Course Of Dual Antiplatelet Therapy Research Articles

Abstract 4124370: DAPT for 1-Month Followed by P2Y12 Inhibitor Monotherapy Versus DAPT for 12-Months After Percutaneous Coronary Intervention: A Systematic Review and Meta Analysis of Randomized Controlled Trials

Background: Dual antiplatelet therapy (DAPT) is well established as standard of care following percutaneous coronary intervention (PCI). Recent trials have shown a potential benefit in the reduction of hemorrhagic events with a shorter course of DAPT. However, the optimal duration of DAPT following PCI remains unclear. Question: Is 1 month of DAPT followed by P2Y12 inhibitor monotherapy superior to the standard 12-month DAPT regimen in terms of cardiovascular outcomes in patients post-PCI? Methods: Medline, PubMed, and Cochrane Central Register of Controlled Trials databases were searched for randomized clinical trials (RCTs) comparing 1-month vs. 12-months of DAPT followed by P2Y12 inhibitor monotherapy post-PCI. The outcomes of interest were cardiovascular death, myocardial infarction, and major bleeding. We used R version 4.1.2 (The R Foundation, 2021) to pool the data using a random-effects model. Heterogeneity was assessed with I2. Results: We included three RCTs reporting data from 22,413 patients, of whom 11,180 (49.8%) were treated with 1-month of DAPT, followed by P2Y12 inhibitor monotherapy. Follow-up ranged from 12 months to 24 months. The incidence of all-cause death (RR 1.20; 95% CI 0.95-1.51; p=0.12) and myocardial infarction (RR 0.86; 95% CI 0.71-1.05; p=0.14) were not significantly different between the groups. However, major bleeding (RR 0.51; 95% CI 0.26-0.99; p=0.048) was significantly reduced with a short course of DAPT followed by P2Y12 inhibitor monotherapy, as compared with standard 12 months of DAPT. Conclusion: Following PCI, a transition from DAPT to P2Y12 inhibitor monotherapy at 1-month is associated with a significant reduction in major bleeding as compared with standard DAPT for 12-months, with no significant change in the incidence of all-cause mortality or myocardial infarction.

Abstract 4124335: Ticagrelor monotherapy the way forward after Percutaneous Coronary Interventions : An updated meta-analysis

Background: With the advent of newer generation drug eluting stents, the chorus for shortening the duration of dual antiplatelet therapy (DAPT) after percutaneous coronary interventions (PCI) is getting louder and louder. Ticagrelor monotherapy after a short course of DAPT has been studied in a few randomized controlled trials with promising results. We conducted a systematic review and meta-analysis comparing the ticagrelor monotherapy with DAPT after short duration DAPT in patients undergoing PCIs. Methods: PubMed, Embase and Cochrane databases were searched for RCTs comparing ticagrelor monotherapy to DAPT after PCI and reported the outcomes of Major Adverse Cardiac Events including death, myocardial infarction or stroke (MACE); Major Adverse Cardiac and Cerebrovascular Events including death, myocardial infarction, stroke, stent thrombosis or target vessel revascularization (MACCE); Major bleeding; Death from any cause; CV death; Stent thrombosis and Target vessel revascularization (TVR). Data were extracted from published reports and quality assessment was performed per Cochrane recommendations. Statistical analysis was performed using Review Manager Web (Cochrane Collaboration). Heterogeneity was examined with I 2 test. Results: Out of 3208 database results, 5 RCTs with 32,393 patients were included; 16,188 (50%) received Ticagrelor monotherapy. Studies had mean follow-up ranging from 12 months to 24 months. Baseline characteristics are as per Table 1. Safety endpoints of major bleeding (HR 0.50; 95% CI 0.38-0.66; p < 0.0001; I 2 = 23 %; Figure 1A), was significantly less with ticagrelor monotherapy. Efficacy endpoints of MACE, MACCE, Death from any cause, CV Death, target vessel revascularization (TVR) and stent thrombosis were not significantly different between ticagrelor and DAPT (Figure 1 and 2). Conclusion: Ticagrelor monotherapy reduces major bleeding as compared to continued DAPT for 12 months after PCI. Major ischemic outcomes were similar in both groups. Ticagrelor monotherapy may be the way forward after short duration of DAPT in patients undergoing PCI.

An analysis of the virtual cardio-oncology research initiative (VICORI) resource: bleeding risk among cancer patients beyond 1-year post-myocardial infarction

Abstract Introduction Cardiovascular disease (CVD) and cancer are common causes of morbidity and mortality. Advancements in treatment strategies for both diseases have resulted in a growing population who live with both conditions. Myocardial infarction (MI) represents approximately 20% of all CVD admissions in cancer patients and 10% of patients who present with an acute MI have cancer. Managing MI patients with cancer require careful balancing of their ischaemic and bleeding risks. While dual antiplatelet therapy (DAPT) increases a patient’s bleeding risk, cancer patients are at further increased risk due to a range of direct and indirect cancer effects. While our recent studies demonstrated an increased bleeding risk in cancer patients in the 1st year after MI (the period of intensive APT), it is currently not known if this risk is sustained beyond this period. VICORI is the world’s first whole-country cardio-oncology research platform, linking data from the National Cancer Registration and Analysis Service, National Institute for Cardiovascular Outcomes Research and Hospital Episode Statistics [1]. We investigated the risk of bleeding among MI patients in the 2nd year post-MI, where a large majority of patients would have completed a course of DAPT, stratified by the presence or absence of cancer. Methods In this retrospective observational study, we investigated the risk of bleeding following an MI between 2006-2019, in patients with and without cancer. Cancer was defined as a diagnosis of cancer in the 1-year preceding MI. Patients who lived past the 1st year after MI were followed-up from 12 to 24 months after their MI. We used inverse probability weighting based on propensity scores to produce a balanced cohort of patients with and without cancer. Cox proportional hazard and flexible parametric modelling were used to investigate cancer as a predictor of bleeding. Subgroup analyses were performed on stent status, MI and cancer type. Results Of 506280 patients presenting with MI, 5666 (1.1%) had cancer while 500614 (98.9%) did not. Prostate (n=1377), colorectal (n=1024), lung (n=490), breast (n=448) and bladder (n=334) cancers were among the most common types of cancers. The rate (hazard) of bleeding in MI was higher in patients with cancer in the 2nd year post-MI (HR:1.42, 95%CI 1.29-1.56) compared to those without. From the flexible parametric survival analysis, the risk of bleeding in cancer patients in the 2nd year post-MI was lower compared to the 1st year but remained statistically significant compared to non-cancer patients. Conclusion In this large real-world study, cancer patients have a persistent, increased bleeding risk beyond the 1-year post-MI period, compared to those without cancer, and this risk differed by type of cancer. Further work is needed to identify specific patient characteristics in each patient sub-group which alters one’s ischaemic or bleeding risk so they can be balanced favourably with personalised strategies.

P2Y12 Receptor Inhibitor for Antiaggregant Therapies: From Molecular Pathway to Clinical Application.

Platelets play a significant role in hemostasis, forming plugs at sites of vascular injury to limit blood loss. However, if platelet activation is not controlled, it can lead to thrombotic events, such as myocardial infarction and stroke. To prevent this, antiplatelet agents are used in clinical settings to limit platelet activation in patients at risk of arterial thrombotic events. However, their use can be associated with a significant risk of bleeding. An enhanced comprehension of platelet signaling mechanisms should facilitate the identification of safer targets for antiplatelet therapy. Over the past decade, our comprehension of the breadth and intricacy of signaling pathways that orchestrate platelet activation has expanded exponentially. Several recent studies have provided further insight into the regulation of platelet signaling events and identified novel targets against which to develop novel antiplatelet agents. Antiplatelet drugs are essential in managing atherothrombotic vascular disease. The current antiplatelet therapy in clinical practice is limited in terms of safety and efficacy. Novel compounds have been developed in response to patient variability and resistance to aspirin and/or clopidogrel. Recent studies based on randomized controlled trials and systematic reviews have definitively demonstrated the role of antiplatelet therapy in reducing the risk of cardiovascular events. Antiplatelet therapy is the recommended course of action for patients with established atherosclerosis. These studies compared monotherapy with a P2Y12 inhibitor versus aspirin for secondary prevention. However, in patients undergoing percutaneous coronary intervention, it is still unclear whether the efficacy of P2Y12 inhibitor monotherapy after a short course of dual antiplatelet therapy depends on the type of P2Y12 inhibitor. This paper focuses on the advanced-stage evaluation of several promising antiplatelet drugs.

Ticagrelor or Clopidogrel Monotherapy vs Dual Antiplatelet Therapy After Percutaneous Coronary Intervention

Among patients undergoing percutaneous coronary intervention (PCI), it remains unclear whether the treatment efficacy of P2Y12 inhibitor monotherapy after a short course of dual antiplatelet therapy (DAPT) depends on the type of P2Y12 inhibitor. To assess the risks and benefits of ticagrelor monotherapy or clopidogrel monotherapy compared with standard DAPT after PCI. MEDLINE, Embase, TCTMD, and the European Society of Cardiology website were searched from inception to September 10, 2023, without language restriction. Included studies were randomized clinical trials comparing P2Y12 inhibitor monotherapy with DAPT on adjudicated end points in patients without indication to oral anticoagulation undergoing PCI. Patient-level data provided by each trial were synthesized into a pooled dataset and analyzed using a 1-step mixed-effects model. The study is reported following the Preferred Reporting Items for Systematic Review and Meta-Analyses of Individual Participant Data. The primary objective was to determine noninferiority of ticagrelor or clopidogrel monotherapy vs DAPT on the composite of death, myocardial infarction (MI), or stroke in the per-protocol analysis with a 1.15 margin for the hazard ratio (HR). Key secondary end points were major bleeding and net adverse clinical events (NACE), including the primary end point and major bleeding. Analyses included 6 randomized trials including 25 960 patients undergoing PCI, of whom 24 394 patients (12 403 patients receiving DAPT; 8292 patients receiving ticagrelor monotherapy; 3654 patients receiving clopidogrel monotherapy; 45 patients receiving prasugrel monotherapy) were retained in the per-protocol analysis. Trials of ticagrelor monotherapy were conducted in Asia, Europe, and North America; trials of clopidogrel monotherapy were all conducted in Asia. Ticagrelor was noninferior to DAPT for the primary end point (HR, 0.89; 95% CI, 0.74-1.06; P for noninferiority = .004), but clopidogrel was not noninferior (HR, 1.37; 95% CI, 1.01-1.87; P for noninferiority > .99), with this finding driven by noncardiovascular death. The risk of major bleeding was lower with both ticagrelor (HR, 0.47; 95% CI, 0.36-0.62; P < .001) and clopidogrel monotherapy (HR, 0.49; 95% CI, 0.30-0.81; P = .006; P for interaction = 0.88). NACE were lower with ticagrelor (HR, 0.74; 95% CI, 0.64-0.86, P < .001) but not with clopidogrel monotherapy (HR, 1.00; 95% CI, 0.78-1.28; P = .99; P for interaction = .04). This systematic review and meta-analysis found that ticagrelor monotherapy was noninferior to DAPT for all-cause death, MI, or stroke and superior for major bleeding and NACE. Clopidogrel monotherapy was similarly associated with reduced bleeding but was not noninferior to DAPT for all-cause death, MI, or stroke, largely because of risk observed in 1 trial that exclusively included East Asian patients and a hazard that was driven by an excess of noncardiovascular death.

Ticagrelor monotherapy after a short course of dual antiplatelet therapy with ticagrelor plus aspirin following percutaneous coronary intervention in patients with versus without diabetes mellitus: a meta-analysis of randomized trials

BackgroundCardiovascular disease (CVD) is one among the major causes of mortality all round the globe. Several anti-platelet regimens have been proposed following percutaneous coronary intervention (PCI). In this analysis, we aimed to show the adverse clinical outcomes associated with ticagrelor monotherapy after a short course of dual antiplatelet therapy (DAPT) with ticagrelor and aspirin following PCI in patients with versus without diabetes mellitus (DM).MethodsElectronic databases were searched by four authors from September to November 2023. Cardiovascular outcomes and bleeding events were the endpoints of this analysis. Revman 5.4 software was used to conduct this meta-analysis. Risk ratio (RR) and 95% confidence intervals (CI) were used to represent the results which were generated.ResultsThree studies with a total number of 22,574 participants enrolled from years 2013 to 2019 were included in this analysis. Results of this analysis showed that DM was associated with significantly higher risks of major adverse cardiovascular events (RR: 1.73, 95% CI: 1.49 – 2.00; P = 0.00001), all-cause mortality (RR: 2.15, 95% CI: 1.73 – 2.66; P = 0.00001), cardiac death (RR: 2.82, 95% CI: 1.42 – 5.60; P = 0.003), stroke (RR: 1.78, 95% CI: 1.16 – 2.74; P = 0.009), myocardial infarction (RR: 1.63, 95% CI: 1.17 – 2.26; P = 0.004) and stent thrombosis (RR: 1.74, 95% CI: 1.03 – 2.94; P = 0.04) when compared to patients without DM.However, thrombolysis in myocardial infarction (TIMI) defined minor and major bleedings, bleeding defined according to the academic research consortium (BARC) type 3c (RR: 1.31, 95% CI: 0.14 – 11.90; P = 0.81) and BARC type 2, 3 or 5 (RR: 1.17, 95% CI: 0.85 – 1.62; P = 0.34) were not significantly different.ConclusionIn patients who were treated with ticagrelor monotherapy after a short course of DAPT with ticagrelor and aspirin, DM was an independent risk factor for the significantly increased adverse cardiovascular outcomes. However, TIMI and BARC defined bleeding events were not significantly different in patients with versus without DM.

The Effects of Clopidogrel Duration on Carotid Artery In-Stent Restenosis

ObjectiveThere is limited data supporting a specific duration for dual antiplatelet therapy in carotid artery stenting (CAS), and most clinical evidence is derived from studies involving coronary interventions. As a result, the appropriate duration of dual antiplatelet therapy after CAS has yet to be determined. We aimed to elucidate whether the duration of dual antiplatelet therapy played a role in the rate of carotid in-stent restenosis. MethodsA retrospective analysis of all patients who underwent CAS at our institution over a 20-year period (1996-2016) was performed (n=279). Patients who did not complete their follow-up duplex studies or were not discharged on clopidogrel were excluded from the study. Patients were separated into short-term (<6 weeks, n=159) and long-term (>6 weeks, n=112) clopidogrel users based on duration of therapy. We defined clinically significant in-stent restenosis as >50% restenosis (PSV = 224 cm/s) in symptomatic patients and >80% restenosis (PSV = 325 cm/s) in asymptomatic patients status-post prior CAS based on published velocity criteria. Rates of in-stent restenosis at 1-year, 2-year, and 5-year intervals were analyzed between the two groups using chi-squared analysis. ResultsDemographic information was largely similar between the two groups; however, short-term clopidogrel users were more likely to have a history of atrial fibrillation (9.43% vs. 1.68%, p=0.008) and were less likely to have a history of CABG (16.35% vs. 29.41%, p=0.009), diabetes (33.34% vs. 49.58%, p=0.006) and CAD (50.31% vs. 63.03%, p=0.035). All patients were on long-term aspirin therapy. There was no significant difference between overall rates of in-stent restenosis between the short-term and long-term clopidogrel users (5.03% vs. 9.24%, p=0.168) within 5 years of the index procedure. Similar results were observed when these groups were evaluated at 1-year (5.61 % vs. 3%, p=0.321), 2-year (2.02% vs. 6.59%, p=0.072), and 5-year (2.24% vs. 3.57%, p=0.635) follow-up. ConclusionNo statistically significant difference was observed in the rate of in-stent restenosis after CAS between short-term and long-term clopidogrel therapy. Patients in whom there is no other indication for longer duration clopidogrel therapy may be considered for shorter duration course of dual antiplatelet therapy following CAS.

Tailoring Antithrombotic Regimens for Percutaneous Coronary Intervention Patients with High Bleeding and Ischemic Risk (TAILOR-BIRISK): Individualized Management and Genotype-Guided De-escalation.

Percutaneous coronary intervention (PCI) is a widely used reperfusion strategy for coronary artery disease, with millions of procedures performed annually. Attention has recently been drawn to a unique population, known as "bi-risk" patients, who have high ischemic and high bleeding risks and undergo PCI. However, there is currently no established definition or optimal antithrombotic therapy for this group. Genotype-guided antithrombotic therapy, which uses cytochrome P450 (CYP) 2C19 gene testing, may offer a more personalized and precise approach. Nevertheless, recent research has shown that routine genetic testing to guide treatment in the PCI population does not improve patient outcomes, preventing it from being routinely recommended in guidelines. This review proposes, for the first time, the definition of the bi-risk population and the concept of TAILOR-BIRISK for their treatment strategies. TAILOR-BIRISK emphasizes de-escalating antithrombotic treatment and suggests that a short course of dual antiplatelet therapy (DAPT) followed by monotherapy by either clopidogrel or ticagrelor 60 mg BID (BID, twice daily) could be a reasonable option for this population. Additionally, the use of CYP2C19 gene testing to guide inhibitor selection can help better individualize and customize the antithrombotic regimen. However, more large-sample randomized control studies should be conducted to further explore the optimal antithrombotic strategy for the bi-risk population.

Navigating the Course of Dual Antiplatelet Therapy After Percutaneous Coronary Intervention: A Review of Guided Approaches.

Dual antiplatelet therapy (DAPT) is the standard approach to prevent thrombotic events in patients undergoing percutaneous coronary intervention and presenting with chronic or acute coronary syndromes. However, a sizeable proportion of patients presents with an impaired or unwarranted response to DAPT depending on genetic polymorphisms or variability in platelet response. Therefore, the concept of changing the type or dose of antiplatelet drugs based on the result of platelet function or genotype tests (ie, guided DAPT) has been introduced. The goal of guided DAPT is to intensify the antiplatelet potency in patients at high risk of thrombotic events (ie, escalation) and to decrease the antiplatelet potency in patients at high risk of bleeding (ie, de-escalation). This review aims to present an up-to-date and comprehensive overview of the latest research findings on DAPT modulation guided by either platelet function or genetic testing, discussing its current indications and future directions.

Safety and Efficacy of Ticagrelor Monotherapy in Patients With Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention: An Individual Patient Data Meta-Analysis of TWILIGHT and TICO Randomized Trials.

Dual antiplatelet therapy with a potent P2Y12 inhibitor coupled with aspirin for 1 year is the recommended treatment for patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). As an alternative, monotherapy with a P2Y12 inhibitor after a short period of dual antiplatelet therapy has emerged as a bleeding reduction strategy. We pooled individual patient data from randomized trials that included patients with ACS undergoing PCI treated with an initial 3-month course of dual antiplatelet therapy followed by ticagrelor monotherapy versus continued ticagrelor plus aspirin. Patients sustaining a major ischemic or bleeding event in the first 3 months after PCI were excluded from analysis. The primary outcome was Bleeding Academic Research Consortium type 3 or 5 bleeding occurring between 3 and 12 months after index PCI. The key secondary end point was the composite of death, myocardial infarction, or stroke. Hazard ratios and 95% CIs were generated using Cox regression with a one-stage approach in the intention-to-treat population. The pooled cohort (n=7529) had a mean age of 62.8 years, 23.2% were female, and 55% presented with biomarker-positive ACS. Between 3 and 12 months, ticagrelor monotherapy significantly reduced Bleeding Academic Research Consortium 3 or 5 bleeding compared with ticagrelor plus aspirin (0.8% versus 2.1%; hazard ratio, 0.37 [95% CI, 0.24-0.56]; P<0.001). Rates of all-cause death, myocardial infarction, or stroke were not significantly different between groups (2.4% versus 2.7%; hazard ratio, 0.91 [95% CI, 0.68-1.21]; P=0.515). Findings were unchanged among patients presenting with biomarker-positive ACS. Among patients with ACS undergoing PCI who have completed a 3-month course of dual antiplatelet therapy, discontinuation of aspirin followed by ticagrelor monotherapy significantly reduced major bleeding without incremental ischemic risk compared with ticagrelor plus aspirin. URL: https://www.crd.york.ac.uk/prospero; Unique identifier: CRD42023449646.

Early Discontinuation of Aspirin Among Patients with Chronic Kidney Disease Undergoing Percutaneous Coronary Intervention with a Drug-Eluting Stent: A Meta-Analysis.

Conflicting evidence exists to support whether short duration of dual antiplatelet therapy (DAPT) followed by P2Y12 inhibitor monotherapy reduces bleeding complications after coronary artery drug-eluting stent (DES) insertion, compared with standard 12-month DAPT, particularly among patients with CKD who are at increased risk of bleeding. A Medline search identified randomized trials comparing up to 3 months of DAPT followed by P2Y12 inhibitor monotherapy versus twelve months of DAPT after insertion of a DES for any indication. Trials were included if they reported ischemic or bleeding outcomes among patients with CKD. The primary outcome was a composite of all-cause mortality, cardiac or cerebrovascular events, stent thrombosis (MACE), and major or minor bleeding events. Secondary outcomes were the individual components of the primary outcome, and clinically significant bleeding. The relative risk (RR) was estimated using a random-effects model. Seven randomized trials were included for a total of 4,996 patients with CKD (14% of the trial population). Early discontinuation of aspirin was associated with a similar incidence of the primary outcome among patients with CKD compared with twelve-month DAPT (RR 0.97; 95% confidence interval (95% CI) 0.73-1.30). The relative risk of MACE was also similar between the two arms (RR 1.02; 95% CI 0.85-1.23). The risk of clinically significant bleeding was significantly lower with early discontinuation of aspirin (RR 0.60; 95% CI 0.46-0.78). P2Y12 inhibitor monotherapy after a shortened course of DAPT appears to be associated with a similar risk of ischemic events and a lower risk of bleeding events after DES insertion among patients with CKD compared to 12-month DAPT.

Bleeding and Ischemic Risks of Ticagrelor Monotherapy After Coronary Interventions

BackgroundIn TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention), among high-risk patients undergoing percutaneous coronary intervention (PCI), ticagrelor monotherapy vs continuation of dual antiplatelet therapy (DAPT) with aspirin and ticagrelor after completing a 3-month course of DAPT was associated with reduced bleeding, without an increase in ischemic events. ObjectivesThis investigation sought to study the clinical benefit of ticagrelor monotherapy vs DAPT by simultaneously modeling its associated potential bleeding benefits and ischemic harms on an individual patient basis. MethodsMultivariable Cox regression models for: 1) Bleeding Academic Research Consortium type 2, 3, or 5 (BARC-2/3/5); and 2) cardiovascular death, nonfatal myocardial infarction, and nonfatal ischemic stroke (major adverse cardiac and cerebrovascular event [MACCE]) were developed using stepwise forward variable selection. The coefficients in the BARC-2/3/5 and MACCE models were used to calculate bleeding and ischemic risk scores, respectively, for each patient (excluding the coefficient for randomized treatment). ResultsIn the total study group (N = 7,119), BARC-2/3/5 occurred in 391 (5.5%) patients, and MACCE occurred in 258 (3.6%). There was a consistent reduction in bleeding events associated with ticagrelor monotherapy compared with DAPT across both bleeding and ischemic risk strata (P interaction = 0.54 and 0.11, respectively). Importantly, this benefit associated with ticagrelor monotherapy was not offset by an increase in MACCE at any level of bleeding or ischemic risk. ConclusionsThree months after PCI, discontinuing aspirin and maintaining ticagrelor monotherapy reduces bleeding in both higher–bleeding risk and lower–bleeding risk patients compared with continued DAPT. This benefit does not appear to be offset by greater ischemic risk. (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention [TWILIGHT]; NCT02270242)

Life-threatening Neutropenia After a Short Course of Dual Antiplatelet Therapy for Minor Stroke (P7-5.017)

<h3>Objective:</h3> We present a case of unexpected severe neutropenia in a patient prescribed a 21-day course of double antiplatelet therapy (aspirin and clopidogrel) for ischemic stroke. <h3>Background:</h3> Antiplatelet agents are the cornerstone of atherosclerotic stroke prevention. In recent years, trials such as CHANCE and POINT have popularized the use of a short (3–4 week) course of dual antiplatelet therapy (aspirin plus a P2Y12 inhibitor) after minor stroke or high-risk transient ischemic attack. While some P2Y12 inhibitors such as ticlopidine have been associated with neutropenia, this side effect is exceedingly rare with clopidogrel and has primarily been reported with prolonged use after coronary stenting. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> An 88-year-old woman presented with acute onset of left face, arm, and leg numbness. National Institutes of Health Stroke Scale was 1 for mild sensory loss. Non-contrast computed tomography (CT) of head showed no evidence of hemorrhage or acute ischemia. Brain magnetic resonance imaging revealed a small area of diffusion positivity in the right thalamus consistent with acute ischemic stroke. She was already taking aspirin 81mg daily; clopidogrel 75mg daily was added for a 21-day course. WBC count during admission had ranged from 4.11–6.27 K/uL. On post-stroke day 23, she presented with three days of malaise, abdominal pain, and fever to 102 °F. WBC and absolute neutrophil count were now markedly low (0.67, &lt;0.01 K/uL, respectively). CT scan of abdomen revealed enterocolitis and early appendicitis. She was diagnosed with febrile neutropenia and treated with broad-spectrum antibiotics and filgrastim. As there was no evidence of hematologic malignancy, it was concluded that her neutropenia was drug-induced secondary to clopidogrel. She gradually recovered and cell counts had normalized at follow-up. <h3>Conclusions:</h3> While rare, severe neutropenia can occur with even brief use of clopidogrel. With the widespread adoption of short course dual antiplatelet therapy after stroke, neurologists should be aware of this association. <b>Disclosure:</b> Dr. Culbertson has nothing to disclose. Dr. Blaszkowsky has nothing to disclose.

Efficacy and Safety of Prolonged Dual Antiplatelet Therapy after Percutaneous Coronary Intervention in Acute Coronary Syndrome Patients.

It remains controversial whether to extend the course of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI). We conducted a study to investigate the benefits and risks of applying DAPT for different durations after PCI in acute coronary syndromes (ACS) patients in China. What's more, we explored the efficacy of extended DAPT regimen based on ticagrelor. This single-center prospective cohort study used data obtained from the PHARM-ACS Patient Registration Database. We included all patients who were discharged between April and December 2018. All patients had at least 18 months of follow-up. Patients were divided into two groups according to the duration of DAPT: a 1-year group and a >1-year group. Potential bias between the two groups was adjusted for by propensity score matching using logistic regression. The primary outcomes were major adverse cardiovascular and cerebrovascular events (MACCE), defined as a composite of death, myocardial infarction, and stroke occurring from 12 months after discharge to follow-up visit. The safety endpoint was any significant bleeding event (BARC ≥ 2). Of 3,205 patients enrolled, 2,201 (68.67%) had DAPT prolonged beyond one year. A total of 2,000 patients were successfully propensity score-matched; patients who received DAPT > 1-year (n = 1000), compared with DAPT = 1-year patients (n = 1000), had a similar risk of MACCE (adjusted HR 0.23, 95% CI 0.05-1.10) and significant bleeding events (adjusted HR 0.63, 95% CI 0.32-1.24). The DAPT > 1-year group had a higher risk of revascularization (adjusted HR 3.36, 95% CI 1.64-6.87). Prolonged DAPT may not be of sufficient benefit to ACS patients within 12-18 months after the index PCI to offset the increased risk of significant bleeding events.

After coronary drug-eluting stent placement, does a longer course of dual antiplatelet therapy lead to decreased thrombotic events?

After coronary drug-eluting stent placement, does a longer course of dual antiplatelet therapy lead to decreased thrombotic events?

P2Y12 Inhibitor Monotherapy: Considerations for Acute and Long-Term Secondary Prevention Post-PCI.

Following percutaneous coronary intervention (PCI), an initial course of dual antiplatelet therapy (DAPT) with aspirin and a inhibitor ( -i) is recommended to minimize the risk of thrombotic complications. After the initial period of DAPT, antiplatelet monotherapy, usually consisting of aspirin, is administered for long-term secondary prevention. However, over the last few years there has been accruing evidence on -i monotherapy, both in the acute (i.e., post-PCI; after a brief period of DAPT, transitioning to monotherapy before six or 12 months in patients with chronic or acute coronary syndrome, respectively) and chronic (i.e., long-term secondary prevention; after completion of six or 12 months of DAPT, in patients with chronic or acute coronary syndrome, respectively) settings. In aggregate, most studies of short DAPT with transition to -i monotherapy showed a reduced risk of bleeding complications, without any significant increase in ischemic events as compared to standard DAPT. On the other hand, the evidence on long-term -i monotherapy is scarce, but results from a randomized trial showed that clopidogrel monotherapy outperformed aspirin monotherapy in terms of net benefit, ischemic events and bleeding. Antiplatelet therapy is also recommended for patients undergoing PCI and with an established indication for long-term oral anticoagulation (OAC). In this scenario, a brief period of triple therapy (i.e., aspirin, -i and OAC) is followed by a course of dual antithrombotic therapy (usually with -i and OAC) and ultimately by lifelong OAC alone. European and American guidelines have been recently updated to provide new recommendations on antithrombotic therapy, including the endorsement of -i monotherapy in different settings. However, some areas of uncertainty still remain and further randomized investigations are ongoing to fulfil current gaps in knowledge. In this review, we assess the current knowledge and evidence on -i monotherapy for the early and long-term secondary prevention in patients undergoing PCI, and explore upcoming research and future directions in the field.

P2Y12 Inhibitors Monotherapy in Patients Undergoing Complex vs Non-Complex Percutaneous Coronary Intervention: A Meta-Analysis of Randomized Trials

BackgroundMonotherapy with P2Y12 inhibitors (P2Y12i) is emerging as alternative strategy to dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI). However, early withdrawal of aspirin as part of P2Y12i monotherapy regimens may pose concerns in high-risk patients, such as those undergoing complex PCI. Our aim was to evaluate the efficacy and safety of P2Y12i monotherapy after a short course of DAPT (1-3-month) compared with standard DAPT (≥12-month) according to PCI complexity. MethodsWe performed a meta-analysis of randomized trials using random effects models to combine hazard ratios (HRs) with 95% confidence intervals (CIs). Within-trial interactions were pooled to estimate heterogeneity between complex and noncomplex PCI strata. The study protocol was registered in the PROSPERO (CRD42021291027). ResultsWe identified 5 trials including 31,627 patients, of whom 8,328 (26.3%) underwent complex PCI. P2Y12i monotherapy compared with standard DAPT was associated with a similar risk of all-cause death, stent thrombosis, and stroke, with no evidence for interaction between complex and noncomplex PCI. We found heterogeneity in the treatment effect of P2Y12i monotherapy vs standard DAPT with respect to myocardial infarction (P-interaction = 0.027). Compared with standard DAPT, P2Y12i monotherapy decreased the risk of myocardial infarction in complex PCI (HR 0.77, 95%CI 0.60-0.99, P = .042), but not in noncomplex PCI patients (HR 1.09, 95%CI 0.90-1.30, P = .382). The risk of major bleeding was significantly reduced by P2Y12i monotherapy with a consistent treatment effect (P-interaction = 0.699) in both complex and noncomplex PCI strata. ConclusionsPatients undergoing complex PCI may derive more benefit and less harm from P2Y12i monotherapy after early aspirin withdrawal compared with standard DAPT.

P2Y12 Inhibitor Monotherapy after Percutaneous Coronary Intervention.

In patients with acute and chronic coronary artery disease undergoing percutaneous coronary intervention (PCI), dual antiplatelet therapy (DAPT) has been the cornerstone of pharmacotherapy for the past two decades. Although its antithrombotic benefit is well established, DAPT is associated with an increased risk of bleeding, which is independently associated with poor prognosis. The improvement of the safety profiles of drug-eluting stents has been critical in investigating and implementing shorter DAPT regimens. The introduction into clinical practice of newer generation oral P2Y12 inhibitors such as prasugrel and ticagrelor, which provide more potent and predictable platelet inhibition, has questioned the paradigm of standard DAPT durations after coronary stenting. Over the last five years, several trials have assessed the safety and efficacy of P2Y12 inhibitor monotherapy after a short course of DAPT in patients treated with PCI. Moreover, ongoing studies are testing the role of P2Y12 inhibitor monotherapy immediately after PCI in selected patients. In this review, we provide up-to-date evidence on the efficacy and safety of P2Y12 inhibitor monotherapy after a short period of DAPT compared to DAPT in patients undergoing PCI as well as outcomes associated with P2Y12 inhibitor monotherapy compared to aspirin for long-term prevention.

Clopidogrel monotherapy following dual antiplatelet therapy in patients with acute coronary syndrome post-drug-eluting stent implantation: a systematic review and direct/indirect treatment comparison

Abstract Background In patients with acute coronary syndromes (ACS) receiving a drug-eluting stent (DES), treatment with dual antiplatelet therapy (DAPT) reduces the risk of recurrent ischemic events. Optimal duration of DAPT depends on patient characteristics and switching to single antiplatelet therapy (SAPT) is recommended after the course of DAPT. Purpose The aim of this study was to evaluate the comparative efficacy and safety of switching to clopidogrel SAPT following DAPT in patients with ACS post DES-implantation. Methods A systematic literature review (SLR) was conducted by searching MEDLINE®, Embase, and CENTRAL up to July 27, 2021. Randomized controlled trials (RCTs) and observational studies that evaluated clopidogrel SAPT following DAPT in adults with ACS post-DES implantation were included. Heterogeneity of included studies was vetted in a feasibility assessment. Random effects meta-analyses were conducted using the metafor package for R. Direct comparisons were conducted for clopidogrel vs. aspirin and clopidogrel vs. DAPT. Using the Bucher method, aspirin vs. DAPT was indirectly compared by taking the difference between their respective pooled treatment effects vs. clopidogrel. A sensitivity analysis was conducted by including studies with a follow-up of 12 months. Results Of 5,349 records identified, seven unique studies (four RCTs and three observational studies) were eligible to be included in the SLR and quantitative treatment comparison. Risk of major adverse cardiovascular events (MACE) was lower in patients who switched to clopidogrel SAPT after DAPT compared with those who switched to aspirin monotherapy (hazard ratio [HR]: 0.72; 95% confidence interval [CI]: 0.54, 0.98), and this difference was significant. No significant difference in risk of MACE was found between switching to clopidogrel SAPT after DAPT and continuation of DAPT (HR: 0.90; 95% CI: 0.65, 1.25). This finding was consistent with the sensitivity analysis representing studies with follow-up of 12 months (HR: 0.95; 95% CI: 0.69, 1.31). Risk of bleeding was not analysed due to insufficient data across included studies for patients with ACS. However, within-study findings from one RCT of 4,136 patients demonstrated a significantly lower risk of bleeding, defined as thrombolysis in myocardial infarction (major and/or minor, for switching to clopidogrel SAPT following DAPT compared with continuation of DAPT (0.54% vs. 1.17% of patients had bleeding [HR: 0.46; 95% CI: 0.23, 0.94]). Conclusion Findings from this SLR suggest switching to clopidogrel SAPT after DAPT in ACS post-DES implantation has a lower risk of MACE compared with switching to aspirin monotherapy, and no difference in the risk of MACE compared with continuation of DAPT. There was insufficient data across the included studies to evaluate the bleeding risk, however, a single study indicated a lower bleeding risk with switching to clopidogrel SAPT. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Sanofi

P2Y12 inhibitors monotherapy in patients undergoing complex vs. non-complex percutaneous coronary intervention: a meta-analysis of randomized trials

Abstract Background Monotherapy with P2Y12 inhibitors (P2Y12i) is emerging as alternative strategy to dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI). However, early withdrawal of aspirin as part of P2Y12i monotherapy regimens may pose concerns in high-risk patients, such as those undergoing complex PCI. Purpose To evaluate the efficacy and safety of P2Y12i monotherapy after a short course of DAPT (1- to 3-month) compared with standard DAPT (≥12-month) according to PCI complexity. Methods We performed a meta-analysis of randomized trials using random effects models to combine hazard ratios (HRs) with 95% confidence intervals (CIs). No restrictions were applied to the type of P2Y12 receptor inhibitor (clopidogrel, prasugrel, or ticagrelor) or to the definition of complex PCI. Within-trial interactions were pooled to estimate heterogeneity between complex and noncomplex PCI strata. The study protocol was registered in the PROSPERO (CRD42021291027). Results We screened 7,502 unique citations, of which 2,948 were screened at title and abstract level and 576 were judged potentially eligible for full-text assessment. We included in the analysis five trials (1–5) enrolling 31,627 patients, of whom 8,328 (26.3%) underwent complex PCI; characteristics of trials and patient populations are summarized in Table 1. Risk estimates for efficacy and safety outcomes associated with P2Y12i monotherapy and standard DAPT across studies included in the analysis, stratified by complex and noncomplex PCI, are reported in Figure 1. P2Y12i monotherapy compared with standard DAPT was associated with a similar risk of all-cause death, stent thrombosis, and stroke, with no evidence for interaction between complex and noncomplex PCI. We found heterogeneity in the treatment effect of P2Y12i monotherapy vs. standard DAPT with respect to myocardial infarction (P-interaction=0.027). Compared with standard DAPT, P2Y12i monotherapy decreased the risk of myocardial infarction in complex PCI (HR 0.77, 95% CI 0.60–0.99, P=0.042), but not in noncomplex PCI patients (HR 1.09, 95% CI 0.90–1.30, P=0.382). The risk of major bleeding was significantly reduced by P2Y12i monotherapy with a consistent treatment effect (P-interaction=0.699) in both complex and noncomplex PCI strata. Conclusions Patients undergoing complex PCI may derive more benefit and less harm from P2Y12i monotherapy after early aspirin withdrawal compared with standard DAPT, resulting in decreased risks of myocardial infarction and bleeding. Funding Acknowledgement Type of funding sources: None.