C lopidogrel on top of aspirin improves clinical outcomes in patients with acute coronary syndrome and those undergoing percutaneous coronary intervention (PCI). 1 Although clopidogrel has been extensively prescribed, interindividual variation in clinical responses has fueled research into personalized pharmacotherapy for patients undergoing drug-eluting stent (DES) implantation.2,3 Clopidogrel has to be biotransformed into its active thiol metabolite to exert its antiplatelet effects; this is accomplished by hepatic cytochrome P450 isoenzymes such as CYP2C19. 4 The CYP2C19 loss-of-function (LOF) alleles (*2 and *3 alleles) result in less formation of active thiol metabolite, causing lack of platelet aggregation inhibition, which translates into a higher rate of subsequent cardiovascular events than noncarriers. Background-More intensive platelet suppression is required in patients with acute myocardial infarction (AMI) than in those with stable angina because of differential platelet activation between AMI and stable angina. In this context, CYP2C19 genotype leading to reduced active metabolite formation may profoundly affect the clinical outcome of clopidogrel therapy in patients with AMI compared with those with stable angina. Methods and Results-Effects of CYP2C19 genotypes on the clinical outcome of clopidogrel therapy were evaluated in 2188 patients (532 patients with AMI and 1656 patients with stable angina) undergoing percutaneous coronary intervention. The primary clinical outcome was a composite of major adverse cardiac and cerebrovascular events defined as death from any cause, nonfatal myocardial infarction, or stroke during 1 year of clopidogrel therapy. Compared with extensive metabolizer, the CYP2C19 poor metabolizer was significantly associated with higher risk of major adverse cardiac and cerebrovascular events in patients with AMI (hazard ratio, 2.88; 95% confidence interval, 1.27-6.53; P=0.011). However, this finding was not seen in patients with stable angina. A significant interaction between CYP2C19 genotypes and disease subsets of AMI and stable angina was identified with respect to major adverse cardiac and cerebrovascular events (adjusted interaction P=0.045). The patients with AMI showed lower percent inhibition of P2Y12 compared with patients with stable angina in CYP2C19 poor metabolizer or CYP2C19 intermediate metabolizer genotype groups but not in CYP2C19 extensive metabolizer genotype group. Conclusions-CYP2C19 poor metabolizer is associated with poor clinical outcome of clopidogrel therapy in Asian patients with AMI but not in those with stable angina possibly because of differential requirement of platelet suppression in patients with AMI and stable angina.
Background:The risk of excessive bleeding prompts physicians to stop multiple antiplatelet agents before minor surgery, which puts coronary stenting patients at risk for adverse thrombotic events.Hypothesis:We hypothesized that most dental extractions can be carried out safely without stopping multiple antiplatelet agents.Methods:All dental extraction patients who had undergone coronary stenting and who were also on oral multiple antiplatelet agents therapy were enrolled. One hundred patients underwent dental procedures without stopping antiplatelet agents. All wounds were sutured and followed up at 24 hours, 1 week, and 1 month after the procedure. There were 2233 patients who had not taken oral antiplatelet agents from a health promotion center and had teeth extracted by the same method. After performing propensity‐score matching for the entire population, a total of 100 matched pairs of patients were created. The primary outcome was a composite of excessive intraextraction blood loss, transfusion, and rehospitalization for bleeding, and the secondary outcome was a composite of death, nonfatal myocardial infarction, target lesion revascularization, and stent thrombosis within 1 month after the procedure.Results:There were 2 excessive intraextraction bleeding cases that continued at the extraction site for 4 and 5 hours, respectively, in the coronary stenting patients, and 1 excessive intraextraction bleeding case that continued for 3 hours in the control patients. There were no cases of transfusion, rehospitalization for bleeding, or major cardiovascular events for the 2 propensity‐matched groups.Conclusions:We found that most dental extractions in coronary stenting patients can be carried out safely without stopping multiple antiplatelet agents.The authors have no conflicts of interest to disclose.This study was supported in part by a grant from Yuhan Corporation, Ltd., Seoul, The Republic of Korea.
SummaryThis study aimed to evaluate the clinical prognostic implications of postprocedural Thrombolysis in Myocardial Infarction (TIMI) flow in acute myocardial infarction patients. A total of 2796 ST-elevation myocardial infarction (STEMI) and 1720 non ST-elevation myocardial infarction (NSTEMI) patients treated in 8 hospitals affiliated with the Catholic University of Korea and Chonnam National University Hospital were analyzed. The study populations were divided according to the final TIMI flow. The primary outcome were the major adverse cardiac events (MACE), defined as a composite of cardiac deaths (CD), nonfatal myocardial infarctions (MI), and target lesion revascularization (TLR). Over a median follow-up of 3.3 years (minimum 2 to maximum 5 years), MACE and CD occurred more frequently in STEMI patients with TIMI !2 group than those with TIMI 3 (MACE: adjusted hazard ratio [aHR], 1.962; 95% confidence interval [CI] 1.513 to 2.546, P < 0.001, CD: aHR, 3.154, CI 2.308 to 4.309, P < 0.001). However, there was no significant difference between the two subgroups in NSTEMI (aHR, 0.932; 95% CI 0.586 to 1.484, P = 0.087). In STEMI patients, good postprocedural TIMI flow after PCI was associated with favorable clinical outcomes. And the effect of poor TIMI flow in STEMI was on death, not the components of MACE. Meanwhile, postprocedural TIMI flow had no effect on long-term outcomes in NSTEMI patients.(Int Heart J 2017; 58: 674-685)
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