scholarly journals New genetic variants associated with major adverse cardiovascular events in patients with acute coronary syndromes and treated with clopidogrel and aspirin

Author(s):  
Xiaomin Liu ◽  
Hanshi Xu ◽  
Huaiqian Xu ◽  
Qingshan Geng ◽  
Wai-Ho Mak ◽  
...  

AbstractAlthough a few studies have reported the effects of several polymorphisms on major adverse cardiovascular events (MACE) in patients with acute coronary syndromes (ACS) and those undergoing percutaneous coronary intervention (PCI), these genotypes account for only a small fraction of the variation and evidence is insufficient. This study aims to identify new genetic variants associated with MACE end point during the 18-month follow-up period by a two-stage large-scale sequencing data, including high-depth whole exome sequencing of 168 patients in the discovery cohort and high-depth targeted sequencing of 1793 patients in the replication cohort. We discovered eight new genotypes and their genes associated with MACE in patients with ACS, including MYOM2 (rs17064642), WDR24 (rs11640115), NECAB1 (rs74569896), EFR3A (rs4736529), AGAP3 (rs75750968), ZDHHC3 (rs3749187), ECHS1 (rs140410716), and KRTAP10-4 (rs201441480). Notably, the expressions of MYOM2 and ECHS1 are downregulated in both animal models and patients with phenotypes related to MACE. Importantly, we developed the first superior classifier for predicting 18-month MACE and achieved high predictive performance (AUC ranged between 0.92 and 0.94 for three machine-learning methods). Our findings shed light on the pathogenesis of cardiovascular outcomes and may help the clinician to make a decision on the therapeutic intervention for ACS patients.

2018 ◽  
Author(s):  
Xiaomin Liu ◽  
Hanshi Xu ◽  
Huaiqian Xu ◽  
Qingshan Geng ◽  
Wai-Ho Mak ◽  
...  

AbstractImportanceAlthough a few studies have reported the effects of several polymorphisms on major adverse cardiovascular events (MACE) in patients with acute coronary syndromes (ACS) and those undergoing percutaneous coronary intervention (PCI), these genotypes account for only a small fraction of the variation and evidence is insufficient. This study aims to identify new genetic variants associated with MACE by large-scale sequencing data.ObjectiveTo identify the genetic variants that caused MACE.DesignAll patients in this study were allocated to dual antiplatelet therapy for up to 12 months and have the follow-up duration of 18 months.SettingA two-stage association study was performed.ParticipantsWe evaluated the associations of genetic variants and MACE in 1961 patients with ACS undergoing PCI (2009-2012), including high-depth whole exome sequencing of 168 patients in the discovery cohort and high-depth targeted sequencing of 1793 patients in the replication cohort.Main Outcomes and MeasureThe primary clinical efficacy endpoint was the major adverse cardiovascular events (MACE) composite endpoint, including cardiovascular death, myocardial infarction (MI), stroke (CT or MR scan confirmed) and repeated revascularization (RR).ResultsWe discovered and confirmed six new genotypes associated with MACE in patients with ACS. Of which, rs17064642 at MYOM2 increased the risk of MACE (hazard ratio [HR] 2.76; P = 2.95 × 10-9) and reached genome-wide significance. The other five suggestive variants were KRTAP10-4 (rs201441480), WDR24 (rs11640115), ECHS1 (rs140410716), AGAP3 (rs75750968) and NECAB1 (rs74569896). Notably, the expressions of MYOM2 and ECHS1 are down-regulated in both animal models and patients with phenotypes related to MACE. Importantly, we developed the first superior classifier for predicting MACE and achieved high predictive accuracy (0.809).Conclusions and RelevanceWe identified six new genotypes associated with MACE and developed a superior classifier for predicting MACE. Our findings shed light on the pathogenesis of cardiovascular outcomes and may help clinician to make decision on the therapeutic intervention for ACS patients.Trial RegistrationThis study has been registered in the Chinese Clinical Trial Registry (http://www.chictr.org.cn, Registration number: ChiCTR-OCH-11001198).


2020 ◽  
Vol 4 (3) ◽  
pp. 185-193
Author(s):  
Turan Erdoğan ◽  
Hakan Duman ◽  
Mustafa Çetin ◽  
Savaş Özer ◽  
Göksel Çinier ◽  
...  

Postdilation is frequently used during coronary interventions to prevent stent malapposition. Currently there are contradictory findings regarding the benefits of postdilation for both intraprocedural and long-term outcomes. We evaluated the impact of postdilation among patients who presented with acute coronary syndromes (ACS) and underwent percutaneous coronary interventions (PCI). A total of 258 consecutive patients who presented with ACS and underwent PCI were included in the study. The patients were followed up for 25±1.7 months for the occurrence of major adverse cardiovascular events (MACE). During follow-up, 65 patients (25.2%) had MACE. Among patients without MACE, intracoronary nitrate infusion was less frequently used (P=0.005), myocardial blush grade was higher (P<0.001), and a drug-eluting stent was more frequently used (P=0.005). No significant differences were noted between groups regarding the predilation, recurrent dilation, postdilation, and other angiographic characteristics. In multivariate analysis, female sex (P=0.047), myocardial blush grade (P=0.038), previous coronary artery disease (P=0.030), and peak troponin level (P=0.002) were found to be predictors of MACE. In patients who were treated with PCI for ACS, performing postdilation did not predict final Thrombolysis in Myocardial Infarction (TIMI) flow grade, corrected TIMI frame count, myocardial blush grade, or MACE.


2019 ◽  
Vol 54 (5) ◽  
pp. 414-422 ◽  
Author(s):  
Rochelle M. Gellatly ◽  
Cia Connell ◽  
Christianne Tan ◽  
Nick Andrianopoulos ◽  
Andrew E. Ajani ◽  
...  

Background: Glycoprotein IIb/IIIa inhibitors (GPIs) are a treatment option in the management of acute coronary syndromes (ACSs). Evidence supporting the use of GPIs predates trials establishing the benefits of P2Y12 inhibitors, routine early invasive therapy, and thrombectomy devices in patients with ACS. Objective: The aim of this study was to determine trends in GPI use and their associated outcomes in contemporary practice. Methods: We assessed GPI use in patients with ACS undergoing percutaneous coronary intervention (PCI) from the Melbourne Interventional Group registry (2005-2013). The primary endpoint was the 30-day incidence of major adverse cardiovascular events (MACE). The safety endpoint was in-hospital major bleeding. Results: GPIs were used in 40.5% of 12 357 patients with ACS undergoing PCI. GPI use decreased over the study period ( P for trend <0.0001). Patients were more likely to receive GPIs if they were younger, presented with a ST-elevation myocardial infarction (STEMI), had more complex (B2/C-type) lesions, and when thrombectomy devices were used (all P < 0.0001). MACE were higher in patients receiving GPI (4.9% vs 4.1%, P = 0.03). Propensity score matching revealed no difference in 30-day mortality and 30-day MACE (odds ratio [OR] = 1.00; 95% CI = 0.99-1.004 and OR = 1.01; 95% CI = 0.99-1.02, respectively). GPI use was associated with more bleeding complications (3.6% vs 1.8%, P < 0.0001). Conclusion and Relevance: GPI use in ACS patients undergoing PCI has declined, and use appears to be dictated by ACS type and lesion complexity, as opposed to high-risk comorbidities. GPI use was associated with a doubling in bleeding complications.


Open Heart ◽  
2021 ◽  
Vol 8 (2) ◽  
pp. e001677
Author(s):  
Leonardo De Luca ◽  
Andrea Rubboli ◽  
Leonardo Bolognese ◽  
Massimo Uguccioni ◽  
Donata Lucci ◽  
...  

ObjectivesNo data on optimal management of patients with acute coronary syndromes (ACS) on long-term direct oral anticoagulants (DOACs) undergoing percutaneous coronary intervention (PCI) are available. Using the data of the Management of Antithrombotic TherApy in Patients with Chronic or DevelOping AtRial Fibrillation During Hospitalization for PCI study, we sought to compare the outcome of patients with ACS and atrial fibrillation (AF) who underwent PCI during uninterrupted DOAC (UDOAC group) and those who interrupted DOAC before PCI (IDOAC group).MethodsThe primary outcomes of our analysis were the incidence of major adverse cardiovascular events (MACEs), a composite of death, cerebrovascular events, recurrent myocardial infarction or revascularisation and net adverse clinical events (NACEs), including major bleeding, at 6 months.ResultsAmong the 132 patients on long-term DOAC, 72 (54.6%) underwent PCI during UDOAC and 60 (45.4%) after IDOAC. The mean CHA2DS2-VASc score was 3.8±1.7 and 3.9±1.3 (p=0.89), while the HAS-BLED score was 2.5±1.0 and 2.5±0.9 (p=0.96), in UDOAC and IDOAC groups, respectively. The median time from hospital admission to PCI was 9.5 (IQR: 2.0–31.5) hours in UDOAC and 45.5 (IQR: 22-5–92.0) hours in IDOAC group (p<0.0001). A radial approach was used in 92%, and a drug-eluting stent was implanted in 98% of patients. At 6 months, the rates of MACE (13.9% vs 16.7%) and NACE (20.8% vs 21.7%) did not differ between UDOAC and IDOAC groups. At multivariable analysis, increasing CHA2DS2-VASc score (HR: 1.39; 95% CIs 1.05 to 1.83; p=0.02) resulted as the only independent predictor of NACE.ConclusionsOur study shows that PCI is a safe procedure during UDOAC in patients with concomitant ACS and AF.


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