Dataset Information

Incidence of major adverse cardiovascular events with genotype test guided antiplatelet treatment strategy after percutaneous coronary intervention.

ABSTRACT:

Objective

To estimate the incidence of major adverse cardiovascular events (MACE) with genotype test-guided antiplatelet therapy in patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome.

Methods

Patients who had undergone PCI for acute coronary syndrome as well as stable coronary artery disease were recruited. Salivary samples were obtained from these patients and genotyped for CYP2C19?2, CYP2C19?3 variations by sequencing method (GAAP x method). Patients were categorized as normal (GG, GG) (29%), intermediate (AG) (52%) or poor metabolizes (homozygous variant AA) (19%). Dual antiplatelets were given based on the genotyping data. Poor metabolizes received newer agent (ticagrelor), intermediate metabolizes received double-dose of clopidogrel and normal metabolizes received therapeutic doses of clopidogrel. All subjects were followed-up for six months.

Results

Based on the genotyping data of CYP2C19?2 and CYP2C19?3 variations, it was found that most patients were categorized as 'intermediate' (78, 51.65%), followed by 'normal' (43, 28.48%) and 'poor' metabolizes (30, 19.87%). Only 3 (1.5%) of 151 patients reported MACE at follow-up.

Conclusions

Genotyping for CYP2C19 variations to assess clopidogrel resistance in patients undergoing PCI and subsequent drug selection helps reduce MACE after coronary intervention.

SUBMITTER: Ramesh S

PROVIDER: S-EPMC7772580 | biostudies-literature | 2020 Nov-Dec

REPOSITORIES: biostudies-literature

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Publications

Incidence of major adverse cardiovascular events with genotype test guided antiplatelet treatment strategy after percutaneous coronary intervention.

Ramesh S S Socrates S S Rajasekaran M A MA Senguttuvan N N

Indian heart journal 20200909 6

<h4>Objective</h4>To estimate the incidence of major adverse cardiovascular events (MACE) with genotype test-guided antiplatelet therapy in patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome.<h4>Methods</h4>Patients who had undergone PCI for acute coronary syndrome as well as stable coronary artery disease were recruited. Salivary samples were obtained from these patients and genotyped for CYP2C19∗2, CYP2C19∗3 variations by sequencing method (GAAP x method). ...[more]

PMID: 33357650

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Project description:OBJECTIVES:This multicenter pragmatic investigation assessed outcomes following clinical implementation of CYP2C19 genotype-guided antiplatelet therapy after percutaneous coronary intervention (PCI). BACKGROUND:CYP2C19 loss-of-function alleles impair clopidogrel effectiveness after PCI. METHODS:After clinical genotyping, each institution recommended alternative antiplatelet therapy (prasugrel, ticagrelor) in PCI patients with a loss-of-function allele. Major adverse cardiovascular events (defined as myocardial infarction, stroke, or death) within 12 months of PCI were compared between patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy. Risk was also compared between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy. Cox regression was performed, adjusting for group differences with inverse probability of treatment weights. RESULTS:Among 1,815 patients, 572 (31.5%) had a loss-of-function allele. The risk for major adverse cardiovascular events was significantly higher in patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy (23.4 vs. 8.7 per 100 patient-years; adjusted hazard ratio: 2.26; 95% confidence interval: 1.18 to 4.32; p = 0.013). Similar results were observed among 1,210 patients with acute coronary syndromes at the time of PCI (adjusted hazard ratio: 2.87; 95% confidence interval: 1.35 to 6.09; p = 0.013). There was no difference in major adverse cardiovascular events between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy (adjusted hazard ratio: 1.14; 95% confidence interval: 0.69 to 1.88; p = 0.60). CONCLUSIONS:These data from real-world observations demonstrate a higher risk for cardiovascular events in patients with a CYP2C19 loss-of-function allele if clopidogrel versus alternative therapy is prescribed. A future randomized study of genotype-guided antiplatelet therapy may be of value.

Project description:Prasugrel is recommended over clopidogrel in poor/intermediate CYP2C19 metabolizers with acute coronary syndrome (ACS) and planned percutaneous coronary intervention (PCI), reducing the risk of ischemic events. CYP2C19 genetic testing can guide antiplatelet therapy in ACS patients.The purpose of this study was to evaluate the cost-utility of genotype-guided treatment, compared with prasugrel or generic clopidogrel treatment without genotyping, from the US healthcare provider's perspective.A decision model was developed to project lifetime economic and humanistic burden associated with clinical outcomes (myocardial infarction [MI], stroke and major bleeding) for the three strategies in patients with ACS. Probabilities, costs and age-adjusted quality of life were identified through systematic literature review. Incremental cost-utility ratios (ICURs) were calculated for the treatment strategies, with quality-adjusted life years (QALYs) as the primary effectiveness outcome. Relative risk of developing myocardial infarction and stroke between patients with and without variant CYP2C19 when receiving clopidogrel were estimated to be 1.34 and 3.66, respectively. One-way and probabilistic sensitivity analyses were performed.Clopidogrel cost USD19,147 and provided 10.03 QALYs versus prasugrel (USD21,425, 10.04 QALYs) and genotype-guided therapy (USD19,231, 10.05 QALYs). The ICUR of genotype-guided therapy compared with clopidogrel was USD4,200. Genotype-guided therapy provided more QALYs at lower costs compared with prasugrel. Results were sensitive to the cost of clopidogrel and relative risk of myocardial infarction and stroke between CYP2C19 variant vs. non-variant. Net monetary benefit curves showed that genotype-guided therapy had at least 70% likelihood of being the most cost-effective alternative at a willingness-to-pay of USD100,000/QALY. In comparison with clopidogrel, prasugrel therapy was more cost-effective with <21% certainty at willingness-to-pay of >USD170,000/QALY.Our modeling analyses suggest that genotype-guided therapy is a cost-effective strategy in patients with acute coronary syndrome undergoing planned percutaneous coronary intervention.

Project description:BackgroundPatients with multiple clinical risk factors are a complex group in whom both bleeding and recurrent ischaemic events often occur during treatment with dual/triple antithrombotic therapy after percutaneous coronary intervention. Decisions on optimal antithrombotic treatment in these patients are challenging and not supported by clear guideline recommendations. A prospective observational cohort study was set up to evaluate patient-related factors, platelet reactivity, genetics, and a broad spectrum of biomarkers in predicting adverse events in these high-risk patients. Aim of the current paper is to present the study design, with a detailed description of the cohort as a whole, and evaluation of bleeding and ischaemic outcomes during follow-up, thereby facilitating future research questions focusing on specific data provided by the cohort.MethodsWe included patients with ≥ 3 predefined risk factors who were treated with dual/triple antithrombotic therapy following PCI. We performed a wide range of haemostatic tests and collected all ischaemic and bleeding events during 6-12 months follow-up.ResultsWe included 524 high-risk patients who underwent PCI within the previous 1-2 months. All patients used a P2Y12 inhibitor (clopidogrel n = 388, prasugrel n = 61, ticagrelor n = 75) in combination with aspirin (n = 397) and/or anticoagulants (n = 160). Bleeding events were reported by 254 patients (48.5%), necessitating intervention or hospital admission in 92 patients (17.5%). Major adverse cardiovascular events (myocardial infarction, stroke, death) occurred in 69 patients (13.2%).ConclusionThe high risk for both bleeding and ischaemic events in this cohort of patients with multiple clinical risk factors illustrates the challenges that the cardiologist faces to make a balanced decision on the optimal treatment strategy. This cohort will serve to answer several future research questions about the optimal management of these patients on dual/triple antithrombotic therapy, and the possible value of a wide range of laboratory tests to guide these decisions.

Project description:In patients undergoing percutaneous coronary intervention (PCI), the standard of care is dual antiplatelet therapy with a P2Y12 inhibitor (clopidogrel, prasugrel, or ticagrelor) and aspirin. Current clinical practice guidelines now recommend more potent P2Y12 inhibitors (prasugrel or ticagrelor) over clopidogrel in acute coronary syndrome (ACS). However, clopidogrel remains the most commonly prescribed P2Y12 inhibitor in the setting of PCI and is also the preferred agent in the treatment and secondary prevention of stroke. Clopidogrel is a prodrug that requires bioactivation by the CYP2C19 enzyme. It has been shown that clopidogrel use in patients who are CYP2C19 no function allele carriers are associated with impaired antiplatelet inhibition and a higher risk of major adverse cardiovascular and cerebrovascular events. Compared to clopidogrel, prasugrel and ticagrelor clinical response is not impacted by CYP2C19 genotype. Even with a demonstrated increased risk of adverse outcomes in CYP2C19 no function allele carriers treated with clopidogrel, routine implementation of CYP2C19 genotyping to guide antiplatelet therapy selection has remained controversial and has not been widely adopted. Recent results from multiple prospective randomized and nonrandomized clinical trials investigating the use of CYP2C19 genotype-guided antiplatelet therapy following PCI have advanced the evidence base demonstrating the clinical utility of this strategy. Multiple recent studies have examined the effects of CYP2C19 genotype on clopidogrel outcomes in the setting of stroke and neurointerventional procedures. In this review, we discern the clinical utility of using CYP2C19 genotype testing to guide antiplatelet therapy prescribing by evaluating the impact of CYP2C19 genotype-guided selection of antiplatelet therapy on clinical outcomes, summarizing emerging data from cardiovascular and neurology clinical studies, and discussing implications for clinical practice guidelines, remaining knowledge gaps and future research directions.

Project description:Background The net clinical benefit of dual antiplatelet therapy (DAPT) reflects the paradoxical effects of an increased risk of bleeding and a reduced risk of major adverse cardiovascular events. A time-constrained approach to DAPT has been recently investigated in 5 multicenter trials including GLOBAL LEADERS, STOPDAPT2 (Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent-2), SMART-CHOICE, TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention), and TICO (Ticagrelor Monotherapy After 3 Months in the Patients Treated With New Generation Sirolimus Stent for Acute Coronary Syndrome). Methods and Results We undertook a pooled analysis of these trials to assess the overall associations between time-constrained P2Y12 inhibitor monotherapy (aspirin-free regimen) for bleeding events, major adverse cardiovascular events, and all-cause mortality as compared to standard care with DAPT for at least 12 months post-percutaneous coronary intervention. We implemented a DerSimonian and Laird random effects meta-analysis using the metafor package in R. 32 361 randomized trial participants, including 16 898 (52.2%) who had a history of acute coronary syndrome, underwent percutaneous coronary intervention, and had outcome data available. P2Y12 inhibitor monotherapy from 1 to 3 months was associated with a reduced risk for bleeding (hazard ratio [HR] 0.60; 95% CI, 0.45-0.81), including in the acute coronary syndrome group in which the magnitude of risk reduction was greatest (HR 0.50; 95% CI, 0.41-0.61). The estimates of the effect of P2Y12 inhibitor monotherapy on the HR were also favorable for major adverse cardiovascular events (0.88; 95% CI, 0.77-1.02) and all-cause mortality (0.85; 95% CI, 0.71-1.03). Conclusions Compared with DAPT for 12 months post-percutaneous coronary intervention, P2Y12 inhibitor monotherapy from 1 to 3 months substantially reduces the risk of major and fatal bleeding and, in addition, confers potentially protective effects, for major adverse cardiovascular events and all-cause mortality. Considering patient safety, the results support a strategy of DAPT for 1 to 3 months followed by aspirin-free P2Y12 inhibitor monotherapy.

Dataset Information

Incidence of major adverse cardiovascular events with genotype test guided antiplatelet treatment strategy after percutaneous coronary intervention.

Objective

Methods

Results

Conclusions

Publications

Incidence of major adverse cardiovascular events with genotype test guided antiplatelet treatment strategy after percutaneous coronary intervention.

Similar Datasets

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