1. Effect of Early revascularization versus delayed revascularization versus medical therapy on inpatient mortality in patients with non ST elevation MI in a community hospital Setting Owais Jeelani,MBBS Mentor:Dr.A.Herle,MD,FACC

2. Background Coronary heart disease is the leading cause of death in the United States, with myocardial infarction a common manifestation of this disease. Of all patients having a myocardial infarction, 25 to 35% die before receiving medical attention, most often from ventricular fibrillation. For those who reach a medical facility, the prognosis is considerably better and has improved over the years: in-hospital mortality rates fell from 11.2% in 1990 to 9.4% in 1999

3. Background In 2006, approximately 1.2 million Americans sustained a myocardial infarction. Of these, two third had a myocardial infarction without ST- segment elevation

4. Background Randomized trials have shown that a routine invasive strategy is beneficial in high-risk patients with acute coronary syndromes.

5. Non-ST Elevation ACS Generally caused by partially occlusive, platelet-rich thrombus Unobstructed lumen thrombus Results from cross-linking of fibrinogen by platelet GP IIb- IIIa receptors at sites of plaque rupture platelet fibrinogen Ruptured plaque GP IIb-IIIa Artery wall

6. Background In patients with myocardial infarction with ST-segment elevation, in which the infarct-related artery is usually occluded and there is ongoing transmural ischemia, it is well established that the earlier primary percutaneous coronary intervention can be performed, the lower the mortality. By contrast, in patients with acute coronary syndromes without ST-segment elevation (including unstable angina and myocardial infarction), the culprit artery is often patent, there is usually no ongoing transmural ischemia, and the patient may have a good response to initial medical treatment.

7. Background Although meta-analyses of previous randomized trials that compared an invasive strategy with a conservative strategy in patients with acute coronary syndromes have shown a benefit for an invasive strategy, the timing of angiography in the invasive-strategy group of these previous studies ranged from as early as 19 hours after randomization in one large trial to as late as 96 hours in another large trial.

8. Invasive vs. Conservative Strategy for UA/NSTEMI – All Studies TIMI IIIB Conservative Invasive VANQWISH MATE FRISC II TACTICS- TIMI 18 VINO RITA-3 # Pts: 1140 16747018 TRUCS ISAR-COOL ICTUS

9. Background Given this wide variation in the timing, there remains substantial uncertainty regarding the optimal timing for intervention in such patients. Small, randomized trials comparing early intervention with delayed intervention have generated conflicting results.

10. Background Although some observational analyses have suggested that earlier intervention, as compared with delayed intervention, may reduce events, others have suggested that outcomes appear to be similar between the two approaches. Also, there has been a suggestion of a hazard associated with routine early intervention.

11. Study Objective Primary endpoint: -Is early revascularization better than delayed revascularization or Medical therapy alone in reducing in hospital mortality in Patients with non ST elevation MI in a community care setting?

12. Secondary endpoint What is the relative mortality of NSTEMI patients undergoing early revascularization vs delayed revascularization vs medical therapy alone? What is the relative length of hospital stay in the three groups studied? What percentage of coronary angiography patients actually underwent intervention (PCI or CABG)?

13. Methods Retrospective Data Analysis of patients at Mercy Hospital who have documented non ST elevation MI from June 2008 to June 2009 Institutional Review Board approval through the Catholic Health System 383 out of 591 patients reviewed were enrolled in the study after meeting the inclusion criteria

14. Inclusion criteria Based on ICD Coding 410.71 Patients with non ST elevation MI with chest pain at rest, lasting > 30 minutes and non- responding to sublingual nitroglycerin tablets in addition to elevated troponins greater than or equal to 0.1.

15. Exclusion criteria Patients with ST elevation MI not fulfilling the above criteria. Patients with MI not fulfilling the above inclusion criteria

16. Analysis of Data Mortality odds ratios used for the comparison of proportion of deaths in each arm (primary end point). Length of Stay comparison evaluated by mean number of days along with 95% confidence interval standard deviations. paired t-test with a p-value of <0.05 deemed statistically significant

18. BASELINE CHARACTERISTICS Variable Early Revascularization Delayed Revascularization P value Medical Management P value 2 Demographic Characteristics Age63.7563.640.938876.870.0001 Male Sex(%)41.9379.340.000138.670.0001 Medical history(%) Previous MI13.97819.560.317421.690.3237 Diabetes30.1023.360.245231.130.3049 Ischemic changes on EKG 44.0828.80.015334.900.9043 Previous Coronary Procedure PCI9.6720.100.027423.580.1411 CABG2.153.260.72192.830.7344

20. Primary Outcome Characteristic No of Patients Revascul arized % Medical % Odd’s ratio for event(95%CI)P-Value for Interaction Overall 202.16613.2070.1455 (0.0543 to 0.3897) 0.0001 Age <65 41.5158.34 0.1692(0.0226 to 1.2646) 0.2143 >65 162.75814.6340.1655(0.0515 to 0.5318) 0.0020 Sex Female 93.4889.230.3315(0.0798 to 1.3776) 0.2163 Male 111.62119.510.068(0.0171 to 0.2697) 0.0001 ST segment deviation No 51.0924.3470.2431 (0.0397 to 1.487) 0.2519 Yes 154.25529.7290.1051(0.0309 to 0.3577) 0.0001 More than 3 Risk Factors No 61.9606.3490.295(0.0524 to 1.6601) 0.3007 Yes 141.14223.250.0772(0.0228 to 0.261) 0.0001

21. Results Primary End-Point –There is statistically significant difference in in- hospital mortality between patients treated with revascularization versus patients treated conservatively. – This difference is reflected in patients >65 yrs of age. –There is no statistically significant difference in in- hospital mortality in patients younger than 65 yrs. –There is statistically significant difference in in- hospital mortality in males, patients with ischemic changes on EKG and patients having more than 3 risk factors.

22. Primary Outcome Characteristic No of Patients Early % Delayed % Odd’s ratio for event(95%CI)P-Value for Interaction Overall 62.15052.17390.99 (0.1778 to 5.5012 ) 0.9899 Age <65 22.0841.19 1.766(0.1079 to 28.8922) 0.6862 >65 42.23 10.734(0.0743 to 7.2639) 0.7914 Sex Female 31.855.350.33(0.0336 to 3.3079) 0.6183 Male 32.561.3693.342(0.204 to 54.710) 0.4136 ST segment deviation No 2 -0.90 - - Yes 44.8785.66030.855(0.1361 to 5.3686) 0.8669 Revascularized No 42.873.750.754(0.0758 to 7.5213) 0.8100 Yes 21.7240.961.807(0.1109 to 29.439) 0.6735

23. Results Primary End-Point - No statistically significant difference in in-hospital mortality in patients treated with early revascularization versus patients treated with delayed vascularization

24. Secondary Outcome Variable Early Revascularization Delayed Revascularization P value Medical Management P value* Length of Stay Mean 4.14 6.04 0.0006 7.900.0001 Age>65 5.25 5.62 0.6090 7.340.0009 Bleeding Complications % 5.376 9.293 0.3487 8.4900.8364 Acute Stroke % 0 1.0860.5523 0.9431.0000 Acute Renal Failure % 6.451 8.8950.6407 11.320 0.2333

25. Results Secondary Outcome –Statistically significant difference in hospital length of stay in patients treated with re vascularization versus patients treated conservatively –Statistically significant difference in hospital length of stay in patients treated with early revascularization versus patients treated with delayed revascularization. –Statistically significant difference in hospital length of stay in patients >65 years treated with revascularization versus patients treated conservatively.

26. Conclusion Revascularization offers benefit in reducing short term mortality over medical therapy alone Benefit is more pronounced in elderly high risk male patients. Immediate catheterization and intervention does not offer a benefit over initial medical stabilization followed by delayed catheterization and intervention

27. How are we doing? Comparison with Action registry data

28. Comparative Data with GWTG Action Registry for 2010 Characteristic2008-2009 % 2010 % Odd’s ratio for event(95%CI)P-Value for Interaction Nation Top10% Unadjusted Death 5.22 7.00.1455 (0.0543 to 0.3897)0.35713.6 Risk Adjusted Death 3.63 4.60.8483 (0.413 to 1.7425) 0.71513.8 Bleeding Events 8 8 1 (0.36 to 2.778) 18 Medications Aspirin 94.2 990.1903(0.0649 to 0.5579) 0.001099 Clopidogrel 68.76 413.1572(2.3307 to 4.2769) 0.000159 Prasugrel - 47 Revascularization overall 55.59 56 0.9603(0.5497 to 1.6775) 1.000036 Within 24 hrs 21 121.477( 0.9595 to 2.2757) 0.081135 Catheterization Within 24 hrs 24 300.7452(0.5374 to 1.0334)0.080854

29. Thinking outside the box…

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