Standard Dual Antiplatelet Therapy Research Articles

P2Y12 monotherapy versus standard dual antiplatelet therapy after percutaneous coronary intervention: a systematic review and meta-analysis

Abstract Funding Acknowledgements None. Introduction Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor after percutaneous coronary intervention (PCI) is the recommended therapy for lowering the ischemic risk among patients with acute coronary syndrome (ACS). However, the increased incidence of bleeding is a major concern. Monotherapy with a P2Y12 inhibitor after short-term DAPT to reduce adverse cardiovascular events and bleeding rates has not been fully established and remains uncertain. This meta-analysis aims to determine the effectiveness of P2Y12 inhibitor monotherapy after short-term DAPT in reducing cardiovascular and bleeding events. Methods A comprehensive search of randomized controlled trials (RCTs) examining the use of short-term DAPT followed by P2Y12 monotherapy in patients with ACS who underwent PCI was conducted. Outcome measures for all-cause mortality, myocardial infarction, and bleeding rates were analyzed using a random-effects model via Review Manager V5.4. Results A total of six randomized controlled trials (RCTs) with 36,724 subjects were analyzed. There were no significant differences in all-cause mortality (RR 0.89 [95% CI: 0.78-1.02], I² = 0%, p = 0.10) and myocardial infarction (RR 1.00 [95% CI: 0.88-1.14], I² = 0%, p = 0.72) between the P2Y12 inhibitor group and dual antiplatelet therapy (DAPT) group. There was a lower rate of major bleeding in the P2Y12 group compared to the DAPT group (RR 0.65 [95% CI: 0.49-0.88], I² = 76%, p = 0.002). The major sources of substantial heterogeneity are due to different intervals of de-escalation and baseline risk factors prior to PCI in each study. Conclusion P2Y12 monotherapy has similar rates of all-cause mortality and myocardial infarction. However, early de-escalation leads to a lower incidence of bleeding. P2Y12 monotherapy showed a 35% decreased risk of bleeding compared to the DAPT strategy. This suggests that P2Y12 monotherapy is a preferable antiplatelet strategy in patients undergoing PCI, especially in the high-risk bleeding population.

P2Y12 Inhibitor Monotherapy after Short Term Dual Antiplatelet Therapy in Acute Coronary Syndrome

Recent studies have shown similar safety and efficacy of short-term dual antiplatelet therapy (DAPT) followed by P2Y12 inhibitor (P2Y12i) monotherapy when compared with standard DAPT. However, the optimal DAPT duration and regimen in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) is still unclear. Online databases were searched for randomized controlled trials (RCTs) evaluating P2Y12i monotherapy after short DAPT (≤3 months) vs standard DAPT (≥12 months) in ACS patients. The outcomes of interest were all cause death, cardiovascular (CV) death, myocardial infarction (MI), stent thrombosis (ST), target-vessel revascularization (TVR) and major bleeding. Random-effects model was used to calculate pooled odds ratios (OR) and 95% confidence intervals (CI). Six RCTs with a total of 23,884 patients (n=11,904 P2Y12i monotherapy, n=11,980 standard DAPT) were included. Compared with standard DAPT, P2Y12i monotherapy after short DAPT was associated with similar odds of all cause death (OR 0.86, 0.65-1.12, p = 0.26) and CV death (OR 0.75, 0.43-1.29, p = 0.29) at 1 year. Similarly, there were no significant differences in rates of MI (OR 1.09, 0.83-1.43, p = 0.53), ST (OR 1.09, 0.71-1.67, p = 0.70) and TVR (OR 0.81, 0.65-1.01, p = 0.07) between the P2Y12i monotherapy and standard DAPT arms. The P2Y12i monotherapy group had significantly lower major bleeding (OR 0.49, 0.38-0.64, p<0.001) when compared to standard DAPT. In conclusion, among patients with ACS undergoing PCI, P2Y12i monotherapy after short DAPT significantly reduces bleeding without increasing ischemic risk when compared to standard DAPT therapy.

Current Strategies to Guide the Antiplatelet Therapy in Acute Coronary Syndromes.

The role of antiplatelet therapy in patients with acute coronary syndromes is a moving target with considerable novelty in the last few years. The pathophysiological basis of the treatment depends on platelet biology and physiology, and the interplay between these aspects and clinical practice must guide the physician in determining the best therapeutic options for patients with acute coronary syndromes. In the present narrative review, we discuss the latest novelties in the antiplatelet therapy of patients with acute coronary syndromes. We start with a description of platelet biology and the role of the main platelet signal pathways involved in platelet aggregation during an acute coronary syndrome. Then, we present the latest evidence on the evaluation of platelet function, focusing on the strengths and weaknesses of each platelet's function test. We continue our review by describing the role of aspirin and P2Y12 inhibitors in the treatment of acute coronary syndromes, critically appraising the available evidence from clinical trials, and providing current international guidelines and recommendations. Finally, we describe alternative therapeutic regimens to standard dual antiplatelet therapy, in particular for patients at high bleeding risk. The aim of our review is to give a comprehensive representation of current data on antiplatelet therapy in patients with acute coronary syndromes that could be useful both for clinicians and basic science researchers to be up-to-date on this complex topic.

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.

Analysis of the therapeutic effect of aspiration thrombectomy for early carotid stent thrombosis

Objective: To investigate the clinical characteristics and the efficacy of thrombus aspiration in patients with early intrastent thrombosis (EST) following carotid artery stenting (CAS). Methods: This study is a retrospective case series, collecting clinical data of five patients who developed EST after CAS in the Department of Neurosurgery, Beijing Chaoyang Hospital, Capital Medical University from January 2021 to September 2023.All patients were male, with an age of (64.0±11.9) years (range:48 to 77 years), accounting for 2.0% (5/244) of CAS procedures during the same period.Among them, three patients did not receive standard dual antiplatelet therapy before the procedure, and one had an inadequate ADP inhibition rate (45.6%).Four patients received XACT carotid stents, while one received a Wallstent carotid stent.All five patients showed significant residual stenosis ranging from 43% to 55% after CAS.Emergency thrombus aspiration was performed in all cases, and data regarding perioperative conditions, vascular patency, and clinical outcomes were collected. Results: The interval between CAS and the occurrence of EST ranged from 3 hours to 14 days.The main clinical symptoms included sudden onset of consciousness disorders and contralateral limb weakness.None of the patients received preoperative intravenous thrombolysis, and thrombus aspiration was performed during the procedure to restore vascular patency.Four cases underwent balloon angioplasty during the procedure, and two cases utilized overlapping stents.Two patients experienced intraoperative embolization of thrombus to the C2 segment.In one case, the embolized thrombus was retrieved using an intracranial thrombectomy stent, while in another case, it was aspirated using a guiding catheter.Postoperatively, all patients had a thrombolysis in cerebral infarction grade of 3, and symptoms improved in four cases.One patient showed no improvement in symptoms, and MRI revealed extensive new infarction in the right frontal and insular regions, adjacent to the right lateral ventricle.Regular follow-up examinations after discharge did not reveal restenosis or embolism within the stent.The follow-up period ranged from 7.6 to 21.2 months, with modified Rankin scale scores of 0 to 1 point in four cases and 2 points in one case, indicating good recovery in all patients. Conclusions: Acute intrastent thrombosis is a rare complication after carotid artery stenting.The combined use of percutaneous thrombus aspiration and endovascular techniques, such as balloon angioplasty and stent overlapping, can rapidly restore vessel patency with favorable outcomes.However, further large-scale clinical studies are needed to confirm the effectiveness of these treatments for acute intrastent thrombosis.

Abbreviated or Standard Dual Antiplatelet Therapy by Sex in Patients at High Bleeding Risk

Abbreviated dual antiplatelet therapy (DAPT) reduces bleeding with no increase in ischemic events in patients at high bleeding risk (HBR) undergoing percutaneous coronary intervention (PCI). To evaluate the association of sex with the comparative effectiveness of abbreviated vs standard DAPT in patients with HBR. This prespecified subgroup comparative effectiveness analysis followed the Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With an Abbreviated vs Standard DAPT Regimen (MASTER DAPT) trial, a multicenter, randomized, open-label clinical trial conducted at 140 sites in 30 countries and performed from February 28, 2017, to December 5, 2019. A total of 4579 patients with HBR were randomized at 1 month after PCI to abbreviated or standard DAPT. Data were analyzed from July 1 to October 31, 2022. Abbreviated (immediate DAPT discontinuation, followed by single APT for ≥6 months) or standard (DAPT for ≥2 additional months, followed by single APT for 11 months) treatment groups. One-year net adverse clinical events (NACEs) (a composite of death due to any cause, myocardial infarction, stroke, or major bleeding), major adverse cardiac or cerebral events (MACCEs) (a composite of death due to any cause, myocardial infarction, or stroke), and major or clinically relevant nonmajor bleeding (MCB). Of the 4579 patients included in the analysis, 1408 (30.7%) were women and 3171 (69.3%) were men (mean [SD] age, 76.0 [8.7] years). Ischemic and bleeding events were similar between sexes. Abbreviated DAPT was associated with comparable NACE rates in men (hazard ratio [HR], 0.97 [95% CI, 0.75-1.24]) and women (HR, 0.87 [95% CI, 0.60-1.26]; P = .65 for interaction). There was evidence of heterogeneity of treatment effect by sex for MACCEs, with a trend toward benefit in women (HR, 0.68 [95% CI, 0.44-1.05]) but not in men (HR, 1.17 [95% CI, 0.88-1.55]; P = .04 for interaction). There was no significant interaction for MCB across sex, although the benefit with abbreviated DAPT was relatively greater in men (HR, 0.65 [95% CI, 0.50-0.84]) than in women (HR, 0.77 [95% CI, 0.53-1.12]; P = .46 for interaction). Results remained consistent in patients with acute coronary syndrome and/or complex PCI. These findings suggest that women with HBR did not experience higher rates of ischemic or bleeding events compared with men and may derive particular benefit from abbreviated compared with standard DAPT owing to these numerically lower rates of events. ClinicalTrials.gov Identifier: NCT03023020.

Impact of ethnicity on antiplatelet treatment regimens for bleeding reduction in acute coronary syndromes: a systematic review and pre-specified subgroup meta-analysis.

Randomized controlled trials (RCTs) testing bleeding reduction strategies using antiplatelet treatment regimens (BRATs) in acute coronary syndromes (ACS) have shown promising results, but the generalizability of these findings may be significantly influenced by the ethnicity of the patients enrolled, given that East Asian (EA) patients show different ischaemic-bleeding risk profile compared to non-EA patients. RCTs comparing a BRAT vs. standard 12-month dual antiplatelet therapy (DAPT) in patients with ACS undergoing percutaneous coronary intervention (PCI) were selected. The primary efficacy endpoint was major adverse cardiovascular events (MACE) as defined in each trial and the primary safety endpoint was minor or major bleeding. Twenty-six RCTs testing seven different BRATs were included. The only strategy associated with a trade-off in MACE was 'upfront unguided de-escalation' in the subgroup of non-EAs (risk ratio 1.16, 95% confidence interval 1.09-1.24). All but aspirin monotherapy-based strategies (i.e. 'short and very short DAPT followed by aspirin') were associated with reduced bleeding compared with standard DAPT in both EA and non-EA patients. There were no significant differences between subgroups, but the lack of RCTs in some of the included strategies and the difference in the certainty of evidence between EA and non-EA patients revealed that the evidence in support of different BRATs in ACS undergoing PCI is influenced by ethnicity. Moreover, absolute risk reduction estimation revealed that some BRATs might be more effective than others in reducing bleeding according to ethnicity. The majority of BRATs are associated with reduced bleeding without any trade-off in hard ischaemic endpoints regardless of ethnicity. However, the supporting evidence and relative safety profiles of different BRATs might be significantly affected by ethnicity, which should be taken into account in clinical practice. This study is registered in PROSPERO (CRD42023416710).

Repeat coronary revascularization in high-risk patients treated with ticagrelor monotherapy after PCI: Insights from the randomized TWILIGHT trial

Abstract Background Repeat revascularization after percutaneous coronary intervention (PCI) remains a major concern, even though its impact on mortality is limited. The effect of ticagrelor monotherapy vs. standard dual antiplatelet therapy (DAPT) on this outcome is unclear. Aim To assess the impact of ticagrelor monotherapy vs. DAPT on repeat revascularization after PCI. Methods In the TWILIGHT trial, high-risk patients who were event-free and adherent to a ticagrelor-based DAPT for 3 months after PCI were randomized to ticagrelor plus aspirin or ticagrelor plus placebo for 12 additional months. In this post-hoc analysis, the primary endpoint was repeat revascularization due to recurrent or persistent symptomatic myocardial ischemia. Secondary endpoints included target lesion revascularization (TLR), target vessel revascularization (TVR) and major adverse cardiac and cerebrovascular events (MACCE) and net adverse clinical events (NACE) (Figure). All endpoints were adjudicated and assessed at 12 months after randomization in the per-protocol population. Results Among 6,759 patients, ticagrelor monotherapy and ticagrelor plus aspirin were associated with a similar risk of repeat revascularization (7.1% vs 6.7%, HR 1.07, 95% CI 0.89-1.29), TLR, TVR and MACCE (Figure), while NACE was lower with ticagrelor monotherapy. Conclusion In high-risk patients undergoing PCI, ticagrelor monotherapy after 3 months of ticagrelor plus aspirin was associated with similar rates of recurrent coronary revascularization and MACCE and a lower risk of NACE compared with continued DAPT.

Abbreviated versus standard dual antiplatelet therapy time after PCI in high bleeding risk patients with acute coronary syndrome - a report from the SWEDEHEART registry

Abstract Background The use of a short duration of dual antiplatelet therapy (DAPT) has become increasingly common in patients with high bleeding risk (HBR). This study aimed to evaluate outcomes for an abbreviated DAPT strategy compared to standard DAPT time strategy for high bleeding risk-patients with acute coronary syndrome (ACS) treated with percutaneous coronary intervention (PCI). Methods A total of 22310 patients from the SWEDEHEART-registry with at least one high bleeding risk criteria who underwent PCI for ACS in Sweden between January 1, 2013, until January 15, 2021, were enrolled. Patients were grouped according to their planned DAPT time at discharge: standard DAPT with 12 months of any P2Y12 inhibitor and aspirin or an abbreviated DAPT duration (&amp;lt;6 months DAPT or 12-month single APT) and matched for intended P2Y12 inhibitor type (clopidogrel or prasugrel/ticagrelor). The primary outcome was net adverse clinical events (NACE) at one year defined as the first occurrence of cardiac mortality or hospitalization due to myocardial infarction, ischemic stroke or clinically significant bleeding. Major adverse cardiovascular events and the individual components of NACE were defined as secondary endpoints. Results No significant difference in NACE was observed between the abbreviated compared to standard DAPT time groups, Kaplan-Meier event rate: 12.9% (n = 584) vs 13.1% (n = 594) hazard ratio (HR) 0.99; 95% confidence interval (CI) 0.88-1.11, p=0.83. No differences were observed for MACE (HR 1.08; 95% CI 0.94-1.25) or any of the elements of the primary composite outcome. The results were consistent in all HBR-subgroups. Conclusion For patients with a high bleeding risk undergoing PCI due to an ACS, an abbreviated DAPT strategy was associated with comparable rates of NACE and MACE as compared to a standard DAPT time strategy. The results add real-world evidence that abbreviated DAPT-regimes can be a viable treatment option for patients with ACS with a high bleeding risk.

Parsimonious versus extensive score: can we simplify bleeding risk stratification after percutaneous coronary intervention without losing specificity?

Abstract Background/Introduction Prediction of bleeding risk in patients receiving dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) has been repeatedly attempted and resulted in multiple risk models. To promote the adoption and use of risk stratification among clinicians, a consortium in the South East of the Netherlands, the "ZON-HR", has created a simple binary variant of the existing logistic models. This model includes commonly available factors which can be incorporated into the PCI report to generate stratification. In this "parsimonious" model, high bleeding risk (HBR) is stratified according to: history of intracranial haemorrhage, previous spontaneous bleeding, Hb &amp;lt; 11 g/dL, eGFR&amp;lt; 30. Purpose We aimed to perform an external validation of our model for bleeding risk and to demonstrate its discriminative value in comparison with the PRECISE DAPT score, an acknowledged risk score. Methods We performed a post hoc analysis of the GLOBAL LEADERS trial, a multicenter randomized trial, comparing ticagrelor monotherapy after one month of DAPT with standard DAPT after PCI. We stratified the patients for HBR according to the ZON-HR or a PRECISE-DAPT score ≥ 25. Bleeding events one year after PCI were compared in the entire population and in subgroups for chronic coronary syndrome (CCS), acute coronary syndrome (ACS), Ticagrelor monotherapy and DAPT. Results Of the 15968 patients included in GLOBAL LEADERS, 1059 patients were excluded due to missing variables required for either model. Among the 14909 patients, 17% had HBR according to the PRECISE DAPT score, 4% according to ZON-HR and 3% according to both. Bleeding events occurred in 8.5% and 13% of HBR defined by PRECISE DAPT or ZON-HR respectively. Patients with HBR according to both models showed 13% bleedings as opposed to 5% in non-HBR. Table 1 presents the sensitivity and specificity. Regression analysis (figure 1) demonstrated that patients with HBR according to either model have significantly more bleedings. This was also significant in all subgroups except for ACS patients receiving standard DAPT when the ZON-HR model was used. Conclusion The ZON-HR model is more conservative compared to the PRECISE DAPT score as depicted by the sensitivity and specificity. This can be explained by the larger number of risk factors used in the PRECISE DAPT score that cumulatively contributes to the sensitivity as opposed to the binary ZON-HR model which is more specific. However, the survival curves and hazard ratios showed good predictive value of both models for bleeding risk in the overall population.Table 1.Figure 1.

Potent P2Y12 Inhibitor Monotherapy for Acute Coronary Syndrome.

Dual antiplatelet therapy (DAPT), consisting of aspirin and a P2Y12inhibitor, has been the principal antiplatelet therapy after drug-eluting stent (DES) implantation in patients with acute coronary syndrome (ACS) and chronic coronary disease. Particularly in patients with ACS, which presents a higher ischemic risk than chronic coronary artery disease, DAPT for up to 12 months is the recommended standard treatment. However, to decrease bleeding events related to the potency of P2Y12inhibitors and a prolonged duration of DAPT, recent studies have suggested P2Y12inhibitor monotherapy after short-term DAPT (1-3 months), which decreased the bleeding risk without an increased ischemic risk. In this article, we discuss the evidence related to the efficacy of a P2Y12inhibitor as single-antiplatelet therapy after short-term DAPT compared with standard DAPT, with a focus on patients with ACS treated with DES.

Thromboembolic complications during and after embolization of unruptured aneurysms: A chronological outcome in periprocedural thromboembolic events.

Ischemic complications develop after elective coil embolization procedures at a certain rate. The prevention of these events has been a longstanding issue for many interventional neuroradiologists. This study aimed to clarify whether procedural ischemic events after unruptured aneurysm embolization decrease over time with perioperative anti-thromboembolic treatment or surgical experience. This study included patients with cerebral aneurysms in our institution between July 2012 and June 2020. Dual-antiplatelet therapy (DAPT) was performed (Phase 1). Thromboembolic events developed at a certain rate; thus, rivaroxaban was administered with single-antiplatelet therapy (SAPT) to improve thromboembolic results (Phase 2), showing better outcomes than in Phase 1. Subsequently, DAPT was administered again (Phase 3). Ischemic complications were evaluated in each phase or compared between the DAPT group and the direct oral anticoagulant (DOAC) with the clopidogrel (DOAC+SAPT) group. Relatively, fewer symptomatic ischemic events were noted in Phase 2 or the DOAC+SAPT group, but the outcome was not better in Phase 3 than in Phase 2. Symptomatic complications were more common in Phase 3 than in Phases 1 and 2. Ischemic complications occurred at a certain rate after endovascular procedures for unruptured aneurysms. The incidence did not decrease over time; particularly, standard DAPT plus postoperative anti-thromboembolic medication did not adequately decrease complications in Phase 3 compared to Phases 1 and 2. Therefore, accumulated experience or a learning curve could not explain the results. DOAC administration might decrease the risk of these events, but further accumulation of evidence or prospective investigation is warranted.

Short dual antiplatelet therapy duration after percutaneous coronary intervention in high bleeding risk patients: Systematic review and meta-analysis.

Dual antiplatelet therapy (DAPT) following percutaneous coronary intervention (PCI) reduces major adverse cardiovascular events (MACE) and stent thrombosis. However, DAPT duration is a concern in high bleeding risk (HBR) patients. We evaluated the effect of short DAPT (1-3 months) compared to standard DAPT (6-12 months) on bleeding and ischemic events in HBR PCI. We searched MEDLINE, Embase and CENTRAL up to August 18, 2022. Randomized controlled trials (RCTs) comparing short DAPT (1-3 months) versus standard DAPT in HBR PCI were included. We assessed risk of bias (RoB) using the Cochrane RoB2 tool, and certainty of evidence using GRADE criteria. Outcomes included MACE, all-cause death, stent thrombosis, major bleeding, and the composite of major or clinically-relevant non-major bleeding. We estimated risk ratios (RR) and 95% confidence intervals (CI) using a random-effects model. From 503 articles, we included five RCTs (n = 7,242) at overall low risk of bias with median follow-up of 12-months. Compared to standard DAPT, short DAPT did not increase MACE (RR 1.02, 95% CI 0.84-1.23), all-cause death (RR 0.92, 95% CI 0.71-1.20) or stent thrombosis (RR 1.47, 95% CI 0.73-2.93). Short DAPT reduced major bleeding (RR 0.34, 95% CI 0.13-0.90) and the composite of major or clinically-relevant non-major bleeding (RR 0.60, 95% CI 0.44-0.81), translating to 21 and 34 fewer events, respectively, per 1000 patients. In HBR PCI, DAPT for 1-3 months compared to 6-12 months reduced clinically-relevant bleeding events without jeopardizing ischemic risk. Short DAPT should be considered in HBR patients receiving PCI.

Dual antiplatelet therapy after percutaneous coronary intervention in patients at high bleeding risk: A systematic review and meta-analysis.

To date, it has not been ascertained whether shortening the duration of dual antiplatelet therapy (DAPT) can benefit high bleeding risk (HBR) patients. This systematic review and meta-analysis was performed to investigate the safety and efficacy of short (≤ 3 months) DAPT in HBR patients after percutaneous coronary intervention (PCI). The PubMed, Embase, and Clinical Trials databases were searched from inception until November 2021 to identify studies that evaluated the safety and efficacy of short DAPT in HBR patients implanted with new-generation drug-eluting stents (DES). Primary endpoints included major bleeding, definite or probable stent thrombosis (ST), and myocardial infarction (MI), while secondary endpoints included all-cause death and ischemic stroke. Based on the fixed and random effect model, the risk ratio (RR) and 95% confidence interval of each endpoint were measured. Five observational studies and one randomized controlled trial were included, involving 15,432 HBR patients. Short DAPT for HBR patients undergoing PCI had a lower incidence of major bleeding in comparison with standard (> 3 months) DAPT (2.3% vs. 3.2%, RR 0.64 [0.44, 0.95], p = 0.03), while short DAPT was comparable to standard DAPT with regard to definite or probable ST (0.4% vs. 0.3%, RR 1.31 [0.77, 2.23], p = 0.32) and MI (2.4% vs. 2.0%, RR 1.17 [0.95, 1.45], p = 0.14). Among HBR patients implanted with new-generation DES, short DAPT was associated with reduced risk of major bleeding without significantly increasing the risk of definite or probable ST and MI in comparison with standard DAPT.

Short-Term DAPT and DAPT De-Escalation Strategies for Patients With Acute Coronary Syndromes: A Systematic Review and Network Meta-Analysis.

Short-term (≤6 months) dual antiplatelet therapy (DAPT) and DAPT de-escalation become attractive for patients with acute coronary syndrome. A systemic search identified randomized controlled trials that included patients with acute coronary syndrome treated using (1) standard DAPT (12 months) with clopidogrel, prasugrel (standard/low dose), or ticagrelor; (2) extended DAPT (≥18 months); (3) short-term DAPT (≤6 months) followed by P2Y12 inhibitor or aspirin; (4) 12-month DAPT with unguided de-escalation from potent P2Y12 inhibitors to low-dose potent P2Y12 inhibitor or clopidogrel at 1 month; and (5) guided selection DAPT with genotype or platelet function tests. The primary efficacy outcome (major adverse cardiovascular events) was a composite of cardiovascular death, myocardial infarction, or stroke. The primary safety outcome was major or minor bleeding. This meta-analysis included 32 randomized controlled trials with 103 497 patients. While there were no differences in efficacy between short, unguided de-escalation and guided selection strategies, unguided de-escalation was associated with reduced risk of major adverse cardiovascular events compared with standard DAPT with clopidogrel or ticagrelor (hazard ratio [95% CI], 0.67 [0.49-0.93] and 0.68 [0.50-0.93]). Both short DAPT followed by P2Y12 inhibitor and unguided de-escalation were associated with reduced risks in safety compared with other strategies, including guided selection (hazard ratio [95% CI], 0.66 [0.47-0.93] and 0.48 [0.33-0.71]). Short DAPT followed by a P2Y12 inhibitor was associated with reduced risk of major bleeding and all-cause death compared with standard, extended DAPT (eg, versus DAPT with clopidogrel; hazard ratio [95% CI], 0.64 [0.42-0.97] and 0.60 [0.44-0.82]). By rankogram, unguided de-escalation strategy was the safest and most effective strategy in reducing major adverse cardiovascular events and major or minor bleeding while short DAPT followed by P2Y12 inhibitor was ranked the best for major bleeding and all-cause death. In patients with acute coronary syndrome, unguided de-escalation was associated with the lowest risk of major adverse cardiovascular events and major or minor bleeding outcomes, while short DAPT followed by P2Y12 inhibitor was associated with the lowest risk of major bleeding and all-cause death.

Rationale and design of the PARTHENOPE trial: A two-by-two factorial comparison of polymer-free vs biodegradable-polymer drug-eluting stents and personalized vs standard duration of dual antiplatelet therapy in all-comers undergoing PCI

BackgroundOver the past few decades, percutaneous coronary intervention (PCI) has undergone significant advancements as a result of the combination of device-based and drug-based therapies. These iterations have led to the development of polymer-free drug-eluting stents. However, there is a scarcity of data regarding their clinical performance. Furthermore, while various risk scores have been proposed to determine the optimal duration of dual antiplatelet therapy (DAPT), none of them have undergone prospective validation within the context of randomized trials. DesignThe PARTHENOPE trial is a phase IV, prospective, randomized, multicenter, investigator-initiated, assessor-blind study being conducted at 14 centers in Italy (NCT04135989). It includes 2,107 all-comers patients with minimal exclusion criteria, randomly assigned in a 2-by-2 design to receive either the Cre8 amphilimus-eluting stent or the SYNERGY everolimus-eluting stent, along with either a personalized or standard duration of DAPT. Personalized DAPT duration is determined by the DAPT score, which accounts for both bleeding and ischemic risks. Patients with a DAPT score <2 (indicating higher bleeding than ischemic risk) receive DAPT for 3 or 6 months for chronic or acute coronary syndrome, respectively, while patients with a DAPT score ≥2 (indicating higher ischemic than bleeding risk) receive DAPT for 24 months. Patients in the standard DAPT group receive DAPT for 12 months. The trial aims to establish the noninferiority between stents with respect to a device-oriented composite end point of cardiovascular death, target-vessel myocardial infarction, or clinically-driven target-lesion revascularization at 12 months after PCI. Additionally, the trial aims to demonstrate the superiority of personalized DAPT compared to a standard approach with respect to a net clinical composite of all-cause death, any myocardial infarction, stroke, urgent target-vessel revascularization, or type 2 to 5 bleeding according to the Bleeding Academic Research Consortium criteria at 24-months after PCI. SummaryThe PARTHENOPE trial is the largest randomized trial investigating the efficacy and safety of a polymer-free DES with a reservoir technology for drug-release and the first trial evaluating a personalized duration of DAPT based on the DAPT score. The study results will provide novel insights into the optimizing the use of drug-eluting stents and DAPT in patients undergoing PCI.

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.

Efficacy and safety of different dual antiplatelet strategies in patients undergoing percutaneous coronary intervention: A systematic review and network meta-analysis.

Dual antiplatelet therapy (DAPT) is key for preventing ischaemic events post-percutaneous coronary intervention (PCI). Various DAPT modifications like the shortened duration or P2Y12 inhibitor (P2Y12i) de-escalation are implemented to reduce bleeding risk. However, these strategies lack direct comparative studies. This study aimed to assess the efficacy and safety of such DAPT strategies, including de-escalated and short DAPT, in patients undergoing PCI. We searched PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases for relevant randomized controlled trials (RCTs). We performed a network meta-analysis (NMA) to estimate risk ratios (RRs) and 95% confidence intervals (CIs). The primary efficacy endpoint was major adverse cardiac events (MACEs), and the primary safety endpoint was major bleeding. Secondary endpoints included individual components of MACEs and net adverse clinical events (NACEs). A total of 17 RCTs comprising 53,156 patients (median age, 62.0 years, 24.8% female) were included. NMA suggested that de-escalation DAPT was associated with a significantly lower risk of MACEs (risk ratio [RR] = 0.79, 95% confidence interval [CI] = 0.64-0.98), bleeding (RR = 0.63, 95% CI = 0.49-0.82), and NACEs (RR = 0.69, 95% CI = 0.60-0.79) compared with standard DAPT. Short DAPT followed by P2Y12i monotherapy exhibited a significantly decreased risk of major bleeding (RR = 0.63, 95% CI = 0.46-0.86) compared with standard DAPT. De-escalation DAPT was the most effective strategy for preventing the risk of MACEs without increasing bleeding events, while short DAPT followed by P2Y12i monotherapy was the most effective strategy for reducing the risk of bleeding among patients undergoing PCI.

Strategy of dual antiplatelet therapy for patients with ST-elevation myocardial infarction and non-ST-elevation acute coronary syndromes: A systematic review and network meta-analysis

BackgroundVarious durations and de-escalation strategies of dual antiplatelet therapy (DAPT) after ST-elevation myocardial infarction (STEMI) or non-ST-elevation acute coronary syndromes (NSTE-ACS) have been tested in randomized controlled trials (RCT)s. However, evidence by specific ACS subtype is unknown. MethodsPubMed, EMBASE, and Cochrane CENTRAL were searched in February 2023. RCTs on DAPT strategies included STEMI or NSTE-ACS patients with standard DAPT (12 months) with clopidogrel or potent P2Y12 inhibitors, short-term DAPT (≤6 months) followed by potent P2Y12 inhibitors or aspirin, unguided de-escalation from potent P2Y12 inhibitors to low-dose potent P2Y12 inhibitors or clopidogrel at one month, and guided selection with genotype or platelet function tests were identified. The primary outcome was the net adverse clinical events (NACE) defined as a composite of major adverse cardiovascular events (MACE) and clinically relevant bleeding events. ResultsTwenty RCTs with a combined total population of 24,745 STEMI and 37,891 NSTE-ACS patients were included. In STEMI patients, unguided de-escalation strategy was associated with a lower rate of NACE compared with standard DAPT using potent P2Y12 inhibitors (HR:0.57; 95% CI:0.34–0.96) without increased risk of MACE. In NSTE-ACS patients, unguided de-escalation strategy was associated with a lower rate of NACE compared with the guided selection strategy (HR:0.65; 95% CI:0.47–0.90), standard DAPT using potent P2Y12 inhibitors (HR:0.62; 95% CI:0.50–0.78) and standard DAPT using clopidogrel (HR:0.73; 95% CI:0.55–0.98) without increased risk of MACE. ConclusionUnguided de-escalation strategy was associated with a reduced risk of NACE and may be the most effective DAPT strategy for STEMI and NSTE-ACS.

Prasugrel Monotherapy After Percutaneous Coronary Intervention With Biodegradable-Polymer Platinum-Chromium Everolimus Eluting Stent for Japanese Patients With Chronic Coronary Syndrome (ASET-JAPAN).

P2Y12 inhibitor monotherapy without aspirin immediately after percutaneous coronary intervention (PCI) has not been tested in East Asian patients, so in this study we aimed to assess the safety and feasibility of reduced dose (3.75 mg/day) prasugrel monotherapy in Japanese patients presenting with chronic coronary syndrome (CCS).Methods and Results: ASET-JAPAN is a prospective, multicenter, single-arm pilot study that completed enrolment of 206 patients from 12 Japanese centers in September 2022. Patients with native de-novo coronary lesions and a SYNTAX score <23 were treated exclusively with biodegradable-polymer platinum-chromium everolimus-eluting stent(s). Patients were loaded with standard dual antiplatelet therapy (DAPT) and following successful PCI and optimal stent deployment, they received low-dose prasugrel (3.75 mg/day) monotherapy for 3 months. The primary ischemic endpoint was a composite of cardiac death, spontaneous target-vessel myocardial infarction, or definite stent thrombosis. The primary bleeding endpoint was Bleeding Academic Research Consortium (BARC) type 3 or 5. At 3-month follow-up, there were no primary bleeding or ischemic events, or any stent thrombosis. This pilot study showed the safety and feasibility of prasugrel monotherapy in selected low-risk Japanese patients with CCS. This "aspirin-free" strategy may be a safe alternative to traditional DAPT following PCI.