ADP-receptor antagonists in patients with acute myocardial infarction complicated by cardiogenic shock: a pooled IABP-SHOCK II and CULPRIT-SHOCK trial sub-analysis

Purpose The purpose of this pooled analysis is to compare the clinical outcome of patients with acute myocardial infarction complicated by cardiogenic shock treated with either clopidogrel or the newer, more potent ADP-receptor antagonists prasugrel or ticagrelor. Patients from the Intraaortic Balloon Pump in Cardiogenic Shock II (IABP-SHOCK II) and Culprit Lesion Only PCI versus Multivessel PCI in Cardiogenic Shock (CULPRIT-SHOCK) trial were included. Methods and results For the current analysis, the primary endpoint was 1-year mortality and the secondary safety endpoint was moderate or severe bleedings until hospital discharge with respect to three different ADP-receptor antagonists. Eight hundred fifty-six patients were eligible for analysis. Of these, five hundred seven patients (59.2%) received clopidogrel, one hundred seventy-eight patients (20.8%) prasugrel and one hundred seventy-one patients (20.0%) ticagrelor as acute antiplatelet therapy. The adjusted rate of mortality after 1-year did not differ between prasugrel and clopidogrel (hazard ratio [HR]: 0.81, 95% confidence interval [CI] 0.60–1.09, padj=0.17) or between ticagrelor and clopidogrel treated patients (HR: 0.86, 95% CI 0.65–1.15, padj=0.31). In-hospital bleeding events were significantly less frequent in patients treated with ticagrelor vs. clopidogrel (HR: 0.37, 95% CI 0.20–0.69, padj=0.002) and not different in patients treated with prasugrel vs. clopidogrel (HR: 0.73, 95% CI 0.43–1.24, padj=0.24), see Table 1. Conclusion This pooled sub-analysis is the largest analysis on safety and efficacy of three oral ADP-receptor antagonists and shows that an acute therapy with either clopidogrel, prasugrel or ticagrelor is no predictor of 1-year mortality. Treatment with ticagrelor seems to be associated with less in-hospital moderate and severe bleeding events in comparison to clopidogrel. FUNDunding Acknowledgement Type of funding sources: Foundation. Main funding source(s): German Heart FoundationEuropean Union 7th Framework Program

Clopidogrel vs. prasugrel vs. ticagrelor in patients with acute myocardial infarction complicated by cardiogenic shock: a pooled IABP-SHOCK II and CULPRIT-SHOCK trial sub-analysis

Aims The aim of this pooled sub-analysis of the Intraaortic Balloon Pump in Cardiogenic Shock II (IABP-SHOCK II) and Culprit Lesion Only PCI versus Multivessel PCI in Cardiogenic Shock (CULPRIT-SHOCK) trial was to compare the clinical outcome of patients with acute myocardial infarction complicated by cardiogenic shock treated either with clopidogrel or the newer, more potent ADP-receptor antagonists prasugrel or ticagrelor. Methods and results For the current analysis the primary endpoint was 1-year mortality and the secondary safety endpoint was moderate or severe bleedings until hospital discharge with respect to three different ADP-receptor antagonists. 856 patients were eligible for analysis. Of these, 507 patients (59.2%) received clopidogrel, 178 patients (20.8%) prasugrel and 171 patients (20.0%) ticagrelor as acute antiplatelet therapy. The adjusted rate of mortality after 1-year did not differ significantly between prasugrel and clopidogrel (hazard ratio [HR]: 0.81, 95% confidence interval [CI] 0.60–1.09, padj = 0.17) or between ticagrelor and clopidogrel treated patients (HR: 0.86, 95% CI 0.65–1.15, padj = 0.31). In-hospital bleeding events were significantly less frequent in patients treated with ticagrelor vs. clopidogrel (HR: 0.37, 95% CI 0.20 -0.69, padj = 0.002) and not significantly different in patients treated with prasugrel vs. clopidogrel (HR: 0.73, 95% CI 0.43 -1.24, padj = 0.24). Conclusion This pooled sub-analysis is the largest analysis on safety and efficacy of three oral ADP-receptor antagonists and shows that acute therapy with either clopidogrel, prasugrel or ticagrelor is no independent predictor of 1-year mortality. Treatment with ticagrelor seems independently associated with less in-hospital moderate and severe bleeding events compared to clopidogrel. This finding might be due to selection bias and should be interpreted with caution. Graphic abstract

Multivessel Intervention in Myocardial Infarction with Cardiogenic Shock: CULPRIT-SHOCK Trial Outcomes in the PL-ACS Registry

Background: The aim of the study was a comparison of culprit-lesion-only (CL-PCI) with the multivessel percutaneous coronary intervention (MV-PCI) in terms of 30-day and 12-month mortality in a national registry. Methods: Patients from the PL-ACS registry with MI and CS were analyzed. Patients meeting the criteria of the CULPRIT-SHOCK trial were divided into two groups: CL-PCI and MV-PCI groups. Results: Of the 3265 patients in the PL-ACS registry with MI complicated by CS, the criteria of the CULPRIT-SHOCK trial were met by 2084 patients (63.8%). The CL-PCI was performed in 883 patients, and MV-PCI was performed in 1045 patients. After the propensity score matching analysis, 617 well-matched pairs were obtained. In a 30-day follow-up, death from any cause occurred in 49.3% in the CL-PCI group and 57.0% in the MV-PCI group (RR 0.86, 95% CI 0.58–0.92, p = 0.0081). After 12 months, the rate of mortality was 62.5% in the CL-PCI group and 68.0% in the MV-PCI group (RR 0.92, 95% CI 0.84–1.01, p = 0.066). Conclusions: The results confirm the validity of CULPRIT-SHOCK findings in a national registry and current guideline-recommended strategy of revascularization limited to the infarct-related artery.

Long-term 5-year outcome of the randomized IMPRESS in severe shock trial: percutaneous mechanical circulatory support versus intra-aortic balloon pump in severe cardiogenic shock

Funding Acknowledgements Type of funding sources: None. Background The role of percutaneous mechanical circulatory support (pMCS) in cardiogenic shock (CS) is still a subject of debate. The IMPRESS in Severe Shock trial is still the largest RCT on the effectiveness of pMCS in CS patients. We performed a follow-up at 5-years of the IMPRESS in Severe Shock trial to assess differences in long-term clinical outcome and functional status between pMCS and intra-aortic balloon pump (IABP) treated patients. Methods The IMPRESS in Severe Shock trial (NTR3450) is an investigator-initiated, multicentre, randomized, open-label trial. Between June 2012 and September 2015, a total of 48 patients with severe CS from AMI with ST-segment elevation undergoing immediate revascularisation were randomized to pMCS with the Impella CP (n = 24) or IABP (n = 24). The trial design and primary end-point results (30-day all-cause mortality) have been previously published. For the 5-year assessment, all-cause mortality and the occurrence of major adverse cardiovascular and cerebrovascular events (MACCE) were evaluated. MACCE consisted of death, myocardial re-infarction, repeat PCI, CABG and stroke. In survivors, a structured interview was conducted and follow-up echocardiography was obtained. Data were analysed according to the intention-to-treat principle. Results Long-term follow-up was performed 5.5 years (IQR 5.3-6.5) after initial randomization and completed for all patients regarding mortality status. Five-year mortality was 50% (n = 12/24) in the pMCS group and 63% (n = 15/24) in the IABP group (RR 0.87, 95% CI 0.47-1.59, p = 0.65). After 6 months, only 3 additional deaths occurred, all in the IABP group. MACCE occurred in 12/24 (50%) of the pMCS patients versus 19/24 (79%) of the IABP patients (p = 0.07) (Figure 1). Myocardial re-infarction occurred in 1 pMCS patient and in 2 IABP patients, repeat PCI in 3 IABP patients, CABG in 1 IABP patient and stroke in 2 pMCS patients and in 2 IABP patients. Among 5-year survivors, follow-up interview was successfully conducted in 11/12 (92%) pMCS and 7/9 (78%) IABP patients. All patients except for one were in NYHA class I or II (pMCS n = 10 [91%] and IABP n = 7 [100%], p = 1.00) and none of the patients had residual angina complaints. Echocardiography was obtained in 10/12 (83%) pMCS and 6/9 (67%) IABP patients. There were no differences in LVEF between the two groups (pMCS 52 ±11% vs. IABP 48 ±10%, p = 0.53). Conclusions In this randomized trial of patients with CS after AMI, there was no difference in long-term 5-year mortality between pMCS (by Impella CP) and IABP treated patients, supporting previously published 30-day and 6-month data. Interestingly, we did observe a not significantly different (p = 0.07) higher occurrence of MACCE in the IABP group. Abstract Figure. Kaplan Meier Impella vs. IABP: MACCE

Impella versus intra-aortic balloon pump in cardiogenic shock: a meta-analysis assessing 30-days mortality

Introduction Cardiogenic shock is linked with eminent morbidity and mortality despite advances in treatment modality. Adjuvant treatment modalities to provide mechanical haemodynamic support in the form of intra-aortic balloon pump (IABP) or Impella are being used among patients with cardiogenic shock. The Impella prunes left ventricular preload, whereas, IABP persuades after load reduction and both contribute to improved cardiac output. A few underpowered randomised control trials (RCTs) and observational studies compared short term mortality benefit of Impella juxtaposed to IABP among patients with cardiogenic shock. Purpose A meta-analysis of RCTs and observational studies researching the short-term mortality in cardiogenic shock comparing Impella to IABP was executed. Methods The databases PubMed, EMBASE and Cochrane were searched systematically to identify relevant RCTs and observational studies contrasting Impella to IABP and reporting 30-days mortality as outcomes. The search terms used were “Impella”, “IAPB”, “intra-aortic balloon pump” and all word variations were utilised. The search was conducted from the debut of the databases up to January 2020. Two reviewers independently and in tandem performed data screening and extraction from identified articles. Inverse variance method with Paule-Mandel estimator for tau2 and Hartung-Knapp adjustment was used to calculate Risk Ratio with 95% confidence interval. Heterogeneity was assessed using I2 statistics. Furthermore, we calculated the 95% predictive interval for the pooled estimate. All statistical analysis for this meta-analysis was carried out using R statistical software version 3.6.2 using the package meta ( ). Additionally, Grading of Recommendations, Assessment, Development and Evaluations (GRADE) criteria were used to assess the certainty of evidence. Results Five studies constituting 728 patients were included in the final analysis. Two were RCTs (ISAR-SHOCK trial and IMPRESS in Severe Shock trial), one study was a propensity score matched observational study and two were unmatched observational studies. There was no difference in the risk of 30-days mortality in patients treated with Impella as compared to IABP [Risk Ratio: 0.97, 95% confidence interval: 0.66–1.41, I2: 32%]. To account for the heterogeneity, we calculated 95% predictive interval: 0.46–2.02. Thus, very low certainty of evidence concluded no difference in the risk of 30-days mortality among cardiogenic shock patients treated with Impella in opposition to IABP. Conclusion This meta-analysis comparing Impella juxtaposed with IABP demonstrated no difference in the risk of 30-days mortality among patients with cardiogenic shock. 30-days Mortality Funding Acknowledgement Type of funding source: None

Outcomes associated with respiratory failure for patients with cardiogenic shock and acute myocardial infarction: a substudy of the culprit-shock trial

Background Respiratory insufficiency with the need for mechanical ventilation (MV) is one of the most common indications for admission to intensive care units. However, little is known about the clinical outcomes of patients with acute myocardial infraction (AMI) complicated by cardiogenic shock (CS) who require mechanical ventilation (MV). The aim of this study was to identify the characteristics, risk factors, and outcomes associated with the provision of MV in this specific high-risk population. Methods Patients with CS complicating AMI and multivessel coronary artery disease from the CULPRIT-SHOCK trial were included. We explored clinical outcome within 30 days in patients not requiring MV, those with MV on admission, and those in whom MV was initiated within the first day after admission. Results Among 683 randomized patients included in the analysis, 17.4% received no MV, 59.7% were ventilated at admission and 22.8% received MV within or after the first day after admission. Patients requiring MV were younger, more frequently non-smokers, had higher body mass indices, presented more often with clinical signs of impaired organ perfusion including worse renal function, higher burden of coronary artery disease, were more likely to have experienced resuscitation within 24h before admission, had worse left ventricular function, and presented more often with non-ST-segment elevation myocardial infarction. The primary endpoint of all-cause death or need for renal replacement therapy occurred in 21.8% of patients without MV, in 53.3% of patients with MV at admission (adjusted odds ratio [aOR] 6.03, 95% confidence interval (CI) 3.17–11.47, p=0.002, compared to patients without) and 65.4% of patients with MV initiated within the first day after admission (aOR 8.09 95% CI 4.32–15.16, p<0.001, compared to patients without). Factors independently associated with the provision of MV on admission included higher body weight, resuscitation within 24h before admission, elevated heart rate and evidence of triple vessel disease. Conclusions Requiring MV in patients with CS complicating AMI is common and independently associated with mortality after adjusting for covariates. Patients with delayed MV initiation appear to be at higher risk of adverse outcomes. Further research is necessary to identify the optimal timing of MV in this high-risk population. Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): Swiss National Foundation