Dataset Information

Ticagrelor or prasugrel in patients with acute coronary syndrome with off-hour versus on-hour presentation: a subgroup analysis of the ISAR-REACT 5 trial.

ABSTRACT:

Objectives

To assess the efficacy and safety of ticagrelor versus prasugrel in patients with acute coronary syndrome (ACS) presenting during off- and on-hours.

Background

The efficacy and safety of ticagrelor versus prasugrel in patients with ACS according to time of hospital presentation remain unknown.

Methods

This post hoc analysis of the ISAR-REACT 5 trial included 1565 patients with ACS presenting off-hours and 2453 patients presenting on-hours, randomized to ticagrelor or prasugrel. The primary endpoint was a composite of death, myocardial infarction, or stroke; the safety endpoint was Bleeding Academic Research Consortium (BARC) type 3-5 bleeding, both at 12 months.

Results

The primary endpoint occurred in 80 patients (10.4%) in the ticagrelor group and 57 patients (7.3%) in the prasugrel group in patients presenting off-hours (hazard ratio [HR] = 1.45; 95% confidence interval [CI] 1.03-2.03; P = 0.033), and 104 patients (8.5%) in the ticagrelor group and 80 patients (6.7%) in the prasugrel group in patients presenting on-hours (HR = 1.29 [0.97-1.73]; P = 0.085), without significant treatment arm-by-presentation time interaction (P_int = 0.62). BARC type 3 to 5 bleeding occurred in 35 patients (5.1%) in the ticagrelor group and 37 patients (5.3%) in the prasugrel group (P = 0.84) in patients presenting off-hours, and 60 patients (5.9%) in the ticagrelor group and 43 patients (4.6%) in the prasugrel group in patients presenting on-hours (P = 0.17).

Conclusions

In patients with ACS planned to undergo an invasive treatment strategy, time of presentation (off-hours vs. on-hours) does not interact significantly with the relative efficacy and safety of ticagrelor vs. prasugrel.

Clinical trial registration

NCT01944800.

SUBMITTER: Behnes M

PROVIDER: S-EPMC10050020 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Ticagrelor or prasugrel in patients with acute coronary syndrome with off-hour versus on-hour presentation: a subgroup analysis of the ISAR-REACT 5 trial.

Behnes Michael M Lahu Shqipdona S Ndrepepa Gjin G Menichelli Maurizio M Mayer Katharina K Wöhrle Jochen J Bernlochner Isabell I Gewalt Senta S Witzenbichler Bernhard B Hochholzer Willibald W Sibbing Dirk D Cassese Salvatore S Angiolillo Dominick J DJ Hemetsberger Rayyan R Valina Christian C Müller Arne A Kufner Sebastian S Hamm Christian W CW Xhepa Erion E Hapfelmeier Alexander A Sager Hendrik B HB Joner Michael M Fusaro Massimiliano M Richardt Gert G Laugwitz Karl-Ludwig KL Neumann Franz-Josef FJ Schunkert Heribert H Schüpke Stefanie S Kastrati Adnan A Akin Ibrahim I

Clinical research in cardiology : official journal of the German Cardiac Society 20220705 4

<h4>Objectives</h4>To assess the efficacy and safety of ticagrelor versus prasugrel in patients with acute coronary syndrome (ACS) presenting during off- and on-hours.<h4>Background</h4>The efficacy and safety of ticagrelor versus prasugrel in patients with ACS according to time of hospital presentation remain unknown.<h4>Methods</h4>This post hoc analysis of the ISAR-REACT 5 trial included 1565 patients with ACS presenting off-hours and 2453 patients presenting on-hours, randomized to ticagrelo ...[more]

PMID: 35789430

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Project description:Background The efficacy and safety of ticagrelor versus prasugrel in patients with acute coronary syndrome and prior myocardial infarction (MI) remain unstudied. We aimed to assess the treatment effect of ticagrelor versus prasugrel according to prior MI status in patients with ACS. Methods and Results Patients with acute coronary syndrome planned for an invasive strategy and randomized to ticagrelor or prasugrel in the ISAR-REACT (Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment) 5 trial were included. The primary end point was the composite of 1-year all-cause death, MI, or stroke; the secondary safety end point was the composite of 1-year Bleeding Academic Research Consortium type 3 to 5 bleeding. The study included 4015 patients (prior MI=631 patients; no prior MI=3384 patients). As compared with patients without prior MI, the primary end point occurred more frequently in patients with prior MI (12.6% versus 7.2%; hazard ratio [HR], 1.78 [95% CI, 1.38-2.29]); the secondary safety end point appears to differ little between patients with and without prior MI (5.8% versus 5.7%, respectively; HR, 1.02 [95% CI, 0.71-1.45]). With regard to the primary end point, ticagrelor versus prasugrel was associated with an HR of 1.62 (95% CI, 1.03-2.55) in patients with prior MI and an HR of 1.28 (95% CI, 0.99-1.65) in patients without prior MI (Pint=0.37). With regard to the secondary safety end point, ticagrelor versus prasugrel was associated with an HR of 1.28 (95% CI, 0.56-2.91) in patients with prior MI and an HR of 1.13 (95% CI, 0.82-1.55) in patients without prior MI (Pint=0.79). Conclusions Patients with acute coronary syndrome and prior MI are at higher risk for recurrent ischemic but not bleeding events. Prasugrel is superior to ticagrelor in reducing the risk of ischemic events without a tradeoff in bleeding regardless of prior MI status. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01944800.

Project description:ImportanceIn patients with acute coronary syndrome (ACS) undergoing invasive treatment, ticagrelor and prasugrel are guideline-recommended P2Y12 receptor inhibitors. The ISAR-REACT5 randomized clinical trial demonstrated superiority for prasugrel, although concerns were raised about the generalizability of some underpowered subgroup analyses.ObjectivesTo emulate a randomized clinical trial evaluating the safety and effectiveness of ticagrelor vs prasugrel under the conditions of routine care in individuals with ACS planned to undergo an invasive treatment strategy.Design, setting, and participantsThis new-user cohort study included secondary data from a German statutory health insurance claims database between January 2012 and December 2021, using 1:1 propensity score nearest-neighbor matching to emulate ISAR-REACT5. Individuals with ACS receiving either ticagrelor or prasugrel treatment after hospital discharge were followed up for 1 year. Eligibility criteria closely emulated those of ISAR-REACT5 and included age of 18 years or older and cardiovascular risk factors. Data were analyzed from May 2023 to May 2024.ExposureOutpatient prescription of ticagrelor or prasugrel.Main outcomes and measuresThe primary end point was the composite of all-cause mortality, myocardial infarction (MI), or stroke within 1 year of outpatient treatment initiation. Secondary end points included individual components of the primary end point and stent thrombosis. The safety end point was major bleeding. A Cox proportional hazards regression model was fitted to the overall cohort.ResultsOf 17 642 propensity score-matched individuals (mean [SD] age, 63.1 [10.9] years; 73.9% male), 8821 received ticagrelor and 8821 received prasugrel. Agreement was met in 11 of 12 predefined agreement metrics when comparing the results with ISAR-REACT5. The primary composite end point of all-cause mortality, MI, or stroke occurred in 815 individuals (9.2%) receiving ticagrelor and 663 (7.5%) receiving prasugrel (hazard ratio [HR], 1.24; 95% CI, 1.12-1.37). Myocardial infarction (HR, 1.20; 95% CI, 1.06-1.36) and stroke (HR, 1.33; 95% CI, 1.02-1.74) each occurred significantly more often in the ticagrelor group. Analysis of all-cause mortality (HR, 1.27; 95% CI, 0.99-1.64), stent thrombosis (HR, 1.11; 95% CI, 0.89-1.30), and major bleeding (HR, 1.12; 95% CI, 0.96-1.32) revealed no significant differences between treatment groups. Subgroup analysis showed that prasugrel was associated with the primary composite end point in fewer individuals with ST-segment elevation MI (338 of 4941 [6.8%] vs 451 of 4852 [9.3%]).Conclusions and relevanceThis cohort study found that prasugrel was associated with lower rates of all-cause mortality, MI, or stroke compared with ticagrelor in individuals with ACS undergoing an invasive treatment strategy in routine care, particularly in individuals with ST-segment elevation MI. The findings suggest that carefully designed database studies can complement and extend findings from randomized clinical trials, informing guidelines and clinical decision-making.

Project description:ImportanceIt is unclear whether ticagrelor or prasugrel hydrochloride is superior for patients with acute coronary syndrome (ACS) treated with percutaneous coronary intervention (PCI).ObjectiveTo assess the safety and efficacy of ticagrelor vs prasugrel for patients with ACS treated with PCI.Design, setting, and participantsA prespecified analysis was performed of a postrandomization subgroup of 3377 patients who presented with ACS and were treated with PCI in the investigator-initiated, multicenter, phase 4, open-label Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 5 randomized clinical trial, conducted from September 1, 2013, to February 28, 2018. Statistical analysis was performed from September 1, 2020, to January 30, 2021. Analysis was performed according to the intention-to-treat principle.InterventionsPatients were randomly assigned to a ticagrelor-based or prasugrel-based strategy. This analysis focuses on the subgroup of patients who underwent PCI that was formed after randomization.Main outcomes and measuresThe primary end point was a composite consisting of all-cause death, myocardial infarction, or stroke at 12 months. The safety end point was Bleeding Academic Research Consortium (BARC) type 3 to 5 bleeding.ResultsThe ticagrelor group comprised 1676 patients (1323 men [78.9%]; mean [SD] age, 64.4 [12.0] years), and the prasugrel group comprised 1701 patients (1341 men [78.8%]; mean [SD] age, 64.7 [12.0] years). The primary end point occurred for 162 patients (9.8%) in the ticagrelor group and 120 patients (7.1%) in the prasugrel group (hazard ratio [HR], 1.41; 95% CI, 1.11-1.78; P = .005). Myocardial infarction occurred in 88 patients (5.3%) in the ticagrelor group compared with 55 patients (3.8%) in the prasugrel group (HR, 1.67; 95% CI, 1.19-2.34; P = .003). The safety end point, BARC type 3 to 5 bleeding, occurred in 84 of 1672 patients (5.3%) in the ticagrelor group and 78 of 1680 patients (4.9%) in the prasugrel group (HR; 1.10; 95% CI, 0.81-1.50; P = .54).Conclusions and relevanceAmong patients presenting with ACS who were treated with PCI, the incidence of the primary composite end point occurred less frequently for patients who received prasugrel compared with those who received ticagrelor. The incidence of bleeding events was comparable between the 2 groups. These results suggest that, for patients presenting with ACS who undergo PCI, a prasugrel-based strategy is superior to a ticagrelor-based strategy. However, because these observations are based on a postrandomization subgroup, these findings should be regarded as hypothesis generating and dedicated randomized clinical trials may be warranted to confirm these findings.Trial registrationClinicalTrials.gov Identifier: NCT01944800.

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:Background Management of patients with non-ST-segment-elevation acute coronary syndrome (NSTE-ACS) is based on 2020 European Society of Cardiology guidelines, which recommend the preferential use of prasugrel over ticagrelor. Because the selection of the respective P2Y12 inhibitor has to consider label restrictions, we sought to evaluate the proportion of patients qualifying for either ticagrelor or prasugrel and reasons for noneligibility in an unselected cohort of patients with acute coronary syndrome. Methods and Results In this retrospective observational study, patients with ST-segment-elevation myocardial infarction (STEMI) or NSTE-ACS presenting consecutively during a 24-month period were enrolled. The eligibility of patients for a dual antiplatelet therapy option was assessed retrospectively. A total of 1502 patients had confirmed acute coronary syndrome (287 STEMI and 1215 NSTE-ACS). Eligibility for ticagrelor and full-dose prasugrel differed significantly for STEMI and NSTE-ACS (93% versus 51%, P<0.0001 versus 80% versus 31%, P<0.0001). Eligibility remained significantly lower (STEMI 78% versus NSTE-ACS 52%) if low-dose prasugrel was considered. Patients eligible for full-dose prasugrel had lower ischemic risk per GRACE (Global Registry of Acute Coronary Events) score (109 points [90-129 points] versus 121 points [98-146 points], P<0.0001) and lower bleeding risk (14 points [13-15 points] versus 20 points [12-29 points], P<0.0001) per PRECISE-DAPT (Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy) score. Conclusions In real life, eligibility for prasugrel in patients requiring dual antiplatelet therapy is considerably lower than for ticagrelor, even in a cohort with high rates of coronary angiography and percutaneous coronary interventions. The recommended use of prasugrel over ticagrelor in current acute coronary syndrome guidelines contrasts with our observations of a substantial disparity on the eligibility. This important aspect has not received appropriate attention yet. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT05774431.

Dataset Information

Ticagrelor or prasugrel in patients with acute coronary syndrome with off-hour versus on-hour presentation: a subgroup analysis of the ISAR-REACT 5 trial.

Objectives

Background

Methods

Results

Conclusions

Clinical trial registration

Publications

Ticagrelor or prasugrel in patients with acute coronary syndrome with off-hour versus on-hour presentation: a subgroup analysis of the ISAR-REACT 5 trial.

Similar Datasets

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