scholarly journals Impact of IRS-1 rs956115 and CYP2C19 rs4244285 Genotypes on Clinical Outcome of Patients Undergoing PCI

2021 ◽  
Author(s):  
Jiaxin Zong ◽  
Yingdan Tang ◽  
Tong Wang ◽  
Inam Ullah ◽  
Ke Xu ◽  
...  
Keyword(s):  
Platelet Reactivity ◽  
Coronary Intervention ◽  
Cardiovascular Death ◽  
Major Adverse Cardiovascular Events ◽  
Cardiovascular Risks ◽  
Clinical Predictors ◽  
Percutaneous Coronary ◽  
Significant Difference ◽  
Artery Disease ◽  
October 17

Abstract Background insulin receptor substrate-1 (IRS-1) rs956115 is associated with vascular risk in patients with coronary artery disease (CAD) and concomitant diabetes. CYP2C19 rs4244285 modulates clopidogrel responsiveness and predicts outcome of CAD. We designed this study to explore the association between IRS-1 rs956115, CYP2C19 rs4244285, and platelet reactivity as well as 1-year outcome in patients with CAD undergoing percutaneous coronary intervention (PCI).Methods IRS-1 rs956115, CYP2C19 rs4244285 genotypes and platelet reactivity were assessed in 1611 post-PCI patients. Major adverse cardiovascular events (MACE) which were defined as a composite of cardiovascular death, myocardial infarction and ischemic stroke over 1-year were evaluated. One-way ANOVA was used to compare the platelet reactivity among different genotypes of rs956115 and rs4244285. Multivariable Cox proportional hazard model analysis was used to estimate the association between genotypes of rs956115 and rs4244285 and risk of MACE.Results At 1 month, patients with rs956115 CG genotype had significantly lower level of residual ADP-induced platelet aggregation (PLADP) than those with CC genotype. PLADP significantly increased with the number of rs4244285 A alleles. Patients with rs956115 CG or GG genotype had a 2.09-fold higher risk of MACE than those with CC genotype (adjusted HR=2.09; 95%CI:1.04-4.19; P=0.0376), and those with rs4244285 GA genotype had a 2.19-fold higher risk than GG homozygotes (adjusted HR=2.19; 95%CI:1.13-4.24; P=0.0200). There was no significant difference in risk between AA and GG homozygotes. No interaction between rs956115 and rs4244285 was observed. Conclusions In post-PCI patients, rs956115 GG/CG and rs4244285 GA genotypes were associated with 2.09- and 2.19-fold cardiovascular risks respectively at 1-year follow-up. The effect of rs956115 appeared to be independent of known clinical predictors, while that of rs4244285 GA could be mediated by lower clopidogrel response. Trial registration: Pharmacogenetic and Pharmacokinetic Study of Clopidogrel (PPSC), NCT01968499. Registered October 17, 2013 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT01968499?term=NCT01968499&draw=1&rank=1

Abstract 291: Platelet Function Monitoring After Percutaneous Coronary Intervention: Updated Meta-analysis of Randomized Trials.

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Akintunde M Akinjero ◽  
Oluwole Adegbala ◽  
Esosa Edo-Osagie ◽  
Nike Akinjero ◽  
Tomi Akinyemiju
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Platelet Function ◽  
Meta Analysis ◽  
Coronary Intervention ◽  
Cardiovascular Death ◽  
Bleeding Complications ◽  
Major Adverse Cardiovascular Events ◽  
Future Research ◽  
Funnel Plot ◽  
Percutaneous Coronary

Background: The need to balance bleeding and clotting risks after percutaneous coronary intervention (PCI) has led to interest in platelet function monitoring as a strategy to improve post-PCI outcomes. The prognostic value of platelet function testing in monitoring response to antiplatelet therapy after PCI remains unclear. Prior studies have been inconclusive. We sought to conduct an updated meta-analysis to address this gap in knowledge. Methods: We conducted a systematic search of EMBASE, PUBMED and the Cochrane libraries for studies since inception to December 2016 on platelet function monitoring. Our search yielded 203 studies, out of which 83 were extracted for full-text review. Only 3 studies met inclusion criteria. We pooled odds ratios using random-effects statistics, Mantel-Haenszel method. I2 and Chi- squared statistic was used to evaluate for heterogeneity. Publication bias was assessed using the funnel plot. Primary outcome was major adverse cardiovascular events (MACE). This was defined in the studies as a composite of cardiovascular death, myocardial infarction, stroke, stent thrombosis, and bleeding complications. Results: The 3 randomized controlled trials that were analyzed involved 3701 patients. There were 550 MACE (29.76%) in the platelet function monitored group compared with 514 (27.74%) in the control. MACE (Figure 1) was not significantly higher for the platelet function monitored group during follow-up compared with control (pooled Odds Ratio:1.11 [95% CI: 0.96-1.28], p = 0.15). Tests for heterogeneity were not significant, with I2 of 0%, Chi2 = 1.52 (p = 0.47); and small study bias was absent on visual inspection of the funnel plot. Conclusions: Platelet function monitoring continues to be used in practice. Results from this meta-analysis show no benefit of platelet function monitoring compared with conventional strategy with regards to MACE after PCI. Future research is needed to further evaluate this finding.

Abstract 17428: Impact of Asymptomatic Cerebral Microbleeds or Lacunar Infarction on Clinical Outcome in Patients With Coronary Artery Disease (CAD) Requiring Percutaneous Coronary Intervention

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Seiji Hokimoto ◽  
Noriaki Tabata ◽  
Tomonori Akasaka ◽  
Kenji Sakamoto ◽  
Kenichi Tsujita ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Percutaneous Coronary Intervention ◽  
Clinical Outcome ◽  
Coronary Intervention ◽  
Cardiovascular Death ◽  
Cerebral Microbleeds ◽  
Lacunar Infarction ◽  
Percutaneous Coronary ◽  
High Incidence ◽  
Artery Disease

Background: Patients with coronary artery disease (CAD) are often complicated with cerebrovascular disease (CVD). Although there are many reports on the relation between stoke with symptomatic signs and CAD, there are few studies on cerebral microbleeds or lacunar infarction without symptomatic signs. The aim was to examine the prevalence of cerebral microbleeds or lacunar infarction without symptoms and clinical outcome in CAD patients. Methods: Among 1,091 consecutive CAD patients who required percutaneous coronary intervention (PCI), patients with non-lacunar infarction more severe than lacunar infarction or old cerebral hemorrhage by computed tomography (CT) or magnetic resonance imaging (MRI) were excluded. We analyzed CAD patients with cerebral microbleeds or lacunar infarction without overt neurological signs (ML group; n=98, 71males) compared with patients without cerebral findings of CT or MRI and stroke history as control (N group; n=762, 525males). Clinical endpoints were cardiovascular death, myocardial infarction (MI), stroke, unstable angina and urgent revascularization. Results: ML group had a high age (72.9±9.6 vs. 69.2±10.8ys; P=0.001), high incidence of diabetes mellitus (58.2 vs. 47.2%; P=0.042), peripheral artery disease (21.4 vs. 11.5%; P=0.005), and renal dysfunction (49.0 vs. 37.3%; P=0.025), and high levels of fibrinogen (435 vs. 402mg/dl; P=0.005), and high brachial-ankle pulse wave velocity (1975 vs. 1786cm/sec; P=0.001) compared with N group. Cardiovascular event rate was significantly higher in ML group than in N group (11.2 vs. 4.7%, P=0.008). Details in clinical outcome were as follows: cardiovascular death (ML group vs. N group, 0 vs. 0.9%; P=0.341), MI (1.0 vs. 0.5%; P=0.544), stroke (4.1 vs.0.7%; P=0.002), unstable angina (5.1 vs. 2.5%; P=0.140), revascularization (2.0 vs. 0.7%; P=0.498), respectively. Multiple regression analysis identified findings of microbleeds or lacunar infarction as a predictor of clinical events (OR, 2.830; 95%CI, 1.328-6.031; P=0.007). Conclusions: There was high incidence of brain MRI or CT findings without symptom in CAD patients. We should pay attention to the asymptomatic patients with microbleeds or lacunar infarction irrespective of overt previous stroke.

Abstract 12728: Untreated Sleep Apnea Syndrome is Associated With Higher Incidence of Cardiovascular Events After Percutaneous Coronary Intervention

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Kazuhiro Fujiyoshi ◽  
Yoshiyasu Minami ◽  
Kohki Ishida ◽  
Miwa Ishida ◽  
Ken-ichiro Wakabayashi ◽  
...  
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Sleep Apnea ◽  
Cardiovascular Events ◽  
Sleep Apnea Syndrome ◽  
Coronary Intervention ◽  
Major Adverse Cardiovascular Events ◽  
Percutaneous Coronary ◽  
Significant Difference ◽  
Apnea Syndrome ◽  
The Impact

Introduction: Sleep apnea syndrome (SAS) is a risk factor of cardiovascular disease. However, the impact of SAS on the clinical course after percutaneous coronary intervention (PCI) remains to be elucidated. Methods: A total of 206 consecutive patients who underwent PCI were included. The incidence of major adverse cardiovascular events (MACE) at 3-year was compared among patients with untreated SAS (untreated SAS group; n=60), those with SAS treated by continuous positive alveolar pressure (CPAP group; n=20) and those without SAS (non-SAS group; n=96). MACE included cardiac death, non-fatal myocardial infarction, target vessel revascularization (TVR), and non-TVR (NTVR). Results: There was no significant difference in baseline clinical characteristics among the untreated SAS group, the CPAP group and the non-SAS groups, other than in age (74.1 ± 9.6 vs. 71.2 ± 0.33 vs. 68.2 ± 10.7, p = 0.002) and hemoglobin A1c levels (6.54 ± 0.87 vs. 6.61 ± 0.58 vs. 6.09 ± 0.70 %, p < 0.001). The incidence of MACE, TLR and TVR was significantly higher in the untreated SAS group than in the CPAP group and the Non-SAS group although there was no significant difference in the incidence of NTVR among the three groups (Figure). The untreated SAS was independently associated with the incidence of 3-year MACE (odds ratio 3.24, 95% confidence interval 1.36-8.20, p = 0.008). Conclusions: The incidence of MACE was significantly higher in patients with untreated SAS than in those treated with CPAP and those without SAS after PCI. The present findings may highlight the importance of SAS management in patients requiring PCI.

Differential Impact of Cigarette Smoking on Prognosis in Women and Men Undergoing Percutaneous Coronary Intervention

Angiology ◽  
2019 ◽  
Vol 71 (3) ◽  
pp. 281-287
Author(s):  
Li Xia Yang ◽  
Zhi Jian Wang ◽  
Dong Mei Shi ◽  
Meng Chai ◽  
Lin Zhang ◽  
...  
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Cigarette Smoking ◽  
Smoking Status ◽  
Coronary Intervention ◽  
Major Adverse Cardiovascular Events ◽  
Target Vessel Revascularization ◽  
Percutaneous Coronary ◽  
Artery Disease

We sought to compare the effects of smoking on clinical outcomes in women and men with coronary artery disease undergoing percutaneous coronary intervention (PCI). We prospectively followed up 10 369 patients undergoing elective PCI. All patients were stratified according to smoking status and sex. The impacts of smoking on long-term major adverse cardiovascular events (MACEs, the composite of all-cause death, myocardial infarction, or target vessel revascularization) were assessed. Among 7773 men and 2596 women undergoing PCI, the prevalence of cigarette smoking was 66.7% (n = 5185) and 11.0% (n = 286; P < .001). During the 3 years of follow-up (median: 20.6 months), smoking increased MACE in both men and women (men 10.8% vs 8.1%, P < .001; women 23.2% vs 6.4%; P < .001). After adjusting for baseline characteristics, smoking had a greater effect on MACE in women (hazard ratio [HR]: 3.68, 95% confidence interval [CI]: 1.86-7.28; P < .001) compared with men (HR: 1.35, 95% CI: 1.03-1.77; P = .005, interaction P = .026). There was a lower prevalence of smoking in women compared to men among patients undergoing PCI. However, smoking confers a higher excess risk for MACE among women compared with men.

scholarly journals Relationship between platelet aggregation and stroke risk after percutaneous coronary intervention: a PENDULUM analysis

2022 ◽  
Author(s):  
Yuji Matsumaru ◽  
Takanari Kitazono ◽  
Kazushige Kadota ◽  
Koichi Nakao ◽  
Yoshihisa Nakagawa ◽  
...  
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Ischemic Stroke ◽  
Cumulative Incidence ◽  
Platelet Reactivity ◽  
Coronary Intervention ◽  
Clinical Trial Registration ◽  
Fatal Stroke ◽  
Increased Risk ◽  
Percutaneous Coronary ◽  
Significant Difference

AbstractIn patients undergoing percutaneous coronary intervention (PCI) with a stent, high on-treatment platelet reactivity may be associated with an increased risk of stroke. This post hoc analysis of the PENDULUM registry compared the risk of post-PCI stroke according to on-treatment P2Y12 reaction unit (PRU) values. Patients aged ≥ 20 years who underwent PCI were stratified by baseline PRU (at 12 and 48 h post-PCI) as either high (HPR, > 208), optimal (OPR, > 85 to ≤ 208), or low on-treatment platelet reactivity (LPR, ≤ 85). The incidences of non-fatal ischemic and non-ischemic stroke through to 12 months post-PCI were recorded. Almost all enrolled patients (6102/6267 [97.4%]) had a risk factor for ischemic stroke, and most were receiving dual antiplatelet therapy. Of the 5906 patients with PRU data (HPR, n = 2227; OPR, n = 3002; LPR, n = 677), 47 had a non-fatal stroke post-PCI (cumulative incidence: 0.68%, ischemic; 0.18%, non-ischemic stroke). Patients with a non-fatal ischemic stroke event had statistically significantly higher post-PCI PRU values versus those without an event (P = 0.037). The incidence of non-fatal non-ischemic stroke was not related to PRU value. When the patients were stratified by PRU ≤ 153 versus > 153 at 12–48 h post-PCI, a significant difference was observed in the cumulative incidence of non-fatal stroke at 12 months (P = 0.044). We found that patients with ischemic stroke tended to have higher PRU values at 12–48 h after PCI versus those without ischemic stroke.Clinical trial registration: UMIN000020332.

scholarly journals ORBITA: What Goes Around, Comes Around… Or Does It?

2018 ◽  
Vol 13 (3) ◽  
pp. 135
Author(s):  
Matthew Jackson ◽  
Azfar Zaman ◽  
◽  
Keyword(s):  
Medical Therapy ◽  
Stable Angina ◽  
Coronary Intervention ◽  
Evidence Base ◽  
Current Evidence ◽  
Placebo Control ◽  
Percutaneous Coronary ◽  
Significant Difference ◽  
Current Evidence Base ◽  
Artery Disease

Current guidelines recommend percutaneous coronary intervention (PCI) in patients with ongoing stable angina symptoms despite optimal medical therapy (OMT), although trials have shown no reduction in death or myocardial infarction. The recently published ORBITA trial compared OMT + PCI with OMT + ‘placebo’ PCI in patients with angina and single-vessel coronary artery disease (CAD), and found no significant difference in treadmill exercise time between the two groups after six weeks. The trial concluded that invasive procedures can be assessed with placebo control while numerous editorials interpreted the trial as showing that PCI has no role in the management of stable angina. However, the highly selected patient population, low ischaemic burden and level of symptoms and high proportion of nonflow-limiting stenoses on invasive physiological testing mean that, while ground-breaking in terms of its methodology, ORBITA does not add to the current evidence base supporting ischaemia-guided revascularisation if symptoms are not controlled on medical therapy alone.

scholarly journals Association of the coronary artery disease risk gene GUCY1A3 with ischaemic events after coronary intervention

2019 ◽  
Vol 115 (10) ◽  
pp. 1512-1518 ◽  
Author(s):  
Thorsten Kessler ◽  
Bernhard Wolf ◽  
Niclas Eriksson ◽  
Daniel Kofink ◽  
Bakhtawar K Mahmoodi ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Stent Thrombosis ◽  
Risk Allele ◽  
Platelet Reactivity ◽  
Coronary Intervention ◽  
Cardiovascular Death ◽  
Impedance Aggregometry ◽  
Increased Risk ◽  
Artery Disease

AbstractAimA common genetic variant at the GUCY1A3 coronary artery disease locus has been shown to influence platelet aggregation. The risk of ischaemic events including stent thrombosis varies with the efficacy of aspirin to inhibit platelet reactivity. This study sought to investigate whether homozygous GUCY1A3 (rs7692387) risk allele carriers display higher on-aspirin platelet reactivity and risk of ischaemic events early after coronary intervention.Methods and resultsThe association of GUCY1A3 genotype and on-aspirin platelet reactivity was analysed in the genetics substudy of the ISAR-ASPI registry (n = 1678) using impedance aggregometry. The clinical outcome cardiovascular death or stent thrombosis within 30 days after stenting was investigated in a meta-analysis of substudies of the ISAR-ASPI registry, the PLATO trial (n = 3236), and the Utrecht Coronary Biobank (n = 1003) comprising a total 5917 patients. Homozygous GUCY1A3 risk allele carriers (GG) displayed increased on-aspirin platelet reactivity compared with non-risk allele (AA/AG) carriers [150 (interquartile range 91–209) vs. 134 (85–194) AU⋅min, P < 0.01]. More homozygous risk allele carriers, compared with non-risk allele carriers, were assigned to the high-risk group for ischaemic events (>203 AU⋅min; 29.5 vs. 24.2%, P = 0.02). Homozygous risk allele carriers were also at higher risk for cardiovascular death or stent thrombosis (hazard ratio 1.70, 95% confidence interval 1.08–2.68; P = 0.02). Bleeding risk was not altered.ConclusionWe conclude that homozygous GUCY1A3 risk allele carriers are at increased risk of cardiovascular death or stent thrombosis within 30 days after coronary stenting, likely due to higher on-aspirin platelet reactivity. Whether GUCY1A3 genotype helps to tailor antiplatelet treatment remains to be investigated.

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