Reperfusion therapy in acute ST-elevation myocardial infarction a comparison between primary percutaneous intervention and thrombolysis in a short- and long-term perspective

Approximately 35,000 people suffer from a heart attack in Sweden annually. Among them, approximately 8000 are diagnosed with a ST-elevation myocardial infarction (STEMI) where timely reperfusion has been shown to save lives. Previous studies that have compared the existing reperfusion strategies, thrombolysis (TL) and primary PCI (PPCI), made use of treatment regimens that since have been improved with the use of mechanical and medical adjunctives. The objective of this thesis was to compare both of these strategies employing updated regimens in accordance to current guidelines with respect to; 1) efficacy in restoring blood flow and myocardial perfusion, 2) clinical outcome and 3) cost-effectiveness. Methods and results: Between November 2001 and May 2003, 205 patients with STEMI were randomized to PPCI with adjunctive abciximab or TL. The low molecular weight heparin enoxaparin was used as anticoagulant in both groups. In 42% treatment was initiated in the pre-hospital phase. The primary end points were the rate of STsegment resolution (STRES) ≥ 50% 120 minutes after inclusion and the rate of normalized (TIMI 3) flow in the infarct related vessel 5-7 days after treatment, serving as surrogates for a beneficial outcome. Secondary end points were the ability to restore myocardial perfusion evaluated angiographically by TIMI Myocardial Perfusion Grade (TMPG) 5-7 days after inclusion in the study, clinical events at 30 days and one year cost-effectiveness. The patients were followed prospectively for one year and, in addition, information on survival status and major clinical events was collected from national registries for an extended follow up period of a median of 5.3 years. STRES≥ 50% was achieved in 68% following PPCI and 64% after TL (n.s.). However, the TIMI 3 rate was higher after PPCI compared to TL (71% vs. 54%, p=0.04). TMPG tended to be better in the PPCI group than in the TL group. An analysis of the evolution of TMPG in the PPCI cohort revealed that there was a significant improvement of myocardial perfusion in the week following PPCI. Thirty day mortality rates were low and similar in the groups. At one year PPCI was tended to be less costly ($-2,505) than TL ($-2,505; n.s.), mainly due to higher costs for re-hospitalizations in the TL group. Primary PCI also lead to an insignificant gain in quality-adjusted survival (0.031 QALYs). A bootstrap analysis indicated that PPCI has a high probability of being cost-effective when a threshold value of $50,000 is employed. A survival analysis at 5.3 years showed a significant benefit from PPCI in terms of the combination of all-cause death and recurrent infarction (p=0.03) as well as for cardiac mortality alone (p=0.02). Conclusion: Primary PCI is more efficient than thrombolysis in re-establishing antegrade flow in the infarctrelated artery and offers a better long term clinical outcome with respect to major cardiac events without an increase in societal costs. Thus, based on the conditions under which this study was performed, primary PCI is a more efficient alternative than thrombolysis for the treatment of ST-elevation myocardial infarction. LIST OF PUBLICATIONS This thesis is based on the following studies, which will be referred to by their Roman numerals. I. Svensson L, Aasa M, Dellborg M, Gibson C.M., Kirtane A, Herlitz J, Ohlsson Å, Karlsson T, Grip L. Comparison of very early treatment with either fibrinolysis or percutaneous coronary intervention facilitated with abciximab with respect to ST recovery and infarct-related artery epicardial flow in patients with acute ST-segment elevation myocardial infarction: The Swedish Early Decision (SWEDES) reperfusion trial. American Heart Journal 2006;151:798.e1-798.e7. II. Aasa M, Kirtane A, Dellborg M, Gibson C.M, Prahl-Abrahamsson U, Svensson L, Grip L. Temporal changes in TIMI myocardial perfusion grade in relation to epicardial flow, ST-resolution and left ventricular function after primary percutaneous coronary intervention. Coronary Artery Disease 2007;18:513-518 III. Aasa M, Henriksson M, Dellborg M, Grip L,Herlitz J, Levin L-Å, Svensson L, Janzon M. Cost and health outcome of primary percutaneous coronary intervention versus early thrombolysis in acute ST-segment elevation myocardial infarctionresults from the SWEDES trial. Submitted for publication. IV. Aasa M, Dellborg M, Herlitz J, Svensson L, Grip L. Sustained risk reduction for cardiac events after primary coronary angioplasty compared with thrombolysis for acute ST-elevation myocardial infarction: five-year results from the Swedish Early Decision (SWEDES) reperfusion trial. Submitted for publication.