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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.

ABSTRACT:

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, p_adj = 0.17) or between ticagrelor and clopidogrel treated patients (HR: 0.86, 95% CI 0.65-1.15, p_adj = 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, p_adj = 0.002) and not significantly different in patients treated with prasugrel vs. clopidogrel (HR: 0.73, 95% CI 0.43 -1.24, p_adj = 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.

SUBMITTER: Orban M

PROVIDER: S-EPMC8405498 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundData are lacking on the effects of the alternation of P2Y12 receptor antagonists (P2Y12) on bleeding and outcome in patients with myocardial infarction (MI) with cardiogenic shock (CS). We compared the effects of different P2Y12 and alternation of P2Y12 (combination) on bleeding and outcome in patients with MI and CS.MethodsData from 247 patients divided into four groups: clopidogrel, ticagrelor, prasugrel, and the combination group, were analyzed. The association between P2Y12 and bleeding as well as 30-day and one-year mortality was examined.ResultsThe highest bleeding rate was observed in patients in the combination group, followed by the clopidogrel, ticagrelor, and prasugrel groups [12(50%) patients, 22(28.2%), 21(18.3%) and 4(13.3%), respectively; p = 0.003]. Bleeding occurred with a similar frequency in the combination and clopidogrel groups (p = 0.081), but more frequently than in the ticagrelor and prasugrel groups (p = 0.002 and p = 0.006, respectively). Bleeding rates were similar in patients receiving P2Y12 alone (p = 0.13). Compared to clopidogrel, both ticagrelor and prasugrel had a lower bleeding risk (aOR: 0.40; 95% CI: 0.18-0.92; p = 0.032 and aOR: 0.20; 95% CI: 0.05-0.85; p = 0.029, respectively) and the combination had a similar bleeding risk (aOR: 2.31; 95% CI: 0.71-7.48; p = 0.16). The ticagrelor and prasugrel groups had more than an 80% and 90% lower bleeding risk than the combination group (aOR: 0.17; 95% CI: 0.06-0.55; p = 0.003 and aOR: 0.09; 95% CI: 0.02-0.44; p = 0.003, respectively). The unadjusted 30-day and one-year mortality were highest in the clopidogrel group, followed by the ticagrelor, prasugrel, and combination groups (44(56.4%) and 55(70.5%) patients died in the clopidogrel group, 53(46.1%) and 56(48.7%) in the ticagrelor group, 12(40%) and 14(46.7%) patients died in the prasugrel, and 6(25%) and 9(37.5%) patients died in the combination group; p = 0.045 and p < 0.0001. After adjustment for confounders, the P2Y12 groups were not independently associated with either 30-day (p = 0.23) or one-year (p = 0.17) mortality risk.ConclusionOur results suggest that the choice of P2Y12 was not associated with treatment outcome. The combination of P2Y12 increased bleeding risk compared with ticagrelor and prasugrel and was comparable to clopidogrel in patients with MI and CS. However, these higher bleeding rates did not result in worse treatment outcomes.

Project description:Cardiogenic shock (CS) is the leading cause of death in patients hospitalized with acute myocardial infarction (AMI). Biomarkers might help in risk stratification and understanding of pathophysiology. Preliminary data suggests that patients with CS face a profound increase in the osteocyte-derived hormone fibroblast growth factor 23 (FGF-23), which acts as a negative regulator of serum phosphate levels. The present study aimed to assess the predictive role of FGF-23 for clinical outcome in a large cohort of CS patients with and without renal dysfunction.In the randomized Intraaortic Balloon Pump in Cardiogenic Shock II (IABP-SHOCK II) trial, 600 patients with CS complicating AMI were assigned to therapy with or without IABP. Our predefined biomarker substudy included 182 patients. Blood sampling was performed in a standardized procedure at three different time points (day 1 (day of admission), day 2 and day 3). Differences in outcome of patients with FGF-23 levels<and>median were compared by log-rank testing. Stepwise logistic regression modeling was performed to identify predictors of death at 30 days and Cox regression analysis for time to death during the first year.At all three time points, nonsurvivors had significantly higher FGF-23 levels compared to survivors (P<0.001 for all). Patients with FGF-23 levels above the median (395 RU/mL [interquartile range 102;2,395]) were characterized by an increased 30-day mortality and 1-year mortality. In multivariable analysis FGF-23 levels remained independent predictors for 30-day (odds ratio per 10log 1.80, 95% confidence interval (CI) 1.11 to 2.92; P=0.02) and 1-year mortality (hazard ratio 1.50, 95% CI 1.11 to 2.04, P=0.009). After stratifying the patients according to their baseline serum creatinine levels, the negative prognostic association of increased FGF-23 was only significant in those with serum creatinine greater than median.In CS, high levels of FGF-23 are independently related to a poor clinical outcome. However, this prognostic association appears only to apply in patients with impaired renal function.ClinicalTrials.gov NCT00491036. Registered 22 June 2007.

Project description:IntroductionEmergency percutaneous coronary intervention (PCI) of the culprit lesion for patients with acute myocardial infarctions is an accepted practice. A majority of patients present with multivessel disease with additional relevant stenoses apart from the culprit lesion. In haemodynamically stable patients, there is increasing evidence from randomised trials to support the practice of immediate complete revascularisation. However, in the presence of cardiogenic shock, the optimal management strategy for additional non-culprit lesions is unknown. A multicentre randomised controlled trial, CULPRIT-SHOCK, is examining whether culprit vessel only PCI with potentially subsequent staged revascularisation is more effective than immediate multivessel PCI. This paper describes the intended economic evaluation of the trial.Methods and analysisThe economic evaluation will be conducted using a pre-trial decision model and within-trial analysis. The modelling-based analysis will provide expected costs and health outcomes, and incremental cost-effectiveness ratio over the lifetime for the cohort of patients included in the trial. The within-trial analysis will provide estimates of cost per life saved at 30 days and in 1 year, and estimates of health-related quality of life. Bootstrapping and cost-effectiveness acceptability curves will be used to address any uncertainty around these estimates. Different types of regression models within a generalised estimating equation framework will be used to examine how the total cost and quality-adjusted life years are explained by patients' characteristics, revascularisation strategy, country and centre. The cost-effectiveness analysis will be from the perspective of each country's national health services, where costs will be expressed in euros adjusted for purchasing power parity.Ethics and disseminationEthical approval for the study was granted by the local Ethics Committee at each recruiting centre. The economic evaluation analyses will be published in peer-reviewed journals of the concerned literature and communicated through the profiles of the authors at www.twitter.com and www.researchgate.net.Trial registration numberNCT01927549; Pre-results.

Project description:BackgroundPotent P2Y12 inhibitors such as ticagrelor and prasugrel are superior to clopidogrel in acute coronary syndrome (ACS) patients treated with percutaneous coronary intervention (PCI). Whether this benefit extends to a patient population with chronic coronary syndromes (CCS) is unclear.AimsWe sought to compare the safety and efficacy of prasugrel and ticagrelor versus clopidogrel in patients undergoing PCI for CCS.MethodsConsecutive patients undergoing PCI for CCS at a tertiary centre between 2014 and 2019 who were discharged on prasugrel or ticagrelor were compared with those on clopidogrel. The primary endpoint was the composite of death and myocardial infarction (MI), with secondary outcomes including rates of bleeding, stroke, and target vessel revascularisation at 1 year.ResultsOverall, 11,508 patients were included in the study (ticagrelor/prasugrel n=2,860 [24.9%], clopidogrel n=8,648 [75.1%]) with an increasing frequency of potent P2Y12 inhibitor use over the study period (ptrend<0.001). Clopidogrel was used more frequently in patients with multimorbid risk factors, whereas anatomical or procedural complexity was associated with ticagrelor/prasugrel use (left main PCI, bifurcation PCI, number of lesions, rotational atherectomy). No difference in the incidence of death or MI was noted across the groups (ticagrelor/prasugrel vs clopidogrel: 2.7% vs 3.1%, adjusted hazard ratio [adjHR] 0.86, 95% confidence interval [CI]: 0.62-1.17; p=0.33) or secondary outcomes including bleeding (adjHR 0.75, 95% CI: 0.46-1.21; p=0.23) on propensity score stratification analysis. Additionally, no difference in the primary outcome was observed across subgroups, including those undergoing complex PCI.ConclusionsTicagrelor and prasugrel are increasingly used in patients with CCS undergoing PCI with similar 1-year efficacy and safety when compared to clopidogrel. Whether use of these agents can be beneficial in patients undergoing PCI for CCS with a high thrombotic and low bleeding risk warrants further study.

Project description:ImportanceMyocardial infarction with a culprit lesion located in the left main or proximal left anterior descending artery compared with other coronary segments is associated with more myocardium at risk and worse clinical outcomes.ObjectiveTo evaluate the association of culprit lesion location with outcomes of culprit-lesion-only percutaneous coronary intervention with optional staged revascularization vs immediate multivessel percutaneous coronary intervention in patients with multivessel disease, myocardial infarction, and cardiogenic shock.Design, setting, and participantsPost hoc analysis of the Culprit Lesion Only Coronary Intervention vs Multivessel Coronary Intervention in Cardiogenic Shock (CULPRIT-SHOCK), an investigator-initiated randomized, open-label clinical trial. Patients with multivessel disease, acute myocardial infarction, and cardiogenic shock were enrolled at 83 European centers from April 2013 through April 2017.InterventionsPatients were randomized to culprit-lesion-only percutaneous coronary intervention with optional staged revascularization or immediate multivessel percutaneous coronary intervention (1:1). For this analysis, patients were stratified by culprit lesion location in the left main or proximal left anterior descending artery group and other-culprit-lesion location group.Main outcomes and measuresEnd points included a composite of death or kidney replacement therapy at 30 days and death at 1 year.ResultsThe median age of the study population was 70 (interquartile range, 60-78 years) and 524 of the study participants were men (76.4%). Of the 685 patients, 33.4% constituted the left main or proximal left anterior descending artery group and 66.6% the other-culprit-lesion location group. The left main or proximal left anterior descending artery group had worse outcomes compared with the other-culprit-lesion location group (56.8% vs 47.5%; P = .02 for the composite end point at 30 days and 59.8% vs 50.1%; P = .02 for death at 1 year). In both groups, culprit-lesion-only vs immediate multivessel percutaneous coronary intervention was associated with a reduced risk of the composite end point at 30 days (49.1% vs 64.3% and 44.1% vs 50.9%; P for interaction = .27). At 1 year, culprit-lesion-only vs immediate multivessel percutaneous coronary intervention was associated with a significantly reduced risk of death in the left main or proximal left anterior descending artery but not the other-culprit-lesion location group (50.0% vs 69.6%; P = .003 and 49.8% vs 50.4%; P = .89; P for interaction = 0.02).Conclusions and relevanceIn patients with multivessel disease with myocardial infarction and cardiogenic shock, a culprit lesion located in the left main or proximal left anterior descending artery vs other coronary segments was associated with worse outcomes. These patients may especially benefit from culprit-lesion-only percutaneous coronary intervention with optional staged revascularization, although further investigation is needed to confirm this finding.Trial registrationClinicalTrials.gov Identifier: NCT01927549.