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CYP2C19 loss-of-function alleles are not associated with clinical outcome of clopidogrel therapy in patients treated with newer-generation drug-eluting stents.

ABSTRACT: CYP2C19 loss-of-function (LOF) alleles adversely affect clinical outcome of clopidogrel therapy. Recent introduction of a newer-generation drug-eluting stent (DES) has significantly reduced the occurrence of stent thrombosis.The aim of this study was to evaluate the impact of CYP2C19 LOF alleles on clinical outcome in patients treated with the newer-generation DES.The effects of CYP2C19 genotypes were evaluated on clinical outcome of clopidogrel therapy in 2062 patients treated with percutaneous coronary intervention using either first-generation DES (sirolimus- and paclitaxel-eluting stent, n = 1349) or newer-generation DES (everolimus- and zotarolimus-eluting stent, n = 713). The primary clinical outcome was major cardiac and cerebrovascular event (MACCE) including cardiac death, nonfatal myocardial infarction, stroke, and stent thrombosis during 1 year of follow-up.CYP2C19 LOF alleles were significantly associated with a higher risk of MACCE in patients treated with first-generation DES (hazard ratio [HR] 2.599, 95% confidence interval [CI] 1.047-6.453; P = 0.034). In contrast, CYP2C19 LOF alleles were not associated with primary outcome in newer-generation DES (HR 0.716, 95% CI 0.316-1.622; P = 0.522). In the further multivariate analysis, CYP2C19 LOF alleles were not associated with MACCE in patients receiving newer-generation DES (adjusted HR 0.540, 95% CI 0.226-1.291; P = 0.166), whereas they were demonstrated to be an independent risk factor for MACCE in those implanted with first-generation DES (adjusted HR 3.501, 95% CI 1.194-10.262; P = 0.022).In contradiction to their clinical impact in first-generation DES era, CYP2C19 LOF alleles may not affect clinical outcome of clopidogrel therapy in patients treated with newer-generation DES.

SUBMITTER: Choi IJ

PROVIDER: S-EPMC4937952 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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CYP2C19 loss-of-function alleles are not associated with clinical outcome of clopidogrel therapy in patients treated with newer-generation drug-eluting stents.

Choi Ik Jun IJ Koh Yoon-Seok YS Park Mahn-Won MW Her Sung Ho SH Choi Yun-Seok YS Park Chul-Soo CS Park Hun-Jun HJ Kim Pum-Joon PJ Chung Wook-Sung WS Kim Ho-Sook HS Shin Jae-Gook JG Seung Ki-Bae KB Chang Kiyuk K

Medicine 20160601 26

CYP2C19 loss-of-function (LOF) alleles adversely affect clinical outcome of clopidogrel therapy. Recent introduction of a newer-generation drug-eluting stent (DES) has significantly reduced the occurrence of stent thrombosis.The aim of this study was to evaluate the impact of CYP2C19 LOF alleles on clinical outcome in patients treated with the newer-generation DES.The effects of CYP2C19 genotypes were evaluated on clinical outcome of clopidogrel therapy in 2062 patients treated with percutaneous ...[more]

PMID: 27368038

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Project description:Background Percutaneous coronary intervention of calcified lesions was associated with worse outcomes in the era of bare-metal and first-generation drug-eluting stents. Data on percutaneous coronary intervention of calcified lesions with newer-generation drug-eluting stents are scarce. Therefore, we investigated the impact of lesion calcification on clinical outcomes in patients undergoing percutaneous coronary intervention with a bioresorbable-polymer sirolimus-eluting stent or a durable-polymer everolimus-eluting stent. Methods and Results Patients (n=2361) from BIOFLOW II, IV, and V trials were categorized into moderate/severe versus none/mild lesion calcification by a core laboratory. End points were target-lesion failure (TLF) (cardiac death, target-vessel myocardial infarction, or target-lesion revascularization) and probable/definite stent thrombosis at 2 years. The agreement in calcification assessment between the operator and the core laboratory was weak (weighted κ, 0.23). Patients with moderate/severe calcification (n=303; 16%) had higher TLF (13.5% versus 8.4%; P=0.003) and stent thrombosis rates (2.1% versus 0.2%; P<0.0001), whereas target-lesion revascularization was not different between the groups (5.0% versus 3.9%; P=0.302). After adjustment, calcification did not emerge as an independent predictor of TLF (adjusted hazard ratio [aHR], 1.37; 95% CI, 0.89-2.08; P=0.148) but did for target-vessel myocardial infarction (aHR, 1.66; 95% CI, 1.03-2.68; P=0.037). TLF rates were similar between bioresorbable-polymer sirolimus-eluting stent and durable-polymer everolimus-eluting stent (12.6% versus 15.4%, P=0.482) in moderate/severe calcification. In none/mild calcification, the bioresorbable-polymer sirolimus-eluting stent showed lower TLF (7.5% versus 10.3%, P=0.045). Conclusions With newer-generation drug-eluting stents, moderate/severe lesion calcification was not associated with more TLF after adjustment for the higher risk of patients with coronary calcification, whereas the rate of target-vessel myocardial infarction was higher. The bioresorbable-polymer sirolimus-eluting stent and durable-polymer everolimus-eluting stent were equally effective and safe in calcified lesions. Registration URL: https://www.clinicaltrials.gov; Unique identifiers: NCT01356888, NCT01939249, NCT02389946.

Project description:BackgroundDiabetes is associated with adverse outcomes after percutaneous coronary intervention with drug-eluting stents (DES), but for prediabetes this association has not been definitely established. Furthermore, in patients with prediabetes treated with contemporary stents, bleeding data are lacking. We assessed 3-year ischemic and bleeding outcomes following treatment with new-generation DES in patients with prediabetes and diabetes as compared to normoglycemia.MethodsFor this post-hoc analysis, we pooled patient-level data of the BIO-RESORT and BIONYX stent trials which both stratified for diabetes at randomization. Both trials were multicenter studies performed in tertiary cardiac centers. Study participants were patients of whom glycemic state was known based on hemoglobin A1c, fasting plasma glucose, or medically treated diabetes. Three-year follow-up was available in 4212/4330 (97.3 %) patients. The main endpoint was target vessel failure, a composite of cardiac death, target vessel myocardial infarction, or target vessel revascularization.ResultsBaseline cardiovascular risk profiles were progressively abnormal in patients with normoglycemia, prediabetes, and diabetes. The main endpoint occurred in 54/489 patients with prediabetes (11.2 %) and 197/1488 with diabetes (13.7 %), as compared to 142/2,353 with normoglycemia (6.1 %) (HR: 1.89, 95 %-CI 1.38-2.58, p < 0.001, and HR: 2.30, 95 %-CI 1.85-2.86, p < 0.001, respectively). In patients with prediabetes, cardiac death and target vessel revascularization rates were significantly higher (HR: 2.81, 95 %-CI 1.49-5.30, p = 0.001, and HR: 1.92, 95 %-CI 1.29-2.87, p = 0.001), and in patients with diabetes all individual components of the main endpoint were significantly higher than in patients with normoglycemia (all p ≤ 0.001). Results were consistent after adjustment for confounders. Major bleeding rates were significantly higher in patients with prediabetes and diabetes, as compared to normoglycemia (3.9 % and 4.1 % vs. 2.3 %; HR:1.73, 95 %-CI 1.03-2.92, p = 0.040, and HR:1.78, 95 %-CI 1.23-2.57, p = 0.002). However, after adjustment for confounders, differences were no longer significant.ConclusionsNot only patients with diabetes but also patients with prediabetes represent a high-risk population. After treatment with new-generation DES, both patient groups had higher risks of ischemic and bleeding events. Differences in major bleeding were mainly attributable to dissimilarities in baseline characteristics. Routine assessment of glycemic state may help to identify patients with prediabetes for intensified management of cardiovascular risk factors.Trial registrationBIO-RESORT ClinicalTrials.gov: NCT01674803, registered 29-08-2012; BIONYX ClinicalTrials.gov: NCT02508714, registered 27-7-2015.

Project description:Background The choice of optimal drug-eluting stent therapy for patients with diabetes mellitus (DM) undergoing percutaneous coronary intervention remains uncertain. We aimed to assess the long-term clinical outcomes after percutaneous coronary intervention with biodegradable polymer sirolimus-eluting stents (BP-SES) versus durable polymer everolimus-eluting stents (DP-EES) in patients with DM. Methods and Results In a prespecified subgroup analysis of the BIOSCIENCE (Ultrathin Strut Biodegradable Polymer Sirolimus-Eluting Stent Versus Durable Polymer Everolimus-Eluting Stent for Percutaneous Coronary Revascularization) trial (NCT01443104), patients randomly assigned to ultrathin-strut BP-SES or thin-strut DP-EES were stratified according to diabetic status. The primary end point was target lesion failure, a composite of cardiac death, target vessel myocardial infarction, and clinically indicated target lesion revascularization, at 5 years. Among 2119 patients, 486 (22.9%) presented with DM. Compared with individuals without DM, patients with DM were older and had a greater baseline cardiac risk profile. In patients with DM, target lesion failure at 5 years occurred in 74 patients (cumulative incidence, 31.0%) treated with BP-SES and 57 patients (25.8%) treated with DP-EES (risk ratio, 1.23; 95% CI, 0.87-1.73 [P=0.24]). In individuals without DM, target lesion failure at 5 years occurred in 124 patients (16.8%) treated with BP-SES and 132 patients (16.8%) treated with DP-EES (risk ratio, 0.98; 95% CI, 0.77-1.26 [P=0.90; P for interaction=0.31]). Cumulative 5-year incidence rates of cardiac death, target vessel myocardial infarction, clinically indicated target lesion revascularization, and definite stent thrombosis were similar among patients with DM treated with BP-SES or DP-EES. There was no interaction between diabetic status and treatment effect of BP-SES versus DP-EES. Conclusions In a prespecified subgroup analysis of the BIOSCIENCE trial, we found no difference in clinical outcomes throughout 5 years between patients with DM treated with ultrathin-strut BP-SES or thin-strut DP-EES. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT01443104.

Dataset Information

CYP2C19 loss-of-function alleles are not associated with clinical outcome of clopidogrel therapy in patients treated with newer-generation drug-eluting stents.

Publications

CYP2C19 loss-of-function alleles are not associated with clinical outcome of clopidogrel therapy in patients treated with newer-generation drug-eluting stents.

Similar Datasets

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