Efficacy Of Dual Antiplatelet Therapy Research Articles

Efficacy of Dual Antiplatelet therapy after Ischemic Stroke According to hsCRP Levels and CYP2C19 Genotype

BackgroundBoth high-sensitive C-reactive protein (hsCRP) and CYP2C19 genotypes are independent predictors of clinical outcomes after ischemic stroke. We aim to evaluate the association of CYP2C19 loss-of-function alleles (LoFA) carrying status with the effects of dual/single antiplatelet therapy at different hsCRP levels using the CHANCE trial. MethodsSubjects with both of CYP2C19 major alleles information (*2, *3, and *17) and hsCRP measurements were enrolled from the prespecified subgroup. CYP2C19 LoFA carriers were defined as patients with either*2 or *3 allele. Cox proportional hazards models were used to assess the interaction of CYP2C19 LoFA carrying status with the effects of dual/single antiplatelet therapy at different hsCRP levels. The primary outcome was recurrent stroke within 90 days. ResultsAmong 2801 patients, 1646 (58.8%) were LoFA carriers, and 922 (32.9%) had elevated hsCRP. In patients with non-elevated hsCRP, there was a significant interaction effect between CYP2C19 LoFA carrying status and dual/single antiplatelet regimens for prevention of recurrent stroke and combined vascular events (p =0.048, 0.048, respectively), but, not in patients with elevated hsCRP (p =0.502, 0.472, respectively). Only among patients with non-elevated hsCRP and non-carrier of CYP2C19 LoFA, dual antiplatelets significantly reduced the risk of recurrent stroke compared with aspirin alone (hazard ratio= 0.44 [0.26-0.74], p=0.003). No significant differences in bleeding were found. ConclusionsNon-elevated hsCRP and non-carrier of CYP2C19 LoFA may predict a better response to dual antiplatelet therapy in reducing stroke recurrence and composite vascular events for patients with minor stroke and high-risk TIA. TRIAL REGISTRATIONclinicaltrials.gov Identifier: NCT00979589

Dual Antiplatelet Versus Alteplase for Early Neurologic Deterioration in Minor Stroke With Versus Without Large Vessel Occlusion: Prespecified Post Hoc Analysis of the ARAMIS Trial.

Dual antiplatelet therapy (DAPT) was noninferior to alteplase in minor nondisabling strokes in the ARAMIS trial (Antiplatelet Versus R-tPA for Acute Mild Ischemic Stroke); however, early neurological deterioration (END) associated with vessel stenosis may benefit from DAPT. We investigated whether the efficacy of DAPT was greater than alteplase in minor strokes with no large vessel occlusion (LVO). This study was a prespecified post hoc analysis of the ARAMIS trial and included patients with responsible vessel examination in the as-treated analysis set of the ARAMIS trial who were divided into LVO group and non-LVO group. In each group, patients were further classified into DAPT and intravenous alteplase treatments. Primary outcome was END at 24 hours defined as more than or equal to 4-point National Institutes of Health Stroke Scale score increase compared with baseline, and safety outcomes were symptomatic intracerebral hemorrhage and bleeding events during study. The primary analysis was estimated with a risk difference calculated by a generalized linear model including adjusted different baseline characteristics between treatments. Of 723 patients from the ARAMIS trial, 480 patients were included: 36 were categorized into LVO group and 444 into non-LVO group, of whom 20 patients had END. Compared with intravenous alteplase, a lower proportion of END was found after DAPT treatment in the non-LVO group (adjusted risk difference, -4.8% [95% CI, -6.9% to -2.6%]; P<0.001), but not in the LVO group (adjusted risk difference, 2.3% [95% CI, -17.6% to 22.3%]; P=0.82). The interaction was marginally significant between groups (P=0.06). In the non-LVO group, a lower proportion of bleeding events was found after DAPT treatment than intravenous alteplase (adjusted risk difference, -6.4% [95% CI, -8.9% to -3.9%]; P<0.001). Other safety outcomes were similar between the 2 treatments. Among minor nondisabling acute ischemic stroke without LVO, DAPT may be superior to intravenous alteplase regarding preventing END with a better safety profile. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03661411.

SAFETY AND EFFICACY OF DUAL ANTIPLATELET THERAPY IN PAKISTANI PATIENTS UNDERGOING PCI: A MULTICENTER STUDY

Percutaneous coronary intervention (PCI) is widely used to treat coronary artery disease (CAD), particularly in patients with acute coronary syndromes. Dual antiplatelet therapy (DAPT), which includes aspirin and a P2Y12 inhibitor such as clopidogrel, ticagrelor, or prasugrel, is the standard post-PCI treatment to prevent thrombotic complications. Despite the benefits of DAPT, its safety and efficacy in the Pakistani population, which has a high prevalence of CAD, are not well-documented. Objective: This study aimed to evaluate the safety and efficacy of DAPT in Pakistani patients undergoing PCI by measuring the incidence of stent thrombosis, bleeding complications, and major adverse cardiac events (MACE) over a 12-month follow-up period. Methods: This prospective observational study was conducted from January 2022 to December 2023 across three centers: Lady Reading Hospital Peshawar, Mardan Medical Complex, and Hayatabad Medical Complex. The study included 300 adult patients scheduled for PCI. Participants received DAPT, consisting of aspirin and a P2Y12 inhibitor, before PCI and continued for at least 12 months post-procedure. Primary outcomes were the incidence of stent thrombosis, bleeding complications, and MACE. Secondary outcomes included improved left ventricular ejection fraction (LVEF), exercise tolerance, and angina symptoms. Data were analyzed using SPSS version 26.0. Results: The mean age of participants was 60 ± 10 years, with 65% male. The overall incidence of stent thrombosis was 3%, bleeding complications occurred 8%, and MACE was observed in 15% of patients. LVEF improved from 42% ± 8% pre-procedure to 50% ± 7% post-procedure (p &lt; 0.001). The six-minute walk test distance increased from 320 ± 55 meters pre-procedure to 370 ± 50 meters post-procedure (p &lt; 0.01). The frequency of angina episodes decreased from 4.2 ± 1.5 to 1.7 ± 0.9 per week (p &lt; 0.001). Conclusion: DAPT significantly improves clinical outcomes in Pakistani patients undergoing PCI, enhancing LVEF and exercise tolerance and reducing angina episodes. However, the risk of bleeding complications necessitates careful patient management. These findings support the continued use of DAPT in this population, emphasizing the need for individualized treatment plans and continuous monitoring.

Blood pressure during long-term cilostazol-based dual antiplatelet therapy after stroke: a post hoc analysis of the CSPS.com trial

We determined the associations of follow-up blood pressure (BP) after stroke as a time-dependent covariate with the risk of subsequent ischemic stroke, as well as those of BP levels with the difference in the impact of long-term clopidogrel or aspirin monotherapy versus additional cilostazol medication on secondary stroke prevention. In a sub-analysis of a randomized controlled trial (CSPS.com), patients between 8 and 180 days after stroke onset were randomly assigned to receive aspirin or clopidogrel alone, or a combination of cilostazol with aspirin or clopidogrel. The percent changes, differences, and raw values of follow-up BP were examined. The primary efficacy outcome was the first recurrence of ischemic stroke. In a total of 1657 patients (69.5 ± 9.3 years, female 29.1%) with median 1.5-year follow-up, ischemic stroke recurred in 74 patients. The adjusted hazard ratio for ischemic stroke of a 10% systolic BP (SBP) increase from baseline was 1.19 (95% CI 1.03–1.36), that of a 10 mmHg SBP increase was 1.14 (1.03–1.28), and that of SBP as the raw value with the baseline SBP as a fixed (time-independent) covariate was 1.14 (1.00–1.31). Such significant associations were not observed in diastolic BP-derived variables. The estimated adjusted hazard ratio curves for the outcome showed the benefit of dual therapy over a wide SBP range between ≈120 and ≈165 mmHg uniformly. Lower long-term SBP levels after ischemic stroke were associated with a lower risk of subsequent ischemic events. The efficacy of dual antiplatelet therapy including cilostazol for secondary stroke prevention was evident over a wide SBP range.

MEASUREMENT OF PLATELET ACTIVATION MARKERS CD62P AND CD63 TO DETERMINE THE EFFICIENCY OF DUAL THERAPY WITH ASPIRIN AND CLOPIDOGREL: A PRELIMINARY STUDY

Background: A dual antiplatelet therapy with aspirin and clopidogrel is advised to prevent stent thrombosis. However, the most appropriate assay for evaluating the antiplatelet effects remains undefined. Objective: This study aimed to assess the efficacy of measuring platelet surface activation markers, CD62P and CD63, using flow cytometry to determine the effectiveness of dual antiplatelet therapy. Methods: Thirty patients who received aspirin plus clopidogrel before cerebral artery stent implantation and thirty unrelated healthy controls were enrolled. The expression of CD62P and CD63 was measured using flow cytometry. The diagnostic performances were evaluated and compared with the conventional light-transmitted aggregometry (LTA) using 5.0 and 20.0 µM of adenosine di-phosphate (ADP). Results: The expression ratios of both markers were significantly lower in the patients receiving dual antiplatelet therapy than controls (p &lt; 0.001). The area under the receiver operating characteristic (ROC) curve (AUC) of CD62P using flow cytometry and the LTA using 5.0 and 20.0 µM of ADP were comparable (0.97 vs. 0.95 and 0.97 vs. 0.96, respectively), whereas those of CD63 was lower than the LTA (0.88 vs. 0.96). The sensitivity of CD62P and CD63 were 71.4% and 60.0%, and the specificity of CD62P and CD63 were 100.0% and 96.7%, respectively. Conclusion: Flow cytometry measurements of CD62P could be utilized to identify the efficacy of dual antiplatelet therapy. Additional studies are suggested to support this issue and its effects on clinical outcomes.

Safety and Efficacy of Dual Antiplatelet Therapy in Patients with Minor Ischemic Stroke or High-risk Transient Ischemic Attack After Intravenous Thrombolysis (P8-5.029)

Safety and Efficacy of Dual Antiplatelet Therapy in Patients with Minor Ischemic Stroke or High-risk Transient Ischemic Attack After Intravenous Thrombolysis (P8-5.029)

Dual antiplatelet therapy versus intravenous tissue plasminogen activator with acute minor ischemic stroke: A systematic review and meta-analysis of safety and efficacy

ObjectivesTo compare the safety and efficacy of Dual Antiplatelet Therapy (DAPT) and Intravenous (IV) Tissue Plasminogen Activator (t-PA) in minor Acute Ischemic Stroke (AIS). Materials and MethodsFollowing Cochrane and PRISMA guidelines, we analyzed observational studies and clinical trials comparing DAPT and IV t-PA in patients with minor AIS. Databases included PubMed, Scopus, and Web of Science. Data extraction included study characteristics, patient demographics, and analyzed outcomes. RevMan 5.3 and OpenMetaAnalyst 2021 were used to analyze the data and assess heterogeneity, respectively. The risk of bias was determined using RoB 2.0 and the Newcastle-Ottawa scale. ResultsThis meta-analysis included five studies with 3,978 DAPT-treated patients and 2,224 IV t-PA-treated patients. We found no significant differences in achieving modified Rankin scale (mRS) scores of 0-1 (OR 1.11, 95 % CI: 0.79, 1.55, p = 0.56) and 0-2 (OR 0.90, 95 % CI: 0.61, 1.31, p = 0.57), as well as combined mRS scores (OR 1.05, 95 % CI: 0.82, 1.34, p = 0.72). Similarly, there were no significant disparities between the two treatment groups in NIHSS score change from baseline (MD 0.32, 95 % CI: -0.35, 0.98, p = 0.35) and in mortality rates (OR 0.87, 95 % CI: 0.26, 2.93, p = 0.83). Notably, in comparison to the IV t-PA group, the DAPT group exhibited a significantly lower incidence of bleeding (OR 0.31, 95 % CI: 0.14, 0.69, p = 0.004) and symptomatic intracranial hemorrhage (sICH) (OR 0.10, 95 % CI: 0.04, 0.26, p < 0.00001). ConclusionsOur meta-analysis found no significant differences in efficacy between DAPT and IV t-PA. However, DAPT demonstrated a significantly lower risk of sICH and bleeding compared with IV t-PA.

Safety and efficacy of combined dual antiplatelet therapy and factor VIII prophylaxis in patients with haemophilia A after acute coronary syndrome.

The increased life expectancy of patients with haemophilia A (HA) has led to a growing prevalence of cardiovascular risk factors and events. There is still scarce evidence on the safety and appropriate duration of dual antiplatelet therapy (DAPT) after acute coronary syndrome (ACS) in HA patients. We describe our experience on the clinical management of Italian HA patients after ACS. Nine patients with congenital HA treated with DAPT after a revascularization procedure performed for ACS have been enrolled and followed at the Angelo Bianchi Bonomi Haemophilia and Thrombosis Center in Milan between 2005 and September 2022. The safety and efficacy of DAPT with or without FVIII prophylaxis were assessed. Ten ACS events occurred in the nine HA patients (four mild and five severe). All events were treated with percutaneous transluminal coronary angioplasty with deployment of 1 to 3 drug-eluting stents followed by DAPT for 1-12 months. All patients except one were treated with FVIII prophylaxis during DAPT aimed at achieving FVIII trough levels ≥20-30IU/dL. DAPT was effective in all cases in preventing early ACS recurrence, with only a late recurrence. We observed two clinically relevant non-major bleeds (one in a patient without FVIII prophylaxis) and three minor bleeds. No venous thrombosis occurred. The long-term secondary antithrombotic prevention consisting of DAPT and FVIII prophylaxis achieving a trough level of 20-30IU/dL can be effective and safe in HA patients.

Abstract WP238: Efficacy of Dual Antiplatelet Therapy After Lacunar versus Non-Lacunar Syndromes in the POINT Trial

Introduction: About 20% of ischemic strokes are lacunar infarcts, the pathophysiology of which differs from that of other stroke etiological subtypes. The POINT trial demonstrated the efficacy of dual antiplatelet therapy (DAPT) for secondary stroke prevention in patients with minor ischemic stroke and high-risk TIA, but it remains unknown whether this benefit differed in lacunar versus non-lacunar strokes. Method: In a secondary analysis of POINT trial data, we compared the efficacy of DAPT in patients with an index lacunar syndrome versus not. A lacunar syndrome was defined based on common classic lacunar syndromes (e.g., pure motor hemiparesis, clumsy-hand dysarthria) and ascertained using subcomponents of the National Institutes of Health Stroke Scale documented at baseline. Our primary efficacy outcome was ischemic stroke and the safety outcome was intracranial hemorrhage. We used survival analysis and tests of interaction to compare the effect of DAPT between the lacunar and non-lacunar subgroups. Result: Among 4,881 patients enrolled in the study, 1,083 (22.1%) were classified as having an index lacunar syndrome. The effect of DAPT on the risk of ischemic stroke did not vary significantly after a lacunar syndrome (HR, 0.76; 95% CI, 0.52-1.09) versus after a non-lacunar syndrome (HR, 0.69; 95% CI, 0.50-0.95) (P value for interaction, 0.70). Similarly, the effect of DAPT on the risk of intracranial hemorrhage did not vary significantly after a lacunar syndrome (HR, 2.82; 95% CI, 0.29-27.1) versus after a non-lacunar syndrome (HR, 2.10; 95% CI, 0.63-6.99) (P for interaction, 0.82). Conclusion: In a post hoc secondary analysis of the POINT trial, we found no evidence of a lesser benefit of DAPT after a minor ischemic stroke or TIA in patients presenting with a lacunar syndrome compared to other stroke subtypes.

Baseline Stroke Risk and Efficacy of Dual-Antiplatelet Therapy: A Post Hoc Analysis of the POINT Trial.

High-risk transient ischemic attacks and minor ischemic strokes are followed by a variable risk of ischemic stroke. We aimed to determine how baseline stroke risk modified the efficacy of clopidogrel-aspirin (referred to here as dual-antiplatelet therapy [DAPT]) for transient ischemic attack and minor ischemic stroke. We performed an unplanned secondary analysis of the POINT trial (Platelet-Oriented Inhibition in New Transient Ischemic Attack and Minor Ischemic Stroke). We first evaluated the associations of the CHA2DS2-VASc and stroke prognosis instrument II (SPI-II) scores with the risk of incident ischemic stroke and major hemorrhage (intracranial hemorrhage or major systemic hemorrhage). We then tested for heterogeneity of the relative and absolute treatment effect of DAPT relative to aspirin across low- and high-risk patient subgroups. A total of 4841 trial participants were included in this analysis, with 2400 participants assigned to treatment with short-term DAPT and 2430 participants to treatment with aspirin and placebo. The dichotomized SPI-II score, but not the CHA2DS2-VASc score (P=0.18), was associated with the risk of incident ischemic stroke. A high-risk SPI-II score (>3) was associated with greater risk of incident ischemic stroke (hazard ratio of incident ischemic stroke relative to low-risk SPI-II score of 1.84 [95% CI, 1.44-2.35]; P<0.001) and numerically greater risk of major hemorrhage though not meeting statistical significance (hazard ratio, 1.80 [95% CI, 0.90-3.57]; P=0.10). The relative risk reduction with DAPT was similar across SPI-II strata (Pinteraction=0.31). The absolute risk reduction for ischemic stroke with DAPT compared with aspirin was nearly 4-fold higher (2.80% versus 0.76%; number needed to treat, 31 versus 131) in the high-risk SPI-II stratum relative to the low-risk stratum. The absolute risk increase for major hemorrhage with DAPT compared with aspirin was 3-fold higher (0.84% versus 0.30%; number needed to harm, 119 versus 331) in the high-risk SPI-II stratum relative to the low-risk stratum. Stratification by baseline stroke risk identifies a patient subgroup that derives greater absolute benefit from treatment with DAPT. URL: https://www.clinicaltrials.gov; Unique identifier: NCT00991029.

E-48 | Safety and Efficacy of Dual Antiplatelet Therapy With Ticagrelor vs Clopidogrel in a Predominantly Hispanic Population

Current guidelines recommend potent P2Y12 platelet inhibitor in patients with acute coronary syndrome post percutaneous coronary intervention(PCI). However, ethnic and racial differences in responsiveness to P2Y12 have been reported. Little is known about the safety and efficacy of dual anti-platelet therapy (DAPT) with potent P2Y12 in the Hispanic population. We evaluated the risks and benefits associated with ticagrelor versus clopidogrel in a predominantly Hispanic population. We conducted a single center retrospective cohort study on patients who had PCI between Jan 2014 and Jun 2021. The safety endpoint was incident bleeding, defined as Bleeding Academic Research Consortium (BARC) ≥2events. Primary efficacy endpoints were all-cause mortality and major adverse cardiovascular event (MACE included death, myocardial infarction, stroke and revascularization). Kaplan Meier curve, log rank test and Cox proportional hazards models were performed to analyze time to specific event endpoint. A propensity scores-adjusted Cox model method was used in the adjusted analysis. Of 830 patients (age 62 ± 12 years, 67% males, 78% Hispanic), 357 (43%) patients received ticagrelor as their DAPT therapy. Patients who received clopidogrel at baseline were older and had more anemia, more bare metal stents and anticoagulation therapy. During an average follow-up of 2.8 ± 2.4 years, death occurred in 38 (4.6%) patients and bleeding events in 46 (5.5%) patients. After propensity scores-adjustment of baseline characteristics, BARC ≥2 bleeding events were not significantly different between ticagrelor and clopidogrel groups (4.76% versus 6.13%, hazard ratio [HR] =0.92, 95% CI:0.48-1.77, p=0.81). While there was no significant difference in the MACE event between the two P2Y12 groups (23.0% versus 22.7%, HR=1.08, 95% CI:0.79-1.48, p=0.65), the mortality rate was significantly lower in ticagrelor group (2.52% versus 6.13%, HR= 0.39, 95% CI:0.17-0.87, p=0.021). In a predominantly Hispanic population, ticagrelor use was associated with a lower mortality rate in patients post PCI compared to clopidogrel, with similar bleeding rates.

Abstract Number ‐ 256: Anti‐Thrombotic Therapy for Stroke Prevention in Cervical Artery Dissection: protocol of a multicenter international study

Introduction Cervical artery dissection (CAD) is a common cause of stroke in the young and carries a high risk of early recurrence. Traditionally, the treatment consisted of antithrombotic therapy for at least 3months. There is mixed evidence on whether antiplatelet therapy is as effective as anticoagulation in such patients, and prior studies are limited by small sample size due to the low incidence of CAD, as well as not investigating more modern treatment regimens such as direct oral anticoagulants (DOAC) and increasingly utilized dual antiplatelet therapy (DAPT) strategies. The Anti‐Thrombotic Therapy for Stroke Prevention in Cervical Artery Dissection (STOP‐CAD)studyaims to compare the safety and effectiveness of different antithrombotic regimens in patients with acute spontaneous CAD. We hypothesize thatdual antiplatelet therapy (DAPT) followed by a single agent has comparable safety and efficacy to anticoagulation in patients with CAD. Methods STOP‐CAD is amulticenter cross‐sectional international retrospective study.All patientsaged 18–89 years with imaging‐confirmed diagnosis of non‐traumatic CAD treated with antithrombotic therapy will be included. Imaging diagnosis will be adjudicated by the principal investigator from each individual site. Patients present with CAD in the setting of major trauma will be excluded. Baseline demographics, clinical, laboratory and imaging information will becollected. Outcomes include subsequent ischemic stroke, symptomatic intracranial hemorrhage, major hemorrhage, recanalization status, and death within 180 days. We will compare the clinical outcomes between antiplatelet and anticoagulation groups using Cox regression models, and the radiographic outcomes across the two groups using logistic regression models. We will use inverse probability of treatment weighting and adjust for prespecified variable as well as variables that differ between the two groups. We will use propensity score matching with and without replacement for the outcome analyses. Results Currently at least 40 international sites have agreed to contribute to this study. Multiple sites have already started the data input process, and more have started the IRB process. We expect the data collection to be completed by the end of December 2022, and the data analysis to be completed by the end of June 2023. Conclusions STOP‐CAD will provide real world data comparing the safety and efficacy of DAPT vs. anticoagulation in patients with cervical artery dissection. In addition, multiple sub‐studies will be conducted using the same database on topics such as efficacy of interventional treatment and predictors of poor outcomes.

Aminotransferase Level and the Effects of Dual Antiplatelet in Minor Stroke or Transient Ischemic Attack: A post hoc Analysis of a Randomized Control Trial

Introduction: This study was intended to evaluate whether the safety and efficacy of dual antiplatelet treatment in patients with minor ischemic stroke (MIS) or transient ischemic attack (TIA) could be modified by the aminotransferase level. Also, we sought to assess the interaction between aminotransferase level and CYP2C19 loss-of-function status on the efficacy of dual antiplatelet therapy. Methods: This study is a post hoc analysis of the Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events (CHANCE) study, a double-blinded randomized control trial. We included 5,133 patients with a complete workup of baseline alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. The primary outcome is stroke or TIA recurrence within 90 days. Cox proportional hazard models were used in the evaluation of the efficacy of antiplatelet treatment in patients with different aminotransferase levels and subgroups categorized by the aminotransferase level × CYP2C19 loss-of-function status. Results: The median age of all the included patients was 62 years; 66.3% of the patients were male. More recurrent stroke or TIA occurred in patients with elevated ALT and AST levels within 90 days compared to patients with normal ALT and AST levels (14.5 vs. 11.2%, p = 0.029). Dual antiplatelet treatment with aspirin and clopidogrel reduced recurrence compared with aspirin alone in patients with both normal (adjusted hazard ratio [HR], 95% confidence interval [CI]: 0.72 [0.60–0.86], p < 0.001) and elevated (adjusted HR [95% CI]: 0. 57 [0. 35–0. 92], p = 0. 020) ALT and AST levels (p = 0.64 for interaction). No significant difference in treatment efficacy on 90-day all-cause death or bleeding events was found. Conclusions: Dual antiplatelet treatment was safe for minor stroke or high-risk TIA patients with mildly elevated aminotransferase. Mild elevation of ALT or AST did not undermine the protective efficacy of the dual antiplatelet regimen in reducing recurrent stroke or TIA within 90 days after MIS or TIA. The interaction between the CYP2C19 loss-of-function allele carrier status and aminotransferase level on the efficacy of dual antiplatelet treatment was not observed.

Dual Antiplatelet Therapy in Patients Aged 75 Years and Older with Coronary Artery Disease: A Meta-Analysis and Systematic Review.

Objectives This systematic review and meta-analysis evaluates the safety and efficacy of dual antiplatelet therapy (DAPT) in elderly patients with acute coronary syndrome (ACS). Background The safety and efficacy of DAPT in elderly patients with ACS is not well characterized. Methods We performed a systematic literature review to identify clinical studies that reported safety and efficacy outcomes after DAPT for ACS in elderly patients. The primary outcomes of primary efficacy endpoint rates and bleeding event rates were reported as random effects risk ratio (RR) with 95% confidence interval. No prior ethical approval was required since all data are public. Results Our search yielded 660 potential studies. We included 8 studies reporting on 29,217 patients. There was a higher risk of bleeding event rates in elderly patients treated with prasugrel or ticagrelor when compared to clopidogrel with a risk ratio of 1.17 (95% CI 1.08 to 1.27, p < 0.05). There was no difference in primary efficacy endpoint rates between elderly patients treated with prasugrel or ticagrelor when compared to clopidogrel with a risk ratio of 0.85 (95% CI 0.68 to 1.07, p=0.17). Conclusions This systematic review and meta-analysis suggests that DAPT with prasugrel or ticagrelor compared to clopidogrel is associated with a higher risk of bleeding events in elderly patients with ACS. There was no difference in the primary efficacy endpoints between the two treatment groups.

Safety and efficacy of dual antiplatelet therapy combining aspirin and ticagrelor in patients with undergoing intracranial stenting procedures.

Thromboembolic complications are one of the major periprocedural complications following neuroendovascular procedures. Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel remain the principal agents for prevention of thromboembolic complications. However, clopidogrel resistance is associated with higher risk of thromboembolic complications. This study investigated the safety and efficacy of DAPT with ticagrelor and aspirin in patients undergoing intracranial stenting procedures. This retrospective study was based on patients with intracranial aneurysms who undergoing intracranial stenting procedures at our institution between August 2017 and July 2020. These patients received DAPT with ticagrelor and aspirin were included. DAPT with 90 mg ticagrelor twice daily and aspirin 100 mg daily was continued for 3 months after the intracranial stenting procedure and aspirin continued for 1 year. In this study, 151 patients were identified. The most common aneurysm location was the internal carotid artery with 127 (71.8%) patients. Of the 151 cases with 160 treated aneurysms, 30 (18.8%) patients were treated by flow diverters (FDs), and 130 (81.2%) by stent-assisted coiling. Five (3.3%) patients had thromboembolic complications. Intraprocedural aneurysmal rupture was observed in one patient because of coil extrusion during coil insertion. None of the patients showed a newly DAPT-related intracerebral hemorrhage. Two patients developed dyspnea, and the symptom resolved without intervention. Furthermore, ecchymoma and gastrointestinal bleeding occurred in one patient respectively. DAPT-related thromboembolic and hemorrhagic complications were not significantly different between the FD group and stent-assisted coiling group. In our study, DAPT combining ticagrelor and aspirin seems to be a safe and efficient treatment for preventing thromboembolic complications in patients with intracranial aneurysms, without any increase in hemorrhagic complications. Ticagrelor may be an effective alternative for patients undergoing neurointervention.

Dual versus Single Antiplatelet Therapy in Medically Treated Acute Myocardial Infarction Patients with Baseline Thrombocytopenia - Insights from a Multi-Institute Cohort Study.

The safety and efficacy of dual antiplatelet therapy (DAPT) in medically treated acute myocardial infarction (AMI) patients with baseline thrombocytopenia (platelet count < 150 × 103/uL) are unclear. In this multi-institute retrospective cohort study, we included 468 patients with medically treated AMI with baseline thrombocytopenia and separated them into single antiplatelet therapy (SAPT) and DAPT groups according to the discharge anti-thrombotic strategy. The primary outcome was net clinical adverse events (NACEs), defined as a composite of death, ischemic events (myocardial infarction, ischemic stroke, and transient ischemic attack), and major bleeding within 30 days. There were 168 patients in the SAPT group (100 taking aspirin and 68 taking clopidogrel) and 300 in the DAPT group. A primary outcome occurred in 35 (24.11 per 100 patient-months) patients in the SAPT group and 39 (14.26 per 100 patient-months) patients in the DAPT group [adjusted hazard ratio (HR): 0.67; 95% confidence interval (CI): 0.40-1.10; p = 0.1145]. Kaplan-Meier curves showed favorable results in the DAPT group (log-rank p = 0.0243). Bleeding events occurred in 18 (10.71 per 100 patient-months) patients in the SAPT group and 18 (6.40 per 100 patient-months) patients in the DAPT group (adjusted HR: 0.66; 95% CI: 0.32-1.36; p = 0.2573). DAPT versus SAPT as discharge anti-thrombotic strategy in thrombocytopenic patients with medically treated AMI did not significantly improve NACEs at 30 days. However, there was a trend towards favorable outcomes in the DAPT group. These results should be interpreted carefully with respect to the relatively limited trial population and study design.

Newer P2Y12 Inhibitors vs Clopidogrel in Acute Myocardial Infarction With Cardiac Arrest or Cardiogenic Shock: A Systematic Review and Meta-analysis

ObjectiveTo evaluate the outcomes, safety, and efficacy of dual antiplatelet therapy (DAPT) with newer P2Y12 inhibitors compared with clopidogrel in patients with acute myocardial infarction (AMI) complicated by cardiac arrest (CA) or cardiogenic shock (CS). Patients and MethodsMEDLINE, EMBASE, and the Cochrane Library were queried systematically from inception to January 2021 for comparative studies of adults (≥18 years) with AMI-CA/CS receiving DAPT with newer P2Y12 inhibitors as opposed to clopidogrel. We compared outcomes (30-day or in-hospital and 1-year all-cause mortality, major bleeding, and definite stent thrombosis) of newer P2Y12 inhibitors and clopidogrel in patients with AMI-CA/CS. ResultsEight studies (1 randomized trial and 7 cohort studies) comprising 1100 patients (695 [63.2%] receiving clopidogrel and 405 [36.8%] receiving ticagrelor or prasugrel) were included. The population was mostly male (68.5%-86.7%). Risk of bias was low for these studies, with between-study heterogeneity and subgroup differences not statistically significant. Compared with the clopidogrel cohort, the newer P2Y12 cohort had lower rates of early mortality (odds ratio [OR], 0.60; 95% CI, 0.45 to 0.81; P=.001) (7 studies) and 1-year mortality (OR, 0.51; 95% CI, 0.36 to 0.71; P<.001) (3 studies). We did not find a significant difference in major bleeding (OR, 1.21; 95% CI, 0.71 to 2.06; P=.48) (6 studies) or definite stent thrombosis (OR, 2.01; 95% CI, 0.63 to 6.45; P=.24) (7 studies). ConclusionIn patients with AMI-CA/CS receiving DAPT, compared with clopidogrel, newer P2Y12 inhibitors were associated with lower rates of early and 1-year mortality. Data on major bleeding and stent thrombosis were inconclusive.

Mono or Dual Antiplatelet Therapy for Treating Patients with Peripheral Artery Disease after Lower Extremity Revascularization: A Systematic Review and Meta-Analysis.

The efficacy of dual antiplatelet therapy (DAPT) for patients with peripheral artery disease (PAD) after lower-limb intervention remains controversial. Currently, the prescription of DAPT after an intervention is not fully recommended in guidelines due to limited evidence. This study compares and analyzes the prognosis for symptomatic PAD patients receiving DAPT versus monotherapy after lower-limb revascularization. Up to November 2021, PubMed/MEDLINE, Embase, and Cochrane databases were searched to identify studies reporting the efficacy, duration, and bleeding complications when either DAPT or monotherapy were used to treat PAD patients after revascularization. Three randomized controlled trials and seven nonrandomized controlled trials were included in our study. In total, 74,651 patients made up these ten studies. DAPT in PAD patients after intervention was associated with lower rates of all-cause mortality (HR = 0.86; 95% CI, 0.79–0.94; p < 0.01), major adverse limb events (HR = 0.60; 95% CI, 0.47–0.78; p < 0.01), and major amputation (HR = 0.78; 95% CI, 0.64–0.96) when follow-up was for more than 1-year. DAPT was not associated with major bleeding events when compared with monotherapy (OR = 1.22; 95% CI, 0.69–2.18; p = 0.50) but was associated with a higher rate of minor bleeding as a complication (OR = 2.54; 95% CI, 1.59–4.08; p < 0.01). More prospective randomized studies are needed to provide further solid evidence regarding the important issue of prescribing DAPT.

Hyperglycemia, Risk of Subsequent Stroke, and Efficacy of Dual Antiplatelet Therapy: A Post Hoc Analysis of the POINT Trial.

BackgroundOne‐quarter of all strokes are subsequent events. It is not known whether higher levels of blood glucose are associated with an increased risk of subsequent stroke after high‐risk transient ischemic attack or minor ischemic stroke.Methods and ResultsWe performed a secondary analysis of the POINT (Platelet Oriented Inhibition in New TIA and Minor Ischemic Stroke) trial to evaluate the relationship between serum glucose hyperglycemia (≥180 mg/dL) versus normoglycemia (<180 mg/dL) before enrollment in the trial and outcomes at 90 days. The primary end point was subsequent ischemic stroke modeled by a multivariable Cox model with adjustment for age, sex, race, ethnicity, study treatment assignment, index event, and key comorbidities. Of 4878 patients included in this study, 267 had a recurrent stroke. There was a higher hazard of subsequent stroke in patients with hyperglycemia compared with normoglycemia (adjusted hazard ratio [HR], 1.50 [95% CI, 1.05–2.14]). Treatment with dual antiplatelet therapy was not associated with a reduced hazard of subsequent stroke in patients with hyperglycemia (HR, 1.18 [95% CI, 0.69–2.03]), though the wide confidence interval does not exclude a treatment effect. When modeled as a continuous variable, there was evidence of a nonlinear association between serum glucose and the hazard of subsequent stroke (P<0.001).ConclusionsHyperglycemia on presentation is associated with an increased risk of subsequent ischemic stroke after high‐risk transient ischemic attack or minor stroke. A rapid, simple assay of serum glucose may be a useful biomarker to identify patients at particularly high risk of subsequent ischemic stroke.RegistrationURL: https://www.clinicaltrials.gov; Unique identifier: NCT0099102.

Safety and efficacy of dual antiplatelet therapy after percutaneous coronary interventions in patients with end-stage liver disease.

The prevalence of coronary artery disease (CAD) increases in patients with end-stage liver disease, with part of them receiving the percutaneous coronary intervention (PCI) as a treatment option. Dual antiplatelet therapy (DAPT), a standard of care after PCI, could result in catastrophic consequences in this population. Before PCI and the start of DAPT, it is recommended to assess patient bleeding risk. Based on novel findings, liver cirrhosis does not necessarily lead to a significant increase in bleeding complications. Furthermore, conventional methods, such as the international normalized ratio, might not be appropriate in assessing individual bleeding risk. The highest bleeding risk among cirrhotic patients has a subgroup with severe thrombocytopenia (< 50 × 109/L) and elevated portal pressure. Therefore, every effort should be made to maintain thrombocyte count above > 50 × 109/L and prevent variceal bleeding. There is no solid evidence for DAPT in patients with cirrhosis. However, randomized trials investigating short (one month) DAPT duration after PCI with new drug-eluting stents (DES) in a high bleeding risk patient population can be implemented in patients with cirrhosis. Based on retrospective studies (with older stents and protocols), PCI and DAPT appear to be safe but with a higher risk of bleeding complications with longer DAPT usage. Finally, novel methods in assessing CAD severity should be performed to avoid unnecessary PCI and potential risks associated with DAPT. When indicated, PCI should be performed over radial artery using contemporary DES. Complementary medical therapy, such as proton pump inhibitors and beta-blockers, should be prescribed for lower bleeding risk patients. Novel approaches, such as thromboelastography and “preventive” upper endoscopies in PCI circumstances, warn clinical confirmation.