Dataset Information

Prasugrel-Based De-Escalation in Patients With Acute Coronary Syndrome According to Renal Function.

ABSTRACT:

Background

Patients with coronary artery disease and impaired renal function are at higher risk for both bleeding and ischemic adverse events after percutaneous coronary intervention (PCI).

Objectives

This study assessed the efficacy and safety of a prasugrel-based de-escalation strategy in patients with impaired renal function.

Methods

We conducted a post hoc analysis of the HOST-REDUCE-POLYTECH-ACS study. Patients with available estimated glomerular filtration rate (eGFR) (n = 2,311) were categorized into 3 groups. (high eGFR: >90 mL/min; intermediate eGFR: 60 to 90 mL/min; and low eGFR: <60 mL/min). The end points were bleeding outcomes (Bleeding Academic Research Consortium type 2 or higher), ischemic outcomes (cardiovascular death, myocardial infarction, stent thrombosis, repeated revascularization, and ischemic stroke), and net adverse clinical event (including any clinical event) at 1-year follow-up.

Results

Prasugrel de-escalation was beneficial regardless of baseline renal function (P for interaction = 0.508). The relative reduction in bleeding risk from prasugrel de-escalation was higher in the low eGFR group than in both the intermediate and high eGFR groups (relative reductions, respectively: 64% (HR: 0.36; 95% CI: 0.15-0.83) vs 50% (HR: 0.50; 95% CI: 0.28-0.90) and 52% (HR: 0.48; 95% CI: 0.21-1.13) (P for interaction = 0.646). Ischemic risk from prasgurel de-escalation was not significant in all eGFR groups (HR: 1.18 [95% CI: 0.47-2.98], HR: 0.95 [95% CI: 0.53-1.69], and HR: 0.61 [95% CI: 0.26-1.39]) (P for interaction = 0.119).

Conclusions

In patients with acute coronary syndrome receiving PCI, prasugrel dose de-escalation was beneficial regardless of the baseline renal function.

SUBMITTER: Yun JP

PROVIDER: S-EPMC9982221 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Publications

Prasugrel-Based De-Escalation in Patients With Acute Coronary Syndrome According to Renal Function.

Yun Jun Pil JP Kang Jeehoon J Park Kyung Woo KW Park Kyungil K Hwang Doyeon D Han Jung-Kyu JK Yang Han-Mo HM Kang Hyun-Jae HJ Koo Bon-Kwon BK Chae In-Ho IH Moon Keon-Woong KW Park Hyun Woong HW Won Ki-Bum KB Jeon Dong Woon DW Han Kyoo-Rok KR Choi Si Wan SW Ryu Jae Kean JK Jeong Myung Ho MH Kim Hyo-Soo HS

JACC. Asia 20230110 1

<h4>Background</h4>Patients with coronary artery disease and impaired renal function are at higher risk for both bleeding and ischemic adverse events after percutaneous coronary intervention (PCI).<h4>Objectives</h4>This study assessed the efficacy and safety of a prasugrel-based de-escalation strategy in patients with impaired renal function.<h4>Methods</h4>We conducted a post hoc analysis of the HOST-REDUCE-POLYTECH-ACS study. Patients with available estimated glomerular filtration rate (eGFR) ...[more]

PMID: 36873753

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Project description:ImportanceDe-escalation of dual-antiplatelet therapy through dose reduction of prasugrel improved net adverse clinical events after acute coronary syndrome (ACS), mainly through the reduction of bleeding without an increase in ischemic outcomes. However, whether such benefits are similarly observed in those receiving complex procedures is unknown.ObjectiveTo investigate whether the benefits of prasugrel dose de-escalation therapy are maintained in the complex percutaneous coronary intervention (PCI) subgroup.Design, setting, and participantsThis was a post hoc analysis of the HOST-REDUCE-POLYTECH-ACS trial, a randomized, open-label, adjudicator-blinded, multicenter trial performed at 35 hospitals in South Korea. Study participants included patients with ACS who were receiving PCI. Data were collected from September 30, 2014, to December 18, 2015, and analyzed from September 17, 2020, to June 15, 2021.Interventions and exposuresPatients were randomized to a prasugrel dose de-escalation (5 mg daily) at 1 month post-PCI group or a conventional (10 mg daily) group. Complex PCI was defined as having at least 1 of the following features: 3 or more stents implanted, 3 or more lesions treated, bifurcation PCI, total stent length 60 mm or larger, left main PCI, or heavy calcification.Main outcomes and measuresThe main analysis end points were MACE (major adverse cardiac event, a composite of cardiovascular death, nonfatal myocardial infarction, stent thrombosis, and repeat revascularization) at 1 year for ischemic outcomes, and BARC (Bleeding Academic Research Consortium) class 2 or higher bleeding events at 1 year for bleeding outcomes.ResultsOf 2271 patients (mean [SD] age, 58.9 [9.0] years; 2024 [89%] male patients) for whom full procedural data were available, 705 patients received complex PCI, and 1566 patients received noncomplex PCI. Complex PCI was associated with higher rates of ischemic outcomes but not with bleeding outcomes. Prasugrel dose de-escalation did not increase the risk of MACE (hazard ratio [HR], 0.88; 95% CI, 0.47-1.66; P = .70 in complex PCI; HR, 0.81; 95% CI, 0.45-1.46; P = .48 in noncomplex PCI; P for interaction = .84) but decreased BARC class 2 or higher bleeding events (HR, 0.25; 95% CI, 0.10-0.61; P = .002 in complex PCI; HR, 0.62; 95% CI, 0.38-1.00; P = .05 in noncomplex PCI; P for interaction = .08), albeit with wide 95% CIs.Conclusions and relevanceIn this post hoc analysis of patients with ACS, prasugrel dose de-escalation compared with conventional therapy was not associated with an increased risk of ischemic outcomes but may reduce the risk of minor bleeding events at 1 year, irrespective of PCI complexity.Trial registrationClinicalTrials.gov Identifier: NCT02193971.

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:BackgroundAcute Kidney Injury (AKI), a common complication of acute coronary syndromes (ACS), is associated with higher mortality and longer hospital stays. The role of cytokines and other mediators is unknown in AKI induced by an ACS (ACS-AKI), leading to several unanswered questions. The worsening of renal function is usually seen as a dichotomous phenomenon instead of a dynamic change, so evaluating changes of the renal function in time may provide valuable information in the ACS-AKI setting. The aim of this study was to explore inflammatory factors associated to de novo kidney injury induced by de novo cardiac injury secondary to ACS.MethodsOne hundred four consecutive patients with ACS were initially included on the time of admission to the Coronary Unit of the Instituto Nacional de Cardiología in Mexico City, from February to May 2016, before any invasive procedure, imaging study, diuretic or anti-platelet therapy. White blood count, hemoglobin, NT-ProBNP, troponin I, C-reactive protein, albumin, glucose, Na+, K+, blood urea nitrogen (BUN), total cholesterol, HDL, LDL, triglycerides, creatinine (Cr), endothelin-1 (ET-1), leukotriene-B4, matrix metalloproteinase-2 and -9, tissue inhibitor of metalloproteinases-1, resolvin-D1 (RvD1), lipoxin-A4 (LXA4), interleukin-1β, -6, -8, and -10 were measured. We finally enrolled 78 patients, and subsequently we identified 15 patients with ACS-AKI. Correlations were obtained by a Spearman rank test. Low-rank regression, splines regressions, and also protein-protein/chemical interactions and pathways analyses networks were performed.ResultsPositive correlations of ΔCr were found with BUN, admission Cr, GRACE score, IL-1β, IL-6, NT-ProBNP and age, and negative correlations with systolic blood pressure, mean-BP, diastolic-BP and LxA4. In the regression analyses IL-10 and RvD1 had positive non-linear associations with ΔCr. ET-1 had also a positive association. Significant non-linear associations were seen with NT-proBNP, admission Cr, BUN, Na+, K+, WBC, age, body mass index, GRACE, SBP, mean-BP and Hb.ConclusionInflammation and its components play an important role in the worsening of renal function in ACS. IL-10, ET-1, IL-1β, TnI, RvD1 and LxA4 represent mediators that might be associated with ACS-AKI. IL-6, ET-1, NT-ProBNP might represent crossroads for several physiopathological pathways involved in "de novo cardiac injury leading to de novo kidney injury".

Dataset Information

Prasugrel-Based De-Escalation in Patients With Acute Coronary Syndrome According to Renal Function.

Background

Objectives

Methods

Results

Conclusions

Publications

Prasugrel-Based De-Escalation in Patients With Acute Coronary Syndrome According to Renal Function.

Similar Datasets

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