Conventional Antiplatelet Therapy Research Articles

Cost-effectiveness analysis of CYP2C19 genotype-guided antiplatelet therapy for patients with acute minor ischemic stroke and high-risk transient ischemic attack in China.

The study aimed to estimate the cost-effectiveness of CYP2C19 genotype-guided antiplatelet therapy using cilostazol and ticagrelor as an alternative to clopidogrel, compared to conventional antiplatelet therapy with clopidogrel and aspirin. A 90-day decision tree and 30-year Markov model were employed to assess the costs and quality-adjusted life years (QALYs) of personalized antiplatelet therapy for patients with minor ischemic stroke and high-risk transient ischemic attack, compared to conventional antiplatelet therapy in the Chinese healthcare system. The primary outcome was the incremental cost-effectiveness ratio (ICER). The data sources included clinical trials, published literature, official documents and local prices. One-way sensitivity analysis and probabilistic sensitivity analysis were performed to confirm the robustness of the findings. The base-case analysis indicated that the CYP2C19 genotype-guided antiplatelet strategy was cost-effective, and cilostazol group and ticagrelor group yielded an ICER of 3327.40 US dollars (USD)/QALY and 3426.92 USD/QALY, respectively, which were less than threshold. The one-way sensitivity analysis showed the results were robust, where the most sensitive parameter was the disability distribution in the modified Rankin scale 3-5. The probabilistic analysis showed that the CYP2C19 genotype-guided antiplatelet therapy with either cilostazol or ticagrelor was 100% cost-effective under the willingness-to-pay threshold. CYP2C19 genotype-guided antiplatelet therapy usingcilostazol and ticagrelor as an alternative to clopidogrel appeared to be more cost-effective than conventional antiplatelet therapy for acute minor ischemic stroke and high-risk transient ischemic attack patients over 30 years in China.

Guided vs. conventional anti-platelet therapy for patients with acute coronary syndrome: A meta-analysis of randomized controlled trials.

Whether guided antiplatelet therapy in patients with acute coronary syndrome (ACS) is effective in improving net clinical benefits compared with conventional antiplatelet therapy remains controversial. Therefore, we assessed the safety and efficacy of guided antiplatelet therapy in patients with ACS and undergoing percutaneous coronary intervention. We searched PubMed, EMBASE, and Cochrane Library databases to select the relevant randomized controlled trials comparing the guided and conventional antiplatelet therapy in patients with ACS. The primary and safety outcomes are major adverse cardiovascular events (MACE) and major bleeding, respectively. The efficacy outcomes included myocardial infarction, stent thrombosis, all-cause death, and cardiovascular death. We selected the relative risk (RR) and 95% confidence intervals (CIs) as effect size and calculated it using the Review Manager software. In addition, we evaluated the final results by trial sequential analysis (registered by PROSPERO, CRD 42020210912). We selected seven randomized controlled trials and included 8,451 patients in this meta-analysis. Guided antiplatelet therapy can significantly reduce the risk of MACE (RR 0.64, 95% CI 0.54-0.76, P < 0.00001), myocardial infarction (RR 0.62, 95% CI 0.49-0.79, P = 0.0001), all-cause death (RR 0.61, 95% CI 0.44-0.85, P = 0.003), and cardiovascular death (RR 0.66, 0.49-0.90, P = 0.009). In addition, there is no significant difference between the two groups in stent thrombosis (RR 0.67, 95% CI 0.44-1.03, P = 0.07) and major bleeding (RR 0.86, 95% CI 0.65-1.13, P = 0.27). The subgroup analysis showed that the guided group based on genotype tests could bring benefits in MACE and myocardial infarction. The guided antiplatelet therapy is not only associated with a comparable risk of bleeding but also with a lower risk of MACE, myocardial infarction, all-cause death, cardiovascular death, and stent thrombosis than the conventional strategy in patients with ACS.

Immunothrombosis and the Role of Platelets in Venous Thromboembolic Diseases.

Venous thromboembolism (VTE) is the third leading cardiovascular cause of death and is conventionally treated with anticoagulants that directly antagonize coagulation. However, recent data have demonstrated that also platelets play a crucial role in VTE pathophysiology. In the current review, we outline how platelets are involved during all stages of experimental venous thrombosis. Platelets mediate initiation of the disease by attaching to the vessel wall upon which they mediate leukocyte recruitment. This process is referred to as immunothrombosis, and within this novel concept inflammatory cells such as leukocytes and platelets directly drive the progression of VTE. In addition to their involvement in immunothrombosis, activated platelets can directly drive venous thrombosis by supporting coagulation and secreting procoagulant factors. Furthermore, fibrinolysis and vessel resolution are (partly) mediated by platelets. Finally, we summarize how conventional antiplatelet therapy can prevent experimental venous thrombosis and impacts (recurrent) VTE in humans.

Antithrombotic Effects of Fostamatinib in Combination with Conventional Antiplatelet Drugs.

New antithrombotic medications with less effect on haemostasis are needed for the long-term treatment of acute coronary syndromes (ACS). The platelet receptor glycoprotein VI (GPVI) is critical in atherothrombosis, mediating platelet activation at atherosclerotic plaque. The inhibition of spleen tyrosine kinase (Syk) has been shown to block GPVI-mediated platelet function. The aim of our study was to investigate if the Syk inhibitor fostamatinib could be repurposed as an antiplatelet drug, either alone or in combination with conventional antiplatelet therapy. The effect of the active metabolite of fostamatinib (R406) was assessed on platelet activation and function induced by atherosclerotic plaque and a range of agonists in the presence and absence of the commonly used antiplatelet agents aspirin and ticagrelor. The effects were determined ex vivo using blood from healthy volunteers and aspirin- and ticagrelor-treated patients with ACS. Fostamatinib was also assessed in murine models of thrombosis. R406 mildly inhibited platelet responses induced by atherosclerotic plaque homogenate, likely due to GPVI inhibition. The anti-GPVI effects of R406 were amplified by the commonly-used antiplatelet medications aspirin and ticagrelor; however, the effects of R406 were concentration-dependent and diminished in the presence of plasma proteins, which may explain why fostamatinib did not significantly inhibit thrombosis in murine models. For the first time, we demonstrate that the Syk inhibitor R406 provides mild inhibition of platelet responses induced by atherosclerotic plaque and that this is mildly amplified by aspirin and ticagrelor.

Impact of proton pump inhibitors on efficacy of antiplatelet strategies with ticagrelor or aspirin after percutaneous coronary intervention: Insights from the GLOBAL LEADERS trial.

BackgroundSeveral studies have suggested that proton pump inhibitors (PPIs) may reduce the antiplatelet effects of clopidogrel and/or aspirin, possibly leading to cardiovascular events.AimsWe aimed to investigate the association between PPI and clinical outcomes in patients treated with ticagrelor monotherapy or conventional antiplatelet therapy after percutaneous coronary intervention (PCI).MethodsThis is a subanalysis of the randomized GLOBAL LEADERS trial, comparing the experimental antiplatelet arm (23‐month ticagrelor monotherapy following 1‐month dual antiplatelet therapy [DAPT]) with the reference arm (12‐month aspirin monotherapy following 12‐month DAPT) after PCI. Patient‐oriented composite endpoints (POCEs: all‐cause mortality, myocardial infarction, stroke, or repeat revascularization) and its components were assessed stratified by PPI use as a time‐dependent covariate in patients with the experiment or reference antiplatelet arm.ResultsAmong 15,839 patients, 2115 patients (13.5%) experienced POCE at 2 years. In the reference arm, the use of PPIs was independently associated with POCE (hazard ratio [HR]: 1.27; 95% confidence interval [CI]: 1.12–1.44) and its individual components, whereas it was not in the experimental arm (HR: 1.04; 95% CI: 0.92–1.19; p interaction = 0.035). During the second‐year follow‐up, patients taking aspirin with PPIs had a significantly higher risk of POCE compared to those on aspirin without PPIs (HR: 1.57; 95% CI: 1.27–1.94), whereas the risk did not differ significantly irrespective of PPI in ticagrelor monotherapy group (HR: 1.03; 95% CI: 0.83–1.28; p interaction = 0.008).ConclusionsIn contrast to conventional antiplatelet strategy, there were no evidence suggesting the interaction between ticagrelor monotherapy and PPIs on increased cardiovascular events, which should be confirmed in further studies.Clinical Trial RegistrationURL: https://clinicaltrials.gov

Point of care CYP2C19 genotyping after percutaneous coronary intervention.

Loss-of-function CYP2C19 variants are associated with increased cumulative ischemic outcomes warranting CYP2C19 genotyping prior to clopidogrel administration. TAILOR-PCI was an international, multicenter (40 sites), prospective, randomized trial comparing rapid point of care (POC) genotype-guided vs. conventional anti-platelet therapy. The performance of buccal-based rapid CYP2C19 genotyping performed by non-laboratory-trained staff in TAILOR-PCI was assessed. Pre-trial training and evaluation involved rapid genotyping of 373 oral samples, with 99.5% (371/373) concordance with Sanger sequencing. During TAILOR-PCI, 5302 patients undergoing PCI were randomized to POC rapid CYP2C19 *2, *3, and *17 genotyping versus no genotyping. At 12 months post-PCI, TaqMan genotyping determined 99.1% (2,364/2,385) concordance with the POC results, with 90.7-98.8% sensitivity and 99.2-99.6% specificity. In conclusion, non-laboratory personnel can be successfully trained for on-site instrument operation and POC rapid genotyping with analytical accuracy and precision across multiple international centers, thereby supporting POC genotyping in patient-care settings, such as the cardiac catheterization laboratory.Clinical Trial Registration: https://www.clinicalTrials.gov (Identifier: NCT01742117).

Efficacy of Buqi Huoxue Decoction Combined with Cardiac Rehabilitation Nursing after Coronary Intervention in Patients with Acute ST-Segment Elevation Myocardial Infarction and Its Influence on Prognosis.

Objective To investigate the efficacy of the application of Buqi Huoxue Decoction combined with cardiac rehabilitation nursing for patients with acute ST-segment elevation myocardial infarction (STEMI) after percutaneous coronary intervention (PCI) and its influence on the prognosis. Methods 120 STEMI patients undergoing PCI were randomly divided into control group, cardiac care group, traditional Chinese medicine and western medicine group (TCM + WM group), and comprehensive treatment group. The control group was treated with a conventional antiplatelet therapy. On the basis of the control group, the cardiac care group was combined with cardiac care treatment. The TCM + WM group was combined with Buqi Huoxue Decoction, and the comprehensive treatment group was combined with cardiac rehabilitation care and Buqi Huoxue Decoction. The total clinical effective rate, readmission rate, and adverse reaction rate of the four groups were measured. Moreover, the myocardial injury markers (creatine kinase isoenzyme (CK-MB), cardiac troponin I (cTnI), and α-Hydroxybutyrate dehydrogenase (α-HBDH)), vascular endothelial function indexes (endothelin (ET-1) and vascular endothelial growth factor (VEGF)), cardiac function indexes (left ventricular ejection fraction (LVEF), left ventricle shortening rate (LFS), left ventricular end diastolic diameter (LVEDd), and left ventricular end systolic diameter (LVESd)), and QOL quality of life score (appetite, spirit, sleep, fatigue, and daily life) were measured. Results The total effective rate of comprehensive treatment group was obviously increased versus to the control group and cardiac care group. The CK-MB, cTnI, α-HBDH, ET-1, LVEDd, and LVESd levels and SAS and SDS scores in the four groups were decreased, and VEGF, LVEF, and FS levels and QOL quality of life scores were increased after treatment. Moreover, the comprehensive treatment group has more significant changes than the other three groups. The readmission rate in comprehensive treatment group was significantly lower than the other three groups, and the difference in the incidence of adverse reactions in the four groups was not statistically significant. Conclusion Buqi Huoxue Decoction combined with cardiac rehabilitation after PCI has a significant clinical effect on STEMI patients with PCI postoperative treatment, which can effectively reduce myocardial injury, improve the patient's cardiac function and vascular endothelial function, and improve the patient's quality of life, which can better improve the prognosis of patients.

Circulating platelet‐derived extracellular vesicles are decreased after remote ischemic preconditioning in patients with coronary disease: A randomized controlled trial

BackgroundBrief nonharmful ischemia, remote ischemic preconditioning (RIPC) has been proposed to confer benefit to patients with coronary artery disease via unknown mechanisms. ObjectivesWe aimed to investigate the effect of RIPC on circulating levels of extracellular vesicles (EVs) and global coagulation and fibrinolytic factors in patients with coronary disease. Patients/MethodsBlood samples were taken from 60 patients presenting for coronary angiography enrolled in a randomized, controlled trial before and after RIPC (3 × 5 min administration of 200 mmHg sphygmomanometer on the arm, n = 31) or sham (n = 29) treatment. Most patients (n = 48) had significant coronary artery disease and all were taking at least one antiplatelet agent. ResultsRemote ischemic preconditioning significantly decreased circulating levels of EVs expressing platelet markers CD41 and CD61 detected by flow cytometry in plasma, whereas no such effect was found on EVs expressing phosphatidylserine, CD62P, CD45, CD11b, CD144, CD31+/CD41–, or CD235a. RIPC had no effect on the overall hemostatic potential assay or circulating antigen levels of tissue plasminogen activator, urokinase, plasminogen activator inhibitor‐1, or plasminogen. Sham treatment had no effect on any studied parameter. Statin use inhibited the effect of RIPC on CD61+ EVs, diabetes modified the effect of RIPC on CD45+ and CD11b+ EVs, and hypertension modified the effect of RIPC on CD235a+ EVs. ConclusionsRemote ischemic preconditioning decreased circulating levels of platelet‐derived EVs in patients with coronary disease taking conventional antiplatelet therapy. This may reflect increased EV clearance/uptake or change in production. Clinical variables may alter the effectiveness of RIPC.

Bedside testing of CYP2C19 vs. conventional clopidogrel treatment to guide antiplatelet therapy in ST-segment elevation myocardial infarction patients

BackgroundST-segment elevation myocardial infarction (STEMI) patients are treated with dual antiplatelet therapy comprising aspirin and a P2Y12 inhibitor. Clopidogrel is widely used in these patients in several areas worldwide, such as Middle East, but is associated to sub-optimal platelet inhibition in up to 1/3 of treated patients. We investigated a CYP2C19 genotype-guided strategy to select the optimal P2Y12 inhibitor. MethodsThis prospective randomized clinical trial included STEMI patients. The standard-treatment group received clopidogrel, while the genotype-guided group were genotyped for CYP2C19 loss-of-function alleles and carriers were prescribed ticagrelor and noncarriers were prescribed clopidogrel. Primary outcome was a combined ischemic and bleeding outcome, comprising myocardial infarction, non-fatal stroke, cardiovascular death, or Platelet Inhibition and Patient Outcomes major bleeding one year after STEMI. ResultsSTEMI patients (755) were randomized into a genotype-guided- (383) and standard-treatment group (372). In the genotype-guided group, 31 patients carrying a loss-of-function allele were treated with ticagrelor, while all other patients in both groups were treated with clopidogrel. Patients in the genotype-guided group had a significantly lower risk of primary outcome (odds ratio (OR) 0.34, 95% confidence interval (CI) 0.20–0.59,), recurrent myocardial infarction (OR 0.25, 95%CI 0.11–0.53), cardiovascular death (OR 0.16, 95%CI0.06–0.42) and major bleeding (OR 0.49, 95%CI 0.32–0.74). There was no significant difference in the rate of stent thrombosis (OR 0.85, 95%CI 0.43–1.71). ConclusionA genotype-guided escalation of P2Y12 inhibitor strategy is feasible in STEMI patients treated with clopidogrel and undergoing PCI and is associated with a reduction of primary outcomes compared to conventional antiplatelet therapy.

Effects of individualized antiplatelet therapy, based on CYP2C19 genotyping, on platelet function in patients underwent percutaneous coronary intervention.

To evaluate the effect of individualized antiplatelet therapy, based on CYP2C19 genotyping, on platelet function in patients underwent PCI and to compare this treatment with conventional antiplatelet therapy. All patients were treated with 100 mg aspirin once a day. Additionally, the CA group received 75 mg clopidogrel once a day. The IA group was divided into extensive metabolizers (EMs, no loss-of-function, i.e. LOF allele, 75 mg clopidogrel once a day), intermediate metabolizers (IMs, carrying one LOF alleles, 75 mg clopidogrel twice daily), and poor metabolizers group (PMs, carrying two LOF alleles, 90 mg ticagrelor twice daily). After taking these antiplatelet medications for ⩾5 days, we assessed platelet function by thromboelastography, and recorded the MAADP (maximum amplitude produced by adenosine diphosphate) value. MAADP > 47 mm was defined as residual HPR, indicating a high risk of thrombosis. MAADP ≤ 31 mm indicated a high risk of bleeding. The proportion of patients with MAADP > 47 mm was significantly lower in the IA group (29.6%) than the CA group (38.1%). The proportion of patients with MAADP ≤ 31 mm was significantly higher in the IA group (31.0%) than the CA group (21.3%). No significant differences were found in the proportions of patients with MAADP > 47 mm or MAADP ≤31 mm when compared between the EMs and IMs group. Individualized antiplatelet therapy, based on CYP2C19 genotyping, can reduce the incidence of HPR in ACS patients after PCI compared to conventional therapy. By taking a double dose of clopidogrel, patients with a CYP2C19 LOF allele can therefore overcome the reduced efficacy of clopidogrel associated with LOF alleles without increasing the risk of bleeding, which is of guiding significance for the management of antiplatelet therapy on ACS patients after PCI especially considering the CYP2C19 LOF alleles that carry an important predictor for the ischemic events. chiCTR-INC-17011550.

Effects of individualized antiplatelet therapy based on CYP2C19 genotype and platelet function on the prognosis of patients after PCI.

To evaluate the effect of individualized antiplatelet therapy based on CYP2C19 genotype and platelet function on the prognosis of patients after percutaneous coronary intervention (PCI) compared with conventional antiplatelet therapy. Patients diagnosed with acute coronary syndromes (ACS) in Shandong Provincial Qianfoshan Hospital from December 2014 to December 2017 were included in this prospective study and randomly divided into conventional (CA) and individualized antiplatelet therapy group (IA) at 1:1 ratio. Patients in the CA group received clopidogrel 75 mg once a day (QD). Group IA was divided into extensive, intermediate, and poor metabolizers according to the results of the CYP2C19 gene test. Three genotypes were given clopidogrel 75 mg QD, 75 mg twice daily (BID) and ticagrelor 90 mg BID respectively. After taking these medicines for a period of time, platelet function was monitored by thromboelastography (TEG) and MAADP values were recorded. MAADP indicates the adenosine diphosphate (ADP) induced platelet function that not inhibited by medicine. High platelet reactivity (HPR) was defined as MAADP > 47mm, indicating a high risk of thrombus, and MAADP ≤ 31 mm indicates a high risk of hemorrhage. For extensive metabolizers (EMs) and intermediate metabolizers (IMs) patients with HPR, the antiplatelet therapy would be changed by the clinician according to the patient's conditions. Major adverse cardiovascular events (MACE) and hemorrhage events were monitored during 1-year follow-up. The patients with MAADP > 47 mm were 89 (28.6%) in the IA group. There were 50 EMs patients with MAADP > 47 mm (33.3%). Of which, there were 2 cases which changed the dosage of clopidogrel to 75 mg BID, 14 cases who changed clopidogrel to ticagrelor. There were 36 IMs patients with MAADP > 47 mm (30.8%). Of which, there were 19 cases who changed clopidogrel to ticagrelor. There was no significant difference in the value of MAADP between EMs and IMs patients. Within 1 year after PCI, the occurrence of MACE in the IA group was significantly lower than that in the CA group (p=0.010). (1) Patients with a CYP2C19 loss-of-function (LOF) gene who take double doses of clopidogrel overcome the decreased efficacy of clopidogrel which partly due to CYP2C19 LOF gene, without increasing the risk of hemorrhage. (2) Individualized antiplatelet therapy based on CYP2C19 genotype and platelet function can significantly reduce the occurrence of MACE (mainly acute non-fatal myocardial infarction) after PCI without increasing the risk of moderate or severe hemorrhage.

Remote ischemic preconditioning inhibits platelet αIIbβ3 activation in coronary artery disease patients receiving dual antiplatelet therapy: A randomized trial

ObjectivesWe investigated whether remote ischemic preconditioning (RIPC) inhibits agonist‐induced conformational activation of platelet αIIbβ3 in patients with coronary artery disease already receiving conventional antiplatelet therapy. Patients/MethodsConsecutive patients with angiographically confirmed coronary artery disease were randomized to RIPC or sham treatment. Venous blood was collected before and immediately after RIPC/sham. Platelet aggregometry (ADP, arachidonic acid) and whole blood platelet flow cytometry was performed for CD62P, CD63, active αIIbβ3 (PAC‐1 binding) before and after stimulation with ADP, thrombin ± collagen, or PAR‐1 thrombin receptor agonist. ResultsPatients (25 RIPC, 23 sham) were well matched, 83% male, age (mean ± standard deviation) 63.3 ± 13.2 years, 95% aspirin, 81% P2Y12 inhibitor. RIPC did not affect platelet aggregation, nor agonist‐induced expression of CD62P, but selectively and significantly decreased αIIbβ3 activation after stimulation with either PAR‐1 agonist peptide or the combination of thrombin + collagen, but not after ADP nor thrombin alone. The effect of RIPC on platelet αIIbβ3 activation was evident in patients receiving both aspirin and P2Y12 inhibitor, and was not associated with an increase in vasodilator‐stimulated phosphoprotein phosphorylation. ConclusionsRemote ischemic preconditioning inhibits conformational activation of platelet αIIbβ3 in response to exposure to thrombin and collagen in patients with coronary artery disease receiving dual antiplatelet therapy. These findings indicate agonist‐specific inhibition of platelet activation by RIPC in coronary artery disease that is not obviated by the prior use of P2Y12 inhibitors.

Platelet reactivity-adjusted antiplatelet therapy in patients with percutaneous coronary intervention: a meta-analysis of randomized controlled trials

Numerous number of evidences show that high on-treatment platelet reactivity is a well-known risk factor for adverse events in patients after percutaneous coronary intervention (PCI). Controversial situations still exist regarding the effectiveness of tailoring antiplatelet therapy according to platelet function monitoring. The PubMed, Embase, and Cochrane Central databases were searched for randomized trials comparing platelet reactivity-adjusted antiplatelet therapy with conventional antiplatelet therapy in patients undergoing PCI. The primary end point was all-cause mortality, major adverse cardiac events (MACE) including cardiovascular (CV) death, nonfatal myocardial infarction (MI), definite/probable stent thrombosis (ST), revascularization, and stroke or transient ischemic attack (TIA). The safety end point was defined as major bleeding events. We derived pooled risk ratios (RRs) with fixed-effect models. Six studies enrolling 6347 patients were included. Compared with conventional treatment, tailoring antiplatelet failed to reduce all-cause mortality (RR: 0.89, 95% confidence interval [CI]: 0.63–1.24, P = 0.48), MACE (RR: 1.02, 95% CI: 0.92–1.14, P = 0.69), MI (RR: 1.07, 95% CI: 0.95–1.21, P = 0.24), CV death (RR: 0.69, 95% CI: 0.40–1.19, P = 0.09), ST (RR: 0.83, 95% CI: 0.50–1.38, P = 0.23), stroke or TIA (RR: 1.08, 95% CI: 0.55–2.12, P = 0.83), revascularization (RR: 0.96, 95% CI: 0.69–1.33, P = 0.79), and major bleeding events (RR: 0.79, 95% CI: 0.53–1.17, P = 0.24).Compared with traditional antiplatelet treatment, tailoring antiplatelet therapy according to platelet reactivity testing failed to reduce all-cause mortality, MACE, and major bleeding events in patients undergoing PCI.

Clinical Study on efficacy of allopurinol in patients with acute coronary syndrome and its functional mechanism

ObjectiveTo investigate the therapeutic effect of allopurinol treatment on acute coronary syndrome and to elucidate its possible mechanism. MethodsPatients with acute coronary syndrome (n = 100) were recruited as research subjects in our hospital. The patients were randomly divided into two groups, an allopurinol group (n = 50) and a control group (n = 50). These two groups were treated with conventional antiplatelet, anticoagulation and anti-ischemic therapy; allopurinol therapy was added to the allopurinol group based on conventional treatment indications. Biochemical markers such as serum creatinine, uric acid, BNP, blood glucose and blood lipid were compared between the two groups. Indicators of oxidative stress and inflammatory response (MDA, OX-LDL, NO, hs-CRP and TNF-α), as well as cardiovascular events during 2-years follow-up, were recorded. ResultsOn admission, there was no difference in serum creatinine, uric acid, BNP, blood glucose or lipid levels between the two groups (P > 0.05). However, after 1 month of treatment, these levels were improved in patients in the allopurinol group compared to the control group (P < 0.05). MDA, OX-LDL, hs-CRP and TNF-α decreased after treatment periods of 14 days and 1 month. They were also decreased at 3 month, 6 month, 1 year, and 2 year follow-up visits. However, data from the allopurinol group demonstrated significantly lower levels than in the control group (P < 0.05). Additionally, compared with the control group, allopurinol treatment significantly elevated the level of NO (P < 0.05). The total effective rates of the allopurinol group are much higher than in the control group for both angina pectoris (93.2% and 76%, respectively) and ECG (96% and 82%, respectively). Most patients in the allopurinol group (n = 40) and the control group (n = 41) received stent implantation with no significant difference shown between them. The incidence of cardiovascular events during 2 years of follow-up in the allopurinol group was 10%; it was 30% in the control group. ConclusionAllopurinol has a remarkable effect in the treatment of ACS and can improve the oxidative stress and inflammatory reaction indicators of patients. The protective mechanism of allopurinol might be achieved by suppressing the secretion and release of inflammatory mediators such as TNF-α, hs-CRP, OX-LDL and MDA while increasing levels of NO.

Prognostic Value of Diffusion-Weighted Imaging (DWI) Apparent Diffusion Coefficient (ADC) in Patients with Hyperacute Cerebral Infarction Receiving rt-PA Intravenous Thrombolytic Therapy.

BackgroundThe aim of this study was to investigate the potential value of apparent diffusion coefficient (ADC) of diffusion-weighted imaging (DWI) in the prognosis of patients with hyperacute cerebral infarction (HCI) receiving intravenous thrombolytic therapy with recombinant tissue plasminogen activator (rt-PA).Material/MethodsFrom June 2012 to June 2015, 58 cases of HCI (<6 h) undergoing rt-PA intravenous thrombolytic therapy (thrombolysis group) and 70 cases of HCI (<6 h) undergoing conventional antiplatelet and anticoagulant therapy (control group) in the same period were collected. DWI was conducted on all the subjects, and ADC maps were generated with Functool software to quantify ADC value. The clinical outcomes of HCI patients were observed for 3 months, and prognostic factors were analyzed.ResultsBefore thrombolysis treatment, the lesion area presented high signal intensity on DWI map and low signal intensity on ADC map, and gradually weakened signal intensity on DWI map and gradually enhanced signal intensity on ADC map were observed after thrombolysis. The ADC values of the thrombolysis group were significantly higher than those of the control group after treatment (24 h, 7 d, 30 d, and 90 d) (all P<0.05), and the ADC and rADC values in the thrombolysis group gradually increased over time (all P<0.05). Multiple logistic regression analysis showed that baseline National Institutes of Health Stroke Scale (NIHSS) score, baseline rADC value, and stroke history were the independent factors for the prognosis of HIC patients with thrombolysis (all P<0.05).ConclusionsThe values of ADC and rADC may provide guidance in the prognosis of HCI patients receiving rt-PA, and the baseline rADC value is the protective factor for the prognosis of HCI patients receiving rt-PA.

Emerging antiplatelet and lipid lowering therapies

Antiplatelet therapy is used widely with proven benefit for the primary prevention of cardiovascular disease as well as for the prevention of further ischemic cardiovascular events in patients with proven coronary artery disease (CAD) and in those with a history of acute coronary syndrome (ACS). The limitations of conventional antiplatelet therapy with aspirin, clopidogrel, or prasugrel, as well as the fact that rates of recurrent ischemic events still remain high with use of these agents, underscore the need to investigate alternative molecules that may be effective in further reducing the occurrence of events without increasing the risk of bleeding. The armamentarium of antiplatelet therapy has been further enriched by ticagrelor, cangrelor, vorapaxar, prasugrel and atopaxar. Ticagrelor was approved in 2011 by the European Medicines Agency swiftly followed by the US Food and Drug Administration. Reversible antiplatelet agents acting as P2Y12 antagonists similar to ticagrelor are cangrelor, and elinogrel. A new class of oral protease-activated receptor-1 (PAR-1) inhibitors, vorapaxar and atopaxar has also been proposed as effective antiplatelets but their clinical benefit is still under debate. The P2Y12 antagonists prasugrel and ticagrelor prevent adverse cardiac outcomes albeit their absolute benefit is very small. The beneficial effect of prasugrel and ticagrelor comes at a cost of an increased risk of bleeding. Furthermore, new adverse effects have also become evident with the new P2Y12 antagonists and these include dyspnea (for all of the reversible P2Y12 antagonists: ticagrelor, cangrelor, and elinogrel) and ventricular pauses for ticagrelor. In addition, the newer P2Y12 antagonists have a peculiar pharmacodynamic profile with a fast onset and offset. Two of these agents, cangrelor and elinogrel, are available as intravenous formulations, which may provide additional benefits in patients who undergo coronary artery bypass graft (CABG) surgery. Trials with the PAR-1 inhibitors have also shown trends toward reductions in cardiac events, but not without the possibility of increased bleeding. Physicians must carefully assess patient-specific factors such as risk of thrombosis, concomitant disease states, age, drug adherence, and aspirin dose, and plan for those patients who will be undergoing CABG when selecting antiplatelet therapy in order to optimally balance bleeding and thrombosis risk. In addition to adequate anti-platelet therapy the treatment of blood lipids is important for the primary and secondary prevention of cardiovascular disease. Elevated low-density lipoprotein cholesterol is an important risk factor for cardiovascular and cerebrovascular events. HMG-CoA reductase inhibitors, or statins, are very effective in lowering cholesterol levels, and in reducing mortality and cardiovascular events in patients with and without cardiovascular disease. The evidence cumulated with the studies conducted with statin has led to the recent recommendations that all patients with known vascular disease, or who are at high risk for vascular disease, should be considered candidates for statin therapy. Nonstatin therapies (either as monotherapy or in addition to statins) to reduce LDL cholesterol by mechanisms that do not involve inhibition of HMG-CoA reductase are likely to be useful for patients in need of LDL reduction; particularly those who either cannot take statins or respond only partially or not at all to statins alone. These therapies include cholesterol absorption inhibitors, Acyl-CoA cholesterol acyl transferase inhibitors, farnesoid X receptor antagonists, sterolregulating binding protein cleavage activating protein, and microsomal triglyceride transfer protein. Recent studies with the PCSK9 have shown that these drugs significantly reduce total and LDL cholesterol in patients with familial hypercholesterolaemia and that are effective in further reducing plasma cholesterol levels in patients receiving statins. Therefore, therapeutic options are becoming available for patients who cannot tolerate full dose statin therapy or for those few patients who are intolerant to statin therapy.

Tailored antiplatelet therapy and clinical adverse outcomes

ObjectiveThe clinical evidence regarding the influence of tailored antiplatelet strategy on adverse outcomes has been controversial. The aim of the study was to evaluate the significance of tailored antiplatelet therapy...

Personalized antiplatelet therapy according to CYP2C19 genotype after percutaneous coronary intervention: A randomized control trial

The objective of this study is to compare personalized antiplatelet therapy according to CYP2C19 phenotype with conventional antiplatelet therapy in patients after percutaneous coronary intervention (PCI). A total of 600 patients with coronary artery disease (CAD) undergoing PCI randomly received a personalized antiplatelet therapy (group A; n=301) or conventional antiplatelet treatment (group B; n=299). For group A, antiplatelet therapy was performed according to CYP2C19 phenotype. For group B, the patients received conventional antiplatelet treatment without detected CYP2C19 genotype. The primary end point was compared between these two groups. This study is registered with the Chinese Clinical Trial Registry (ChiCTR-TRC-11001807). The primary end point occurred in 27 patients assigned to conventional treatment as compared with 8 patients assigned to personalized therapy (cumulative event rate, 9.03% vs. 2.66%; P<0.01). The composite rate of death, myocardial infarction, or stroke at 180 days occurred in 3 and 18 patients in the two groups, respectively (cumulative event rate, 1.0% and 6.2%, P<0.01). The cumulative 180-day incidence of ST was significantly lower in group A than in group B (0.66% vs. 3.01%, P=0.032). The 180-day incidence of MI (0.33% vs. 3.01%, P=0.011) and death (0.33% vs. 2.34%, P=0.011) was fewer than that in control, respectively. We did not find the significant difference in bleeding events between the 2 groups. Personalized antiplatelet therapy according to CYP2C19 genotype after PCI can significantly decrease the incidence of major adverse cardiovascular events and the risk of 180-day ST in Chinese population.

Advances in antiplatelet technologies to improve cardiovascular disease morbidity and mortality: a review of ticagrelor.

Antiplatelet therapy is widely used with proven benefit for the prevention of further ischemic cardiac complications in patients with acute coronary syndrome. Treatment guidelines for acute coronary syndrome and percutaneous coronary intervention now recommend the use of oral antiplatelet agents including ticagrelor, prasugrel, or clopidogrel in combination with aspirin to comprise dual antiplatelet therapy for the prevention of recurrent ischemic events. The limitations of conventional antiplatelet therapy with clopidogrel or prasugrel include the potential for low response to clopidogrel identified through platelet reactivity or genetic testing, increased risk of bleeding with prasugrel, or slower return to normal platelet activity in patients who received either prasugrel or clopidogrel prior to emergent or planned surgical procedures. This review will discuss the pharmacokinetic and pharmacodynamic properties of ticagrelor in comparison to conventional P2Y12 receptor inhibitors and its utility in patients identified as low responders to clopidogrel. Completed clinical studies and substudies comparing ticagrelor to clopidogrel and ongoing clinical trials evaluating ticagrelor in acute coronary syndrome patients will also be reviewed.

PERSONALISED ANTIPLATELET THERAPY ACCORDING TO CYP2C19 GENOTYPE AFTER PERCUTANEOUS CORONARY INTERVENTION IN CHINESE POPULATION: A RANDOMISED CONTROL TRIAL

ObjectivesThe purpose of this study was to compare personalised antiplatelet therapy according to CYP2C19 phenotype with conventional antiplatelet therapy in patients after percutaneous coronary intervention (PCI).BackgroundRecent studies have demonstrated that...