOSTASIS IXa + Ca ++ + VIII RIVAROXABAN Oral Factor Xa Inhibitor Prothrombin Coagulation X Xa Tissue Factor + VII THROMBIN Receptor activation PAR -1,3,4 134 Fibrinogen Platelet Aggregation IIb/IIIa IIb/IIIa PAR-1 Platelet Platelet l t Ib Platelet Adhesion Ia Collagen Vessel Wall Fibrinogen Fibrin Formation Coughlin SR, Nature 2000;407: ; Perzborn E et al. Nat Rev Drug Discov. 2011;10(1):61-75

5 ATLAS ACS 2-TIMI 51: STEMI In ATLAS ACS 2-TIMI 51, rivaroxaban reduced recurrent CV events across the spectrum of ACS. The present analysis reports the results of the pre-specified subgroup of STEMI patients, in whom long-term anticoagulant therapy has been of particular interest.

6 STUDY DESIGN 7817 STEMI Patients (From a total of Patients with Recent ACS) Stabilized 1-7 Days Following the Index Event Median 4.7 Days Stratified by Thienopyridine Use at MD Discretion + ASA 75 to 100 mg/day N= mg BID N= mg BID N=2584 PRIMARY ENDPOINTS: EFFICACY: CV Death, MI, Stroke (Ischemic, Hemorrhagic, or Uncertain) SAFETY: TIMI major bleeding not associated with CABG

7 ANALYSIS STEMI KM event rates at 24 mos. Log-rank test stratified by intent to use a thienopyridine. Efficacy data for the intention to treat (ITT) analysis to provide complete accounting of events, as well for modified ITT (mitt). The mitt events are a subset of ITT events. Observed follow-up time >9 and similar in each treatment group.

8 NATIONAL LEAD INVESTIGATORS ARGENTINA M. Amuchastegui AUSTRALIA PAylward P. BELGIUM F. Van de Werf BRAZIL J. Nicolau BULGARIA N. Gotcheva CANADA P. Theroux/M. Le May CHILE R. Corbalan CHINA R. Gao COLOMBIA R. Botero CROATIA M. Bergovec CZECH REPUBLIC P. Widimsky DENMARK S. Eggert Jensen EGYPT J&J/Bayer FRANCE G. Montalescot GERMANY E. Giannitsis/H. Katus GREECE J&J/Bayer HUNGARY R. Gabor Kiss INDIA V. Chopra ISRAEL S. Meisel ITALY LATVIA A. Erglis LITHUANIA B. Petrauskiene MALAYSIA K.H. Sim MEXICO G. Llamas Esperon MOROCCO J&J/Bayer NETHERLANDS T. Oude Ophuis/M. van Hessen NEW ZEALAND H.White PHILIPPINES J&J/Bayer POLAND RUSSIA M. Ruda SERBIA Z. Vasilijevic i SLOVAKIA T. Duris SPAIN A. Betriu SWEDEN M. Dellborg THAILAND P. Sritara TUNISIA H. Haouala TURKEY Z. Yigit UKRAINE D. Ardissino M. Tendera A. Parkhomenko JAPAN PORTUGAL UNITED KINGDOM J&J/Bayer J. Morais I. Squire KOREA ROMANIA UNITED STATES d s y K. B. Seung D. Vinereanu C. M. Gibson 44 Countries 766 Sites

9 BASELINE CHARACTERISTICS mg BID mg BID Age, mean (SD) 60.8 (8.9) 61.5 (8.8) 61.3 (8.6) Male Sex 78% 79% 79% Prior MI 17% 16% 17% Diabetes 3 29% 29% Hypertension 59% 58% 58% Hypercholesterolemia 4 41% 41% Thienopyridine (Clopidogrel or Ticlopidine) 97% 96% 97% PCI at Index Hosp 71% 7 71%

10 PRIMARY EFFICACY ENDPOINT Stroke Cardio ovascula ar Death h, MI, or 1 8% ITT: HR 0.81 (95% CI ) P=0.019 N=2599 6% N=5128 mitt: HR 0.85 (95% CI ) P=0.09 Days 10.6% 8.

11 Stroke Cardio ovascula ar Death h, MI, or STEMI 1% PRIMARY EFFICACY ENDPOINT: 30 Days ITT: HR 0.71 (95% CI ) P= % 1.7% mitt: HR 0.71 (95% CI ) P=0.042 Days

12 Stroke Cardio ovascula ar Death h, MI, or STEMI 1 1 8% 6% PRIMARY EFFICACY ENDPOINT: While on Aspirin and Thienopyridine ITT: HR 0.78 (95% CI ) P=0.010 mitt: HR 0.82 (95% CI ) P=0.061 Days 11.8% 7.9%

13 EFFICACY ENDPOINTS: 5 mg BID CV Death, MI, or Stroke CV Death 1 ITT: HR 0.81 (95% CI ) P= % 5% ITT: HR 0.92 (95% CI ) P= % 6% % 5 mg BID 5 mg BID 1% mitt: HR 0.86 (95% CI ) P=0.17 Days mitt: HR 0.94 (95% CI ) P=0.73

14 EFFICACY ENDPOINTS: 2.5 mg BID CV Death, MI, or Stroke CV Death All-cause Death 1 ITT: HR 0.81 (95% CI ) P= % 5% 10.6% ITT: HR 0.60 ITT: HR % (95% CI ) P= (95% CI ) P= % 6% 8.7% 3% 3% 2.5 mg BID 2.5% 3. 1% mg BID 1% mg BID mitt: HR 0.85 (95% CI ) P=0.14 mitt: HR 0.58 (95% CI ) P=0.006 mitt: HR 0.60 (95% CI ) P=0.007

15 EFFICACY ENDPOINTS: 2.5 mg BID While on Aspirin and Thienopyridine CV Death, MI, or Stroke CV Death All-cause Death 1 1 ITT: HR 0.79 (95% CI ) P= % ITT: HR 0.51 (95% CI ) P= % 3.8% ITT: HR 0.52 (95% CI ) P= % 3% 3% 6% mg BID 1.7% 1% 2.5 mg BID 1% 2.5 mg BID mitt: HR 0.83 (95% CI ) P=0.13 mitt: HR 0.45 (95% CI ) P=0.003 mitt: HR 0.48 (95% CI ) P=0.004

16 TIM I non-ca ABG Ma ajor Blee eding STEMI 3% 1% PRIMARY SAFETY ENDPOINT 2.5 mg BID vs : HR 3.63 (95% CI ) P< mg BID vs : HR 5.47 (95% CI ) P< mg BID N= mg BID N=2566 N=2607 Days 2.7% 1.7% 0.6%

17 OTHER SAFETY ENDPOINTS Ka aplan-meie er Event Ra ates at 2 Ye ears 7% 6% 5% 3% 1% 2.5 mg vs 5 mg P= % 2.46% 1.08% Non-CABG TIMI Major or Minor Bleeding 2.5 mg BID 5 mg BID mg vs 5 mg P=0.018 Fatal Bleeding mg vs P< mg vs P< mg vs P= mg vs P=0.12

18 SUMMARY In patients with a recent STEMI: reduced recurrent cardiovascular events. This benefit emerged early and was evident in patients t treated with aspirin and clopidogrel. increased the rate of major bleeding, but there was no significant increase in fatal bleeding. 2.5 mg BID resulted in a survival benefit and less bleeding than 5 mg BID.

19 CONCLUSION STEMI Treatment with very low dose rivaroxaban (2.5 mg BID) offers an effective strategy to reduce thrombotic events in patients following a STEMI.