Dataset Information

P2Y12 Inhibitors for Non-ST-Segment Elevation Acute Coronary Syndrome: A Systematic Review and Network Meta-Analysis.

ABSTRACT:

Background

For patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS), prasugrel was recommended over ticagrelor in a recent randomized controlled trial, although more data are needed on the rationale. Here, the effects of P2Y12 inhibitors on ischemic and bleeding events in patients with NSTE-ACS were investigated.

Methods

Clinical trials that enrolled patients with NSTE-ACS were included, relevant data were extracted, and a network meta-analysis was performed.

Results

This study included 37,268 patients with NSTE-ACS from 11 studies. There was no significant difference between prasugrel and ticagrelor for any end point, although prasugrel had a higher likelihood of event reduction than ticagrelor for all end points except cardiovascular death. Compared with clopidogrel, prasugrel was associated with decreased risks of major adverse cardiovascular events (MACE) (hazard ratio [HR], 0.84; 95% CI, 0.71-0.99) and myocardial infarction (HR, 0.82; 95% CI, 0.68-0.99) but not an increased risk of major bleeding (HR, 1.30; 95% CI, 0.97-1.74). Similarly, compared with clopidogrel, ticagrelor was associated with a reduced risk of cardiovascular death (HR, 0.79; 95% CI, 0.66-0.94) and an increased risk of major bleeding (HR, 1.33; 95% CI, 1.00-1.77; P = .049). For the primary efficacy end point (MACE), prasugrel showed the highest likelihood of event reduction (P = .97) and was superior to ticagrelor (P = .29) and clopidogrel (P = .24).

Conclusion

Prasugrel and ticagrelor had comparable risks for every end point, although prasugrel had the highest probability of being the best treatment for reducing the primary efficacy end point. This study highlights the need for further studies to investigate optimal P2Y12 inhibitor selection in patients with NSTE-ACS.

SUBMITTER: Fujisaki T

PROVIDER: S-EPMC10353270 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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Publications

P2Y12 Inhibitors for Non-ST-Segment Elevation Acute Coronary Syndrome: A Systematic Review and Network Meta-Analysis.

Fujisaki Tomohiro T Kuno Toshiki T Briasoulis Alexandros A Misumida Naoki N Takagi Hisato H Latib Azeem A

Texas Heart Institute journal 20230501 3

<h4>Background</h4>For patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS), prasugrel was recommended over ticagrelor in a recent randomized controlled trial, although more data are needed on the rationale. Here, the effects of P2Y12 inhibitors on ischemic and bleeding events in patients with NSTE-ACS were investigated.<h4>Methods</h4>Clinical trials that enrolled patients with NSTE-ACS were included, relevant data were extracted, and a network meta-analysis was performed.< ...[more]

PMID: 37302149

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Project description:ImportancePretreatment of patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) with P2Y12 receptor antagonists is a common practice despite the lack of definite evidence for its benefit.ObjectiveTo investigate the association of P2Y12 receptor antagonist pretreatment vs no pretreatment with mortality, stent thrombosis, and in-hospital bleeding in patients with NSTE-ACS undergoing percutaneous coronary intervention (PCI).Design, setting, and participantsThis cohort study used prospective data from the Swedish Coronary Angiography and Angioplasty Registry of 64 857 patients who underwent procedures between 2010 and 2018. All patients who underwent PCI owing to NSTE-ACS in Sweden were stratified by whether they were pretreated with P2Y12 receptor antagonists. Associations of pretreatment with P2Y12 receptor antagonists with the risks of adverse outcomes were investigated using instrumental variable analysis and propensity score matching. Data were analyzed from March to June 2019.ExposuresPretreatment with P2Y12 receptor antagonists.Main outcomes and measuresThe primary end point was all-cause mortality within 30 days. Secondary end points were 1-year mortality, stent thrombosis within 30 days, and in-hospital bleeding.ResultsIn total, 64 857 patients (mean [SD] age, 64.7 [10.9] years; 46 809 [72.2%] men) were included. A total of 59 894 patients (92.4%) were pretreated with a P2Y12 receptor antagonist, including 27 867 (43.7%) pretreated with clopidogrel, 34 785 (54.5%) pretreated with ticagrelor, and 1148 (1.8%) pretreated with prasugrel. At 30 days, there were 971 deaths (1.5%) and 101 definite stent thromboses (0.2%) in the full cohort. Pretreatment was not associated with better survival at 30 days (odds ratio [OR], 1.17; 95% CI, 0.66-2.11; P = .58), survival at 1 year (OR, 1.34; 95% CI, 0.77-2.34; P = .30), or decreased stent thrombosis (OR, 0.81; 95% CI, 0.42-1.55; P = .52). However, pretreatment was associated with increased risk of in-hospital bleeding (OR, 1.49; 95% CI, 1.06-2.12; P = .02).Conclusions and relevanceThis cohort study found that pretreatment of patients with NSTE-ACS with P2Y12 receptor antagonists was not associated with improved clinical outcomes but was associated with increased risk of bleeding. These findings support the argument that pretreatment with P2Y12 receptor antagonists should not be routinely used in patients with NSTE-ACS.

Project description:ObjectiveTo review, inventory and compare available diagnostic tools and investigate which tool has the best performance for prehospital risk assessment in patients suspected of non-ST-segment elevation acute coronary syndrome (NSTE-ACS).MethodsSystematic review and meta-analysis. Medline and Embase were searched up till 1 April 2021. Prospective studies with patients, suspected of NSTE-ACS, presenting in the primary care setting or by emergency medical services (EMS) were included. The most important exclusion criteria were studies including only patients with ST-elevation myocardial infarction and studies before 1995, the pretroponin era. The primary end point was the final hospital discharge diagnosis of NSTE-ACS or major adverse cardiac events (MACE) within 6 weeks. Risk of bias was evaluated by the Quality Assessment of Diagnostic Accuracy Studies Criteria.Main outcome and measuresSensitivity, specificity and likelihood ratio of findings for risk stratification in patients suspected of NSTE-ACS.ResultsIn total, 15 prospective studies were included; these studies reflected in total 26 083 patients. No specific variables related to symptoms, physical examination or risk factors were useful in risk stratification for NSTE-ACS diagnosis. The most useful electrocardiographic finding was ST-segment depression (LR+3.85 (95% CI 2.58 to 5.76)). Point-of-care troponin was found to be a strong predictor for NSTE-ACS in primary care (LR+14.16 (95% CI 4.28 to 46.90) and EMS setting (LR+6.16 (95% CI 5.02 to 7.57)). Combined risk scores were the best for risk assessment in an NSTE-ACS. From the combined risk scores that can be used immediately in a prehospital setting, the PreHEART score, a validated combined risk score for prehospital use, derived from the HEART score (History, ECG, Age, Risk factors, Troponin), was most useful for risk stratification in patients with NSTE-ACS (LR+8.19 (95% CI 5.47 to 12.26)) and for identifying patients without ACS (LR-0.05 (95% CI 0.02 to 0.15)).DiscussionImportant study limitations were verification bias and heterogeneity between studies. In the prehospital setting, several diagnostic tools have been reported which could improve risk stratification, triage and early treatment in patients suspected for NSTE-ACS. On-site assessment of troponin and combined risk scores derived from the HEART score are strong predictors. These results support further studies to investigate the impact of these new tools on logistics and clinical outcome.FundingThis study is funded by ZonMw, the Dutch Organisation for Health Research and Development.Trial registration numberThis meta-analysis was published for registration in PROSPERO prior to starting (CRD York, CRD42021254122).

Project description:ObjectiveTo investigate comorbid conditions with prognostic influence in non-ST-segment elevation acute coronary syndrome (NSTEACS).Patients and methodsThe study group consisted of a derivation cohort of 1017 patients (admitted from October 1, 2002, through October 1, 2008) and an external validation cohort of 652 patients (admitted from February 1, 2006, through September 30, 2009). Comorbid conditions, including risk factors and components of the Charlson comorbidity index (ChCI) and coronary artery disease-specific index, were recorded. The main outcome was one-year mortality.ResultsDuring follow-up, 103 patients died. After adjusting for variables associated with NSTEACS characteristics (base model), 5 comorbid conditions predicted mortality: severe or mild renal failure (hazard ratio [HR], 2.9 and HR, 1.6, respectively), dementia (HR, 3.1), peripheral artery disease (HR, 2.0), previous heart failure (HR, 2.6), and previous myocardial infarction (HR, 1.4). A simple comorbidity index (SCI) was developed using these variables, (per point: HR, 1.6; 95% confidence interval, 1.4-1.8; P = .0001). Adding the SCI, Charlson comorbidity index, or coronary artery disease-specific index to the base model resulted in a gain of 6.58%, 5.00%, and 4.04%, respectively, in discriminative ability (P = .001), without significant differences among the 3 indices. In patients with comorbid conditions, the highest risk period was in the first weeks after NSTEACS. The strength of the association between SCI and mortality rate was similar in the external validation cohort (HR, 1.3; 95% confidence interval, 1.1-1.6; P = .001).ConclusionRenal dysfunction, dementia, peripheral artery disease, previous heart failure, and previous myocardial infarction are the comorbid conditions that predict mortality in NSTEACS. A simple index using these variables proved to be as accurate as the more complex comorbidity indices for risk stratification. In-hospital management of patients with comorbid conditions merits further investigation.

Project description:BackgroundPerioperative antiplatelet agents potentially increase bleeding after non-ST-segment elevation (NSTE) acute coronary syndromes (ACS). The protease-activated receptor 1 antagonist vorapaxar reduced cardiovascular events and was associated with increased bleeding versus placebo in NSTE ACS, but its efficacy and safety in noncardiac surgery (NCS) remain unknown. We aimed to evaluate ischemic, bleeding, and long-term outcomes of vorapaxar in NCS after NSTE ACS.Methods and resultsIn the TRACER trial, 2202 (17.0%) patients underwent major or minor NCS after NSTE ACS over 1.5 years (median); continuing study treatment perioperatively was recommended. The primary ischemic end point for this analysis was cardiovascular death, myocardial infarction, stent thrombosis, or urgent revascularization within 30 days of NCS. Safety outcomes included 30-day NCS bleeding and GUSTO moderate/severe bleeding. Overall, 1171 vorapaxar and 1031 placebo patients underwent NCS. Preoperative aspirin and thienopyridine use was 96.8% versus 97.7% (P=0.235) and 89.1% versus 86.1% (P=0.036) for vorapaxar versus placebo, respectively. Within 30 days of NCS, no differences were observed in the primary ischemic end point between vorapaxar and placebo groups (3.4% versus 3.9%; adjusted odds ratio 0.81, 95% CI 0.50 to 1.33, P=0.41). Similarly, no differences in NCS bleeding (3.9% versus 3.4%; adjusted odds ratio 1.41, 95% CI 0.87 to 2.31, P=0.17) or GUSTO moderate/severe bleeding (4.2% versus 3.7%; adjusted odds ratio 1.15, 95% CI, 0.72 to 1.83, P=0.55) were observed. In a 30-day landmarked analysis, NCS patients had a higher long-term risk of the ischemic end point (adjusted hazard ratio 1.62, 95% CI 1.33 to 1.97, P<0.001) and GUSTO moderate/severe bleeding (adjusted hazard ratio 5.63, 95% CI 3.98 to 7.97, P<0.001) versus patients who did not undergo NCS, independent of study treatment.ConclusionNCS after NSTE ACS is common and associated with more ischemic outcomes and bleeding. Vorapaxar after NSTE ACS was not associated with increased perioperative ischemic or bleeding events in patients undergoing NCS.

Dataset Information

P2Y12 Inhibitors for Non-ST-Segment Elevation Acute Coronary Syndrome: A Systematic Review and Network Meta-Analysis.

Background

Methods

Results

Conclusion

Publications

P2Y12 Inhibitors for Non-ST-Segment Elevation Acute Coronary Syndrome: A Systematic Review and Network Meta-Analysis.

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