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

OBJECTIVETo analyze and assess the impact of clopidogrel given preoperatively in coronary artery bypass grafting (CABG) surgery.

METHODSFrom January 2005 to January 2007, 440 consecutive patients undergoing CABG surgery were divided into two groups: the clopidogrel group (with clopidogrel exposure in 5 days prior to surgery, n = 90) and the control group (without clopidogrel exposure > 5 days prior to surgery, n = 350). Patients undergoing emergency surgery because of failed percutaneous transluminal coronary angioplasty and cardiogenic shock, associated valvular surgery, redo-CABG were excluded. Patients who received aspirin and/or heparin treatment before surgery were included.

RESULTSThere was no significant difference in two groups regarding age, gender,diabetes mellitus and hypertension. Compared to the control group, patients in clopidogrel group had a higher prevalence of angina class III or IV (66.7% vs. 40.0%, P < 0.01), received more often revascularization within 48 h (41.1% vs. 14.3%, P = 0.02), and had received more frequently stenting (56.7% vs. 13.4%, P < 0.01). Chest tube drainage was significantly increased during the first 24 h following CABG in the clopidogrel group (800 ml vs. 350 ml, P < 0.01). Patients of the clopidogrel group also required more transfusion of packed red blood cells and fresh frozen plasma. Overall re-exploration rate because of bleeding was remarkably higher in the clopidogrel group (4.4% vs. 1.1%, P < 0.01).

CONCLUSIONSClopidogrel exposure in 5 days or less prior to CABG surgery significantly increases the risk of postoperative bleeding, the need for perioperative transfusion and the incidence of re-exploration. For the elective CABG patient, we suggest that the surgery should to be performed 5 days or more after clopidogrel exposure.

Aged ; Coronary Artery Bypass ; Female ; Humans ; Male ; Middle Aged ; Platelet Aggregation Inhibitors ; adverse effects ; Postoperative Hemorrhage ; chemically induced ; Preoperative Care ; Retrospective Studies ; Ticlopidine ; adverse effects ; analogs & derivatives ; Treatment Outcome

The hemorrhagic side effects associated with the use of clopidogrel are within the acceptable range and occur mainly at skin or gastrointestinal sites. We report a case of spontaneous spinal epidural hematoma (SSEH) in a 60-yr-old woman who was treated with clopidogrel for frequent transient ischemic attacks. To our knowledge, this is the second reported case of clopidogrel-induced SSEH. The patient's symptoms and past history of clopidogrel use suggested the diagnosis and made the procedure proceed quickly to operate SSEH 9 hr after the onset of paraplegia. The outcome was excellent. Therefore, with the popularity of antiplatelet prescription, physicians should keep in mind and urgently treat this unusual but critical side effect.
Aged ; Brain/pathology ; Cerebral Angiography ; Female ; Hematoma, Epidural, Spinal/*chemically induced ; Humans ; Ischemia/drug therapy ; Magnetic Resonance Imaging ; Platelet Aggregation Inhibitors/*adverse effects ; Ticlopidine/adverse effects/*analogs & derivatives ; Time Factors ; Treatment Outcome

No abstract available.
Aspirin/*adverse effects/therapeutic use ; Cardiovascular Diseases/prevention & control ; Drug Therapy, Combination ; Drug-Eluting Stents ; Endoscopy, Gastrointestinal ; Gastrointestinal Hemorrhage/*chemically induced/mortality/prevention & control ; Humans ; Platelet Aggregation Inhibitors/*adverse effects/therapeutic use ; Risk Factors ; Ticlopidine/analogs & derivatives/therapeutic use

Adult ; Angina Pectoris ; therapy ; Angioplasty, Balloon, Coronary ; adverse effects ; Aspirin ; therapeutic use ; Coronary Thrombosis ; etiology ; prevention & control ; Drug-Eluting Stents ; adverse effects ; Humans ; Male ; Platelet Aggregation Inhibitors ; therapeutic use ; 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 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

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

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

BACKGROUNDAdenosine phosphate-mediated platelet aggregation is a prognostic factor for major adverse cardiac events in patients who have undergone selective percutaneous coronary interventions. This study aimed to assess whether an adjusted loading dose of clopidogrel could more effectively inhibit platelet aggregation in patients undergoing selected percutaneous coronary intervention.

METHODSA total of 205 patients undergoing selected percutaneous coronary intervention were enrolled in this multicenter, prospective, randomized study. Patients receiving domestic clopidogrel (n = 104) served as the Talcom (Taijia) group; others (n = 101) received Plavix, the Plavix group. Patients received up to 3 additional 300-mg loading doses of clopidogrel to decrease the adenosine phosphate-mediated platelet aggregation index by more than 50% (the primary endpoint) compared with the baseline. The secondary endpoint was major adverse cardiovascular events at 12 months.

RESULTSCompared with the rational loading dosage, the tailored loading dosage better inhibited platelet aggregation based on a > 50% decrease in adenosine phosphate-mediated platelet aggregation (rational loading dosage vs. tailored loading dosage, 48% vs. 73%, P = 0.028). There was no significant difference in the eligible index between the Talcom and Plavix groups (47% vs. 49% at 300 mg; 62% vs. 59% at 600 mg; 74% vs. 72% at 900 mg; P > 0.05) based on a standard adenosine diphosphate-mediated platelet aggregation decrease of > 50%. After 12 months of follow-up, there were no significant differences in major adverse cardiac events (2.5% vs. 2.9%, P = 5.43). No acute or subacute stent thrombosis events occurred.

CONCLUSIONAn adjusted loading dose of clopidogrel could have significant effects on antiplatelet aggregation compared with a rational dose, decreasing 1-year major adverse cardiac events in patients undergoing percutaneous coronary interventions based on adenosine phosphate-mediated platelet aggregation with no increase in bleeding.

Adenosine Diphosphate ; pharmacology ; Aged ; Angioplasty, Balloon, Coronary ; Female ; Humans ; Male ; Middle Aged ; Platelet Aggregation ; drug effects ; Platelet Aggregation Inhibitors ; administration & dosage ; Prospective Studies ; Ticlopidine ; administration & dosage ; adverse effects ; analogs & derivatives