Antiplatelet Therapy After Endovascular Intracranial Aneurysm Surgery: Comparative Effectiveness and Safety Insights from Systematic Review and Meta-Analysis.

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Current guidelines recommend dual antiplatelet therapy (DAPT) that includes aspirin and the platelet P2Y12 ADP receptor antagonist clopidogrel after percutaneous coronary intervention (PCI). These recommendations are based on data that DAPT with the P2Y12 inhibitors clopidogrel reduces major adverse cardiac events after PCI in stable angina and acute coronary syndrome (ACS) patients when compared with aspirin, or aspirin in combination with warfarin.1 Despite treatment with DAPT, patients with ACS undergoing PCI are at elevated risk for recurrent ischemic events compared with stable angina patients in part because of increased platelet thrombotic activity in ACS. In addition, there is considerable interindividual variability in the degree of platelet inhibition achieved by clopidogrel, and high residual platelet activity in the setting of clopidogrel therapy (hyporesponsiveness) is associated with adverse cardiovascular (CV) events after PCI. Clopidogrel hyporesponsiveness is related to a variety of clinical and genetic factors that alter pharmacokinetics, and diabetes, congestive heart failure (CHF), and obesity are associated with reduced efficacy. Clopidogrel is a prodrug that requires conversion by the hepatic cytochrome P450 system (CYP) to an active metabolite, and it can take up to 6 hours for clopidogrel to have maximal effect after the loading dose. Genetic polymorphisms that reduce CYP activity result in decreased hepatic metabolism of clopidogrel. Among persons treated with clopidogrel, carriers of specific reduced function CYP2C19 alleles have impaired clopidogrel conversion, significantly lower levels of active metabolite, diminished platelet inhibition, and higher rates of adverse CV events and stent thrombosis after PCI.2 The prevalence of CYP2C19 polymorphisms ranges from 30% to 60% depending on ethnicity.2,3 Medications that inhibit CYP activity also reduce clopidogrel conversion, and some proton pump inhibitors (PPI) that reduce CYP function (eg, omeprazole) diminish clopidogrel metabolite levels and efficacy measured by platelet function testing. The interaction between clopidogrel and …

Atherothrombosis is the major pathophysiological process responsible for the occurrence of severe ischemic events in patients with cardiovascular diseases. In the United States, atherothrombosis strongly influenced mortality in 2004: One in 2.8 deaths was due to CVD, 1 in 5 deaths to coronary heart disease, and 1 in 17 deaths to stroke.1 Because cardiovascular disease is a progressive and systemic disease, long-term antithrombotic therapies that effectively target the entire arterial vasculature and modulate the key components responsible for thrombus generation are essential to improve patient outcomes. Because platelet activation is determined by multiple receptor-mediated signaling pathways, clinical studies have evaluated the efficacy of multidrug administration in the prevention of atherothrombotic complications.2,3 The major concern with these therapies is the critical balance between anti-ischemic effect and bleeding risk. This review summarizes our understanding of the role of combination antiplatelet therapies in the treatment and prevention of atherothrombosis. Platelet activation and aggregation play a pivotal role in the generation of occlusive thrombus at the site of coronary arterial plaque rupture. In addition, platelets influence various endothelial and inflammatory responses during the initiation and progression of atherosclerosis. Under normal conditions, anucleate circulating platelets are in a quiescent state. Healthy vascular endothelium prevents adhesion and activation of platelets by producing antithrombotic factors such as CD39 (ectoADPase), prostaglandin I2, nitric oxide, heparin, matrix metalloproteinase-9, protein S, and thrombomodulin.3,4 Endothelial activation and denudation and frank atherosclerotic plaque rupture expose the subendothelial matrix and release prothrombotic factors during acute coronary syndromes (ACS) and percutaneous interventions. These processes result in localized platelet adhesion and platelet activation. After adhesion to the exposed subendothelial matrix, platelets are activated by shear and the soluble agonists thromboxane A2 (TxA2), ADP, and thrombin. TxA2 is produced from arachidonic acid, which originates from membrane phospholipids and …

Objective To systematically evaluate the risk of major bleeding and major adverse cardiac events(MACE) in patients with acute coronary syndrome(ACS) after combined use of novel oral anticoagulants (NOAC) and antiplatelet therapy. Methods Randomized controlled trials (RCTs) about NOAC treatment for ACS patients with basic antiplatelet therapy in related databases (up to July 2018) were searched. The outcome indicators included major bleeding events (safety indicators) and MACE (effectiveness indicators). Quality of methodology was evaluated using bias risk assessment tool of Cochrane collaboration networks. Meta-analysis was performed using RevMan 5.3 software. Results A total of 6 RCTs were entered, including comparative studies of single antiplatelet therapy (SAPT) or dual antiplatelet therapy (DAPT) combined with NOAC and combined with placebo or warfarin, involving 20 070 patients. Drugs used in the trial group included apixaban, rivaroxaban, and dabigatran etexilate. The quality evaluation showed that 4 of the 6 RCTs were with low risks of bias and 2 with high risks of bias. The meta-analysis showed that the risk of clinical major bleeding events in patients in the SAPT+ NOAC group was significantly higher than that in the SAPT+ placebo group [3.14% (44/1 402) vs. 1.07% (19/1 770), RR=3.47, 95%CI: 2.01-5.97, P 0.05 for both). Conclusions Combination of anticoagulants and SAPT or DAPT in ACS patients may all increase the risk of clinical major bleeding, but combination of SAPT and NOAC may reduce the risk of MACE, and should be used after weighing. For patients who must be treated with triple antithrombotic therapy, DAPT combined with NOAC can be chosen and warfarin should be avoided. Key words: Anticoagulants; Administration, oral; Acute coronary syndrome; Hemorrhage; Cardiovascular diseases; Meta-analysis; Randomized controlled trial

Flow diversion for intracranial aneurysm treatment traditionally requires dual antiplatelet therapy, creating a clinical dilemma balancing between ischemic and hemorrhagic risks, particularly for those with increased hemorrhagic risks such as ruptured aneurysms. Novel surface-modified flow diversion devices, such as the Pipeline Flex Embolization Device with Shield Technology, reduce thrombogenicity. This technology offers the opportunity to use a de-escalated antiplatelet therapy regimen. However, robust clinical evidence about the safety of this approach on the Pipeline Shield is lacking. Therefore, we compared the safety of single versus dual antiplatelet therapy in patients with intracranial aneurysms treated with this device. We performed a retrospective single-center comparative study of patients treated with either single or dual antiplatelet therapy. The primary endpoint was major ischemic stroke (NIHSS score increase of ≥4 points for >24 hours) within 1 year. Secondary endpoints included minor and transient ischemic events, in-stent stenosis, major hemorrhagic events, and aneurysm occlusion rates. The primary endpoint data were analyzed using the Kaplan-Meier method. A total of 172 patients were included, with 91 in the single antiplatelet therapy group and 81 in the dual antiplatelet therapy group. The main drug used for single antiplatelet therapy was clopidogrel (95.6%). The single antiplatelet therapy group included a significantly greater proportion of patients with aneurysms in higher-risk, non-ICA locations (16.0% vs. 4.4%; P = .004). Despite this baseline imbalance, the estimated 1-year risk of major ischemic stroke did not differ significantly between groups (2.2% [2/91; 95% CI, 0-5.2%] vs. 1.3% [1/81; 95% CI, 0-3.7%]; P = .62). The rates of minor or transient ischemic events, major hemorrhage, in-stent stenosis, and complete aneurysm occlusion were comparable between the groups. In this exploratory study, no statistically significant difference was observed between the safety profiles of clopidogrel-based single and dual antiplatelet therapies for patients treated with the Pipeline Shield, despite the higher-risk baseline characteristics in the single-therapy cohort. These preliminary findings suggest that clopidogrel monotherapy might be a feasible alternative in select patients, potentially simplifying treatment and reducing DAPT-associated hemorrhagic complications.

Efficacy and safety of single versus dual antiplatelet therapy in carotid artery stenting

Introduction: The optimal antiplatelet therapy following Left atrial appendage occlusion (LAAO) in atrial fibrillation patients who are not candidates for long-term oral anticoagulation therapy (OAC) is subject to debate. Hypothesis: Is single antiplatelet therapy (SAPT) safe and effective when compared to dual antiplatelet therapy (DAPT) in patients with high bleeding risk? Methods: We conducted a comprehensive search for all studies that compared the use of SAPT with DAPT following LAAO for patients in whom OAC is deemed highly risky or contraindicated. The outcomes of our study were device-related thrombosis (DRT), stroke and systemic embolization (SSE), and major bleeding (MB). The risk ratio (RR) with 95% confidence intervals (CIs) are presented as summary statistics and were calculated using a random-effects model. Results: A total of 15 observational studies with 3231 patients (SAPT, n=1036; DAPT, n=2195; 64.5% men; median follow-up duration 12 months; mean age 74.7±8.5 years; CHA2DS2-VASc score 4.3±1.6; HASBLED score 3.2±1.2) were included. For DRT, data were available from 10 studies (2910 patients); there was no difference between SAPT and DAPT groups (2.6% vs. 2.3%; RR: 1.41; 95%CI: 0.77-2.59; P=0.26; I 2 :0%). For SSE (8 studies, 959 patients); although numerically more events were observed in the SAPT group, there was no statistical difference between the two groups in the pooled analysis (2.9% vs. 1.5%; RR: 5.43; 95%CI: 0.74-39.81; P=0.1; I 2 :78%). Finally, for MB (8 studies, 1818 patients); although numerically more events were observed in the DAPT group, there was no statistical difference between the two arms (2.3% vs. 3.2%; RR: 1.90; 95%CI: 0.46-7.87; P=0.37; I 2 :72%). Conclusions: Our study showed comparable safety and efficacy profiles for SAPT and DAPT after LAAO. Adequately powered randomized studies determining the optimal antithrombotic therapy in the first weeks after LAAO are warranted in patients at high risk for bleeding.

There is a lack of consensus regarding the optimal antithrombotic therapy (ATT) after popliteal and infrapopliteal (PIP) endovascular therapy (EVT). Currently, dual antiplatelet therapy (DAPT) for 3 months and single antiplatelet therapy (SAPT) are the most prescribed regimens in the Netherlands. Thus far, no randomized comparison has been performed on the optimal ATT approach. Therefore, this study compared the efficacy and safety of 3-month DAPT with SAPT following PIP EVT. Retrospective analysis of prospectively collected data from a multicenter registry. The Dutch chronic lower limb-threatening ischemia registry (THRILLER) collected prospective data on patients enrolled between January 2021 and October 2023. As for ATT, only patients prescribed antiplatelet therapy (APT), were included in this analysis. The primary efficacy outcome was a composite of 3-month major adverse cardiovascular events (MACEs, ie, myocardial infarction, cerebrovascular event, cardiovascular death), major adverse limb events (MALEs, ie, major amputation, reintervention), and non-cardiovascular death. Secondary efficacy outcomes were 3-month MACE, MALE, and all-cause mortality. The primary safety outcome was major bleeding according to the 'Thrombolysis In Myocardial Infarction' (TIMI) classification. Descriptive statistics and Cox proportional hazard models were applied. In total, 460 of 840 THRILLER patients used DAPT or SAPT as ATT and were therefore included in the analysis. Of these, 322 (70%) received DAPT and 138 (30%) received SAPT. In total, 73 (15.9%) primary efficacy outcomes were observed of which 21 (15.2%) events in the SAPT group and 52 (16.1%) events in the DAPT group. No significant differences were observed between SAPT and DAPT for the primary efficacy outcomes or any of the secondary efficacy outcomes. In both groups, one case of major bleeding was observed. The findings suggest that 3 months of DAPT is not superior to SAPT. A well-powered randomized trial is warranted to assess the efficacy and safety of post-procedural DAPT in chronic limb-threatening ischemia (CLTI) patients undergoing PIP EVT.Clinical ImpactThis manuscript reports on the efficacy and safety outcomes of 3 months of DAPT versus SAPT, which are commonly chosen therapies following popliteal and infrapopliteal endovascular therapy. No significant difference was found between the two groups regarding major adverse cardiovascular events, all-cause death, major amputation, or major bleeding. Therefore, 3 months of DAPT does not seem superior to SAPT. These results suggest that SAPT appears to be a sufficient alternative when considering 3 months of DAPT. Further research should verify these outcomes and focus on the efficacy and safety of prolonged DAPT suppletion after endovascular therapy.

Background and purposeThe present strategies regarding poststent management for cerebral venous sinus stenosis (CVSS) are inconsistent. Herein, we compared the safety and efficacy of oral anticoagulants (OACs) plus single antiplatelet therapy and dual antiplatelet therapy for CVSS poststenting.MethodsA real-world observational study conducted from January 2009 through October 2019 enrolled patients who were diagnosed with CVSS and received stenting. Patients were divided into two groups according to the management they received poststenting. Group 1: OACs plus a single antiplatelet agent (clopidogrel 75 mg or aspirin 100 mg) and Group 2: dual antiplatelet therapy (clopidogrel 75 mg plus aspirin 100 mg). The safety (such as major or minor bleeding or venous thrombosis) and efficacy (the incidences of cerebral venous sinus restenosis, intrastent thrombosis, or stent displacement) of the two groups were compared.ResultsThere were a total of 110 eligible patients in the final analysis, including 79 females and 31 males with a mean age of 43.42 ± 13.23 years. No major bleeding or venous thrombosis occurred in either of the two groups. Two minor bleeding events occurred in group 2 (one with subcutaneous bleeding points in both lower limbs, another with submucosal bleeding in the mouth), whereas no bleeding events occurred in Group 1. In addition, at the 1-year follow-up, one case of intraluminal restenosis and two cases of in-stent thrombi occurred in Group 2, while none occurred in Group 1. Neither stenosis at stent-adjacent segments nor stent migration was detected in either group during the 1-year following stent placement.ConclusionOACs plus single antiplatelet therapy and dual antiplatelet therapy alone are both safe and efficacious management strategies after CVSS stent placement. The former may have more advantages than the latter for inhibiting intrastent thrombosis. However, further research by larger, multicenter clinical trials is needed.

Dual antiplatelet therapy and oral anticoagulation in combination with aspirin represent recommended treatment regimens after left atrial appendage closure (LAAC). As most patients receiving LAAC have high bleeding risk, less aggressive antithrombotic treatments are needed, such as single antiplatelet therapy. We sought to compare both ischemic and bleeding outcomes in patients receiving single antiplatelet therapy (SAPT) or dual antiplatelet therapy (DAPT) after successful LAAC. Data on consecutive patients undergoing percutaneous LAAC between 2009 and 2023 were prospectively collected including 1-year follow-up. Propensity score matching was performed for patients discharged under SAPT and DAPT. The primary end point was the 1-year composite of cardiovascular death, stroke, systemic embolism, or device-related thrombosis (DRT). The secondary end points included major bleeding and DRT. Of 1033 patients discharged with antiplatelet therapy, 154 patients receiving SAPT were compared with 230 matched patients receiving DAPT. The primary end point was similar between the study groups (SAPT 11.0% vs DAPT 8.3%; rate ratio, 1.14; 95% confidence interval [CI], 0.83-1.55; P = .420). Consistently, we found no difference in terms of both major bleeding (SAPT 9.7% vs DAPT 12.6%; hazard ratio, 0.77; 95% CI, 0.43-1.39; P = .387) and DRT (2.6% vs 1.1%; rate ratio, 1.47; 95% CI, 0.89-2.43; P = .130) between the SAPT and DAPT groups. In this propensity score matching analysis of a single-center LAAC cohort, ischemic and bleeding outcomes did not differ at 1 year for patients discharged with SAPT or DAPT. These results have to be confirmed in an adequately powered randomized clinical trial.

Optimal antithrombotic/anticoagulation therapy in patients on chronic oral anticoagulation (OAC) undergoing drug-eluting stent (DES) implantation is unknown. We investigated the efficacy and safety of two regimens of antithrombotic/anticoagulation therapy in patients who present for DES implantation whilst on OAC. We included a series of 515 patients on OAC who underwent DES implantation between 2002 and 2007. Based on predefined clinical and echocardiographic criteria, 306 patients continued OAC (triple therapy) and 209 patients discontinued OAC (dual therapy) for the time they received antiplatelet therapy with clopidogrel and aspirin [stent-related antithrombotic treatment (SRAT)]. The primary end point was a composite of death, myocardial infarction, stent thrombosis or stroke. During SRAT the primary endpoint was observed in 13 patients in the group with triple therapy versus 15 patients in the group with dual therapy [Kaplan-Meier estimates 4.2% and 7.2%, odds ratio (OR) = 0.61, 95% confidence interval (CI) 0.29-1.28; P = 0.19]. At 2 years of follow-up, the primary endpoint was observed in 35 patients in the group with triple therapy versus 36 patients in the group with dual therapy (Kaplan-Meier estimates 14.1% and 18.0%, OR = 0.76, 95% CI: 0.48-1.21; P = 0.25). Two-year incidence of major bleeding was 1.4% (n = 4, triple therapy) versus 3.1% (n = 6, dual therapy) (P = 0.34). In patients on chronic OAC undergoing DES implantation, clinical and echocardiographic criteria help to define postprocedural antithrombotic/anticoagulation therapy. Based on these criteria, both a double antiplatelet therapy (clopidogrel plus aspirin) and a triple therapy (OAC plus clopidogrel plus aspirin) are associated with favourable safety and efficacy.

Background: Ischemic stroke remains a leading cause of mortality and long-term disability, with recurrent events contributing significantly to the global disease burden. While single antiplatelet therapy (SAPT) is standard for secondary prevention, the clinical benefit and safety of dual antiplatelet therapy (DAPT) in diverse populations remain underexplored. Objective: This study aimed to compare the efficacy and safety of single versus dual antiplatelet therapy in preventing recurrent ischemic stroke, focusing on reduction in recurrent stroke rates and major adverse events among high-risk patients. Methods: In this single-center, parallel-group randomized controlled trial, 100 patients with confirmed ischemic stroke were enrolled and randomized equally to SAPT (aspirin) or DAPT (aspirin plus clopidogrel). Patients aged 40–70 years with recent ischemic stroke were included, while those with contraindications to antiplatelet agents, bleeding disorders, or significant comorbidities were excluded. Data were collected using standardized case forms; primary outcome was recurrent stroke within three months, and secondary outcomes included major bleeding and mortality. The study protocol received ethical approval according to the Declaration of Helsinki. Statistical analysis was performed using SPSS version 25, with chi-square tests and logistic regression applied as appropriate. Results: Of 100 randomized patients, 96 completed follow-up (SAPT: n=48, DAPT: n=48). Recurrent ischemic stroke occurred in 22.9% of SAPT and 10.4% of DAPT patients (relative risk 0.46; 95% CI 0.16–1.14; p=0.099), while major bleeding events were observed in 4.2% (SAPT) and 8.3% (DAPT) (p=0.412). No significant difference in all-cause mortality was observed. DAPT was associated with a clinically meaningful, though not statistically significant, reduction in adverse events. Conclusion: Dual antiplatelet therapy may offer additional clinical protection against recurrent ischemic stroke compared to single therapy, supporting its consideration for secondary prevention in high-risk patients. These findings inform individualized treatment decisions and highlight the need for further multicenter trials to confirm long-term efficacy and safety.

Efficacy and Safety of Single versus Dual Antiplatelet Therapy for Coiling of Unruptured Aneurysms

Background: The optimal antithrombotic regimen for patients with coexistent atrial fibrillation (AF) and coronary artery disease (CAD) requiring percutaneous coronary intervention (PCI) remains controversial. Methods: We performed a chart review of 2,645 consecutive patients with non-ST elevation or ST elevation myocardial infarction at a regional cardiac centre, to examine the clinical characteristics and discharge antithrombotic medications of patients with coexistent AF (known or new onset AF with CHADS 2 ≥1), treated with PCI. Results: Among 2,645 patients, 94 eligible patients were analyzed and 30 (32%) were prescribed triple therapy (TT) at hospital discharge. CHADS 2 score was the major predictor of the decision to prescribe TT ( P=0.002). Conclusion: Approximately one-third of the patients with AF undergoing PCI were prescribed TT at hospital discharge. Clinicians are generally following national guidelines and internationally-developed consensus statements, and focus on stroke risk despite the risks of bleeding and insufficient evidence supporting the benefits of TT.

Introduction: Tracheostomy is one of the most frequent surgical procedures carried out in critically ill patients. The most popular technique today is the percutaneous dilatational tracheostomy (PDT) which uses serial dilators over a guide wire and is usually done at the bedside in the intensive care unit (ICU) under bronchoscopic guidance. Antiplatelet agents have become a mainstay therapy for vascular diseases; yet they increase the risk of bleeding. The aim of this study is to determine the bleeding risk for patients on antiplatelet therapy who underwent PDT. Methods: A retrospective analysis of patients who underwent PDT admitted to ICU between 2006 and 2021. All data were extracted from electronic health record (EPIC) and operative reports. Minor bleeding is defined as bleeding requiring application of temporary pressure or change of dressing. Major bleeding is defined as bleeding requiring packing with surgicel or transfusion of red blood cells, fresh frozen plasma or platelets. Antiplatelet therapy (APT) is defined as receiving therapy up to and within 24 hours of PDT. Single antiplatelet therapy (SAT) is ASA alone and dual antiplatelet therapy (DAT) is ASA/clopidogrel combination. Results: A total of 677 PDTs were identified and analyzed (567 patients that did not receive antiplatelet therapy [NAT group] and 100 APT group [93 SAT and 17 DAT]). Compared to the NAT group, the APT group were older (71 +/- 12 vs 58 +/- 20, p = 0.0001), had similar gender (male: 60 % vs 60 %, p = 1.0), and similar BMI (29 +/- 9 vs 28 +/- 7, p = 0.2). For minor bleeding (5.1 % in NAT group), the SAT group and DAT group had more bleeding (17 % for SAT, p = 0.0001, and 17.6 % for DAT, p = 0.02). Major bleeding did not significantly differ between SAT and NAT groups (1.1 % vs 0.4 %, p = 0.2), but was significantly higher for DAT group compared to NAT group (5.9 % vs 0.4 %, p = 0.003). Conclusions: In a large single center, there was no significant major bleeding when PDT was performed while patients are on ASA, but there was significantly more major bleeding when patients were on both ASA and clopidogrel. This data should be confirmed in large multicenter prospective studies.