Impact of CYP2C19＊2 and CYP2C19＊3 Polymorphisms on the Response to Clopidogrel and Running Cost Analyses

We investigated the variability in the PFT （platelet function test） response to CYP2C19 polymorphisms and compared it with the clinical presentation. Furthermore, running cost analyses were done. One-hundred and seventy Saudi Arabian patients who were stable on 75 mg clopidogrel for ≥1 month for various cardiac indications were enrolled. We extracted DNA using the MagNA Pure LC instrument. CYP2C19 genotyping for the alleles, ＊1, ＊2 and ＊3, was conducted by real-time PCR （polymerase chain reaction）. The PFT was carried out by VerifyNow P2Y12 assay for all patients. Clinical events were documented retrospectively for all patients. One hundred and seventeen patients presented with the wild variant 1/1, 19 patients with 1/2, and 34 patients with 2/2. We could not detect ＊3. There was a significant association between different genotyping and percentage inhibitions （P = 0.0002）. 1/1 patients tended to be moderate-to-extensive metabolisers, whereas most of the other patients were slow metabolisers. The cost of doing the PFT was 250 SR （Saudi Riyals）/patient and 200 SR/patient for kits and materials （excluding equipment and labour）. The PFT varied considerably with polymorphisms, but showed no significant associations with clinical symptoms.

A Multicenter, Randomized, Double-Blind, and Placebo-Controlled Study of the Effects of Tongxinluo Capsules in Acute Coronary Syndrome Patients with High On-Treatment Platelet Reactivity

Background： High platelet reactivity （HPR） during clopidogrel treatment predicts postpercutaneous coronary intervention （PCI） ischemic events strongly and independently. Tongxinluo capsules （TCs） are a traditional Chinese medicine formulation used as antiplatelet treatment. However, its efficacy against HPR is not known. The aim of the present study was to evaluate the effects of TCs in acute coronary syndrome （ACS） patients with HPR. Methods： This multicenter, randomized, double-blind, placebo-controlled study prospectively analyzed 136 ACS patients with HPR who underwent PCI. The patients were enrolled from November 2013 to May 2014 and randomized to receive placebo or TCs in addition to standard dual antiplatelet therapy （DAPT） with aspirin and clopidogrel. The primary end points were the prevalence of HPR at 30 days and the mean change in P2YIz reaction units （PRUs） between baseline and 30 days. Survival curves were constructed with Kaplan-Meier estimates and compared by log-rank tests between the two groups. Results： Both groups had a significantly reduced prevalence of HPR at 30 days versus baseline, but the TC group, compared with the placebo group, had greater reduction （ 15.8% vs. 24.8%, P = 0.013）, especially among patients with one cytochrome P450 2C 19 loss of function （LOF） allele （χ2 = 2.931, P = 0.047）. The TC group also had a lower prevalence of HPR （33.3% vs. 54.2%, t - 5.284, P 0.022） and superior performance in light transmittance aggregometry and higher levels of high-sensitivity C-reactive protein （hsCRP）, but the composite prevalence ofischemic events did not differ significantly （χ2 = 1.587, P = 0.208）. Conclusions： In addition to standard DAPT with aspirin and clopidogrel, TCs further reduce PRU and hsCRP levels, especially in patients carrying only one LOF allele. The data suggest that TCs could be used in combination therapy for ACS patients with HPR undergoing PCI.

Intensified Antiplatelet Treatment Reduces Major Cardiac Events in Patients with Clopidogrel Low Response： A Meta-analysis of Randomized Controlled Trials

Background：Clopidogrel low response （CLR） is an independent risk factor of adverse outcomes in patients undergoing percutaneous coronary intervention （PCI）,and intensified antiplatelet treatments （IAT） guided by platelet function assays might overcome laboratory CLR.However,whether IAT improves clinical outcomes is controversial.Methods：Relevant trials were identified in PubMed,the Cochrane Library,and the Chinese Medical Journal Network databases from their establishment to September 9,2014.Trials were screened using predefined inclusion criteria.Conventional meta-analysis and cumulative meta-analysis were performed using the Review Manager 5.0 and STATA 12.0 software programs.Results：Thirteen randomized controlled trials involving 5111 patients with CLR were recruited.During a follow-up period of 1-12 months,the incidences of cardiovascular （CV） death,nonfatal myocardial infarction （MI）,and stent thrombosis were significantly lower in the IAT arm than in the conventional antiplatelet treatment arm （relative risk [RR] =0.45,95% confidence interval [CI]：0.36-0.57,P 〈 0.000,01）,whereas bleeding was similar between the two arms （RR =1.05,95% CI：0.86-1.27,P =0.65）.Conclusions：IAT guided by platelet function assays reduces the risk of CV death,nonfatal MI,and stent thrombosis （ST） without an increased risk of bleeding in patients undergoing PCI and with CLR.