OBJECTIVETo assess the association of CYP2C19 gene polymorphisms with the incidence of ischemic stroke among patients receiving clopidogrel therapy following coronary stenting for coronary artery disease.

METHODSClinical data of patients receiving clopidogrel therapy after coronary stenting were retrospectively studied. For a case-control study, 137 patients with acute cerebral infarction and 122 non-stroke patients were selected. Based on the variants of the CYP2C19 gene detected by a DNA microarray assay, the patients were further divided into the wild-type group(CYP2C19*1/*1) and mutant group(defined by the presence of at least one loss-of-function allele, including CYP2C19*1/*2, CYP2C19*1/*3, CYP2C19*2/*2, CYP2C19*2/*3 and CYP2C19*3/*3). The incidences of ischemic stroke in the two groups were compared through a chi-square analysis. The influence of CYP2C19 gene polymorphisms and clopidogrel therapy on the incidence of ischemic stroke was analyzed through multivariable logistic regression.

RESULTSA total of 259 patients were enrolled. The case and control groups showed no difference in terms of gender and age. There were 123 cases (47.5%) in the CYP2C19 wild-type group and 136 cases (52.5%) in the mutant group. The incidence of ischemic stroke of mutant group was significantly higher than that of wild-type group (59.9% vs. 44.3%, X2=6.398, P=0.042). Multivariate analysis revealed that loss-of-function polymorphisms of the CYP2C19 gene carried a 1.13 times greater risk for ischemic stroke compared to wild-type genotype (OR=2.13, 95%CI: 1.23-3.71).

CONCLUSIONThe efficacy of clopidogrel for the prevention of ischemic stroke in post-coronary stent patients may be reduced by the insufficiency of the CYP2C19 gene. The dosage of clopidogrel therapy should be adjusted based on its polymorphisms.

Brain Ischemia ; prevention & control ; Cytochrome P-450 CYP2C19 ; genetics ; Genotype ; Humans ; Percutaneous Coronary Intervention ; adverse effects ; Platelet Aggregation Inhibitors ; therapeutic use ; Polymorphism, Genetic ; Stents ; adverse effects ; Stroke ; prevention & control ; Ticlopidine ; analogs & derivatives ; therapeutic use

BACKGROUNDClopidogrel 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.

METHODSRelevant 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.

RESULTSThirteen 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).

CONCLUSIONSIAT 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.

Cardiovascular Diseases ; mortality ; Humans ; Myocardial Infarction ; prevention & control ; Percutaneous Coronary Intervention ; adverse effects ; Platelet Aggregation Inhibitors ; therapeutic use ; Randomized Controlled Trials as Topic ; Stents ; adverse effects ; Ticlopidine ; analogs & derivatives ; therapeutic use

BACKGROUNDThe efficacy and safety of telmisartan combined with clopidogrel, leflunomide, or both drugs for immunoglobulin A nephropathy (IgAN) are unclear. This study was designed to evaluate the efficacy and safety of telmisartan combined with clopidogrel, leflunomide, or both drugs for IgAN.

METHODSIt is a multicenter, prospective, double-dummy randomized controlled trial. Primary IgAN patients were recruited in 13 renal units across Beijing, China, from July 2010 to June 2012. After a 4-week telmisartan (80 mg/d) wash-in, 400 patients continuing on 80 mg/d telmisartan were randomly assigned to additionally receive placebo (Group A), 50 mg/d clopidogrel (Group B), 20 mg/d leflunomide (Group C), or 50 mg/d clopidogrel and 20 mg/d leflunomide (Group D). The 24-week intervention was completed by 360 patients. The primary endpoint was change in 24-h proteinuria at 24 weeks. A linear mixed-effect model was used to analyze the changes at 4, 12, and 24 weeks. Generalized estimating equations were used to evaluate changes in hematuria grade. This trial was registered at the Chinese Clinical Trial Registry.

RESULTSThe effects of telmisartan combined with leflunomide on changes in proteinuria (0.36 [95% confidence interval (CI) 0.18-0.55] g/d, P < 0.001), in serum uric acid (76.96 [95% CI 57.44-96.49] μmol/L, P < 0.001), in serum creatinine (9.49 [95% CI 6.54-12.44] μmol/L, P < 0.001), and in estimated glomerular filtration rate (-6.72 [95% CI-9.46 to -3.98] ml·min-1·1.73 m-2, P < 0.001) were statistically significant, whereas they were not statistically significant on changes in systolic and diastolic blood pressure and weight (P > 0.05). Telmisartan combined with clopidogrel had no statistical effect on any outcome, and there was no interaction between the interventions. No obvious adverse reactions were observed.

CONCLUSIONSTelmisartan combined with leflunomide, not clopidogrel, is safe and effective for decreasing proteinuria in certain IgAN patients.

TRIAL REGISTRATIONchictr.org.cn, ChiCTR-TRC-10000776; http://www.chictr.org.cn/showproj.aspx?proj=8760.

Adolescent ; Adult ; Benzimidazoles ; adverse effects ; therapeutic use ; Benzoates ; adverse effects ; therapeutic use ; Blood Pressure ; drug effects ; China ; Creatinine ; blood ; Female ; Glomerular Filtration Rate ; drug effects ; Glomerulonephritis, IGA ; blood ; drug therapy ; Humans ; Isoxazoles ; adverse effects ; therapeutic use ; Kidney Function Tests ; Male ; Middle Aged ; Prospective Studies ; Ticlopidine ; adverse effects ; analogs & derivatives ; therapeutic use ; Treatment Outcome ; Uric Acid ; blood ; Young Adult

BACKGROUND/AIMS: Combination single-pill therapy can improve cost-effectiveness in a typical medical therapy. However, there is a little evidence about the efficacy and tolerability of combination single-pill antiplatelet therapy after percutaneous coronary intervention (PCI) with drug-eluting stents (DES). METHODS: From June to November 2012, in total, 142 patients who met the following criteria were enrolled: at least 18 years old; successful PCI with DES at least 3 months earlier; and regular medication of aspirin and clopidogrel with no side effects. After VerifyNow P2Y12 and aspirin assays, the combination single pill of aspirin and clopidogrel was given and laboratory tests were repeated 6 weeks later. RESULTS: At baseline, the incidence of aspirin resistance, defined as aspirin reaction unit (ARU) > or = 550, was 9.2%, that of clopidogrel resistance, defined as P2Y12 reaction unit (PRU) > or = 230, was 46.5%, and that of percent inhibition of PRU < 20% was 32.4%. At follow-up, the incidence of resistance by ARU value was 7.0%, 50.0% by PRU value, and 35.9% by percentage inhibition of PRU, respectively. The mean values of ARU (431.5 +/- 63.6 vs. 439.8 +/- 55.2; p = 0.216) and PRU (227.5 +/- 71.4 vs. 223.3 +/- 76.0; p = 0.350) were not significantly different before versus after antiplatelet-combination single-pill therapy. Five adverse events (3.5%) were observed during the study period. CONCLUSIONS: Combination single-pill antiplatelet therapy, which may reduce daily pill burden for patients after PCI with DES, demonstrated similar efficacy to separate dual-pill antiplatelet therapy.
Aged ; Antiplatyhelmintic Agents/*administration & dosage/adverse effects ; Aspirin/*administration & dosage/adverse effects ; Drug Combinations ; Drug Resistance ; *Drug-Eluting Stents ; Female ; Humans ; Intention to Treat Analysis ; Male ; Middle Aged ; Myocardial Ischemia/blood/diagnosis/*therapy ; Percutaneous Coronary Intervention/adverse effects/*instrumentation ; Platelet Function Tests ; Prospective Studies ; Tablets ; Ticlopidine/administration & dosage/adverse effects/*analogs & derivatives ; Time Factors ; Treatment Outcome

Aspirin ; adverse effects ; therapeutic use ; Cerebral Hemorrhage ; chemically induced ; Humans ; Ischemic Attack, Transient ; drug therapy ; Male ; Middle Aged ; Ticlopidine ; adverse effects ; analogs & derivatives ; therapeutic use

We report a case of delayed cerebral infarction due to stent longitudinal folding deformation following carotid artery stenting using a self-expandable stent with an open-cell design. The stented segment of the left common carotid artery was divided into two different lumens by this folding deformation, and the separated lumens became restricted with in-stent thrombosis. Although no established method of managing this rare complication exists, a conservative approach was taken with administration of anticoagulant and dual antiplatelet therapy. No neurological symptoms were observed during several months of clinical follow-up after discharge.
Aged ; Anticoagulants/therapeutic use ; Carotid Arteries/radiography ; Cerebral Infarction/*diagnosis/therapy ; Humans ; Male ; Platelet Aggregation Inhibitors/therapeutic use ; Stents/*adverse effects ; Thrombosis/drug therapy/*etiology ; Ticlopidine/analogs & derivatives/therapeutic use ; Tomography, X-Ray Computed

OBJECTIVETo determine the impact of adjunctive Buchang Naoxintong Capsule (, NXT) on dual antiplatelet therapy in patients with cytochrome P450 2C19*2 (CYP2C19*2) polymorphism undergoing percutaneous coronary intervention (PCI).

METHODSNinety patients with CYP2C19*2 polymorphism were enrolled, and their genotypes were confirmed by polymerase chain reaction (PCR). The patients were randomly assigned to receive either adjunctive NXT (triple group, 45 cases) or dual antiplatelet therapy (dual group, 45 cases) using a computer-generated randomization sequence and sealed envelopes. Platelet function was assessed at baseline and 7 days after treatment with conventional aggregometry. Subsequent major adverse cardiovascular events (MACE, including sudden cardiac arrest and acute coronary syndrome) were recorded during a 12-month follow-up.

RESULTSBaseline platelet function measurements were similar in both groups. After 7 days, percent inhibitions of maximum platelet aggregation and late platelet aggregation were significantly greater in the triple versus dual group (42.3%±16.0% vs. 20.8%±15.2%, P<0.01, and 54.7%±18.3% vs. 21.5%±29.2%, P<0.01, respectively). During the 12-month follow-up, the rate of subsequent MACE (6/45) was significantly lower in the triple group compared with the dual group (14/45; P<0.05).

CONCLUSIONAdjunctive NXT to maintenance dose clopidogrel (75 g) could enhance the antiplatelet effect and decrease subsequent MACE in patients with the CYP2C19*2 polymorphism undergoing PCI.

Adenosine Diphosphate ; pharmacology ; Cytochrome P-450 CYP2C19 ; genetics ; Drugs, Chinese Herbal ; adverse effects ; pharmacology ; Female ; Follow-Up Studies ; Humans ; Kaplan-Meier Estimate ; Maintenance Chemotherapy ; Male ; Middle Aged ; Platelet Aggregation ; drug effects ; Platelet Aggregation Inhibitors ; adverse effects ; pharmacology ; Platelet Function Tests ; Polymorphism, Genetic ; Ticlopidine ; adverse effects ; analogs & derivatives ; pharmacology ; Treatment Outcome

BACKGROUNDThe combination of cilostazol, aspirin and clopidogrel (triple antiplatelet therapy, TAT) after a percutaneous coronary intervention has been used as an alternative therapy. We performed a meta-analysis to evaluate the efficacy and safety of TAT for patients after percutaneous coronary intervention (PCI).

METHODSWe systematically searched Pubmed, Embase and Web of Science databases to identify all randomized controlled trials (RCTs) that compared dual antiplatelet therapy (DAT) with and without cilostazol after PCI. All analyses were conducted using Review Manager 5.0.

RESULTSThe final analysis consisted of 4474 patients from ten studies. The combined results suggested that there was a lower risk of cardiac death (relative risk (RR) = 0.55, 95% confidence interval (CI): 0.31 - 0.98, P < 0.05) and major adverse cardiac events (MACEs) (RR = 0.63, 95% CI: 0.54 - 0.74, P < 0.05) in patients treated with TAT as compared to those with DAT follow-ups after six months to one year; no significant difference was observed in bleeding and non-fatal myocardial infarction (MI) (RR = 1.14, 95% CI: 0.80 - 1.64, P > 0.05; RR = 0.87, 95% CI: 0.42 - 1.83, P > 0.05). However, the rate of adverse drug reaction was higher in patients receiving TAT than in patients receiving DAT (RR = 2.21, 95% CI: 1.84 - 2.66, P < 0.05). Moreover, there was a lower risk of stent thrombosis in patients treated with TAT as compared to those treated with DAT (RR = 0.44, 95% CI: 0.21 - 0.94, P < 0.05). The TAT group had a reduced risk of target lesion revascularization (TLR) (RR = 0.60, 95% CI: 0.43 - 0.82, P = 0.001) and target vessel revascularization (TVR) than the DAT group (RR = 0.56, 95% CI: 0.45 - 0.71, P < 0.05). The number of MACEs was lower for patients in the TAT group than in the DAT group with diabetes mellitus sub-analysis (RR = 0.41, 95% CI: 0.28 - 0.61, P < 0.05). But no significant difference was observed between the two groups regarding MACEs in patients with drug-eluting stent implantations (RR = 0.82, 95% CI: 0.65 - 1.03, P > 0.05).

CONCLUSIONTAT could significantly reduce the rates of MACEs and cardiac death in comparison to DAT, but more attention should be paid to adverse side effects of the drugs.

Aspirin ; administration & dosage ; Drug Therapy, Combination ; Humans ; Percutaneous Coronary Intervention ; Platelet Aggregation Inhibitors ; administration & dosage ; adverse effects ; Publication Bias ; Stents ; adverse effects ; Tetrazoles ; administration & dosage ; Ticlopidine ; administration & dosage ; analogs & derivatives

Anticonvulsants ; adverse effects ; Aryl Hydrocarbon Hydroxylases ; genetics ; Asian Continental Ancestry Group ; genetics ; Camptothecin ; analogs & derivatives ; metabolism ; Carbamazepine ; adverse effects ; Cytochrome P-450 CYP2C19 ; Glucuronosyltransferase ; genetics ; HLA-A Antigens ; genetics ; HLA-B Antigens ; genetics ; Humans ; Platelet Aggregation Inhibitors ; metabolism ; Stevens-Johnson Syndrome ; genetics ; Ticlopidine ; analogs & derivatives ; metabolism ; Topoisomerase I Inhibitors ; metabolism

OBJECTIVETo evaluate the effectiveness and safty of tranexamic acid in patients receiving on-pump coronary artery bypass grafting (CABG) without clopidogrel and aspirin cessation.

METHODSThe current study is a prospective, randomized and placebo-control trial. A total of 116 patients receiving selective on-pump CABG with their last ingestion of clopidogrle and aspirin within 7 days preoperatively were recruited. Despite 6 patients withdrawal their consent, the rest 110 were randomized to receive tranexamic acid or placebo. The tranexamic acid regimen was a bolus of 10 mg/kg followed by a maintenance of 10 mg·kg(-1)·h(-1) throughout the surgery. The primary outcome was the volume of allogeneic erythrocyte transfused perioperatively.

RESULTSBaseline characteristics were comparable between the groups. In patients receiving tranexamic acid and placebo respectively, the volume of allogeneic erythrocyte transfused was 4.0 (7.5) units and 6.0(6.0) units (W = 1021, P < 0.01). In these 2 groups respectively, blood loss was 930 (750) ml and 1210 (910) ml (W = 1042, P < 0.01), the incidence of major bleeding was 50.9% and 76.4% (χ(2) = 7.70, P < 0.01), the incidence of reoperation was 0 and 9.1% (χ(2) = 5.24, P = 0.02); the volume of plasma transfused was 400 (600) ml and 600 (650) ml (W = 1072, P = 0.01), the exposure of plasma was 60.0% and 85.5% (χ(2) = 8.98, P < 0.01) and the exposure to any allogeneic blood products was 85.5% and 98.2% (χ(2) = 5.93, P = 0.01). Perioperative mortality, morbidity and the incidence of adverse events were balanced between the groups without statistical significance.

CONCLUSIONTranexamic acid reduced significantly postoperative bleeding and transfusion in patients receiving on-pump CABG without clopidogrel and aspirin cessation.

Aged ; Aged, 80 and over ; Aspirin ; therapeutic use ; Blood Transfusion ; Coronary Artery Bypass ; Female ; Humans ; Male ; Middle Aged ; Postoperative Hemorrhage ; prevention & control ; Prospective Studies ; Ticlopidine ; analogs & derivatives ; therapeutic use ; Tranexamic Acid ; adverse effects ; therapeutic use