Efficacy Of Antiplatelet Therapy Research Articles

Antiplatelet agents in patients with intermediate coronary artery stenosis and deferred revascularization

Abstract Background There is no specific recommendation regarding optimal antiplatelet therapy after deferral of revascularization in patients with established coronary artery disease. Objectives The current study investigated safety and efficacy of antiplatelet therapy in patients with intermediate coronary artery stenosis in whom revascularization was deferred based on fractional flow reserve (FFR). Methods In the Korean National Health Insurance Service database 2013-2020, we identified 4,657 patients who had intermediate coronary artery disease on angiography for which revascularization was deferred based on FFR. During this period, reimbursement criteria of FFR were patients with no previous evidence of myocardial ischemia and intermediate coronary artery stenosis (50-70%) by quantitative coronary angiography. Patients were then classified into two groups according to initiation of antiplatelet therapy after the index procedure. Primary efficacy outcome was major adverse cardiac and cerebrovascular events (MACCE), a composite of all-cause death, myocardial infarction, unplanned revascularization, and stroke, during 5 years of follow-up. Primary safety outcome was any gastrointestinal bleeding. Results After propensity score matching in a 1:1 ratio, there were 1,634 patients in antiplatelet therapy group and 1,634 in no therapy group (total N=3,268). The risk of MACCE was similar between the two groups (24.8% vs. 24.7%; adjusted hazard ratio [aHR], 0.97; 95% confidence interval [CI], 0.84-1.13; P=0.745). However, the risk of any gastrointestinal bleeding was higher in antiplatelet therapy group than no therapy group (2.2% vs. 1.2%; aHR, 2.07, 95% CI, 1.08-4.00). These results were consistently found in subgroup analyses. Conclusions In patients with intermediate coronary artery stenosis with deferred revascularization based on FFR, antiplatelet therapy was not associated with reduced risk of ischemic events but increased risk of gastrointestinal bleeding.

Effect of Antiplatelet Therapy on Survival and Organ Support–Free Days in Critically Ill Patients With COVID-19

The efficacy of antiplatelet therapy in critically ill patients with COVID-19 is uncertain. To determine whether antiplatelet therapy improves outcomes for critically ill adults with COVID-19. In an ongoing adaptive platform trial (REMAP-CAP) testing multiple interventions within multiple therapeutic domains, 1557 critically ill adult patients with COVID-19 were enrolled between October 30, 2020, and June 23, 2021, from 105 sites in 8 countries and followed up for 90 days (final follow-up date: July 26, 2021). Patients were randomized to receive either open-label aspirin (n = 565), a P2Y12 inhibitor (n = 455), or no antiplatelet therapy (control; n = 529). Interventions were continued in the hospital for a maximum of 14 days and were in addition to anticoagulation thromboprophylaxis. The primary end point was organ support-free days (days alive and free of intensive care unit-based respiratory or cardiovascular organ support) within 21 days, ranging from -1 for any death in hospital (censored at 90 days) to 22 for survivors with no organ support. There were 13 secondary outcomes, including survival to discharge and major bleeding to 14 days. The primary analysis was a bayesian cumulative logistic model. An odds ratio (OR) greater than 1 represented improved survival, more organ support-free days, or both. Efficacy was defined as greater than 99% posterior probability of an OR greater than 1. Futility was defined as greater than 95% posterior probability of an OR less than 1.2 vs control. Intervention equivalence was defined as greater than 90% probability that the OR (compared with each other) was between 1/1.2 and 1.2 for 2 noncontrol interventions. The aspirin and P2Y12 inhibitor groups met the predefined criteria for equivalence at an adaptive analysis and were statistically pooled for further analysis. Enrollment was discontinued after the prespecified criterion for futility was met for the pooled antiplatelet group compared with control. Among the 1557 critically ill patients randomized, 8 patients withdrew consent and 1549 completed the trial (median age, 57 years; 521 [33.6%] female). The median for organ support-free days was 7 (IQR, -1 to 16) in both the antiplatelet and control groups (median-adjusted OR, 1.02 [95% credible interval {CrI}, 0.86-1.23]; 95.7% posterior probability of futility). The proportions of patients surviving to hospital discharge were 71.5% (723/1011) and 67.9% (354/521) in the antiplatelet and control groups, respectively (median-adjusted OR, 1.27 [95% CrI, 0.99-1.62]; adjusted absolute difference, 5% [95% CrI, -0.2% to 9.5%]; 97% posterior probability of efficacy). Among survivors, the median for organ support-free days was 14 in both groups. Major bleeding occurred in 2.1% and 0.4% of patients in the antiplatelet and control groups (adjusted OR, 2.97 [95% CrI, 1.23-8.28]; adjusted absolute risk increase, 0.8% [95% CrI, 0.1%-2.7%]; 99.4% probability of harm). Among critically ill patients with COVID-19, treatment with an antiplatelet agent, compared with no antiplatelet agent, had a low likelihood of providing improvement in the number of organ support-free days within 21 days. ClinicalTrials.gov Identifier: NCT02735707.

230 Antiplatelet therapy and outcome in COVID-19. Results from a multi-centre international prospective registry (HOPE-COVID)

AimsStandard therapy for Corona-virus-19 disease (COVID-19) is mainly developed for critical ill patients. Autopsy studies showed high prevalence of platelet-fibrin rich micro-thrombi in several organs. Aim of the study was to evaluate safety and efficacy of antiplatelet therapy (APT) in COVID-19 hospitalized patients and its impact on survival.Methods and results7824 consecutive patients with COVID-19 were enrolled in a multicentre-international prospective registry (HOPE-COVID-19). Clinical data and in-hospital complications were recorded. Antiplatelet (AP) regimen, including aspirin and other antiplatelet drugs, was obtained for each patient. During hospitalization 730 (9%) patients received AP drugs with single (93%, n = 680) or dual APT (7%, n = 50). Patients treated with APT were older (74 ± 12 vs. 63 ± 17 years, P < 0.01), more frequently male (68% vs. 57%, P < 0.01) and had higher prevalence of diabetes (39% vs. 16%, P < 0.01). Patients treated with APT compared with no APT showed no differences in terms of in-hospital mortality (18% vs. 19%, P = 0.64, Log Rank P = 0.23), need of invasive ventilation (8.7% vs. 8.5%, P = 0.88), embolic events (2.9% vs. 2.5% P = 0.34) and bleeding (2.1% vs. 2.4%, P = 0.43) but shorter duration of mechanical ventilation (8 ± 5 vs. 11 ± 7 days, P = 0.01); however, when comparing patients with APT vs. no APT and no anticoagulation therapy, APT was associated with lower mortality rates (Log Rank P < 0.01, relative risk 0.79, 95% CI: 0.70–0.94). At multivariable analysis in-hospital APT was associated with a lower mortality risk (relative risk 0.39, 95% CI: 0.32–0.48, P < 0.01).ConclusionsAPT during hospitalization for COVID-19 could be associated with lower mortality risk and shorter duration of mechanical ventilation, without increased risk of bleeding.

Antiplatelet therapy and outcome in patients with COVID-19. Results from a multi-center international prospective registry (HOPE-COVID19)

BackgroundNo standard therapy is currently recommended for Corona-virus-19 disease (COVID-19). Autopsy studies showed high prevalence of platelet-fibrin rich micro-thrombi in several organs. Aim of the study was to evaluate safety and efficacy of antiplatelet therapy (APT) in COVID-19 hospitalized patients and its impact on survival.Methods7824 consecutive patients with COVID-19 were enrolled in a multicenter-international prospective registry (HOPE-COVID19). Clinical data and in-hospital complications were recorded. AP regimen, including aspirin and other antiplatelet drugs, was obtained for each patient.ResultsDuring hospitalization 730 (9.3%) patients received AP drugs with single (93%, n=680) or dual APT (7%, n=50). Patients treated with APT were older (73±12 vs 62±17 years, p<0.01), more frequently male (70% vs 64%, p<0.01) and had higher prevalence of diabetes (39.5% vs 17%, p<0.01).Patients treated with APT showed no differences in terms of in-hospital mortality (18% vs 19%, p=0.64, Log Rank p=0.23), need of invasive ventilation (8.7% vs 8.5%, p=0.88) and bleeding (2.1% vs 2.4%, p=0.43); However, after excluding patients treated only with anticoagulation, APT was associated with lower mortality rates (Log Rank p<0.01, relative risk 0.79, 95% CI 0.70–0.94) (Figure 1).At multivariable analysis including age, gender, diabetes, hypertension, respiratory failure, pre-hospital therapy with antiplatelet drugs, in-hospital APT, and anticoagulation therapy, in-hospital APT was associated with a lower mortality risk (relative risk 0.29, 95% CI 0.22–0.38, p<0.001).ConclusionsAPT during hospitalization for COVID-19 could be associated with lower mortality risk without increased risk of bleeding. Randomized trials are needed to confirm these preliminary data.Funding AcknowledgementType of funding sources: None. Figure 1

Antiplatelet therapy and outcome in COVID-19: the Health Outcome Predictive Evaluation Registry

BackgroundStandard therapy for COVID-19 is continuously evolving. Autopsy studies showed high prevalence of platelet-fibrin-rich microthrombi in several organs. The aim of the study was therefore to evaluate the safety and...

The Phenomenon of Clopidogrel High On-Treatment Platelet Reactivity in Ischemic Stroke Subjects: A Comprehensive Review.

Clopidogrel is increasingly being used for the secondary prevention of ischemic stroke according to the updated guidelines on acute stroke management. Failure to achieve a drug response is referred to as clopidogrel resistance. Similarly, a higher activation of platelets during clopidogrel therapy—high on-treatment platelet reactivity—is equivalent to a reduced effectiveness of a therapy. Clopidogrel resistance is considered to be a common and multifactorial phenomenon that significantly limits the efficacy of antiplatelet agents. The aim of the current study is to review the latest literature data to identify the prevalance and predictors of clopidogrel high on-treatment platelet reactivity among stroke subjects and to establish the potential impact on clinical outcomes and prognosis. Clinical databases were searched by two independent researchers to select relevant papers on the topic, including all types of articles. Several important predictors contributing to clopidogrel resistance were identified, including genetic polymorphisms, the concomitant use of other drugs, or vascular risk factors, in particular nonsmoking and diabetes. Clopidogrel high on-treatment platelet reactivity has a negative impact on the clinical course of stroke, worsens the early- and long-term prognoses, and increases the risk of recurrent vascular events. Platelet function testing should be considered in selected stroke individuals, especially those predisposed to clopidogrel resistance, for whom an improvement in the efficacy of antiplatelet therapy is essential. This particular group may become the greatest beneficiaries of the modification of existing therapy based on platelet function monitoring.

Efficacy and Safety of Prasugrel by Stroke Subtype: A Sub-Analysis of the PRASTRO-I Randomized Controlled Trial.

Aims: The efficacy of antiplatelet therapy may vary among different disease subtypes. Prasugrel is generally a more potent, consistent, and fast-acting platelet inhibitor than clopidogrel. This sub-analysis of the phase III comparison of PRAsugrel and clopidogrel in Japanese patients with ischemic STROke (PRASTRO-I) trial aimed to assess the differences in efficacy of these treatments for each stroke subtype.Methods: In the PRASTRO-I trial, a total of 3,753 patients with ischemic stroke were recruited from 224 centers throughout Japan and randomized (1:1) to prasugrel (3.75 mg/day) or clopidogrel (75 mg/day) for 96 weeks. For the sub-analysis, strokes were classified as large-artery atherosclerosis, small-artery occlusion (lacunar), stroke of other etiology, and stroke of undetermined etiology. The cumulative incidence of primary events (ischemic stroke, myocardial infarction, and death from other vascular cause) and hazard ratios (HRs) were calculated for each subgroup.Results: For patients with large-artery atherosclerosis, the primary event incidence was 3.8% in the prasugrel group and 4.8% in the clopidogrel group (HR 0.79; 95% confidence interval [CI] 0.45–1.41). For patients with small-artery occlusion, the incidence was 3.3% in the prasugrel group and 3.9% in the clopidogrel group (HR 0.82; 95% CI 0.45–1.50). For patients with stroke of undetermined etiology, the incidence was 4.6% in the prasugrel group and 3.0% in the clopidogrel group (HR 1.56; 95% CI 0.90–2.72). The incidence of bleeding was similar across subtypes.Conclusions: Although statistical significance was not reached, the efficacy of prasugrel was potentially different between stroke subtypes, warranting further studies.

Antiplatelet therapy in patients with aneurysmal subarachnoid hemorrhage: Impact on the delayed cerebral ischemia and clinical outcome. A meta-analysis

Background Delayed cerebral ischemia (DCI) strongly impacts clinical outcomes after aneurysmal SAH. The effect of the antiplatelet therapy (AT) on DCI has been described with heterogeneous results. Purpose To analyze the efficacy of AT on DCI and clinical outcomes in patients with SAH. Data Sources A systematic search of three databases was performed for studies published from 1990 to 2019. Study Selection According to PRISMA guidelines, we included studies comparing the rates of DCI and clinical outcomes among SAH patients with and without AT. Data Analysis Random-effects meta-analysis was used to pool the following: DCI, mortality and good outcome rates. Data Synthesis Including 7 studies, 1060 and 1762 SAH patients were surgically and endovascularly treated with (cases) and without (controls) AT, respectively. Overall, AT did not significantly decrease DCI rate compared to the control group (219/1060 vs. 485/1762,OR = 0.781, 95%CI = 0.46-1.31, P= .33). Among patients treated endovascularly, there was a trend toward lower DCI rates after AT (157/778 vs. 413/1410,OR = 0.552, 95%CI = 0.273-1.115, P = .06). Long-term (> 2 weeks) AT tended to be associated with a lower incidence of DCI (63/438 vs. 96/353,OR = 0.379, 95%CI = 0.12-1.2, P= .06). Good outcome rate was significantly higher (803/1144 vs. 1175/1775,OR = 1.368, 95%CI = 1.117-1.676, P= .002), and mortality rate was significantly lower among the AT group (79/672 vs. 97/571,OR = 0.656, 95%CI = 0.47-0.91, P= .01). Limitations Heterogeneity was high for most of the outcomes. Conclusions Overall, the incidence of DCI seems to not be significantly reduced among the AT group. However, DCI tends to be lower both among subjects with long-term AT and among patients with endovascular treatments and antiplatelet administration. Poor outcome and mortality rates are significantly reduced among the AT group.

Blood Cell Parameters and Predicting Coronary In-Stent Restenosis.

Major advances in coronary interventional techniques and pharmacotherapy as well as the use of drug-eluting stents (DESs) have considerably reduced the risk of in-stent restenosis (ISR). However, ISR remains a major clinical challenge. Inflammation and platelet activation are important processes that underlie the pathophysiology of ISR. Parameters related to blood cells, entailing both cell count and morphology, are useful markers of the inflammatory response and platelet activation in clinical practice. Recent studies have highlighted several new combined or derived parameters related to blood cells that independently predict ISR after DES implantation. The neutrophil/lymphocyte ratio, an inflammatory marker, is regarded as a predictor of the risk of ISR and the stability of atherosclerotic plaques. The mean platelet volume, a widely used platelet activation parameter, has been shown to be a predictor of the risk of ISR and the efficacy of antiplatelet therapy. Other markers considered include the platelet/lymphocyte ratio, red blood cell distribution width, and platelet distribution width. This review provides an overview of these parameters that may help stratify the risk of coronary angiographic and clinical outcomes related to ISR.

Application of thrombelastography in antiplatelet therapy in children with Kawasaki disease

Objective To evaluate the efficacy of antiplatelet agents in patients with Kawasaki disease (KD) by using thrombelastography (TEG). Methods A retrospective study of KD patients admitted in our hospital from May 2016 to December 2016 was conducted.Platelet inhibition rates of Arachidonic acid pathway(AA%) and Adenosine diphosphate pathway were assessed using TEG platelet mapping.The effects of aspirin and dipyridamole on platelet inhibition were compared, and the differences of platelet inhibition rates in different aspirin dose and duration of medication were determined. Results There were significant individual differences in the inhibition of platelets by aspirin and dipyridamole.The inhibition rate of aspirin on platelets[M(P25, P75)] was 62.45% (35.58%, 90.95%), which was higher than that of dipyridamole[23.75% (11.60%, 48.38%)], there was significant difference (P<0.01). The incidence of dipyridamole resistance in children with KD (56.75%) was higher than that in patients with resistance to aspirin (35.71%), and there was significant difference (P<0.01). There was a linear correlation between platelet inhibition rates of two antiplatelet agents in children with KD (r=0.351, P<0.01). There was no significant difference in the effect of aspirin and dipyridamole on platelet inhibition rate after 4 days of administration.There was no significant difference in the effect of different doses of aspirin on AA%. Conclusion TEG is an effective way to evaluate the efficacy of antiplatelet therapy in children with KD. Key words: Mucocutaneous lymphnode syndrome; Thrombelastography; Children; Therapy; Platelet aggregation inhibitors

Efficacy of antiplatelet therapy for treating lacunar infarct: Meta-analysis

Objective To evaluate the efficacy of antiplatelet agents in secondary prevention of patients with lacunar infarct (LACI). Methods Retrieve relevant randomized controlled trials (RCTs) that reported antiplatelet therapy in patients with LACI from online databases (January 1, 1980-November 20, 2016) in PubMed, EMBASE/SCOPUS and Cochrane Online Library with key words: stroke, lacunar infarction, platelet aggregation inhibitors, antiplatelet, randomized controlled trial. Quality of studies was evaluated by using Jadad Scale and Cochrane Handbook for Systematic Reviews of Interventions. All data were pooled by RevMan 5.3 software for Meta-analysis. A network Meta-analysis was done by R software Gemtc and JAGS software. Results A total of 4068 articles were enrolled and 12 high - quality RCTs (Jadad ≥ 4 scores) with 24 969 eligible participants were finally included after excluding duplicates and those not meeting the inclusion criteria. Meta-analysis showed single antiplatelet therapy was more effective than placebo in reducing ischemic stroke recurrence rate ( RR = 0.480, 95%CI: 0.300-0.780; P = 0.003) and any stroke recurrence rate ( RR = 0.780, 95%CI: 0.630-0.970; P = 0.030). The efficacy of single antiplatelet therapy was not significantly different from that of dual antiplatelet therapy (ischemic stroke recurrence rate: RR = 0.900, 95%CI: 0.760-1.050, P = 0.170; any stroke recurrence rate: RR = 0.910, 95%CI: 0.820-1.010, P = 0.070). Network Meta-analysis (four interventions including aspirin, placebo, cilostazol and ticlopidine) showed that cilostazol was associated with a significant reduction in recurrence of any stroke compared with aspirin ( OR = 0.341, 95% CrI: 0.011-0.673) and placebo ( OR = 0.615, 95% CrI: 0.191-1.042). Conclusions Single antiplatelet therapy could significantly reduce the recurrence of any stroke, especially ischemic stroke in patients with LACI. There is no evidence showing that dual antiplatelet therapy is probably better than single therapy. Cilostazol is better than aspirin in reducing any stroke recurrence in the treatment of LACI. DOI: 10.3969/j.issn.1672-6731.2017.03.004

ACP Journal Club: review: in lacunar stroke, single antiplatelet therapy reduces recurrent stroke more than placebo.

Source Citation Kwok CS, Shoamanesh A, Copley HC, et al. Efficacy of antiplatelet therapy in secondary prevention following lacunar stroke: pooled analysis of randomized trials. Stroke. 2015;46:101...

Abstract 600: Novel Assays to Determine in vivo Platelet Activation

In vivo platelet activation is associated with several pathologic entities, including acute coronary syndrome, essential thrombocythemia, anti-phospholipid antibody syndrome, diabetes and metabolic syndrome. The need for more robust biomarkers with which to assess platelet activation in vivo in human diseases is well recognized. Our lab has developed two novel assays to study in vivo platelet activation and rate of turnover. During platelet activation, malondialdehyde (MDA) is produced by the thromboxane synthase in amounts equimolar to thromboxane A2 and also non-enzymatically by lipid peroxidation resulting from the oxidative processes that accompany activation. MDA is a reactive dicarbonyl that reacts with amines, notably lysines on proteins, yielding covalent modifications of the proteins that then accumulate over the lifetime of the platelet. We developed an LC/MS/MS method for quantification of the most stable of three MDA adducts, the dilysyl-MDA crosslink, employing a [13C12] labeled internal standard. We found that activation of platelets with arachidonic acid leads to an increase in the levels of dilysyl-MDA crosslinks in platelets, which is inhibited by the thromboxane synthase inhibitor, ozagrel, by the cyclooxygenase inhibitor, aspirin, and by scavengers of reactive carbonyls, 3- methoxysalicylamine and Salicylamine. High platelet turnover has been associated with increased risk for thrombosis and failure of antiplatelet agents. We propose a novel approach to studying platelet turnover by labeling platelets in vivo by oral administration of aspirin containing a deuterium labeled acetyl group (d3-aspirin). We can measure the clearance of d3-labeled platelets by using LC/MS/MS to measure the tryptic peptide (SLK) of COX-1 labeled with d3. This approach avoids exposure to radioactivity and the artifact resulting from manipulation of platelets labeled ex vivo. The results of this study provide two novel assays with the potential to serve as markers of in vivo platelet activation and turnover, which may be useful in predicting thrombotic risk and efficacy of antiplatelet therapy in patients with medical conditions associated with platelet hyperactivity and high rate of platelet turnover.

Cilostazol may prevent cardioembolic stroke in patients undergoing antiplatelet therapy

Objectives:Randomised trials have shown the efficacy of antiplatelet therapy with cilostazol to prevent secondary ischaemic stroke. Recently, cilostazol has been reported to prevent the development and/or recurrence of atrial fibrillation (AF), which can potentially prevent cardioembolic stroke in patients undergoing antiplatelet therapy. Herein, we examined the impact of prior antiplatelet therapy with cilostazol on the incidence of cardioembolic stroke, which had not been fully investigated.Methods:Using the multicenter retrospective study of stroke risk in antithrombotic therapy (RESTATE) database, we analysed consecutive patients with primary or secondary stroke under single antiplatelet therapy. We evaluated the characteristics of ischaemic stroke based on the type of antiplatelet agent used: aspirin, ticlopidine/clopidogrel or cilostazol.Results:Of 1069 consecutive patients with primary or secondary stroke during antithrombotic therapy from January to December 2012, 615 patients received single antiplatelet therapy (293 and 322 cases of primary and secondary strokes, respectively). Interestingly, the percentage of cardioembolic infarction was significantly lower in patients taking cilostazol compared with other agents. Multivariate regression analysis found that age (OR: 1.03, 95% CI: 1.01–1.06, P = 0.0029), serum creatinine (OR: 1.17, 95% CI: 1.03–1.34, P = 0.0198), aspirin (OR: 1.75, 95% CI: 1.00–3.22, P = 0.0486), cilostazol (OR: 0.19, 95% CI: 0.03–0.73, P = 0.0125), and smoking (OR: 1.86, 95% CI: 1.16–2.94, P = 0.0102) were independently associated with cardioembolic stroke.Conclusions:Cilostazol may prevent cardioembolic stroke in patients undergoing antiplatelet therapy. This could be a novel strategy for cardioembolic stroke prevention potentially by affecting cardiac remodelling, in contrast to secondary anticoagulant therapy.

Efficacy of antiplatelet therapy in secondary prevention following lacunar stroke: pooled analysis of randomized trials.

Lacunar stroke accounts for ≈25% of ischemic stroke, but optimal antiplatelet regimen to prevent stroke recurrence remains unclear. We aimed to evaluate the efficacy of antiplatelet agents in secondary stroke prevention after a lacunar stroke. We searched MEDLINE, Embase, and the Cochrane library for randomized controlled trials that reported risk of recurrent stroke or death with antiplatelet therapy in patients with lacunar stroke. We used random effects meta-analysis and evaluated heterogeneity with I(2). We included 17 trials with 42,234 participants (mean age 64.4 years, 65% male) and follow up ranging from 4 weeks to 3.5 years. Compared with placebo, any single antiplatelet agent was associated with a significant reduction in recurrence of any stroke (risk ratio [RR] 0.77, 0.62-0.97, 2 studies) and ischemic stroke (RR 0.48, 0.30-0.78, 2 studies), but not for the composite outcome of any stroke, myocardial infarction, or death (RR 0.89, 0.75-1.05, 2 studies). When other antiplatelet agents (ticlodipine, cilostazol, and dipyridamole) were compared with aspirin, there was no consistent reduction in stroke recurrence (RR 0.91, 0.75-1.10, 3 studies). Dual antiplatelet therapy did not confer clear benefit over monotherapy (any stroke RR 0.83, 0.68-1.00, 3 studies; ischemic stroke RR 0.80, 0.62-1.02, 3 studies; composite outcome RR 0.90, 0.80-1.02, 3 studies). Our results suggest that any of the single antiplatelet agents compared with placebo in the included trials is adequate for secondary stroke prevention after lacunar stroke. Dual antiplatelet therapy should not be used for long-term stroke prevention in this stroke subtype.

Impact of sex and gender on the efficacy of antiplatelet therapy: the female perspective.

Ischemic heart disease is the single leading cause of death and a significant cause of morbidity among women in industrialized countries. Current guidelines recommend antiplatelet therapy as the main cornerstone for the prevention and treatment of cardiovascular disease. Unfortunately, evidence is emerging that the response to antiplatelet drugs differs according to sex, although the biological basis for this gender disparity is unknown. In order to explain the epidemiological data showing a more severe clinical expression of cardiovascular disease in addition to adverse outcomes despite optimal pharmacological and interventional approaches in women compared to men, differences in platelet reactivity related to sex and gender are currently under investigation. In this report, we review available data from clinical trials of antiplatelet drugs administered for primary and secondary prevention, focusing on the underenrollment of female subjects in interventional randomized studies and weak community awareness of the impact of cardiovascular disease on life expectancy in women. Based on our findings, the development of real gender-oriented evidence-based guidelines for antiplatelet use in the setting of cardiovascular disease is urgently required.

Impact of hemodialysis on local vessel healing and thrombus formation after drug-eluting stent implantation

BackgroundAlthough hemodialysis (HD) is a suggested risk factor for stent thrombosis, its contribution to local vessel healing after drug-eluting stent (DES) implantation is unclear. MethodsA total of 121 patients (152 lesions treated with DES) who underwent 8-month follow-up coronary angiography with optical coherence tomography (OCT) were enrolled, and the findings were compared between patients with and without HD. To match baseline differences, mid-term OCT findings of 42 propensity score-matched lesions (21 non-HD vs. 21 HD) were compared. Effects of HD on the efficacy of antiplatelet therapy were also evaluated by VerifyNow assay (Accumetrics, San Diego, CA, USA). ResultsPatients with HD had a significantly higher rate of thrombus formation than those without (64% vs. 33%, p=0.007), although the baseline parameters and lesion characteristics differed between the groups. Multivariate logistic regression analysis revealed that HD was associated with an increased risk of thrombus formation (odds ratio 5.991, 95% confidence interval: 1.972–18.199, p=0.002). Even after propensity-matching for patient background and balancing of angiographic and OCT variables, the risk of thrombus formation remained significantly higher in HD patients. The P2Y12-reaction unit was significantly increased after HD (Pre HD: 211±75 vs. Post HD: 262±59, p=0.01), but patients without HD showed no increase during the same elapsed time (221±88 vs. 212±96, p=0.19). ConclusionsHD is a potential risk factor for subclinical thrombus attachment after DES therapy. Systemic problems, such as residual platelet reactivity, associated with HD as well as local vessel features in HD patients might contribute to the increased incidence of thrombus attachment and subsequent onset of thrombotic event after DES implantation.

Ambient hemolysis and activation of coagulation is different between HeartMate II and HeartWare left ventricular assist devices

Thromboembolic and bleeding events in patients with a left ventricular assist device (LVAD) are still a major cause of complications. Therefore, the balance between anti-coagulant and pro-coagulant factors needs to be tightly controlled. The principle hypothesis of this study is that different pump designs may have an effect on hemolysis and activation of the coagulation system. Referring to this, the HeartMate II (HMII; Thoratec Corp, Pleasanton, CA) and the HeartWare HVAD (HeartWare International Inc, Framingham, MA) were investigated. For 20 patients with LVAD support (n = 10 each), plasma coagulation, full blood count, and clinical chemistry parameters were measured. Platelet function was monitored using platelet aggregometry, platelet function analyzer-100 system ( Siemens, Marburg, Germany), vasodilator-stimulated phosphoprotein phosphorylation assay, immature platelet fraction, platelet-derived microparticles, and von Willebrand diagnostic. Acquired von Willebrand syndrome could be detected in all patients. Signs of hemolysis, as measured by lactate dehydrogenase levels (mean, 470 U/liter HMII, 250 U/liter HVAD; p < 0.001), were more pronounced in the HMII patients. In contrast, D-dimer analysis indicated a significantly higher activation of the coagulation system in HVAD patients (mean, 0.94 mg/liter HMII, 2.01 mg/liter HVAD; p < 0.01). The efficacy of anti-platelet therapy using clopidogrel was not sufficient in more than 50% of the patients. Our results support the finding that all patients with rotary blood pumps suffered from von Willebrand syndrome. In addition, a distinct footprint of effects on hemolysis and the coagulation system can be attributed to different devices. As a consequence, the individual status of the coagulation system needs to be controlled in long-term patients.

Light transmittance aggregometry with non-adjusted PRP is more suitable for clinical laboratory monitoring antiplatelet therapy

Objective In this study,maximum platelet aggregation rate of Light transmittance aggregometry (LTA) for coronary heart disease (CHD) patients taking antiplatelet drug and patients without antiplatelet therapy was measured in non-adjusted and platelet count-adjusted platelet-rich plasma (PRP).The aim of this study is to compare which method is superior in evaluation of antiplatelet drug effect. Methods This is a methodology comparative research.560 CHD outpatients and inpatients that visited Beijing Anzhen Hospital of the Capital University of Medical Sciences from May to June,2012 were chosen,who were treated with aspirin monotherapy,or patients on combination therapy with aspirin and clopidogrel,as well as patients without antiplatelet therapy.LTA was performed in non-adjusted (improved method) and platelet count (200×109/L) -adjusted PRP (original method),using 6μmol/L adenosine diphosphate (ADP) and 0.5 mmol/L arachidonic acid (ARA) as agonists.The maximum aggregation rates in 5 min were detected,and consistency and differences of the two methods were compared. Results There is no statistically significant correlation between maximum aggregation rate and platelet count in PRP with 6μmol/L ADP or 0.5 mmol/L ARA as agonists in all subgroups including aspirin monotherapy,combination therapy with aspirin and clopidogrel and patients without antiplatelet therapy (-0.21≤r≤0.111,P>0.05).The maximum aggregation rate using ADP as agonists in original method is decreased compared with improved method,there is statistically significant difference in all subgroups including patients without antiplatelet therapy,aspirin monotherapy,combination therapy with aspirin and clopidogrel less than one week and more than one week.The variability of platelet aggregation rate using ADP as agonists with improved method is lower than that with original method in all subgroups.Yet the maximum aggregation rates using ADP as agonists with improved method and original method correlate well with each other in all subgroups (r=0.78,0.73,0.40,0.71,P<0.01).In the subgroup of subjects without antiplatelet therapy using ARA as agonist,platelet aggregation rate is decreased in original method compared with improved method,there is statistically significant difference,and the variability of the aggregation rate with improved method is also lower than that with original method,ranging from 62%-98% relative to 5%-89%.The decrease of aggregation rate using ARA as agonist for patients taking antiplatelet drug compared with patients without antiplatelet therapy can be detected both with improved method and original method. Conclusion Non-adjusted PRP in LTA is more convenient and time-saving,and it also means less effects on platelet in vitro.Therefore,non-adjusted PRP is more suitable for monitoring efficacy of antiplatelet therapy in clinical laboratory.(Chin J Lab Med,2013,36:405-409) Key words: Platelet aggregation inhibitors; Platelet count; Platelet aggregation; Nephelometry and turbidimetry; Treatment outcome

Role of CYP450 in Antiplatelet Therapy: Considerations for Patients at Risk for Further Cardiovascular or Cerebrovascular Problems

Objective: To determine how interactions with cytochrome P450 ( CYP450) isoenzyme pathways may influence the selection of antiplatelet therapy in patients with cardiovascular and cerebrovascular disease. Data Sources: A MEDLINE search (1966-September 2012) was performed using the following MeSH search terms: clopidogrel, prasugrel, ticagrelor, aspirin, dipyridamole, drug interactions, polymorphism, cytochrome P450, platelets, platelet reactivity testing, and platelet function. In addition, reference citations were reviewed. Study Selection and Data Extraction: Selected studies analyzed the effects of CYP450 isoenzymes on the efficacy of antiplatelet therapy and potential drug-drug interactions. Data Synthesis: Antiplatelet therapy is pivotal in reducing the risk of acute coronary syndromes. Thienopyridines are commonly prescribed for antiplatelet drug therapy; however, a multitude of factors can influence their efficacy, given that thienopyridines require activation through CYP450 isoenzymes. Genetic polymorphisms in CYP450 isoenzymes and the susceptibility of drug-drug interactions mediated through the CYP450 system have led to variability in antiplatelet response. Two factors in particular have been prime targets in elucidating the role of CYP450 isoenzymes on thienopyridine activity and bioavailability: CYP2C19*2 polymorphisms and drug interactions with proton pump inhibitors. Additionally, many studies have surfaced in an attempt to quantify a patient's response to antiplatelet therapy but, to date, none has determined whether platelet reactivity testing is mandatory prior to initiation of therapy or whether it correlates with clinical efficacy. This review spotlights the pharmacokinetic and pharmacodynamic influences that CYP450 isoenzymes exert on antiplatelet therapies and attempts to categorize the role of platelet reactivity testing in determining the clinical significance of drug interactions. Conclusions: Suboptimal responses to antiplatelet therapy may occur because of interactions with CYP450 isoenzyme pathways. Further studies are warranted to clarify the impact of genetic polymorphisms and drug-drug interactions on clinical outcomes in patients with cardiovascular/cerebrovascular disease.