Benefit Of Dual Antiplatelet Therapy Research Articles

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 < 0.001). The six-minute walk test distance increased from 320 ± 55 meters pre-procedure to 370 ± 50 meters post-procedure (p < 0.01). The frequency of angina episodes decreased from 4.2 ± 1.5 to 1.7 ± 0.9 per week (p < 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.

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.

Antiplatelet therapy around CABG: the latest evidence.

The optimal antiplatelet strategy in patients after coronary artery bypass graft (CABG) surgery is unclear. We review the evidence on the efficacy and safety of DAPT after CABG and discuss potential novel antiplatelet strategies that reduce the risk of bleeding without loss of efficacy. Adding the potent P2Y12 inhibitor ticagrelor to aspirin for 1 year after CABG is associated with a reduction in the risk of vein graft failure, at the expense of an increased risk of clinically important bleeding. Ticagrelor monotherapy is not associated with better efficacy than aspirin alone, but is not associated with increased bleeding risk. Dual antiplatelet therapy (DAPT) is recommended after acute coronary syndrome events, but aspirin as single antiplatelet therapy remains the cornerstone of antithrombotic therapy in stable ischemic heart disease because of a lack of solid evidence on the benefit of DAPT on clinical outcomes. Shorter duration DAPT, based on the pathophysiology of vein graft failure, may be a promising strategy that requires testing in adequately powered randomized trials.

Net clinical benefit of dual antiplatelet therapy in elderly patients with acute coronary syndrome: A systematic review and meta-analysis.

Contemporary dual antiplatelet therapy (DAPT) strategies, such as short-term DAPT or de-escalation of DAPT, have emerged as attractive strategies to treat patients with acute coronary syndrome (ACS). However, it remains uncertain whether they are suitable for elderly patients. PubMed, Embase, and Cochrane CENTRAL databases were searched in September 2022. Randomized controlled trials (RCTs) investigating DAPT strategies, including standard (12 months), short-term, uniform de-escalation, and guided-selection strategies for elderly patients with ACS (age ≥ 65 years) were identified, and a network meta-analysis was conducted. The primary endpoint was the net clinical benefit outcome, a composite of major adverse cardiovascular events (MACEs: cardiovascular death, myocardial infarction, or stroke) and clinically relevant bleeding (equivalent to bleeding of at least type 2 according to the Bleeding Academic Research Consortium). The secondary outcomes were MACE and major bleeding. Sixteen RCTs with a combined total of 47,911 patients were included. The uniform de-escalation strategy was associated with an improved net clinical benefit compared with DAPT using potent P2Y12 inhibitors. The short-term DAPT strategy was associated with reduced risks of the primary outcome and major bleeding compared with DAPT using potent P2Y12 inhibitors, however, it was ranked as the least effective strategy for MACE compared with other DAPT strategies. Uniform de-escalation and short-term DAPT strategies may be advantageous for elderly patients, but need to be tailored based on individual bleeding and ischemic risks. Further RCTs of contemporary DAPT strategies specifically designed for elderly patients are warranted to confirm the findings of the present study.

334 AMYLOID-BETA 1-40 AND DAPT IN ACUTE MYOCARDIAL INFARCTION

Abstract Background Atherosclerotic plaque destabilization and platelet activation is a prompt and progressive process that is the basis of acute coronary syndromes (ACS). Amyloid-β 1-40 (Aβ (1-40)), is highly expressed in atherosclerotic plaques and is released in plasma by activated platelets. Some animal studies suggested that an increase in amyloid precursor protein (sAPP770) levels upon atherosclerotic plaque activation, anticipates myocardial injury. Platelets inhibition is the keystone in the management of patients with ACS, but the data regarding the benefits of Dual Antiplatelet Therapy (DAPT) before coronary angiography is still disputed. Methods In a large prospective cohort of 1038 patients hospitalized for AMI (both STEMI 702 /NSTEMI 333 patients), we evaluated the impact of DAPT on Aβ (1-40) levels, the correlation with inflammatory biomarkers, and Aβ (1-40) prognostic value on long-term mortality. Results The median concentration of Aβ (1-40) in plasma at admission was 90.47 (54.49-130.47) pg/ml. At hospital admission patients on DAPT had significantly lower levels of Aβ (1-40) compared to patients receiving only aspirin (67.56 (42.7-120.23) pg/ml vs. 92.25 (56.16-131.17) pg/ml, p=0.004), independently of patients’ gender or diagnosis STEMI/NSTEMI. Aβ (1-40) positively correlated with older age and higher levels of CRP and TNFα. There was no significant difference among patients who received DAPT therapy and those who did not towards age, presence of chronic renal failure, hypertension, nor in the rate of revascularization procedures (both percutaneous coronary intervention and bypass). Kaplan-Meier analysis showed that higher Aβ ​​(1-40) levels during the 49-month follow-up were associated with higher mortality risk (p&amp;lt;0.0001). Also, at multivariate Cox regression analysis Aβ ​​(1-40) level (HR =1.003 (95% CI, 1.001-1.005), p=0.017 was predictive for mortality, together with older age, higher interleukin (Il)-1β, worse left ventricular systolic function, and GFR ≤ 60 mL/min. Conclusions STEMI/NSTEMI patients receiving DAPT at hospital admission, have a significantly lower plasma concentration of Aβ (1-40), which is an independent predictor of long-term mortality.

Comparison of Unguided De-Escalation Versus Guided Selection of Dual Antiplatelet Therapy After Acute Coronary Syndrome: A Systematic Review and Network Meta-Analysis.

The benefit of dual antiplatelet therapy (DAPT) for reducing ischemic events is greatest in the early period of acute coronary syndrome, and recent randomized controlled trials have investigated the unguided de-escalation strategy of changing potent P2Y12 inhibitors to less potent or reduced-dose P2Y12 inhibitors 1 month after acute coronary syndrome. However, it remains unclear which strategy is more effective and safer: the uniform unguided de-escalation strategy versus the personalized guided selection of DAPT with genotype or platelet function tests. PubMed, EMBASE, and Cochrane Central were searched for articles published from database inception to September 10, 2021. Randomized controlled trials investigating DAPT using clopidogrel, low-dose prasugrel, standard-dose prasugrel, ticagrelor, unguided de-escalation strategy, and guided selection strategy for patients with acute coronary syndrome were included. Hazard ratios and relative risk estimates were extracted from each study. The estimates were pooled using a random-effects network meta-analysis. The primary efficacy outcome was major adverse cardiovascular events, defined as a composite of cardiovascular death, myocardial infarction, or stroke. The primary safety outcome was major or minor bleeding. Secondary outcomes were all-cause death, cardiovascular death, myocardial infarction, stroke, stent thrombosis, and major bleeding. This study included 19 randomized controlled trials with 69 746 patients. Compared with guided selection of DAPT, unguided de-escalation of DAPT was associated with a decreased risk of the primary safety outcome (hazard ratio, 0.48 [95% CI, 0.33-0.72]) without increased risks of major adverse cardiovascular events (hazard ratio, 0.82 [95% CI, 0.53-1.28]) or any secondary outcomes. The results were similar when the guided selection strategy was divided into platelet function-guided and genotype-guided strategies. Compared with guided selection of DAPT, unguided de-escalation of DAPT decreased bleeding without increasing ischemic events in patients after acute coronary syndrome. If a strategy of de-escalation is chosen, these findings do not support the routine use of personalized guiding tests. URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42021273082.

Mirror Mirror on the Wall, Which Is the Most Protective Antithrombotic Therapy of Them All?

Antiplatelet therapy remains a matter of controversy in patients undergoing carotid endarterectomy (CEA). It is still not clear whether the benefit of dual antiplatelet therapy (DAPT) in terms of peri-procedural stroke is counterbalanced by the increased risk of bleeding. To answer this question, Ku et al.1 aimed to add new information compared with a recently published meta-analysis.2,3 Overall data from 47 411 patients (30% receiving DAPT; mixed symptomatic status) reported in 11 studies (two randomised controlled trials [RCTs]) were included.

Joint statement from the European Atherosclerosis Society and European Society of Vascular Medicine focuses on patients with peripheral arterial disease

Joint statement from the European Atherosclerosis Society and European Society of Vascular Medicine focuses on patients with peripheral arterial disease

Dual Antiplatelet Therapy Using Cilostazol in Patients With Stroke and Intracranial Arterial Stenosis.

BackgroundLong‐term benefit of dual antiplatelet therapy (DAPT) over single antiplatelet therapy (SAPT) for the prevention of recurrent stroke has not been established in patients with intracranial arterial stenosis. We compared the efficacy and safety of DAPT with cilostazol and clopidogrel or aspirin to those of SAPT with clopidogrel or aspirin in patients with intracranial arterial stenosis, who were recruited to the Cilostazol Stroke Prevention Study for Antiplatelet Combination trial, a randomized controlled trial in high‐risk Japanese patients with ischemic stroke.Methods and ResultsWe compared the vascular and hemorrhagic events between DAPT and SAPT in patients with ischemic stroke and symptomatic or asymptomatic intracranial arterial stenosis of at least 50% in a major intracranial artery. Patients were placed in two groups: 275 were assigned to receive DAPT and 272 patients SAPT. The risks of ischemic stroke (hazard ratio [HR], 0.47; 95% CI, 0.23–0.95); and composite of stroke, myocardial infarction, and vascular death (HR, 0.48; 95% CI, 0.26–0.91) were lower in DAPT than SAPT, whereas the risk of severe or life‐threatening bleeding (HR, 0.72; 95% CI, 0.12–4.30) did not differ between the 2 treatment groups.ConclusionsDAPT using cilostazol was superior to SAPT with clopidogrel or aspirin for the prevention of recurrent stroke and vascular events without increasing bleeding risk among patients with intracranial arterial stenosis after stroke.RegistrationURL: https://www.clinicaltrials.gov; Unique identifier: NCT01995370.

Carotid Stenosis and Recurrent Ischemic Stroke: A Post-Hoc Analysis of the POINT Trial.

Randomized trials demonstrated the benefit of dual antiplatelet therapy in patients with minor ischemic stroke or high-risk transient ischemic attack. We sought to determine whether the presence of carotid stenosis was associated with increased risk of ischemic stroke and whether the addition of clopidogrel to aspirin was associated with more benefit in patients with versus without carotid stenosis. This is a post-hoc analysis of the POINT trial (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke) that randomized patients with minor ischemic stroke or high-risk transient ischemic attack within 12 hours from last known normal to receive either clopidogrel plus aspirin or aspirin alone. The primary predictor was the presence of ≥50% stenosis in either cervical internal carotid artery. The primary outcome was ischemic stroke. We built Cox regression models to determine the association between carotid stenosis and ischemic stroke and whether the effect of clopidogrel was modified by ≥50% carotid stenosis. Among 4881 patients enrolled POINT, 3941 patients met the inclusion criteria. In adjusted models, ≥50% carotid stenosis was associated with ischemic stroke risk (hazard ratio, 2.45 [95% CI, 1.68-3.57], P<0.001). The effect of clopidogrel (versus placebo) on ischemic stroke risk was not significantly different in patients with <50% carotid stenosis (adjusted hazard ratio, 0.68 [95% CI, 0.50-0.93], P=0.014) versus those with ≥50% carotid stenosis (adjusted hazard ratio, 0.88 [95% CI, 0.45-1.72], P=0.703), P value for interaction=0.573. The presence of carotid stenosis was associated with increased risk of ischemic stroke during follow-up. The effect of added clopidogrel was not significantly different in patients with versus without carotid stenosis. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03354429.

Abstract 14325: Pooled Analysis of Bleeding, Major Adverse Cardiovascular Events and Mortality in Clinical Trials of Time-constrained Dual-antiplatelet Therapy After Percutaneous Coronary Intervention

Introduction: The net clinical benefit of dual antiplatelet therapy (DAPT) reflects the paradoxical effects of an increased risk of bleeding and a reduced risk of major adverse cardiovascular events (MACE). A time-constrained approach to DAPT has been recently investigated in five multicenter trials including GLOBAL LEADERS, STOP-DAPT2, SMART-CHOICE, TWIGHLIGHT and TICO. Methods: We undertook a pooled analysis of these trials to assess the overall associations between time-constrained P2Y12 inhibitor monotherapy (“aspirin free regimen”) for bleeding events, MACE and all-cause mortality as compared to standard care with DAPT for at least 12 months post-PCI. We implemented a DerSimonian and Laird random effects meta-analysis using the metafor package in R. Results: 32,361 randomized trial participants, including 16,898 (52.2%) with a history of ACS, underwent PCI and had outcome data available. P2Y12 inhibitor monotherapy from 1 - 3 months was associated with a reduced risk for bleeding (hazard ratio (HR) (95% confidence interval (CI)) 0.60 (0.45, 0.81); p=0.024), including in the ACS group in which the magnitude of risk reduction was greatest (HR (95% CI) 0.50 (0.41, 0.61). The estimates of the effect of P2Y12 inhibitor monotherapy on the hazard were also favorable for MACE (0.88 (0.77, 1.02)) and all-cause mortality (95% CI 0.85 (0.71, 1.03)). Conclusions: Compared with DAPT for 12 months post-PCI, P2Y12 inhibitor monotherapy from 1-3 months substantially reduces the risk of major and fatal bleeding and, in addition, potentially protective effects, for MACE and all-cause mortality. Considering patient safety, the results support a strategy of DAPT for 1-3 months followed by ‘aspirin free’ P2Y12 inhibitor monotherapy.

Abstract 12787: Meta-analysis of Dual Antiplatelet Theraphyversus Single Antiplatelet Theraphyafter Transcatheter Aortic Valve Implatation: A Popular Forecast

Background: Despite improving experience and techniques, ischemic and bleeding complications after transcatheter aortic valve implantation (TAVI) remain prevalent and affect survival. Recent guidelines recommend dual antiplatelet therapy (DAPT) in the initial period after TAVI. Explorative studies have suggested DAPT is associated with higher rate of major bleeding without a decrease in thromboembolic complications. Purpose: To compare DAPT (aspirin plus clopidogrel) versus single antiplatelet therapy (SAPT) (as aspirin) alone as antithrombotic treatment following TAVI for the prevention of cerebrovascular events, bleeding events and all-cause death. Methods: We systematically searched PubMed, Embase and Cochrane databases, in April 2020, for both interventional or observational studies comparing DAPT with (SAPT) following TAVI. Random-effects and meta-analysis for DAPT and SAPT were performed. Results: Nine studies were included (six registry-based or unrandomized studies and three randomized clinical trials) providing a total of 19389 patients, and 631 pooled stroke or transient ischemic attack. There was no statistically difference between DAPT and SAPT for the prevention of cerebrovascular events after TAVI (pooled OR 1.04 [0.85, 1.26], P=0.04, I 2 = 0%). Similarly, there was a similar rate of all-cause mortality (pooled OR 1.07 [0.81, 1.42], P=0.33, I 2 = 50%). Furthermore, the rate of major bleeding or life-threatening events was significantly higher for the DAPT compared with SAPT group (pooled OR 1.46 [1.19, 1.78], P&lt;0.01, I 2 = 79%), although with a considerable amount of heterogeneity between studies in the magnitude of effect. Conclusions: Our pooled data suggests that after TAVI, the clinical benefit of DAPT compared to SAPT is questionable. The POPular-TAVI trial Cohort A is expected to clarify this research question during 2020.

Ischemic and bleeding risk stratification in diabetic patients after acute coronary syndrome based on insulin requirement

Abstract Background Diabetes is a known risk factor for a first or recurrent cardiovascular event, however, its association with an increased risk of bleeding is controversial. To date, no study has explored the prognostic weight of insulin therapy in the setting of ACS. Purpose To investigate the differential role of insulin versus no insulin therapy on ischemic and bleeding risks in patients with diabetes and ACS. Methods START-ANTIPLATELET is a prospective, real-world multicenter registry including consecutive patients admitted for ACS. For the purpose of this analysis, patients were stratified according to diabetes status and insulin therapy. We compared 1-year rates of major adverse cardiovascular events, a composite of cardiovascular death, myocardial infarction and stroke, and of any bleeding, according to diabetes status (no diabetes, diabetes not on insulin therapy, diabetes on insulin therapy). In addition, we evaluated the net clinical benefit of dual antiplatelet therapy with the newer P2Y12 inhibitors (ticagrelor or prasugrel) vs dual antiplatelet therapy with clopidogrel according to diabetes status. Results In an overall population of 907 patients, 198 had diabetes, 10.6% of whom were on insulin. From non-diabetic patients to diabetic patients not on insulin and diabetic patients on insulin there was a stepwise decrease of MACE-free survival (log-rank p 0.039) with incidence of events at 1 year being 3.8%, 6.8% (adjusted p vs no diabetes 0.49) and 12.5% (adjusted p vs no diabetes 0.047), respectively (Figure, panel A). The rates of any bleeding were higher in patients on insulin (20.8% vs 8.8% in those without diabetes and 5.8% in diabetic patients not receiving insulin; log-rank p 0.028; Figure, panel B). Multivariable analysis demonstrated an almost 5-fold increase of any bleeding in diabetic patients with vs without insulin (OR 4.98, 95% CI 1.46–16.92; p=0.010). In the overall population, the incidence of the net composite endpoint including MACE or major bleeding with the use of ticagrelor/prasugrel on top of aspirin was significantly lower compared to use of clopidogrel (4.7% vs 8.4%; OR 0.54, 95% CI 0.30–0.94, p=0.031). This net clinical benefit in patients receiving a newer P2Y12 inhibitor was regardless of the diabetes status (p for interaction 0.48). Conclusions In this cohort of ACS patients, the presence of diabetes stratified by insulin therapy was associated with a graded increase in the 1-year rates of MACE. Conversely, insulin therapy significantly contributed to the overall increase of bleeding risk in diabetes. Funding Acknowledgement Type of funding source: None

Dose de carga do inibidor P2Y12 antes do laboratório de hemodinâmica no enfarte agudo do miocárdio com supradesnivelamento do segmento ST – Será mesmo a melhor estratégia?

Introduction and ObjectivesIn ST‐segment elevation myocardial infarction (STEMI) the benefit of dual antiplatelet therapy is unequivocal, but the optimal time to administer the loading dose (LD) of a P2Y12 inhibitor is the subject of debate and disagreement. The main aim of this study was characterize current practice in Portugal and to assess the prognostic impact of P2Y12 inhibitor LD administration strategy, before versus during or after primary percutaneous coronary intervention (PCI). MethodsThis multicenter retrospective study based on the Portuguese National Registry on Acute Coronary Syndromes included patients with STEMI and PCI performed between October 1, 2010 and September 19, 2017. Two groups were established: LD before PCI (LD‐PRE) and LD during or after PCI (LD‐CATH). ResultsA total of 4123 patients were included, 66.3% in the LD‐PRE group and 32.4% in the LD‐CATH group. Prehospital use of a P2Y12 inhibitor was a predictor of the composite bleeding endpoint (major bleeding, need for transfusion or hemoglobin [Hb] drop >2g/dl), Hb drop >2g/dl and reinfarction. There were no differences between groups in major adverse events (MAE) (in‐hospital mortality, reinfarction and stroke) or in‐hospital mortality. ConclusionsPrehospital use of a P2Y12 inhibitor was associated with an increased risk of bleeding, predicting the composite bleeding outcome and Hb drop >2g/dl, with no differences in mortality or MAE, calling into question the benefit of this strategy.

P2Y12 inhibitor loading dose before catheterization in ST-segment elevation myocardial infarction: Is this the best strategy?

Abstract Introduction and objectives In ST-segment elevation myocardial infarction (STEMI) the benefit of dual antiplatelet therapy is unequivocal, but the optimal time to administer the loading dose (LD) of a P2Y12 inhibitor is the subject of debate and disagreement. The main aim of this study was characterize current practice in Portugal and to assess the prognostic impact of P2Y12 inhibitor LD administration strategy, before versus during or after primary percutaneous coronary intervention (PCI). Methods This multicenter retrospective study based on the Portuguese National Registry on Acute Coronary Syndromes included patients with STEMI and PCI performed between October 1, 2010 and September 19, 2017. Two groups were established: LD before PCI (LD-PRE) and LD during or after PCI (LD-CATH). Results A total of 4123 patients were included, 66.3% in the LD-PRE group and 32.4% in the LD-CATH group. Prehospital use of a P2Y12 inhibitor was a predictor of the composite bleeding endpoint (major bleeding, need for transfusion or hemoglobin [Hb] drop >2 g/dl), Hb drop >2 g/dl and reinfarction. There were no differences between groups in major adverse events (MAE) (in-hospital mortality, reinfarction and stroke) or in-hospital mortality. Conclusions Prehospital use of a P2Y12 inhibitor was associated with an increased risk of bleeding, predicting the composite bleeding outcome and Hb drop>2 g/dl, with no differences in mortality or MAE, calling into question the benefit of this strategy.

Ticagrelor and prasugrel are independent predictors of improved long-term survival in ACS patients.

AimTo investigate the long‐term clinical benefit of dual antiplatelet therapy with potent P2Y12 inhibitors compared to clopidogrel in patients with acute coronary syndrome (ACS).MethodsIn this prospective multicenter observational study, we enrolled 708 patients with ACS treated with clopidogrel (n = 137), ticagrelor (n = 260) or prasugrel (n = 311). Major adverse cardiac events (MACE; over 1 year) and long‐term mortality (median: 5.6 years; interquartile range [IQR] 4.9‐6.5 years) were assessed. Multiple electrode aggregometry (MEA) was used to measure adenosine diphosphate (ADP)‐ and arachidonic acid (AA)‐induced platelet aggregation.ResultsType of P2Y12 inhibitor emerged as an independent predictor of long‐term mortality and MACE: patients treated with potent platelet inhibitors prasugrel or ticagrelor were at lower risk for long‐term mortality (adjusted hazard ratio [HR] = 0.44; 95% CI: 0.22‐0.92; P = .028) or MACE (adjusted HR = 0.38; 95% CI: 0.20‐0.73; P = .004) than those treated with clopidogrel independent from clinical risk factors. In contrast, the efficacy of clopidogrel decreased with increasing severity of ACS: platelet aggregation was 37% higher in patients with ST segment elevation myocardial infarction (STEMI) and 25% higher in patients with non‐ST elevation myocardial infarction (non‐STEMI) compared to patients with unstable angina (P = .039). Patients with diabetes achieved less potent ADP‐ and AA‐induced platelet inhibition under clopidogrel, compared to patients without diabetes (P = .045; P = .030, respectively).ConclusionIn the setting of ACS, treatment with ticagrelor or prasugrel reduced long‐term mortality and 1‐year MACE as compared to clopidogrel.

Pooled Analysis of Bleeding, Major Adverse Cardiovascular Events, and All-Cause Mortality in Clinical Trials of Time-Constrained Dual-Antiplatelet Therapy After Percutaneous Coronary Intervention.

BackgroundThe net clinical benefit of dual antiplatelet therapy (DAPT) reflects the paradoxical effects of an increased risk of bleeding and a reduced risk of major adverse cardiovascular events. A time‐constrained approach to DAPT has been recently investigated in 5 multicenter trials including GLOBAL LEADERS, STOPDAPT2 (Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus‐Eluting Cobalt‐Chromium Stent‐2), SMART‐CHOICE, TWILIGHT (Ticagrelor With Aspirin or Alone in High‐Risk Patients After Coronary Intervention), and TICO (Ticagrelor Monotherapy After 3 Months in the Patients Treated With New Generation Sirolimus Stent for Acute Coronary Syndrome).Methods and ResultsWe undertook a pooled analysis of these trials to assess the overall associations between time‐constrained P2Y12 inhibitor monotherapy (aspirin‐free regimen) for bleeding events, major adverse cardiovascular events, and all‐cause mortality as compared to standard care with DAPT for at least 12 months post‐percutaneous coronary intervention. We implemented a DerSimonian and Laird random effects meta‐analysis using the metafor package in R. 32 361 randomized trial participants, including 16 898 (52.2%) who had a history of acute coronary syndrome, underwent percutaneous coronary intervention, and had outcome data available. P2Y12 inhibitor monotherapy from 1 to 3 months was associated with a reduced risk for bleeding (hazard ratio [HR] 0.60; 95% CI, 0.45‐0.81), including in the acute coronary syndrome group in which the magnitude of risk reduction was greatest (HR 0.50; 95% CI, 0.41‐0.61). The estimates of the effect of P2Y12 inhibitor monotherapy on the HR were also favorable for major adverse cardiovascular events (0.88; 95% CI, 0.77‐1.02) and all‐cause mortality (0.85; 95% CI, 0.71‐1.03).ConclusionsCompared with DAPT for 12 months post‐percutaneous coronary intervention, P2Y12 inhibitor monotherapy from 1 to 3 months substantially reduces the risk of major and fatal bleeding and, in addition, confers potentially protective effects, for major adverse cardiovascular events and all‐cause mortality. Considering patient safety, the results support a strategy of DAPT for 1 to 3 months followed by aspirin‐free P2Y12 inhibitor monotherapy.

Higher early recurrence risk and potential benefit of dual antiplatelet therapy for minor stroke with watershed infarction: subgroup analysis of CHANCE.

The aim was to explore the risk of early stroke recurrence within 3months after watershed infarction and to investigate whether early dual antiplatelet therapy is more effective in decreasing such risk. Patients enrolled in the Clopidogrel in High-risk Patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial and who had acute infarction on diffusion-weighted imaging were included in this subgroup analysis. All magnetic resonance images were read centrally by two neurologists who were blinded to the patients' baseline and outcome information. The primary outcome was any stroke recurrence within 3months. The hazard ratios were adjusted by known predictors of stroke recurrence. Of the 1089 patients with magnetic resonance imaging data enrolled in CHANCE, 834 (76.58%) patients had acute infarcts on diffusion-weighted imaging. The median and range of duration from randomization to stroke recurrence was 1.5 (1-6) days. Patients with watershed infarction had higher risk of stroke recurrence than those without (17.20% vs. 6.34%) within the first week after initial stroke; the hazard ratio (95% confidence interval) was 2.799 (1.536-5.101) adjusted by age, sex, smoking, body mass index, medical history, time to randomization, open-label aspirin dose at first day, single or dual antiplatelet therapy, National Institutes of Health Stroke Scale score at randomization, in-hospital treatment and white matter lesions, P<0.001. There was no interaction between antiplatelet therapy and the presence of watershed infarction (P=0.544). Minor stroke with watershed infarction has high recurrent risk in the first week. Dual antiplatelet therapy may be safely implemented, yet watershed infarction mechanisms of hypoperfusion and emboli may not be addressed.

Treatment of Extracranial Arterial Dissection: the Roles of Antiplatelet Agents, Anticoagulants, and Stenting.

Cervicocephalic arterial dissection (CeAD) is the most commonly identified cause of stroke in young healthy individuals. The management of acute ischemic stroke due to the diagnosed or suspected CeAD is well established and is appropriate for thrombolysis. There is a substantial risk of stroke recurrence in the early post-stroke period. The optimum method of stroke prevention in the subacute period remains debatable. In our review, we focused on the management of recurrent stroke in CeAD, the choice of various antithrombotic agents for stroke risk reduction with regard to specific pathogenetic mechanisms of dissections, and the utility of endovascular therapy. Recent studies suggest that various pathogenetic types of CeAD based on radiologic characteristics may be associated with greater risk of thrombogenicity, especially in the early post-stroke period. The use of anticoagulants has been shown to be effective in the eliminating microembolic signals (MES) detected by transcranial Doppler (TCD). The only randomized trial that compared combinations of antiplatelet agents and vitamin K-agonist anticoagulation did not find significant difference in risk of stroke, major bleeding, or mortality. The benefit of dual antiplatelet therapy cannot be excluded. Limited data on the use of direct oral anticoagulant agents (DOAC) is currently available. Endovascular therapy with stenting, while potentially effective, may pose significant risk of complications. Therefore, it needs to be carefully considered on a case-to-case basis. The recurrence of ischemic stroke in patients with CeAD is overall rare. No significant difference in treatment with various antiplatelet and anticoagulant agents has been shown in randomized trials. Only a few studies were based on radiological characteristics of dissections. An ongoing randomized trial is investigating the role of MES and the efficacy of antiplatelet versus anticoagulation agents. The role of DOAC agents has yet to be determined in clinical trials. Stenting in CeAD is an effective revascularization technique and may be considered in selected patients. However, current data is only based on low evidence level findings from small studies, lacking longitudinal outcomes and prognosis.

Outcomes Associated With Clopidogrel-Aspirin Use in Minor Stroke or Transient Ischemic Attack

Dual antiplatelet therapy with clopidogrel and aspirin is effective for secondary prevention after minor ischemic stroke or transient ischemic attack (TIA). Uncertainties remained about the optimal duration of dual antiplatelet therapy for minor stroke or TIA. To obtain precise estimates of efficacy and risk of dual antiplatelet therapy after minor ischemic stroke or TIA. This analysis pooled individual patient-level data from 2 large-scale randomized clinical trials that evaluated clopidogrel-aspirin as a treatment to prevent stroke after a minor stroke or high-risk TIA. The Clopidogrel in High-Risk Patients With Acute Non-Disabling Cerebrovascular Events (CHANCE) trial enrolled patients at 114 sites in China from October 1, 2009, to July 30, 2012. The Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial enrolled patients at 269 international sites from May 28, 2010, to December 19, 2017. Both were followed up for 90 days. Data analysis occurred from November 2018 to May 2019. In the 2 trials, patients with minor stroke or high-risk TIA were randomized to clopidogrel-aspirin or aspirin alone within 12 hours (POINT) or 24 hours (CHANCE) of symptom onset. The primary efficacy outcome was a major ischemic event (ischemic stroke, myocardial infarction, or death from ischemic vascular causes). The primary safety outcome was major hemorrhage. The study enrolled 5170 patients (CHANCE) and 4881 patients (POINT). Analysis included individual data from 10 051 patients (5016 in the clopidogrel-aspirin treatment group and 5035 in the control group) with a median age of 63.2 (interquartile range, 55.0-72.9) years; 6106 patients (60.8%) were male. Clopidogrel-aspirin treatment reduced the risk of major ischemic events at 90 days compared with aspirin alone (328 of 5016 [6.5%] vs 458 of 5035 [9.1%]; hazard ratio [HR], 0.70 [95% CI, 0.61-0.81]; P < .001), mainly within the first 21 days (263 of 5016 [5.2%] vs 391 of 5035 [7.8%]; HR, 0.66 [95% CI, 0.56-0.77]; P < .001), but not from day 22 to day 90. No evidence of heterogeneity of treatment outcome across trials or prespecified subgroups was observed. Major hemorrhages were more frequent in the clopidogrel-aspirin group, but the difference was nonsignificant. In this analysis of the POINT and CHANCE trials, the benefit of dual antiplatelet therapy appeared to be confined to the first 21 days after minor ischemic stroke or high-risk TIA.