Background

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 theUnited States, with myocardial infarction a common manifestationof this disease. • Of all patients having a myocardial infarction, 25 to 35% die before receiving medical attention, most often from ventricularfibrillation. For those who reach a medical facility, the prognosisis considerably better and has improved over the years: in-hospitalmortality rates fell from 11.2% in 1990 to 9.4% in 1999

3. Background • In 2006, approximately 1.2 million Americanssustained 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 strategyis beneficial in high-risk patients with acute coronary syndromes.

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

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

7. Background • Although meta-analyses of previous randomized trials that comparedan invasive strategy with a conservative strategy in patientswith acute coronary syndromes have shown a benefit for an invasivestrategy, the timing of angiography in the invasive-strategygroup of these previous studies ranged from as early as 19 hoursafter randomization in one large trial to as late as 96 hoursin another large trial.

8. Invasive vs. Conservative Strategy for UA/NSTEMI – All Studies ISAR-COOL RITA-3 VINO VANQWISH TRUCS MATE TACTICS-TIMI 18 ICTUS TIMI IIIB FRISC II Invasive Conservative # Pts: 1140 1674 7018

9. Background • Given this wide variation in the timing,there remains substantial uncertainty regarding the optimaltiming for intervention in such patients. • Small, randomizedtrials comparing early intervention with delayed interventionhave generated conflicting results.

10. Background • Although some observationalanalyses have suggested that earlier intervention, as comparedwith delayed intervention, may reduce events, others havesuggested that outcomes appear to be similar between the twoapproaches. • Also, there has been a suggestion of a hazardassociated 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

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.

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

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

29. Thinking outside the box…

30. References • 1. Keeley EC, Boura JA, Grines CL. Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials. Lancet 2003;361:13-20 • 2. Mehta SR, Cannon CP, Fox KA, et al. Routine vs selective invasive strategies in patients with acute coronary syndromes: a collaborative meta-analysis of randomized trials. JAMA 2005; 293:2908-2917.  Bavry AA, Kumbhani DJ, Rassi AN, Bhatt DL, 3.Askari AT. Benefit of early invasive therapy in acute coronary syndromes: a meta-analysis of contemporary randomized clinical trials. J Am Coll Cardiol 2006;48:1319-1325.  • 4.Cannon CP, Gibson CM, Lambrew CT, et al. Relationship of symptom-onset-to-balloon time and door-to-balloon time with mortality in patients undergoing angioplasty for acute myocardial infarction. JAMA 2000;283:2941-2947.  • 5.Antman EM, Hand M, Armstrong PW, et al. 2007 Focused Update of the ACC/AHA 2004 Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2008;117:296-329. [Erratum, Circulation 2008;117(6):e162.]  • 6.Fuster V, Badimon L, Badimon JJ, Chesebro JH. The pathogenesis of coronary artery disease and the acute coronary syndromes. N Engl J Med 1992;326:310-318.  • 7.Cannon CP, Weintraub WS, Demopoulos LA, et al. Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes treated with the glycoprotein IIb/IIIa inhibitor tirofiban. N Engl J Med 2001;344:1879-1887 • 8.Invasive compared with non-invasive treatment in unstable coronary-artery disease: FRISC II prospective randomised multicentre study. Lancet 1999;354:708-715.  • 9.Fox KA, Poole-Wilson P, Clayton TC, et al. 5-Year outcome of an interventional strategy in non-ST-elevation acute coronary syndrome: the British Heart Foundation RITA 3 randomised trial. Lancet 2005;366:914-920.  • 10.Spacek R, Widimsky P, Straka Z, et al. Value of first day angiography/angioplasty in evolving non-ST segment elevation myocardial infarction: an open multicenter randomized trial. Eur Heart J 2002;23:230-238 • 11.Neumann FJ, Kastrati A, Pogatsa-Murray G, et al. Evaluation of prolonged antithrombotic pretreatment ("cooling-off" strategy) before intervention in patients with unstable coronary syndromes: a randomized controlled trial. JAMA 2003;290:1593-1599. • 12.de Winter RJ, Windhausen F, Cornel JH, et al. Early invasive versus selectively invasive management for acute coronary syndromes. N Engl J Med 2005;353:1095-1104 • 13.Riezebos RK, Ronner E, Ter Bals E, et al. Immediate versus deferred coronary angioplasty in non-ST-elevation acute coronary syndromes. Heart 2008 December 22 . • 14.Mehta SR, Granger CB, Boden WE, et al. Early versus delayed invasive intervention in acute coronary syndromes. N Engl J Med 2009;360:2165-2175.