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

PCI Strategies in Patients with Acute Myocardial Infarction and Cardiogenic Shock

BACKGROUND: In patients who have acute myocardial infarction with cardiogenic shock, early revascularization of the culprit artery by means of percutaneous coronary intervention (PCI) improves outcomes. However, the majority of patients with cardiogenic shock have multivessel disease, and whether PCI should be performed immediately for stenoses in nonculprit arteries is controversial. METHODS: In this multicenter trial, we randomly assigned 706 patients who had multivessel disease, acute myocardial infarction, and cardiogenic shock to one of two initial revascularization strategies: either PCI of the culprit lesion only, with the option of staged revascularization of nonculprit lesions, or immediate multivessel PCI. The primary end point was a composite of death or severe renal failure leading to renal-replacement therapy within 30 days after randomization. Safety end points included bleeding and stroke. RESULTS: At 30 days, the composite primary end point of death or renal-replacement therapy had occurred in 158 of the 344 patients (45.9%) in the culprit-lesion-only PCI group and in 189 of the 341 patients (55.4%) in the multivessel PCI group (relative risk, 0.83; 95% confidence interval [CI], 0.71 to 0.96; P=0.01). The relative risk of death in the culprit-lesion-only PCI group as compared with the multivessel PCI group was 0.84 (95% CI, 0.72 to 0.98; P=0.03), and the relative risk of renal-replacement therapy was 0.71 (95% CI, 0.49 to 1.03; P=0.07). The time to hemodynamic stabilization, the risk of catecholamine therapy and the duration of such therapy, the levels of troponin T and creatine kinase, and the rates of bleeding and stroke did not differ significantly between the two groups. CONCLUSIONS: Among patients who had multivessel coronary artery disease and acute myocardial infarction with cardiogenic shock, the 30-day risk of a composite of death or severe renal failure leading to renal-replacement therapy was lower among those who initially underwent PCI of the culprit lesion only than among those who underwent immediate multivessel PCI. (Funded by the European Union 7th Framework Program and others; CULPRIT-SHOCK ClinicalTrials.gov number, NCT01927549 .)

Clinical Outcomes According to ECG Presentations in Infarct-Related Cardiogenic Shock in the Culprit Lesion Only PCI vs Multivessel PCI in Cardiogenic Shock Trial

Background: The impact of ECG presentations of acute myocardial infarction (AMI) in cardiogenic shock is unknown. Research Question: In myocardial infarction with cardiogenic shock, is there a difference in the outcomes and effect of revascularization strategies between non-ST-segment elevation myocardial infarction (NSTEMI) and left bundle branch block myocardial infarction (LBBBMI) vs ST-segment elevation myocardial infarction (STEMI)? Study Design and Methods: Cardiogenic shock patients from the CULPRIT-SHOCK trial with NSTEMI or LBBBMI were compared with STEMI patients for 30-day and 1-year all-cause mortality. The interaction between ECG presentation and the effect of revascularization strategies on outcomes was evaluated. Results: Of 665 cardiogenic shock patients analyzed, 55.9% demonstrated STEMI, 29.3% demonstrated NSTEMI, and 14.7% demonstrated LBBBMI. Patients differed in mean age (68.0 years in STEMI patients, 71.0 years in NSTEMI patients, and 73.5 years in LBBBMI patients; P =.015), cardiovascular risk factors, and angiographic severity. No difference was found in the 30-day risk of death between NSTEMI and STEMI patients (48.7% vs 43.0%; adjusted OR [aOR], 1.05; 95% CI, 0.66-1.67; P =.85), nor between LBBBMI and STEMI patients (59.2% vs 43.0%; aOR, 1.31; 95% CI, 0.73-2.34; P =.36). Although the univariate risk of death by 1 year was higher in NSTEMI and LBBBMI patients compared with STEMI patients, ECG presentation was not an independent risk factor of mortality after adjustment (NSTEMI vs STEMI: 56.4% vs 46.8%; aOR, 1.21; 95% CI, 0.76-1.92; P =.42; LBBBMI vs STEMI: 69.4% vs 46.8%; aOR, 1.59; 95% CI, 0.89-2.84; P =.12). ECG presentation did not modify the effect of the revascularization strategy on 30-day and 1-year mortality (P =.91 and P =.97 for interaction). Interpretation: In patients with cardiogenic shock, NSTEMI and LBBBMI presentations reflect higher-risk profiles than STEMI presentations, but are not independent risk factors of mortality. ECG presentations did not modify the treatment effect, supporting culprit-lesion-only percutaneous coronary intervention as the preferred strategy across the AMI spectrum

PCI strategies in patients with acute myocardial infarction and cardiogenic shock

In patients who have acute myocardial infarction with cardiogenic shock, early revascularization of the culprit artery by means of percutaneous coronary intervention (PCI) improves outcomes. However, the majority of patients with cardiogenic shock have multivessel disease, and whether PCI should be performed immediately for stenoses in nonculprit arteries is controversial. In this multicenter trial, we randomly assigned 706 patients who had multivessel disease, acute myocardial infarction, and cardiogenic shock to one of two initial revascularization strategies: either PCI of the culprit lesion only, with the option of staged revascularization of nonculprit lesions, or immediate multivessel PCI. The primary end point was a composite of death or severe renal failure leading to renal-replacement therapy within 30 days after randomization. Safety end points included bleeding and stroke. At 30 days, the composite primary end point of death or renal-replacement therapy had occurred in 158 of the 344 patients (45.9%) in the culprit-lesion-only PCI group and in 189 of the 341 patients (55.4%) in the multivessel PCI group (relative risk, 0.83; 95% confidence interval [CI], 0.71 to 0.96; P=0.01). The relative risk of death in the culprit-lesion-only PCI group as compared with the multivessel PCI group was 0.84 (95% CI, 0.72 to 0.98; P=0.03), and the relative risk of renal-replacement therapy was 0.71 (95% CI, 0.49 to 1.03; P=0.07). The time to hemodynamic stabilization, the risk of catecholamine therapy and the duration of such therapy, the levels of troponin T and creatine kinase, and the rates of bleeding and stroke did not differ significantly between the two groups. Among patients who had multivessel coronary artery disease and acute myocardial infarction with cardiogenic shock, the 30-day risk of a composite of death or severe renal failure leading to renal-replacement therapy was lower among those who initially underwent PCI of the culprit lesion only than among those who underwent immediate multivessel PCI. (Funded by the European Union 7th Framework Program and others; CULPRIT-SHOCK ClinicalTrials.gov number, NCT01927549 .