Dual Antiplatelet Therapy Of Aspirin Research Articles

Hyperacute thrombosis of a vertebral artery stent with a single missed dose of a P2Y12 inhibitor and poor stent wall apposition: illustrative case.

Iatrogenic vertebral artery injury during surgery can cause pseudoaneurysm, hemorrhage, thrombosis, ischemia, or death. Strategies to prevent cerebrovascular embolic complications include surgical ligation, endovascular stenting, and/or antiplatelet therapy. A 73-year-old female with a known right vertebral artery occlusion underwent a C2-3 laminectomy, complicated by left vertebral artery injury and occlusion with subsequent posterior circulation ischemia. She underwent immediate angioplasty and stenting of the injured artery with undersized drug-eluting stents. Dual antiplatelet therapy of aspirin 81 mg daily and ticagrelor 90 mg twice daily was initiated. On two occasions, more than 6 months after stenting, holding a single ticagrelor dose led to in-stent thrombosis and embolic stroke within hours of the missed dose. Lifelong therapy with ticagrelor was favored over further procedural intervention. It is recommended to prioritize optimal wall stent apposition with oversized stents in patients without collateral circulation. The risk of thromboembolism due to poorly apposed stents is very high, even in delayed (> 6 months) settings. Stent construct revision or bypass grafting may not be feasible or desirable options. For patients without wall apposition, endothelialization may not occur, necessitating lifelong P2Y12 inhibitor therapy to prevent recurrent thromboembolic events. https://thejns.org/doi/10.3171/CASE24296.

Navigating Choices: A Questionnaire-based Study on Usage of Antiplatelet Therapies in Management of Acute Coronary Syndrome in India

Percutaneous coronary intervention (PCI) is a common invasive cardiac procedure used to treat acute coronarysyndrome (ACS). The main objective of anticoagulant therapy in PCI is to minimize the risk of plaque rupture and decreasethe formation of blood clots. Understanding clinicians' prescription patterns is crucial for optimizing treatment strategiesfor patients with ACS who have undergone PCI. Methods: It was a cross-sectional, questionnaire-based, noninterventionalstudy which included questionnaire responses from 136 cardiologists, regarding usage of antiplatelets in ACS management.Results: Ticagrelor and aspirin dual antiplatelet therapy (DAPT) is favored by 54% cardiologists in managing ACS patientswho have undergone PCI, regardless of the presence or absence of type 2 diabetes mellitus (T2DM). Further, 78% of theparticipants preferred long-term DAPT over short-term and medium-term alternatives. Forty percent respondents preferreda 1-month triple antithrombotic therapy (TAT) for PCI patients with atrial fibrillation. Additionally, the study emphasizedthe importance of considering factors like age, bleeding history, hemoglobin, and creatinine clearance in determining theoptimal antithrombotic strategy. Conclusion: This study contributes valuable insights into the real-world practices of healthcare practitioners, paving the way for more informed and personalized ACS management strategies in Indian patients.

Trends in Dual Antiplatelet Therapy of Aspirin and Clopidogrel and Outcomes in Ischemic Stroke Patients Noneligible for POINT/CHANCE Trial Treatment.

Recent clinical trials established the benefit of dual antiplatelet therapy with aspirin and clopidogrel (DAPT-AC) in early-presenting patients with minor ischemic stroke. However, the impact of these trials over time on the use and outcomes of DAPT-AC among the patients with nonminor or late-presenting stroke who do not meet the eligibility criteria of these trials has not been delineated. In a multicenter stroke registry, this study examined yearly changes from April 2008 to August 2022 in DAPT-AC use for stroke patients ineligible for CHANCE/POINT (Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events/Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke) clinical trials due to National Institutes of Health Stroke Scale >4 or late arrival beyond 24 hours of onset. A total of 32 118 patients (age, 68.1±13.1 years; male, 58.5%) with National Institutes of Health Stroke Scale of 4 (interquartile range, 1-7) were analyzed. In 2008, DAPT-AC was used in 33.0%, other antiplatelets in 62.7%, and no antiplatelet in 4.3%. The frequency of DAPT-AC was relatively unchanged through 2013, when the CHANCE trial was published, and then increased steadily, reaching 78% in 2022, while other antiplatelets decreased to 17.8% in 2022 (Ptrend<0.001). From 2011 to 2022, clinical outcomes nonsignificantly improved, with an average relative risk reduction of 2%/y for the composite of stroke, myocardial infarction, and all-cause mortality, both among patients treated with DAPT-AC and patients treated with other antiplatelets. Use of DAPT-AC in stroke patients with stroke ineligible for recent DAPT clinical trials increased markedly and steadily after CHANCE publication in 2013, reaching deployment in nearly 4 of every 5 patients by 2022. The secondary prevention in patients with ischemic stroke seems to be gradually improving, possibly due to the enhancement of risk factor control.

Interplay among proton pump inhibitors, platelet reactivity and CYP2C19 genotyping in clopidogrel-treated patients after drug-eluting stent implantation

Abstract Background Several published data suggested that concomitant use of clopidogrel and proton pump inhibitors (PPIs) is associated with reduced antiplatelet efficacy of clopidogrel and increased adverse clinical outcomes. We sought to evaluate the interplay between PPI and clopidogrel on platelet reactivity and long-term clinical outcomes in patients after percutaneous coronary intervention (PCI) with drug-eluting stent (DES) implantation. Methods The PTRG-DES (Platelet function and genoType-Related long-term proGnosis in DES-treated patients) registry is a multi-center, real-world registry of patients who underwent PCI with DES and received dual antiplatelet therapy of aspirin and clopidogrel in South Korea. Patients prescribed with PPI were compared to those without the use of PPI (the control group). The primary outcome was a composite of all-cause death, myocardial infarction, stent thrombosis, and stroke at 5 years. Secondary outcomes included cardiac death, major bleeding, and gastrointestinal bleeding. Adjusted outcomes were compared after 1:2 propensity score (PS) matching analysis. Results Among 13,160 patients, 2235 (17.0%) were prescribed with concomitant PPI at the time of clopidogrel loading. Average age was 64.4 years, 67.2% were men, and 35.1% had diabetes. The PPI group demonstrated a higher on-treatment P2Y12 reaction unit than the control group (p&amp;lt;0.001). The 5-year cumulative incidence of the composite primary outcome was higher in the PPI group (12.1% vs. 9.8%, log-rank p&amp;lt;0.001). After PS matching, the primary outcome was similar between the two groups (12.9% vs. 12.1%, log-rank p=0.24). However, the PPI group with CYP2C19 poor metabolizers showed an increased adjusted risk of the primary outcome (hazard ratio 2.69, p&amp;lt;0.001). Conclusions PPI use in patients with clopidogrel administration after DES implantation was associated with increased platelet reactivity, but similar cardiovascular outcomes in real-world practice. Physicians should be careful when administering PPI with clopidogrel in patients with CYP2C19 poor metabolizers.Distribution of P2Y12 reaction unitCumulative Incidence of outcomes

Antiplatelet Treatment Patterns and Outcomes for Secondary Stroke Prevention in the United Kingdom.

Stroke is a leading cause of death and disability worldwide. Antiplatelet therapies are recommended to reduce the risk of recurrent stroke in patients with ischemic stroke/transient ischemic attack (IS/TIA). This study evaluated outpatient antiplatelet treatment patterns and outcomes for secondary stroke prevention (SSP) among UK adults without atrial fibrillation who were hospitalized for IS/TIA. This retrospective observational study utilized data from the UK Clinical Practice Research Datalink linked with Hospital Episode Statistics data (01/01/2011-30/06/2019). Treatment patterns included type and duration of treatments. Treatment outcomes included IS, myocardial infarction, major bleeding, and cardiovascular-related and all-cause mortality. Descriptive statistics were reported. Of 9270 patients, 13.9% (1292) might not receive antithrombotic therapy within 90days of hospital discharge. Of 7978 patients who received antiplatelet therapies, most used clopidogrel (74.8%) or aspirin (16.7%) single antiplatelet therapy and clopidogrel + aspirin dual antiplatelet therapy (DAPT, 5.9%). At 1-year post-hospitalization, 36.9, 43.3, and 35.1% of those receiving these treatments discontinued them, respectively, and of the patients initiating DAPT, 62.3% switched to single antiplatelet therapy. At 1-year post-discharge, the incidence rate (per 100 person-years) of IS, myocardial infarction, major bleeding, cardiovascular-related mortality, and all-cause mortality among the treated were 6.5, 0.7, 4.1, 5.0, and 7.3, respectively, and among the untreated were 14.9, 0.7, 8.6, 28.1, and 39.8, respectively. In the United Kingdom, 13.9% of patients hospitalized for stroke might not have any antiplatelet treatment to prevent secondary stroke; among the treated, clopidogrel, aspirin, and DAPT were commonly used. These study findings suggest that improved anti-thrombotic therapies for long-term SSP treatment are needed, which may lead to higher treatment and persistence rates and, therefore, improved outcomes in this population.

Effect of ticagrelor and clopidogrel dual antiplatelet therapy on MPVLR, MAADP, and AA inhibition rate in acute coronary syndrome patients after percutaneous coronary intervention.

To explore the effects of ticagrelor and clopidogrel dual antiplatelet therapy on the mean platelet volume-to-lymphocyte ratio (MPVLR), maximum amplitude of adenosine diphosphate-induced platelet-fibrin clots (MAADP), and arachidonic acid (AA) inhibition rates in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI). A total of 120 patients with ACS undergoing elective PCI in our hospital between March 2020 and November 2021 were recruited. Patients were divided into 2 groups using the random number table method, with 60 patients in each group. The control group received clopidogrel + aspirin dual antiplatelet therapy, while the study group received ticagrelor + aspirin dual antiplatelet therapy. MPVLR, MAADP, and AA inhibition rates were compared between the 2 groups. Platelet activation indices, platelet micro PNA-223, and platelet gelsolin levels were measured before and 4 weeks after PCI. Changes in cardiac function indices, bleeding rates, and major adverse cardiovascular events (MACE) were compared between groups. The MAADP score of the study group was lower than that of the control group 3 days after surgery (P < .05). Compared with before surgery, CD62p, CD63, miR-223, PAC-1, platelet membrane glycoprotein IIb/IIIa complex, and gelsolin levels markedly decreased in both groups 4 weeks after surgery (P < .05). The platelet activation index and platelet miR-223 and gelsolin levels were significantly lower in the study group than in the control group 4 weeks after surgery (P < .05). The overall platelet inhibition effect was significantly better in the study group than in the control group (P < .05). Compared with before surgery, the left ventricular ejection fraction and stroke volume were significantly increased, and the left ventricular end-diastolic volume and left ventricular end-diastolic diameter significantly decreased in both groups 4 weeks after surgery (P < .05). No significant differences were found between the 2 groups in terms of the incidence of bleeding events or MACE (P > .05). Ticagrelor is more effective than clopidogrel for platelet inhibition after PCI in patients with ACS and is worthy of clinical recommendation.

Effect of cocoa (Theobroma cacao L.) on platelet function testing profiles in patients with coronary artery disease: ECLAIR pilot study

IntroductionThis prospective pharmacodynamic nutraceutical study assessed the effect of a 1-week trial of 30 g/day of 65% cocoa (dark chocolate) (Theobroma cacao L.) consumption intervention on platelet reactivity.MethodsPatients with stable...

Pipeline flow diversion with adjunctive coil embolization for internal carotid artery aneurysms following an intradural component: results in 46 consecutive aneurysms from a Japanese single-center experience.

In the treatment of an intracranial aneurysm with the flow diverter, the combined use of coil embolization can help promote subsequent progressive thrombosis within the aneurysm sac and reduce the risk of delayed aneurysm rupture. This study retrospectively reviewed outcomes of patients who had undergone the Pipeline Embolization Device (PED) with adjunctive coil embolization (PED/coil) at a single center to determine its safety and efficiency. Patients with internal carotid artery aneurysms following an intradural component were selected for PED/coil between 2015 and 2020. All patients were premedicated with dual antiplatelet therapy of aspirin plus clopidogrel or prasugrel. A minimal number of PEDs were deployed, with coils inserted using a stent-jail technique, avoiding dense packing. A total of 46 aneurysms (43 patients; median dome size, 11.6mm; median neck width, 6.3mm) were treated with PED/coil. The median volume embolization ratio was 14.8%. The degree of angiographic filling at the 6-month and latest angiography showed complete occlusion in 60.5% (26/43) and 70.5% (31/44), respectively. Small (< 10mm) aneurysms achieved a higher complete occlusion rate in the early period; a lower cumulative incidence of aneurysm occlusion was observed in large and giant (≥ 10mm) aneurysms (P = .024). The median clinical follow-up was 22months, and no aneurysm ruptures occurred. Favorable clinical outcomes were achieved, with permanent neurological morbidity of 4.7% and no mortality. PED/coil demonstrated a high angiographic occlusion rate at an early stage. Loosely packed coils are sufficient to obliterate aneurysms effectively.

The Effect of Low-Dose Ticagrelor on Platelet Function Profiles in Patients With Stable Coronary Artery Disease in Trinidad: The TWIST Pilot Study.

IntroductionThis prospective, pharmacodynamic study aimed to explore the potential applicability of a low-dose ticagrelor regimen in a heterogeneous Trinidadian subpopulation.MethodsPatients with stable coronary artery disease (n = 25) who were actively treated with dual antiplatelet therapy of aspirin 81 mg daily and clopidogrel 75 mg daily were recruited. Platelet function was measured with the VerifyNow P2Y12 assay (Accriva Diagnostics, San Diego, CA, USA) and assessed before initiation of and after 14 days of treatment with a low-dose ticagrelor 45 mg twice daily maintenance dose regimen. Results were compared with a paired t test.ResultsThe mean P2Y12 reaction units (PRU) score on ticagrelor was significantly less compared to that of clopidogrel (50.4, 95% confidence interval (CI) 29–73.9; vs. 149.6, 95% CI 129.4–169.9; p value < 0.001). Of the patients, 4% experienced Medical Research Council class 1 dyspnea, and Bleeding Academic Research Consortium class 1 bleeding on the ticagrelor regimen (one patient each).ConclusionsSignificantly attenuated platelet reactivity was seen on the low ticagrelor maintenance dose as compared to clopidogrel. This dedicated pharmacodynamic study could be applicable and informative for Trinidadian stable coronary artery disease patients. Further studies are required to confirm these exploratory findings.(Funded by the University of the West Indies, St. Augustine).Trial RegistrationClinicalTrials.gov number NCT04206176.

Outcomes and strategy of tailored antiplatelet therapy with ticagrelor in patients undergoing transcarotid artery revascularization

ObjectiveAntiplatelet drug resistance is associated with periprocedural ischemic complications in patients undergoing intravascular stent implantation. Nonresponders are subject to increased risk of stent thrombosis and in-stent stenosis, and high on-treatment platelet reactivity (HTPR) is present in up to 44% of patients taking clopidogrel, a widely used component of dual antiplatelet therapy (DAPT). Evidence points to ticagrelor as a viable alternative to overcome HTPR on clopidogrel. Studies have shown fewer thromboembolic events with ticagrelor therapy; however, results on bleeding risk are mixed, and its safety and efficacy in hybrid operative techniques have yet to be established. Transcarotid artery revascularization (TCAR) is a hybrid procedure to treat severe carotid stenosis. The objective of this study was to establish the safety and efficacy of ticagrelor as part of DAPT in patients undergoing TCAR and to develop a protocol to ensure adequate antithrombotic protection throughout the operative course. MethodsData were collected retrospectively for patients undergoing TCAR on DAPT of aspirin and ticagrelor for symptomatic (≥50%) or asymptomatic (≥80%) carotid stenosis. Preoperative platelet reactivity was determined using Thromboelastography with Platelet Mapping (Haemonetics Corporation, Braintree, Mass), with adequate platelet reactivity defined as maximal amplitude produced by adenosine diphosphate <50 mm. The primary safety end point was 30-day major bleeding event rate. Primary efficacy end points were 30-day incidence of ipsilateral cerebrovascular ischemic event (stroke or transient ischemic attack), myocardial infarction, and death. Secondary end points were postoperative length of hospital stay, procedure time, and clamp/flow reversal time. ResultsSixty-seven TCAR procedures with patients receiving periprocedural DAPT of ticagrelor and aspirin were performed during the study period. Patients had an average age of 79 years, and 28 (42%) were symptomatic. The mean procedure time was 45.8 ± 9.2 minutes, with a mean clamp/flow reversal time of 4.8 ± 1.5 minutes, and mean postoperative length of hospital stay of 3.1 ± 2.2 days for inpatients and 1.3 ± 0.8 days for outpatients. Technical success was achieved in all cases, with no 30-day major bleeding events and no occurrence of ipsilateral cerebrovascular ischemic event, myocardial infarction, or death. ConclusionsInitial experience with ticagrelor as part of DAPT in patients undergoing TCAR demonstrated its safety and efficacy in both symptomatic and asymptomatic disease. No bleeding events or thromboembolic complications occurred. Furthermore, a protocol to administer ticagrelor to assay for HTPR on ticagrelor and consequent medication and patient management is proposed. Ticagrelor may represent a safe and effective alternative to overcome clopidogrel nonresponsiveness in DAPT regimens for TCAR.

Impact of renal function on clinical outcomes after PCI in ACS and stable CAD patients treated with ticagrelor: a prespecified analysis of the GLOBAL LEADERS randomized clinical trial.

Impaired renal function (IRF) is associated with increased risks of both ischemic and bleeding events. Ticagrelor has been shown to provide greater absolute reduction in ischemic risk following acute coronary syndrome (ACS) in those with versus without IRF. A pre-specified sub-analysis of the randomized GLOBAL LEADERS trial (n = 15,991) comparing the experimental strategy of 23-month ticagrelor monotherapy (after 1-month ticagrelor and aspirin dual anti-platelet therapy [DAPT]) with 12-month DAPT followed by 12-month aspirin after percutaneous coronary intervention (PCI) in ACS and stable coronary artery disease (CAD) patients stratified according to IRF (glomerular filtration rate < 60ml/min/1.73m2). At 2years, patients with IRF (n = 2171) had a higher rate of the primary endpoint (all-cause mortality or centrally adjudicated, new Q-wave myocardial infarction [MI](hazard ratio [HR] 1.64, 95% confidence interval [CI] 1.35-1.98, padj = 0.001), all-cause death, site-reported MI, all revascularization and BARC 3 or 5 type bleeding, compared with patients without IRF. Among patients with IRF, there were similar rates of the primary endpoint (HR 0.82, 95% CI 0.61-1.11, p = 0.192, pint = 0.680) and BARC 3 or 5 type bleeding (HR 1.10, 95% CI 0.71-1.71, p = 0.656, pint = 0.506) in the experimental versus the reference group. No significant interactions were seen between IRF and treatment effect for any of the secondary outcome variables. Among ACS patients with IRF, there were no between-group differences in the rates of the primary endpoint or BARC 3 or 5 type bleeding; however, the rates of the patient-oriented composite endpoint (POCE) of all-cause death, any stroke, MI, or revascularization (pint = 0.028) and net adverse clinical events (POCE and BARC 3 or 5 type bleeding) (pint = 0.045), were lower in the experimental versus the reference group. No treatment effects were found in stable CAD patients categorized according to presence of IRF. IRF negatively impacted long-term prognosis after PCI. There were no differential treatment effects found with regard to all-cause death or new Q-wave MI after PCI in patients with IRF treated with ticagrelor monotherapy. The trial has been registered with ClinicalTrials.gov, number NCT01813435.

Recurrent Stroke in a Ghanaian Patient With Polycythemia

BackgroundPolycythemia is a rare but important preventable cause of stroke with potential for recurrence when not identified and appropriately managed. Case PresentationThis is a case of a 55-year-old Ghanaian who presented to our tertiary facility after a 2-month delay with a history of sudden onset of right-sided hemiparesis and expressive aphasia. He had suffered a previous stroke with left hemiparesis 2 years previously where hypertension and polycythemia were identified and treatment initiated. However, patient defaulted treatment for 18 months prior to the onset of recurrent stroke. A cranial CT scan revealed chronic right and subacute left middle cerebral artery territorial infarcts. Presenting hematocrit was 71%. Treatments initiated included high dose hydroxyurea, venesections, and dual antiplatelet therapy of Aspirin and Clopidogrel. He has since been discharged and remains stable under follow-up with moderate functional deficits– Modified Rankin score of 3/6 and the hematocrit of 54% at 3 months postdischarge. ConclusionsDefault of therapy for polycythemia is associated with a profound risk of recurrent strokes requiring patient education and support to prevent the devastating consequence of this modifiable but rare cause of stroke. This case report highlights the challenges of instituting secondary prevention for stroke in resource-limited settings.

What is the Role for Glycoprotein IIb/IIIa Inhibitor Use in the Catheterization Laboratory in the Current Era?

In the era of dual antiplatelet therapy of aspirin and clopidogrel and systematic stent implantation, Glycoprotein IIb/IIIa Inhibitors (GPI), including abciximab, eptifibatide and tirofiban, proved beneficial in improving early outcome of Percutaneous Coronary Intervention (PCI), especially in higher risk clinical and/or anatomical subsets. This was associated however, with an increased incidence of bleeding complications. To review whether the established results of GPI in PCI are maintained in the contemporary era of more effective antiplatelet agents (i.e., prasugrel, ticagrelor and cangrelor) and safer anticoagulants (i.e., bivalirudin) and interventional techniques (i.e., radial approach). The most relevant evidence on the use of GPI in stable coronary artery disease, non-STelevation coronary syndromes and ST-elevation myocardial infarction was reviewed. Overall the relative efficacy and safety of GPI in contemporary PCI is maintained, largely irrespective of the use of more effective antiplatelet agents and/or safer anticoagulants and interventional techniques. However, an increase in the absolute occurrence of major and/or minor bleeding and/or need for blood transfusions is generally observed. Because of the persistent benefit of GPI in limiting early ischemic complications, especially in higher risk clinical and/or anatomical subsets, and the associated risk of increased bleeding complications, also in contemporary PCI, these agents should currently be used on a selective rather than routine basis, including bail out administration for peri-procedural thrombotic complications.

Dual antiplatelet therapy versus single antiplatelet therapy after transaortic valve replacement: Meta-analysis.

The current guidelines recommend empirical therapy with DAPT of aspirin and clopidogrel for six months after TAVR. This recommendation is based on expert consensus only. Giving the lack of clear consensus on treatment strategy following TAVR. Goal of this meta-analysis is to assess the efficacy and safety of mono-antiplatelet therapy (MAPT) versus dual antiplatelet therapy (DAPT) following transcatheter aortic valve replacement (TAVR). We performed a meta-analysis from randomized clinical trials (RCTs) and prospective studies that tested DAPT vs. MAPT for all-cause mortality and major bleeding of 603 patients. The primary efficacy outcomes were 30 days mortality and stroke. The primary safety outcomes were major bleeding and major vascular complications. We included 603 patients from 4 studies. The use of MAPT was associated with similar mortality rate (5.9% vs. 6.6%; RR = 0.92; 95% CI 0.49-1.71; P = 0.68) and stroke rate compared with DAPT (1.3% vs. 1.3%; RR 1.04; 95% CI 0.27 to 4.04; P = 0.81). There was no difference in major vascular complication (4.2% vs. 8.9%; RR 0.52; 95% CI 0.23 to 1.18; P = 0.17) or minor vascular complication (4.2% vs. 7.3%; RR 0.58; 95% CI 0.25 to 1.34; P = 0.14). However, MAPT was associated with significantly less risk of major bleeding (4.9% vs. 14.5%; RR 0.37; 95% CI 0.20 to 0.70; P < 0.01) but no difference in minor bleeding (4.2% vs. 3.6%; RR 1.16; 95% CI 0.43 to 3.10; P = 0.85). MAPT use after TAVR is associated with lower rates of major bleeding compared with DAPT with no significant difference in mortality, stroke or vascular complications.

The Risk of Bleeding in Triple Antiplatelet Therapy: Cilostazol Added to Aspirin and Clopidogrel for Coronary Artery Disease Patients Who Underwent Percutaneous Coronary Intervention: A Meta-Analysis Study of Randomized Controlled Trials

BACKGROUND: A novel cilostazol-based triple antiplatelet therapy (TAT) was shown in a trial to have a lower restenosis rate than the usual clopidogrel and aspirin dual antiplatelet therapy (DAPT) among patients with coronary artery disease (CAD) who underwent percutaneous coronary intervention. However, TAT may also be associated with an increased risk of bleeding. A systematic review would show further evidence regarding the risk of bleeding among TAT-treated patients. MAIN OBJECTIVE: To determine the risk of bleeding with TAT composed of cilostazol, aspirin and clopidogrel for CAD patients who underwent percutaneous coronary intervention. METHODS: This systematic review included randomized controlled trials (RCT) published from 2005 to 2014. Only one study was blinded. These studies compared the risk of major bleeding between DAPT and TAT. Meta-analysis of this outcome was conducted using Review Manager (RevMan) Version 5.3 2014. RESULTS: The overall relative risk (RR) of major bleeding in TAT patients was 1.23 (CI 95% 0.90, 1.67; z=1.30, p=0.19). The heterogeneity of results of the seven studies was not statistically significant (p=0.88; I2=0%). When isolating those studies with favorable outcome with TAT, the risk of bleeding demonstrated in five studies was also not statistically significant (p=0.11; I2=0%). Sensitivity analysis on two studies with wider deviation and slightly lower rates of bleeding showed no significant influence on the risk of bleeding (RR 0.78; CI 0.29, 2.09; p=0.63; I2=0%). CONCLUSION: Compared with DAPT, the trend towards increased major bleeding in cilostazol -based TAT did not reach statistical significance.

Antiplatelet Therapy in Noncardioembolic Stroke: A Review of Current Evidence.

AbstractAcute stroke is a leading cause of death and disability in the developed world. Among survivors, the risk of stroke recurrence is highest within the first few days, and up to 15% will be affected within the first year. In the case of noncardioembolism, antiplatelets, such as aspirin, clopidogrel, and the combination of aspirin and dipyridamole, remain the mainstay of treatment. Aspirin given immediately is beneficial, but when combined with clopidogrel is associated with a higher risk of bleeding. Dual antiplatelet therapy of aspirin and dipyridamole was no more effective than clopidogrel in reducing stroke recurrence. In symptomatic extracranial atherosclerosis, surgery within 2 weeks of the index event will benefit, but in strokes due to intracranial atherosclerosis and small vessel disease, medical therapy alone is recommended. The purpose of this review is to discuss the various trials of antiplatelet therapies in acute and long-term stroke prevention in mechanisms excluding cardioembolism.

The Personalization of Clopidogrel Antiplatelet Therapy: The Role of Integrative Pharmacogenetics and Pharmacometabolomics.

Dual antiplatelet therapy of aspirin and clopidogrel is pivotal for patients undergoing percutaneous coronary intervention. However, the variable platelets reactivity response to clopidogrel may lead to outcome failure and recurrence of cardiovascular events. Although many genetic and nongenetic factors are known, great portion of clopidogrel variable platelets reactivity remain unexplained which challenges the personalization of clopidogrel therapy. Current methods for clopidogrel personalization include CYP2C19 genotyping, pharmacokinetics, and platelets function testing. However, these methods lack precise prediction of clopidogrel outcome, often leading to insufficient prediction. Pharmacometabolomics which is an approach to identify novel biomarkers of drug response or toxicity in biofluids has been investigated to predict drug response. The advantage of pharmacometabolomics is that it does not only predict the response but also provide extensive information on the metabolic pathways implicated with the response. Integrating pharmacogenetics with pharmacometabolomics can give insight on unknown genetic and nongenetic factors associated with the response. This review aimed to review the literature on factors associated with the variable platelets reactivity response to clopidogrel, as well as appraising current methods for the personalization of clopidogrel therapy. We also aimed to review the literature on using pharmacometabolomics approach to predict drug response, as well as discussing the plausibility of using it to predict clopidogrel outcome.

Assessment of Dual-Antiplatelet Regimen for Pipeline Embolization Device Placement: A Survey of Major Academic Neurovascular Centers in the United States

Flow diversion with the Pipeline Embolization Device (PED) currently is adopted for treatment of a variety of intracranial aneurysms. The elevated risk of thromboembolic complications associated with the device necessitates the need for administration of antiplatelet agents. We sought to assess current dual-antiplatelet therapy practices patterns and their associated costs after PED placement. An online questionnaire that assessed dual-antiplatelet regimens after flow diversion for treatment of intracranial aneurysms was developed and disseminated to 80 neurosurgeons at major academic cerebrovascular centers. Pricing information from 2 of the largest prescription payers in Massachusetts was used to calculate the monthly cost of these agents. Twenty-six responses (32.5%) were received. All respondents (100%) affirmed using clopidogrel and aspirin dual-antiplatelet therapy as a first-line regimen. Twenty-three (88.5%) routinely use platelet function testing. Eleven respondents (42.3%) each identified that they administer aspirin/ticagrelor and aspirin/prasugrel to clopidogrel hypo- or nonresponders. For uninsured patients, prasugrel was found to have the highest cumulative monthly cost ($471), followed by ticagrelor ($396), clopidogrel ($149), and ticlopidine ($110). Significant heterogeneity in dual-antiplatelet regimens after PED placement and associated costs exists at major academic neurovascular centers. The most commonly used first-line dual-antiplatelet regimen consists of aspirin and clopidogrel. Two major alternate protocols involving ticagrelor and prasugrel are administered to clopidogrel hyporesponders. The optimal dual-antiplatelet regimen for patients with cerebrovascular conditions has not been established, given limited prospective data within the neurointerventional literature.

Antiplatelet Therapy of Cilostazol or Sarpogrelate with Aspirin and Clopidogrel after Percutaneous Coronary Intervention: A Retrospective Cohort Study Using the Korean National Health Insurance Claim Database.

Background/ObjectivesAddition of cilostazol or sarpogrelate to the standard dual antiplatelet therapy of aspirin and clopidogrel has been implemented in patients that underwent percutaneous coronary intervention (PCI) with stents in Korea. This study aimed to evaluate the efficacy and safety of triple antiplatelet therapies.MethodsThis retrospective cohort study was performed using the Korean National Insurance Claim Data of the Health Insurance Review and Assessment Service from January 1, 2009 to December 31, 2014. The study cohort population consisted of patients with ischemic heart diseases and a history of PCI. They were treated with antiplatelet therapy of aspirin, clopidogrel (AC); aspirin, clopidogrel, cilostazol (ACCi); or aspirin, clopidogrel, sarpogrelate (ACSa) during the index period from January 1, 2010 to December 31, 2011. During the follow-up period up to December 31, 2014, the major adverse cardiac or cerebral events (MACCE) including death, myocardial infarction, target lesion revascularization, and ischemic stroke were assessed. Bleeding complications were also evaluated as adverse drug events.ResultsOut of 93,876 patients with PCI during the index period, 69,491 patients started dual (AC) or triple therapy (ACSa or ACCi). The clinical outcomes of comparing ACSa and ACCi therapy showed beneficial effects in the ACSa group in the prevention of subsequent cardiac or cerebral events. After Propensity score-matching between ACSa and ACCi groups, there were significant differences in MI and revascularization, with corresponding HR of 0.38 (95% CI, 0.20–0.73) and 0.66 (95% CI, 0.53–0.82) in ACSa vs. ACCi at 12 months, respectively. At the 24-month follow-up, the triple therapy groups (ACS or ACC) had a higher incidence of MACCE compared to the dual therapy (AC) group; ACSa vs. AC HR of 1.69 (95% CI, 1.62–1.77); ACC vs. AC HR of 1.22 (95% CI, 1.06–1.41). There was no significant difference in severe or life-threatening bleeding risk among three groups; ACSa vs. AC, HR of 0.68 (95% CI, 0.37–1.24), ACCi vs. AC, HR of 0.91 (95% CI, 0.77–1.09).ConclusionSarpogrelate-containing triple antiplatelet therapy demonstrated comparable rates of MACCE prevention to the conventional dual antiplatelet therapy after PCI without significantly increasing bleeding risk during the two-year follow-up period.

CYP2C19 and CES1 polymorphisms and efficacy of clopidogrel and aspirin dual antiplatelet therapy in patients with symptomatic intracranial atherosclerotic disease.

OBJECT Symptomatic intracranial atherosclerotic disease (ICAD) has a high risk of recurrent stroke. Genetic polymorphisms in CYP2C19 and CES1 are associated with adverse outcomes in cardiovascular patients, but have not been studied in ICAD. The authors studied CYP2C19 and CES1 single-nucleotide polymorphisms (SNPs) in symptomatic ICAD patients. METHODS Genotype testing for CYP2C19*2, (*)3, (*)8, (*)17 and CES1 G143E was performed on 188 adult symptomatic ICAD patients from 3 medical centers who were medically managed with clopidogrel and aspirin. Testing was performed prospectively at 1 center, and retrospectively from a DNA sample biorepository at 2 centers. Multiple logistic regression and Cox regression analysis were performed to assess the association of these SNPs with the primary endpoint, which was a composite of transient ischemic attack (TIA), stroke, myocardial infarction, or death within 12 months. RESULTS The primary endpoint occurred in 14.9% of the 188 cases. In multiple logistic regression analysis, the presence of the CYP2C19 loss of function (LOF) alleles *2, *3, and *8 in the medically managed patients was associated with lower odds of primary endpoint compared with wild-type homozygotes (odds ratio [OR] 0.13, 95% CI 0.03-0.62, p = 0.0101). Cox regression analysis demonstrated the CYP2C19 LOF carriers had a lower risk for the primary endpoint, with hazard ratio (HR) of 0.27 (95% CI 0.08-0.95), p = 0.041. A sensitivity analysis of a secondary composite endpoint of TIA, stroke, or death demonstrated a significant trend in multiple logistic regression analysis of CYP2C19 variants, with lower odds of secondary endpoint in patients carrying at least 1 LOF allele (*2, *3, *8) than in wild-type homozygotes (OR 0.27, 95% CI 0.06-1.16, p = 0.078). Cox regression analysis demonstrated that the carriers of CYP2C19 LOF alleles had a lower risk forthe secondary composite endpoint (HR 0.22, 95% CI 0.05-1.04, p = 0.056). CONCLUSIONS This is the first study examining genetic variants and their effects in symptomatic ICAD. Variant alleles of CYP2C19 (*2, *3, *8) were associated with lower odds of the primary and secondary composite endpoints. However, the direction of the association was opposite of what is expected based on this SNP. This may reflect an incomplete understanding of this genetic variation and its effect in symptomatic ICAD and warrants further investigations.