Comparison of Effect of Ischemic Postconditioning on Cardiovascular Mortality in Patients With ST-Segment Elevation Myocardial Infarction Treated With Primary Percutaneous Coronary Intervention With Versus Without Thrombectomy

Abstract

In patients with ST-segment elevation myocardial infarction (STEMI), ischemic postconditioning (iPOST) have shown ambiguous results in minimizing reperfusion injury. Previous findings show beneficial effects of iPOST in patients with STEMI treated without thrombectomy. However, it remains unknown whether the cardioprotective effect of iPOST in these patients persist on long term. In the current study, all patients were identified through the DANAMI-3-iPOST database. Patients were randomized to conventional primary percutaneous coronary intervention (PCI) or iPOST in addition to PCI. Cumulative incidence rates were calculated, and multivariable analyses stratified according to thrombectomy use were performed. The primary end point was a combination of cardiovascular mortality and hospitalization for heart failure. From 2011 to 2014, 1,234 patients with STEMI were included with a median follow-up of 4.8 years. In patients treated without thrombectomy (n = 520), the primary end point occurred in 15% (48/326) in the iPOST group and in 22% (42/194) in the conventional group (unadjusted hazard ratio [HR] 0.62, 95% confidence interval [CI] 0.41 to 0.94, p = 0.023). In adjusted Cox analysis, iPOST remained associated with reduced long-term risk of cardiovascular mortality (HR 0.53, 95% CI 0.29 to 0.97, p = 0.039). In patients treated with thrombectomy (n = 714), there was no significant difference between iPOST (17%, 49/291) and conventional treatment (17%, 72/423) on the primary end point (unadjusted HR 1.01, 95% CI 0.70 to 1.45, p = 0.95). During a follow-up of nearly 5 years, iPOST reduced long-term occurrence of cardiovascular mortality and hospitalization for heart failure in patients with STEMI treated with PCI but without thrombectomy. In patients with ST-segment elevation myocardial infarction (STEMI), ischemic postconditioning (iPOST) have shown ambiguous results in minimizing reperfusion injury. Previous findings show beneficial effects of iPOST in patients with STEMI treated without thrombectomy. However, it remains unknown whether the cardioprotective effect of iPOST in these patients persist on long term. In the current study, all patients were identified through the DANAMI-3-iPOST database. Patients were randomized to conventional primary percutaneous coronary intervention (PCI) or iPOST in addition to PCI. Cumulative incidence rates were calculated, and multivariable analyses stratified according to thrombectomy use were performed. The primary end point was a combination of cardiovascular mortality and hospitalization for heart failure. From 2011 to 2014, 1,234 patients with STEMI were included with a median follow-up of 4.8 years. In patients treated without thrombectomy (n = 520), the primary end point occurred in 15% (48/326) in the iPOST group and in 22% (42/194) in the conventional group (unadjusted hazard ratio [HR] 0.62, 95% confidence interval [CI] 0.41 to 0.94, p = 0.023). In adjusted Cox analysis, iPOST remained associated with reduced long-term risk of cardiovascular mortality (HR 0.53, 95% CI 0.29 to 0.97, p = 0.039). In patients treated with thrombectomy (n = 714), there was no significant difference between iPOST (17%, 49/291) and conventional treatment (17%, 72/423) on the primary end point (unadjusted HR 1.01, 95% CI 0.70 to 1.45, p = 0.95). During a follow-up of nearly 5 years, iPOST reduced long-term occurrence of cardiovascular mortality and hospitalization for heart failure in patients with STEMI treated with PCI but without thrombectomy. Treatments and reperfusion strategies of patients with ST-segment elevation myocardial infarction (STEMI) have improved and become more preventive of adverse complications after STEMI, yet additional myocardial injury may occur immediately after restoration of coronary blood flow and may account for up to 50% of the damage to myocardium, a phenomenon called reperfusion injury.1Lønborg J Vejlstrup N Kelbæk H Holmvang L Jørgensen E Helqvist S Saunamäki K Ahtarovski KA Bøtker HE Kim WY Clemmensen P Engstrøm T. Final infarct size measured by cardiovascular magnetic resonance in patients with ST elevation myocardial infarction predicts long-term clinical outcome: an observational study.Eur Heart J Cardiovasc Imaging. 2013; 14: 387-395Crossref PubMed Scopus (114) Google Scholar, 2Hausenloy DJ Botker HE Engstrom T Erlinge D Heusch G Ibanez B Kloner RA Ovize M Yellon DM Garcia-Dorado D. 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ST-segment elevation myocardial infarction.Nat Rev Dis Primers. 2019; 5: 39Crossref PubMed Scopus (108) Google Scholar, 5Nepper-Christensen L Lønborg J Høfsten DE Sadjadieh G Schoos MM Pedersen F Jørgensen E Kelbæk H Haahr-Pedersen S Flensted Lassen J Køber L Holmvang L Engstrøm T Clinical outcome following late reperfusion with percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction.Eur Heart J Acute Cardiovasc Care. 2021; 10: 523-531Crossref Scopus (3) Google Scholar, 6Desta L Jernberg T Löfman I Hofman-Bang C Hagerman I Spaak J Persson H. Incidence, temporal trends, and prognostic impact of heart failure complicating acute myocardial infarction. The SWEDEHEART Registry (Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies): a study of 199,851 patients admitted with index acute myocardial infarctions, 1996 to 2008.JACC Heart Fail. 2015; 3: 234-242Crossref PubMed Scopus (119) Google Scholar Thus, ischemic postconditioning (iPOST) by repetitive brief interruptions of blood flow before establishment of final reperfusion, has demonstrated ambiguous results in minimizing reperfusion injury.7Zhao ZQ Corvera JS Halkos ME Kerendi F Wang NP Guyton RA Vinten-Johansen J. Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic preconditioning.Am J Physiol Heart Circ Physiol. 2003; 285: H579-H588Crossref PubMed Scopus (1946) Google Scholar, 8Lønborg J Kelbaek H Vejlstrup N Jørgensen E Helqvist S Saunamäki K Clemmensen P Holmvang L Treiman M Jensen JS Engstrøm T. 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Ischemic postconditioning inhibits apoptosis after acute myocardial infarction in pigs.Heart Surg Forum. 2010; 13: E305-E310Crossref PubMed Scopus (26) Google Scholar, 11Engstrøm T Kelbæk H Helqvist S Høfsten DE Kløvgaard L Clemmensen P Holmvang L Jørgensen E Pedersen F Saunamaki K Ravkilde J Tilsted HH Villadsen A Aarøe J Jensen SE Raungaard B Bøtker HE Terkelsen CJ Maeng M Kaltoft A Krusell LR Jensen LO Veien KT Kofoed KF Torp-Pedersen C Kyhl K Nepper-Christensen L Treiman M Vejlstrup N Ahtarovski K Lønborg J Køber L Third Danish Study of Optimal Acute of Patients ST of ischemic postconditioning during primary percutaneous coronary intervention for patients with ST-segment elevation myocardial infarction: a randomized clinical 2017; PubMed Scopus Google Scholar, X N M C X A M. postconditioning of effects on infarct size following primary percutaneous coronary Heart J. PubMed Scopus Google Scholar, Kim Yu WY JS Kim DS Ischemic postconditioning during primary percutaneous coronary the effects of postconditioning on myocardial reperfusion in patients with ST-segment elevation myocardial infarction randomized 2013; PubMed Scopus Google Scholar group the Third Study of Optimal Acute of Patients with ST-segment the effect of iPOST during primary percutaneous coronary intervention (PCI) conventional PCI on the primary outcome of mortality and hospitalization for heart failure in patients with DE Kelbæk H Helqvist S Kløvgaard L Holmvang L Clemmensen P Torp-Pedersen C Tilsted HH Bøtker HE Jensen LO Køber L Engstrøm T The Third Danish Study of Optimal Acute of Patients with ST-segment myocardial infarction: ischemic postconditioning or conventional primary and treatment of and of the Heart J. 2015; PubMed Scopus Google Scholar iPOST to the primary end T Kelbæk H Helqvist S Høfsten DE Kløvgaard L Clemmensen P Holmvang L Jørgensen E Pedersen F Saunamaki K Ravkilde J Tilsted HH Villadsen A Aarøe J Jensen SE Raungaard B Bøtker HE Terkelsen CJ Maeng M Kaltoft A Krusell LR Jensen LO Veien KT Kofoed KF Torp-Pedersen C Kyhl K Nepper-Christensen L Treiman M Vejlstrup N Ahtarovski K Lønborg J Køber L Third Danish Study of Optimal Acute of Patients ST of ischemic postconditioning during primary percutaneous coronary intervention for patients with ST-segment elevation myocardial infarction: a randomized clinical 2017; PubMed Scopus Google Scholar a iPOST reduced risk of mortality and hospitalization for heart failure in patients were treated with L Høfsten DE Helqvist S Lassen JF Tilsted HH Holmvang L Pedersen F F R L Bøtker HE Terkelsen CJ Maeng M Jensen LO Aarøe J Kelbæk H Køber L Engstrøm T Lønborg J. of postconditioning and thrombectomy in patients with myocardial PubMed Scopus Google Scholar an of the long-term prognostic impact of iPOST in patients with STEMI treated with and without thrombectomy. The was an randomized strategies in patients with iPOST T Kelbæk H Helqvist S Høfsten DE Kløvgaard L Clemmensen P Holmvang L Jørgensen E Pedersen F Saunamaki K Ravkilde J Tilsted HH Villadsen A Aarøe J Jensen SE Raungaard B Bøtker HE Terkelsen CJ Maeng M Kaltoft A Krusell LR Jensen LO Veien KT Kofoed KF Torp-Pedersen C Kyhl K Nepper-Christensen L Treiman M Vejlstrup N Ahtarovski K Lønborg J Køber L Third Danish Study of Optimal Acute of Patients ST of ischemic postconditioning during primary percutaneous coronary intervention for patients with ST-segment elevation myocardial infarction: a randomized clinical 2017; PubMed Scopus Google Scholar H Høfsten DE Køber L Helqvist S Kløvgaard L Holmvang L Jørgensen E Pedersen F Saunamäki K Kofoed KF Lønborg J Ahtarovski K Vejlstrup N Bøtker HE Terkelsen CJ Ravkilde J Tilsted HH Villadsen Aarøe J Jensen SE Raungaard B Jensen LO Clemmensen P P Torp-Pedersen C Engstrøm T. conventional in patients with ST-segment elevation myocardial infarction an PubMed Scopus Google Scholar and T Kelbæk H Helqvist S Høfsten DE Kløvgaard L Holmvang L Jørgensen E Pedersen F Saunamäki K Clemmensen P Ravkilde J Tilsted HH Villadsen Aarøe J Jensen SE Raungaard B Køber L treatment of the in patients with ST-segment elevation myocardial infarction and an 2015; PubMed Scopus Google Scholar of the study and have T Kelbæk H Helqvist S Høfsten DE Kløvgaard L Clemmensen P Holmvang L Jørgensen E Pedersen F Saunamaki K Ravkilde J Tilsted HH Villadsen A Aarøe J Jensen SE Raungaard B Bøtker HE Terkelsen CJ Maeng M Kaltoft A Krusell LR Jensen LO Veien KT Kofoed KF Torp-Pedersen C Kyhl K Nepper-Christensen L Treiman M Vejlstrup N Ahtarovski K Lønborg J Køber L Third Danish Study of Optimal Acute of Patients ST of ischemic postconditioning during primary percutaneous coronary intervention for patients with ST-segment elevation myocardial infarction: a randomized clinical 2017; PubMed Scopus Google DE Kelbæk H Helqvist S Kløvgaard L Holmvang L Clemmensen P Torp-Pedersen C Tilsted HH Bøtker HE Jensen LO Køber L Engstrøm T The Third Danish Study of Optimal Acute of Patients with ST-segment myocardial infarction: ischemic postconditioning or conventional primary and treatment of and of the Heart J. 2015; PubMed Scopus Google L Høfsten DE Helqvist S Lassen JF Tilsted HH Holmvang L Pedersen F F R L Bøtker HE Terkelsen CJ Maeng M Jensen LO Aarøe J Kelbæk H Køber L Engstrøm T Lønborg J. of postconditioning and thrombectomy in patients with myocardial PubMed Scopus Google Scholar long-term study of the DANAMI-3-iPOST included 1,234 patients with STEMI years. Patients were admitted to of the primary PCI in between 2011 to with of with in myocardial infarction flow in on the STEMI was acute with of and ST-segment elevation in or on on included patients were the DANAMI-3-iPOST database. on and and before STEMI The was through a to Danish The and to all Danish and between all M Pedersen L The Danish a in J PubMed Scopus Google Scholar was the M Pedersen L The Danish a in J PubMed Scopus Google Scholar on according to the of and and the of was the of Registry on of and the primary and of The Danish of of J PubMed Scopus Google Scholar on hospitalization for heart failure after STEMI was the Registry according to or or M V Pedersen L The Danish a of and 2015; PubMed Scopus Google Scholar patients were to conventional PCI or iPOST in with T Kelbæk H Helqvist S Høfsten DE Kløvgaard L Clemmensen P Holmvang L Jørgensen E Pedersen F Saunamaki K Ravkilde J Tilsted HH Villadsen A Aarøe J Jensen SE Raungaard B Bøtker HE Terkelsen CJ Maeng M Kaltoft A Krusell LR Jensen LO Veien KT Kofoed KF Torp-Pedersen C Kyhl K Nepper-Christensen L Treiman M Vejlstrup N Ahtarovski K Lønborg J Køber L Third Danish Study of Optimal Acute of Patients ST of ischemic postconditioning during primary percutaneous coronary intervention for patients with ST-segment elevation myocardial infarction: a randomized clinical 2017; PubMed Scopus Google Scholar was the of the The primary end point of study was a combination of cardiovascular mortality and hospitalization for heart failure. were the of the primary outcome and to a long included cardiovascular mortality a of the primary outcome mortality or for the of on long-term following F V Kelbæk H K Helqvist S J Holmvang L Clemmensen P Engstrøm T P Saunamäki K Jørgensen and long-term of in patients treated with primary PCI for PubMed Scopus Google Scholar mortality was a end point in the DANAMI-3-iPOST T Kelbæk H Helqvist S Høfsten DE Kløvgaard L Clemmensen P Holmvang L Jørgensen E Pedersen F Saunamaki K Ravkilde J Tilsted HH Villadsen A Aarøe J Jensen SE Raungaard B Bøtker HE Terkelsen CJ Maeng M Kaltoft A Krusell LR Jensen LO Veien KT Kofoed KF Torp-Pedersen C Kyhl K Nepper-Christensen L Treiman M Vejlstrup N Ahtarovski K Lønborg J Køber L Third Danish Study of Optimal Acute of Patients ST of ischemic postconditioning during primary percutaneous coronary intervention for patients with ST-segment elevation myocardial infarction: a randomized clinical 2017; PubMed Scopus Google Scholar In the of was by and by an T Kelbæk H Helqvist S Høfsten DE Kløvgaard L Clemmensen P Holmvang L Jørgensen E Pedersen F Saunamaki K Ravkilde J Tilsted HH Villadsen A Aarøe J Jensen SE Raungaard B Bøtker HE Terkelsen CJ Maeng M Kaltoft A Krusell LR Jensen LO Veien KT Kofoed KF Torp-Pedersen C Kyhl K Nepper-Christensen L Treiman M Vejlstrup N Ahtarovski K Lønborg J Køber L Third Danish Study of Optimal Acute of Patients ST of ischemic postconditioning during primary percutaneous coronary intervention for patients with ST-segment elevation myocardial infarction: a randomized clinical 2017; PubMed Scopus Google L Høfsten DE Helqvist S Lassen JF Tilsted HH Holmvang L Pedersen F F R L Bøtker HE Terkelsen CJ Maeng M Jensen LO Aarøe J Kelbæk H Køber L Engstrøm T Lønborg J. of postconditioning and thrombectomy in patients with myocardial PubMed Scopus Google Scholar the the was by and and for heart failure and cardiovascular mortality The follow-up the occurrence of the outcome of of or study end were for or median and and or and were the or Cumulative incidence was the risk of was to and adjusted hazard ratio and 95% confidence interval were by Cox hazard analysis, and a for between iPOST and thrombectomy in the DANAMI-3-iPOST on the primary and end was performed. 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In the DANAMI-3-iPOST there was a significant between thrombectomy and iPOST on cardiovascular mortality = but no between thrombectomy and iPOST on the primary end point = or hospitalization for heart failure = The primary end point occurred in patients treated with iPOST and in patients treated with conventional PCI. was no significant between iPOST and included end The of follow-up study of the DANAMI-3-iPOST patients with STEMI with myocardial infarction flow treated with primary PCI was iPOST reduced cardiovascular mortality and hospitalization for heart failure in patients treated without thrombectomy. was by reduced cardiovascular and iPOST remained associated with outcome after for no benefit of iPOST on clinical in patients treated with thrombectomy. Previous have effects of have a cardioprotective effect of iPOST in patients with J Kelbaek H Vejlstrup N Jørgensen E Helqvist S Saunamäki K Clemmensen P Holmvang L Treiman M Jensen JS Engstrøm T. Cardioprotective effects of ischemic postconditioning in patients treated with primary percutaneous coronary intervention, evaluated by magnetic resonance.Circ Cardiovasc Interv. 2010; 3: 34-41Crossref PubMed Scopus (226) Google T Kelbæk H Helqvist S Høfsten DE Kløvgaard L Clemmensen P Holmvang L Jørgensen E Pedersen F Saunamaki K Ravkilde J Tilsted HH Villadsen A Aarøe J Jensen SE Raungaard B Bøtker HE Terkelsen CJ Maeng M Kaltoft A Krusell LR Jensen LO Veien KT Kofoed KF Torp-Pedersen C Kyhl K Nepper-Christensen L Treiman M Vejlstrup N Ahtarovski K Lønborg J Køber L Third Danish Study of Optimal Acute of Patients ST of ischemic postconditioning during primary percutaneous coronary intervention for patients with ST-segment elevation myocardial infarction: a randomized clinical 2017; PubMed Scopus Google Scholar, X N M C X A M. postconditioning of effects on infarct size following primary percutaneous coronary Heart J. PubMed Scopus Google Scholar, Kim Yu WY JS Kim DS Ischemic postconditioning during primary percutaneous coronary the effects of postconditioning on myocardial reperfusion in patients with ST-segment elevation myocardial infarction randomized 2013; PubMed Scopus Google Scholar the ambiguous results by the between the effect of Targeting reperfusion injury in the of primary percutaneous coronary or 2015; PubMed Scopus Google Scholar In to beneficial cardioprotective effects of thrombectomy was in to of the included T Kelbæk H Helqvist S Høfsten DE Kløvgaard L Clemmensen P Holmvang L Jørgensen E Pedersen F Saunamaki K Ravkilde J Tilsted HH Villadsen A Aarøe J Jensen SE Raungaard B Bøtker HE Terkelsen CJ Maeng M Kaltoft A Krusell LR Jensen LO Veien KT Kofoed KF Torp-Pedersen C Kyhl K Nepper-Christensen L Treiman M Vejlstrup N Ahtarovski K Lønborg J Køber L Third Danish Study of Optimal Acute of Patients ST of ischemic postconditioning during primary percutaneous coronary intervention for patients with ST-segment elevation myocardial infarction: a randomized clinical 2017; PubMed Scopus Google Scholar, X N M C X A M. postconditioning of effects on infarct size following primary percutaneous coronary Heart J. PubMed Scopus Google Scholar, Kim Yu WY JS Kim DS Ischemic postconditioning during primary percutaneous coronary the effects of postconditioning on myocardial reperfusion in patients with ST-segment elevation myocardial infarction randomized 2013; PubMed Scopus Google Scholar The of iPOST effect in patients treated with thrombectomy remains the thrombectomy reperfusion and the for effect of iPOST thrombectomy may the effect of iPOST the may late to L Høfsten DE Helqvist S Lassen JF Tilsted HH Holmvang L Pedersen F F R L Bøtker HE Terkelsen CJ Maeng M Jensen LO Aarøe J Kelbæk H Køber L Engstrøm T Lønborg J. of postconditioning and thrombectomy in patients with myocardial PubMed Scopus Google Scholar an stratified by use of thrombectomy in DANAMI-3-iPOST an between iPOST and reduced risk of mortality and hospitalization for heart L Høfsten DE Helqvist S Lassen JF Tilsted HH Holmvang L Pedersen F F R L Bøtker HE Terkelsen CJ Maeng M Jensen LO Aarøe J Kelbæk H Køber L Engstrøm T Lønborg J. of postconditioning and thrombectomy in patients with myocardial PubMed Scopus Google Scholar However, mortality of or for the of on long-term following F V Kelbæk H K Helqvist S J Holmvang L Clemmensen P Engstrøm T P Saunamäki K Jørgensen and long-term of in patients treated with primary PCI for PubMed Scopus Google Scholar the impact of mortality to ischemic heart analyses cardiovascular mortality all patients with an of Thus, the cardioprotective effect of iPOST in patients with STEMI were treated with thrombectomy in with the findings of Nepper-Christensen L Høfsten DE Helqvist S Lassen JF Tilsted HH Holmvang L Pedersen F F R L Bøtker HE Terkelsen CJ Maeng M Jensen LO Aarøe J Kelbæk H Køber L Engstrøm T Lønborg J. of postconditioning and thrombectomy in patients with myocardial PubMed Scopus Google Scholar iPOST reperfusion injury an treatment in patients with STEMI, in thrombectomy J Kelbaek H Vejlstrup N Jørgensen E Helqvist S Saunamäki K Clemmensen P Holmvang L Treiman M Jensen JS Engstrøm T. Cardioprotective effects of ischemic postconditioning in patients treated with primary percutaneous coronary intervention, evaluated by magnetic resonance.Circ Cardiovasc Interv. 2010; 3: 34-41Crossref PubMed Scopus (226) Google L Høfsten DE Helqvist S Lassen JF Tilsted HH Holmvang L Pedersen F F R L Bøtker HE Terkelsen CJ Maeng M Jensen LO Aarøe J Kelbæk H Køber L Engstrøm T Lønborg J. of postconditioning and thrombectomy in patients with myocardial PubMed Scopus Google Targeting reperfusion injury in the of primary percutaneous coronary or 2015; PubMed Scopus Google Scholar thrombectomy may to and in primary T Kelbæk H Helqvist S Høfsten DE Kløvgaard L Clemmensen P Holmvang L Jørgensen E Pedersen F Saunamaki K Ravkilde J Tilsted HH Villadsen A Aarøe J Jensen SE Raungaard B Bøtker HE Terkelsen CJ Maeng M Kaltoft A Krusell LR Jensen LO Veien KT Kofoed KF Torp-Pedersen C Kyhl K Nepper-Christensen L Treiman M Vejlstrup N Ahtarovski K Lønborg J Køber L Third Danish Study of Optimal Acute of Patients ST of ischemic postconditioning during primary percutaneous coronary intervention for patients with ST-segment elevation myocardial infarction: a randomized clinical 2017; PubMed Scopus Google Targeting reperfusion injury in the of primary percutaneous coronary or 2015; PubMed Scopus Google S V JA F S H P B A S G B in myocardial infarction: an thrombectomy 2017; PubMed Scopus Google Scholar thrombectomy have effect on the in treatment with thrombectomy was randomized and in between treatment have the findings in patients treated with thrombectomy stratified by randomized treatment show impact on the study L Høfsten DE Helqvist S Lassen JF Tilsted HH Holmvang L Pedersen F F R L Bøtker HE Terkelsen CJ Maeng M Jensen LO Aarøe J Kelbæk H Køber L Engstrøm T Lønborg J. of postconditioning and thrombectomy in patients with myocardial PubMed Scopus Google Scholar and the current results in adjusted analyses after randomized clinical trials to the impact of iPOST in patients with the results of the Ischemic in STEMI Patients with PCI the effect of iPOST in patients with STEMI without use of thrombectomy. study has to observational and and Patients were to thrombectomy and were more in the conventional the between treatment it patients were treated with thrombectomy have may a effect of iPOST may have The of study were by a in the of the follow-up and according to for to with to clinical end However, the for heart failure has a of to in Danish J K T T Bøtker HE M. of cardiovascular in the Danish a PubMed Scopus Google Scholar of were by and on may have the study The Danish of of J PubMed Scopus Google Scholar findings ischemic postconditioning in patients with STEMI treated with primary PCI but without thrombectomy long-term cardiovascular mortality and hospitalization for heart and the effect to findings iPOST to and by the but to the of the study, randomized clinical trials to the cardioprotective effect of iPOST in patients with STEMI treated without thrombectomy. has and and a Torp-Pedersen has for and Køber has and to Engstrøm has and with

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