Comparison of Dual Antiplatelet Therapies for Minor, Nondisabling, Acute Ischemic Stroke: A Bayesian Network Meta-Analysis.

Importance: Dual antiplatelet therapy (DAPT) appears to be an effective treatment option for minor (nondisabling) acute ischemic stroke. This conclusion is based on trials that include both transient ischemic attack (TIA) and minor stroke; however, these 2 conditions may differ. Objective: To compare DAPT regimens specifically for minor stroke. Data Sources: PubMed was searched for randomized clinical trials published up to November 4, 2023. Search terms strategy included TIA, transient ischemic attack, minor stroke, or moderate stroke, with the filter randomized controlled trial. Unpublished data on minor stroke were sourced from authors and/or institutions. Study Selection: Trials testing DAPT within the first 24 hours of a minor stroke (defined as a National Institutes of Health Stroke Scale score ≤5) were included by consensus. Of 1508 studies screened, 6 (0.3%) initially met inclusion criteria and were reviewed. Data Extraction and Synthesis: The study was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines by multiple observers. Bayesian fixed-effect network meta-analysis was conducted. Secondary analysis performed for high-risk TIA alone. Main Outcomes and Measures: Treatments were ranked using a probability measure called surface under the cumulative rank curve (SUCRA). The primary outcome was subsequent ischemic stroke at 90 days. Secondary outcomes included major hemorrhage, mortality, and hemorrhagic stroke. The number needed to treat (NNT) and number needed to harm (NNH) were obtained. Results: Five trials were included that described 28 148 patients, of whom 22 203 (78.9%) had a minor stroke. Of these, 13 995 (63.0%) were in DAPT groups and 8208 (37.0%) in aspirin (acetylsalicylic acid) groups. Aspirin and ticagrelor had a 94% probability of being the superior treatment for minor stroke (SUCRA, 0.94) for the primary outcome. Both aspirin and ticagrelor (NNT, 40; 95% CI, 31-64) and aspirin and clopidogrel (NNT, 58; 95% CI, 39-136) were superior to aspirin alone in the prevention of recurrent ischemic stroke at 90 days. Both treatments had higher rates of major hemorrhage than aspirin alone (NNH for aspirin and ticagrelor, 284; 95% CI, 108-1715 vs NNH for aspirin and clopidogrel, 330; 95% CI, 118-3430), but neither had increased risk of hemorrhagic stroke or death. For high-risk TIA, ticagrelor and aspirin had a 60% probability (SUCRA, 0.60) and clopidogrel and aspirin had a 40% probability (SUCRA 0.40) of being a superior treatment; neither was optimum, but both were superior to aspirin alone for the primary outcome. Conclusions and Relevance: These findings suggest that DAPT with aspirin and ticagrelor has higher probability of being the superior treatment among patients with minor stroke when presence of CYP2C19 loss-of-function alleles has not been excluded. For patients with TIA, the superiority of aspirin and ticagrelor vs aspirin and clopidogrel was not demonstrated.

Temporal trends in use of antisecretory agents among patients administered clopidogrel-based dual antiplatelet therapy after percutaneous coronary intervention.

BACKGROUND: Antisecretory drugs are commonly prescribed with clopidogrel-based dual antiplatelet therapy (DAPT) to prevent gastrointestinal bleeding in high-risk patients after percutaneous coronary intervention (PCI). However, omeprazole and esomeprazole (inhibiting proton pump inhibitors [PPIs]) may increase cardiovascular event rates on co-administration with clopidogrel. This study aimed to examine trends in the use of antisecretory agents in patients administered clopidogrel-based DAPT and the concomitant use of clopidogrel and inhibiting PPIs. METHODS: We used National Inpatient Sample data compiled by the Health Insurance Review & Assessment Service from 2009 to 2020. Further, we identified patients who were prescribed clopidogrel-based DAPT after PCI and investigated the concomitant use of antisecretory agents with clopidogrel. To verify the annual trend of drug utilization, we used the Cochran-Armitage trend test. RESULTS: From 2009 to 2020, the percentage of H2 receptor antagonist users decreased steadily (from 82.5% in 2009 to 25.3% in 2020); instead, the percentage of PPI users increased (from 23.7% in 2009 to 82.0% in 2020). The use of inhibiting PPI also increased (from 4.2% in 2009 to 30.7% in 2020). Potassium competitive acid blockers (P-CABs) were rarely used before 2019; however, in 2020, it accounted for 7.8% of the antisecretory users. CONCLUSIONS: Our study demonstrates that the use of inhibiting PPIs increased steadily in patients administered clopidogrel-based DAPT therapy. This is a major concern since the concomitant use of inhibiting PPIs with clopidogrel could increase the risk of cardiovascular events.

One- versus three-month dual antiplatelet therapy in high bleeding risk patients undergoing percutaneous coronary intervention for non-ST-segment elevation acute coronary syndromes.

BACKGROUND: A short dual antiplatelet therapy (DAPT) duration has been proposed for patients at high bleeding risk (HBR) undergoing drug-eluting coronary stent (DES) implantation. Whether this strategy is safe and effective after a non-ST-segment elevation acute coronary syndrome (NSTE-ACS) remains uncertain. AIMS: We aimed to compare the impact of 1-month versus 3-month DAPT on clinical outcomes after DES implantation among HBR patients with or without NSTE-ACS. METHODS: This is a prespecified analysis from the XIENCE Short DAPT programme involving three prospective, international, single-arm studies evaluating the safety and efficacy of 1-month (XIENCE 28 USA and Global) or 3-month (XIENCE 90) DAPT among HBR patients after implantation of a cobalt-chromium everolimus-eluting stent. Ischaemic and bleeding outcomes associated with 1- versus 3-month DAPT were assessed according to clinical presentation using propensity score stratification. RESULTS: Of 3,364 HBR patients (1,392 on 1-month DAPT and 1,972 on 3-month DAPT), 1,164 (34.6%) underwent DES implantation for NSTE-ACS. At 12 months, the risk of the primary endpoint of death or myocardial infarction was similar between 1- and 3-month DAPT in patients with (hazard ratio [HR] 1.09, 95% confidence interval [CI]: 0.71-1.65) and without NSTE-ACS (HR 0.88, 95% CI: 0.63-1.23; p-interaction=0.34). The key secondary endpoint of Bleeding Academic Research Consortium (BARC) Type 2-5 bleeding was consistently reduced in both NSTE-ACS (HR 0.57, 95% CI: 0.37-0.88) and stable patients (HR 0.84, 95% CI: 0.61-1.15; p-interaction=0.15) with 1-month DAPT. CONCLUSIONS: Among HBR patients undergoing implantation of an everolimus-eluting stent, 1-month, compared to 3-month DAPT, was associated with similar ischaemic risk and reduced bleeding at 1 year, irrespective of clinical presentation.

Safety and efficacy of stent-assisted coil embolization with periprocedural dual antiplatelet therapy for the treatment of acutely ruptured intracranial aneurysms.

PURPOSE: Despite growing evidence for the effectiveness of stent-assisted coil embolization (SAC) in treating acutely ruptured aneurysms, the safety of stent placement in acute phase remains controversial because of concerns for stent-induced thromboembolism and hemorrhagic events attributable to the necessity of antiplatelet therapy. Therefore, we investigated the safety and efficacy of SAC with periprocedural dual antiplatelet therapy (DAPT) compared with the coiling-only technique to determine whether it is a promising treatment strategy for ruptured aneurysms. METHODS: We retrospectively evaluated 203 enrolled patients with acutely ruptured aneurysms, categorizing them into two groups: SAC and coiling-only groups. Comparative analyses between the two groups regarding angiographic results, clinical outcomes, and procedure-related complications were performed. A subgroup analysis of procedural complications was conducted on patients who did not receive chronic antithrombotic medications to alleviate their influence before hospitalization. RESULTS: 130 (64.0%) patients were treated using the coiling-only technique, whereas 73 (36.0%) underwent SAC. There was a trend to a higher complete obliteration rate (p = 0.061) and significantly lower recanalization rate (p = 0.030) at angiographic follow-up in the SAC group compared to the coiling-only group. Postprocedural cerebral infarction occurred less frequently in the SAC group (8.2%) than in the coiling-only group (17.7%), showing a significant difference (p = 0.044). Although the ventriculostomy-related hemorrhage rate was significantly higher in the SAC group than in the coiling-only group (26.2% vs. 9.3%, p = 0.031), the incidence of symptomatic ventriculostomy-related hemorrhage was comparable. Subgroup analysis excluding patients receiving chronic antithrombotic medications showed similar results. CONCLUSION: SAC with periprocedural DAPT could be a safe and effective treatment strategy for acutely ruptured aneurysms. Moreover, it might have a protective effect on postprocedural cerebral infarction without increasing the risk of symptomatic hemorrhagic complications.

Ticagrelor alone versus ticagrelor plus aspirin from month 1 to month 12 after percutaneous coronary intervention in patients with acute coronary syndromes (ULTIMATE-DAPT): a randomised, placebo-controlled, double-blind clinical trial.

BACKGROUND: Following percutaneous coronary intervention with stent placement to treat acute coronary syndromes, international clinical guidelines generally recommend dual antiplatelet therapy with aspirin plus a P2Y12 receptor inhibitor for 12 months to prevent myocardial infarction and stent thrombosis. However, data on single antiplatelet therapy with a potent P2Y12 inhibitor earlier than 12 months after percutaneous coronary intervention for patients with an acute coronary syndrome are scarce. The aim of this trial was to assess whether the use of ticagrelor alone, compared with ticagrelor plus aspirin, could reduce the incidence of clinically relevant bleeding events without an accompanying increase in major adverse cardiovascular or cerebrovascular events (MACCE). METHODS: In this randomised, placebo-controlled, double-blind clinical trial, patients aged 18 years or older with an acute coronary syndrome who completed the IVUS-ACS study and who had no major ischaemic or bleeding events after 1-month treatment with dual antiplatelet therapy were randomly assigned to receive oral ticagrelor (90 mg twice daily) plus oral aspirin (100 mg once daily) or oral ticagrelor (90 mg twice daily) plus a matching oral placebo, beginning 1 month and ending at 12 months after percutaneous coronary intervention (11 months in total). Recruitment took place at 58 centres in China, Italy, Pakistan, and the UK. Patients were required to remain event-free for 1 month on dual antiplatelet therapy following percutaneous coronary intervention with contemporary drug-eluting stents. Randomisation was done using a web-based system, stratified by acute coronary syndrome type, diabetes, IVUS-ACS randomisation, and site, using dynamic minimisation. The primary superiority endpoint was clinically relevant bleeding (Bleeding Academic Research Consortium [known as BARC] types 2, 3, or 5). The primary non-inferiority endpoint was MACCE (defined as the composite of cardiac death, myocardial infarction, ischaemic stroke, definite stent thrombosis, or clinically driven target vessel revascularisation), with an expected event rate of 6·2% in the ticagrelor plus aspirin group and an absolute non-inferiority margin of 2·5 percentage points between 1 month and 12 months after percutaneous coronary intervention. The two co-primary endpoints were tested sequentially; the primary superiority endpoint had to be met for hypothesis testing of the MACCE outcome to proceed. All principal analyses were assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT03971500, and is completed. FINDINGS: Between Sept 21, 2019, and Oct 27, 2022, 3400 (97·0%) of the 3505 participants in the IVUS-ACS study were randomly assigned (1700 patients to ticagrelor plus aspirin and 1700 patients to ticagrelor plus placebo). 12-month follow-up was completed by 3399 (>99·9%) patients. Between month 1 and month 12 after percutaneous coronary intervention, clinically relevant bleeding occurred in 35 patients (2·1%) in the ticagrelor plus placebo group and in 78 patients (4·6%) in the ticagrelor plus aspirin group (hazard ratio [HR] 0·45 [95% CI 0·30 to 0·66]; p<0·0001). MACCE occurred in 61 patients (3·6%) in the ticagrelor plus placebo group and in 63 patients (3·7%) in the ticagrelor plus aspirin group (absolute difference -0·1% [95% CI -1·4% to 1·2%]; HR 0·98 [95% CI 0·69 to 1·39]; pnon-inferiority<0·0001, psuperiority=0·89). INTERPRETATION: In patients with an acute coronary syndrome who had percutaneous coronary intervention with contemporary drug-eluting stents and remained event-free for 1 month on dual antiplatelet therapy, treatment with ticagrelor alone between month 1 and month 12 after the intervention resulted in a lower rate of clinically relevant bleeding and a similar rate of MACCE compared with ticagrelor plus aspirin. Along with the results from previous studies, these findings show that most patients in this population can benefit from superior clinical outcomes with aspirin discontinuation and maintenance on ticagrelor monotherapy after 1 month of dual antiplatelet therapy. FUNDING: The Chinese Society of Cardiology, the National Natural Scientific Foundation of China, and the Jiangsu Provincial & Nanjing Municipal Clinical Trial Project. TRANSLATION: For the Mandarin translation of the abstract see Supplementary Materials section.

Optimizing Dual Antiplatelet Therapy in the Perioperative Period for Spine Surgery After Recent Percutaneous Coronary Intervention: A Comprehensive Review, Synthesis, and Catalyst for Protocol Formulation.

The increased incidence of spine surgery within the past decade has highlighted the importance of robust perioperative management to improve patient outcomes overall. Coronary artery disease is a common medical comorbidity present in the population of individuals who receive surgery for spinal pathology that is often treated with dual antiplatelet therapy (DAPT) after percutaneous coronary intervention. Discontinuation of DAPT before surgical intervention is typically indicated; however, contradictory evidence exists in the literature regarding the timing of DAPT use and discontinuation in the perioperative period. We review the most recent cardiac and spine literature on the intricacies of percutaneous coronary intervention and its associated risks in the postoperative period. We further propose protocols for DAPT use after both elective and urgent spine surgery to optimize perioperative care.

Ticagrelor with or without aspirin following percutaneous coronary intervention in high-risk patients with concomitant peripheral artery disease: A subgroup analysis of the TWILIGHT randomized clinical trial.

BACKGROUND: The optimal antiplatelet regimen after percutaneous coronary intervention (PCI) in patients with peripheral artery disease (PAD) is still debated. This analysis aimed to compare the effect of ticagrelor monotherapy versus ticagrelor plus aspirin in patients with PAD undergoing PCI. METHODS: In the TWILIGHT trial, patients at high ischemic or bleeding risk that underwent PCI were randomized after 3 months of dual antiplatelet therapy (DAPT) to aspirin or matching placebo in addition to open-label ticagrelor for 12 additional months. In this post-hoc analysis, patient cohorts were examined according to the presence or absence of PAD. The primary endpoint was Bleeding Academic Research Consortium (BARC) 2, 3, or 5 bleeding. The key secondary endpoint was a composite of all-cause death, myocardial infarction (MI), or stroke. Endpoints were assessed at 12 months after randomization. RESULTS: Among 7,119 patients, 489 (7%) had PAD and were older, more likely to have comorbidities, and multivessel disease. PAD patients had more bleeding or ischemic complications than no-PAD patients. Ticagrelor monotherapy compared to ticagrelor plus aspirin was associated with less BARC 2, 3, or 5 bleeding in PAD (4.6% vs 8.7%; HR 0.52; 95%CI 0.25-1.07) and no-PAD patients (4.0% vs 7.0%; HR 0.56; 95%CI 0.45-0.69; interaction P-value .830) and a similar risk of death, MI, or stroke in these 2 groups (interaction P-value .446). CONCLUSIONS: Despite their higher ischemic and bleeding risk, patients with PAD undergoing PCI derived a consistent benefit from ticagrelor monotherapy after 3 months of DAPT in terms of bleeding reduction without any relevant increase in ischemic events. CLINICAL TRIAL REGISTRY INFORMATION:: https://www. CLINICALTRIALS: gov/study/NCT02270242.

Ticagrelor or Clopidogrel Monotherapy vs Dual Antiplatelet Therapy After Percutaneous Coronary Intervention: A Systematic Review and Patient-Level Meta-Analysis.

Importance: 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. Objective: To assess the risks and benefits of ticagrelor monotherapy or clopidogrel monotherapy compared with standard DAPT after PCI. Data Sources: MEDLINE, Embase, TCTMD, and the European Society of Cardiology website were searched from inception to September 10, 2023, without language restriction. Study Selection: 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. Data Extraction and Synthesis: 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. Main Outcomes and Measures: 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. Results: 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). Conclusions and Relevance: 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.

Prasugrel Single Antiplatelet Therapy versus Aspirin and Clopidogrel Dual Antiplatelet Therapy for Flow Diverter Treatment for Cerebral Aneurysms: A Retrospective Multicenter Study.

BACKGROUND AND PURPOSE: The optimal antiplatelet regimen after flow diverter treatment of cerebral aneurysms is still a matter of debate. A single antiplatelet therapy might be advantageous in determined clinical scenarios. This study evaluated the efficacy and safety of prasugrel single antiplatelet therapy versus aspirin and clopidogrel dual antiplatelet therapy. MATERIALS AND METHODS: We performed a post hoc analysis of 4 retrospective multicenter studies including ruptured and unruptured aneurysms treated with flow diversion using either prasugrel single antiplatelet therapy or dual antiplatelet therapy. Primary end points were the occurrence of any kind of procedure- or device-related thromboembolic complications and complete aneurysm occlusion at the latest radiologic follow-up (mean, 18 months). Dichotomized comparisons of outcomes were performed between single antiplatelet therapy and dual antiplatelet therapy. Additionally, the influence of various patient- and aneurysm-related variables on the occurrence of thromboembolic complications was investigated using multivariable backward logistic regression. RESULTS: A total of 222 patients with 251 aneurysms were included, 90 (40.5%) in the single antiplatelet therapy and 132 (59.5%) in the dual antiplatelet therapy group. The primary outcome-procedure- or device-related thromboembolic complications-occurred in 6 patients (6.6%) of the single antiplatelet therapy and in 12 patients (9.0%) of the dual antiplatelet therapy group (P = .62; OR, 0.712; 95% CI, 0.260-1.930). The primary treatment efficacy end point was reached in 82 patients (80.4%) of the single antiplatelet therapy and in 115 patients (78.2%) of the dual antiplatelet therapy group (P = .752; OR, 1.141; 95% CI, 0.599-2.101). Logistic regression showed that non-surface-modified flow diverters (P = .014) and fusiform aneurysm morphology (P = .004) significantly increased the probability of thromboembolic complications. CONCLUSIONS: Prasugrel single antiplatelet therapy after flow diverter treatment may be as safe and effective as dual antiplatelet therapy and could, therefore, be a valid alternative in selected patients. Further prospective comparative studies are required to validate our findings.

PRECISE-DAPT, ARC-HBR, or Simplified Clinical Evaluation for the Prediction of Major Bleeding After Percutaneous Coronary Intervention in older Patients.

Older patients have been remarkably underrepresented in bleeding risk cohorts. Thus, the PRECISE-DAPT (Derivation and validation of the predicting bleeding complications in patients undergoing stent implantation and subsequent dual antiplatelet therapy) and Academic Research Consortium for High Bleeding Risk (ARC-HBR) scores are not validated in older adults. Therefore, we sought to evaluate the PRECISE-DAPT and ARC-HBR scores in an exclusively older population and assess the prognostic value of a truly simplified clinical evaluation (SCE), consisting of only 3 binary clinical variables (hemoglobin <11 g/100 ml, previous bleeding, and anticipated use of anticoagulants). This is a retrospective analysis of the prospective single-center older-HCD registry. Consecutive patients aged ≥75 years who underwent percutaneous coronary intervention from 2012 to 2019 were included. The primary end point was postdischarge bleeding at 12 months of follow-up, defined according to the Bleeding Academic Research Consortium 3 or 5 criteria. A total of 693 patients with a mean age of 81 (±4.4) years were included in the study and 60 patients (6.8%) met the primary end point. The PRECISE-DAPT and ARC-HBR scores did not significantly predict postdischarge bleeding in the Cox regression models (hazard ratio 1.65 [0.78 to 3.42] and 1.46 [0.72 to 4.24], respectively), whereas the SCE outperformed both scores (hazard ratio 2.47, 1.34 to 4.49). All 3 scores exhibited a moderate discriminatory potential, as determined by a receiver-operating characteristic curve analysis (areas under the curve 0.601, 0.621, and 0.616, respectively), with no significant differences between them. The SCE showed an Integrated Discrimination Improvement of 0.25, p = 0.02 (SCE vs ARC-HBR) and 0.24, p = 0.01 (SCE vs PRECISE-DAPT), with an Net Reclassification Improvement of 6.54%, p = 0.37 and 7.12%, p = 0.43, respectively. In conclusion, the PRECISE-DAPT score and ARC-HBR criteria showed insufficient predictive value in older adults. A truly SCE consisting of 3 easily accessible variables not only provides equal discriminatory potential but also demonstrates superior predictive value, as determined by Cox regression models. This makes it a highly appealing tool for risk stratification, pending its evaluation in larger prospective studies.

De-escalation of dual antiplatelet therapy for patients with acute coronary syndrome after percutaneous coronary intervention: a systematic review and network meta-analysis.

OBJECTIVES: To compare dual antiplatelet therapy (DAPT) de-escalation with five alternative DAPT strategies in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). DESIGN: We conducted a systematic review and network meta-analysis (NMA). Parallel-arm randomised controlled trials (RCTs) comparing DAPT strategies were included and arms of interest were compared via NMA. Partial ranking of each identified arm and for each investigated endpoint was also performed. SETTING AND PARTICIPANTS: Adult patients with ACS (≥18 years) undergoing PCI with indications for DAPT. SEARCH METHODS: A comprehensive search covered several databases (PubMed, Embase, Cochrane Central, MEDLINE, Conference Proceeding Citation Index-Science) from inception to 15 October 2023. Medical subject headings and keywords related to ACS, PCI and DAPT interventions were used. Reference lists of included studies were screened. Clinical trials registers were searched for ongoing or unpublished trials. INTERVENTIONS: Six strategies were assessed: T1 arm: acetylsalicylic acid (ASA) and prasugrel for 12 months; T2 arm: ASA and low-dose prasugrel for 12 months; T3 arm: ASA and ticagrelor for 12 months; T4 arm: DAPT de-escalation (ASA+P2Y12 inhibitor for 1-3 months, then single antiplatelet therapy with potent P2Y12 inhibitor or DAPT with clopidogrel); T5 arm: ASA and clopidogrel for 12 months; T6 arm: ASA and clopidogrel for 3-6 months. MAIN OUTCOME MEASURES: Primary outcome: Cardiovascular mortality. SECONDARY OUTCOMES: bleeding events (all, major, minor), stent thrombosis (ST), stroke, myocardial infarction (MI), all-cause mortality, major adverse cardiovascular events (MACE). RESULTS: 23 RCTs (75 064 patients with ACS) were included. No differences in cardiovascular mortality, all-cause death, recurrent MI or MACE were found when the six strategies were compared, although with different levels of certainty of evidence. ASA and clopidogrel for 12 or 3-6 months may result in a large increase of ST risk versus ASA plus full-dose prasugrel (OR 2.00, 95% CI 1.14 to 3.12, and OR 3.42, 95% CI 1.33 to 7.26, respectively; low certainty evidence for both comparisons). DAPT de-escalation probably results in a reduced risk of all bleedings compared with ASA plus full-dose 12-month prasugrel (OR 0.49, 95% CI 0.26 to 0.81, moderate-certainty evidence) and ASA plus 12-month ticagrelor (OR 0.52, 95% CI 0.33 to 0.75), while it may not increase the risk of ST. ASA plus 12-month clopidogrel may reduce all bleedings versus ASA plus full-dose 12-month prasugrel (OR 0.66, 95% CI 0.42 to 0.94, low certainty) and ASA plus 12-month ticagrelor (OR 0.70, 95% CI 0.52 to 0.89). CONCLUSIONS: DAPT de-escalation and ASA-clopidogrel regimens may reduce bleeding events compared with 12 months ASA and potent P2Y12 inhibitors. 3-6 months or 12-month aspirin-clopidogrel may increase ST risk compared with 12-month aspirin plus potent P2Y12 inhibitors, while DAPT de-escalation probably does not.

Tailoring antiplatelet therapy in older patients with coronary artery disease.

The older population represents a unique subset of patients due to a higher rate of comorbidities and risk factors, which can lead to a higher rate of ischemic and bleeding events. As a result, older adults are mainly underrepresented or excluded from randomized trials. Although the advancement in the percutaneous coronary intervention field with the development of new technologies, techniques, and potent antiplatelet therapy led to a reduction of ischemic risk, there is still a concern regarding bleeding hazards. Apart from the global utilization of less invasive trans-radial approach and proton pump inhibitors to reduce bleeding risk, proper tailoring of antiplatelet therapy in the older person is imperative. So far, several antiplatelet drugs have been introduced in different clinical scenarios, with dual antiplatelet therapy (combination of acetylsalicylic acid and P2Y12 inhibitor) recommended after percutaneous coronary intervention. The decision on the choice of antiplatelet drug and the DAPT duration is challenging and should be based on the relationship between ischemia and bleeding with the purpose of reducing ischemic events but not at the expense of increased bleeding complications. This is particularly important in the older population, where the evidence is obscure. The main objective of this review is to summarize the available evidence on contemporary antiplatelet therapy and different approaches of de-escalation strategies in older patients after percutaneous coronary intervention.

What is the context?The older population represents a unique subset of patients due to a higher rate of comorbidities, risk factors, and unfavorable prognostic features, which can lead to a higher rate of ischemic and bleeding events. They are either excluded or underrepresented in most randomized clinical trials, which is why guidelines recommendation should be taken cautiously. Thus, the decision on the choice of antiplatelet therapy and its duration after percutaneous coronary intervention in older adults is challenging and should be tailored to a particular patient to avoid bleeding complications but not at the expense of increased ischemic events.What is new?In this review, we summarize all available evidence on contemporary antiplatelet therapy and different approaches of de-escalation strategies in older patients after percutaneous coronary intervention. In particular, several recommended approaches in patients with high bleeding risk, are thoroughly discussed in this review: De-escalation strategies with discontinuation of one antiplatelet drugDe-escalation strategy with switching between P2Y12 inhibitorsDe-escalation strategy based on dose reductionFinally, based on the current knowledge on factors contributing to high bleeding risk and the aforementioned antiplatelet modification approaches, in this review, we propose antiplatelet algorithm after percutaneous coronary intervention in older adults.What is the impact?The review provides comprehensive knowledge on antiplatelet therapy in older population and may help in tailoring antiplatelet therapy in this unique subset of patients.

Bleeding and Ischemic Risk Prediction in Patients With High Bleeding Risk (an EVOLVE Short DAPT Analysis).

The EVOLVE Short DAPT study demonstrated the safety of truncated dual antiplatelet therapy (DAPT) in patients with a high bleeding risk (HBR) treated with SYNERGY stent(s) (Boston Scientific Company, Marlborough, Massachusetts). In this population, bleeding and ischemic risk prediction may further inform DAPT decisions. This post hoc analysis of the EVOLVE Short DAPT study identified predictors of ischemic and bleeding events up to 15 months using Cox proportional hazard models. The predicted probabilities of bleeding were calculated using the Breslow method. Of 2,009 enrolled patients, 96.9% of the patients met at least 1 HBR criteria. At 15 months, the cumulative incidences of bleeding and ischemic events were 6.3% and 6.0%, respectively. The risk of bleeding was increased in patients who received oral anticoagulants (hazard ratio [HR] 2.24, 95% confidence interval [CI] 1.50 to 3.36, p <0.001) or had peripheral vascular disease (HR 1.61, 95% CI 1.01 to 2.56, p = 0.045). The risk of ischemic events was increased in patients with diabetes (HR 1.86, 95% CI 1.24 to 2.78, p <0.01) or congestive heart failure (HR 2.06, 95% CI 1.39 to 3.04, p <0.001). Renal insufficiency/failure was associated with both endpoints. There was a strong positive correlation between the predicted probability of ischemic and bleeding events (R = 0.77, p <0.001). In 617 patients with a predicted bleeding risk <4%, ischemic events predominated, and the ischemic and bleeding rates were higher in patients with a predicted bleeding risk ≥4%. Within an HBR cohort, specific characteristics identify patients at a higher risk for ischemic and separately, bleeding events. Increased bleeding risk is tied to increased ischemic risk. In conclusion, standardized risk models are needed to inform DAPT decisions in patients with a higher risk. Clinical Trial Registration: NCT02605447.

Platelet P2Y12 Inhibitor Monotherapy after Percutaneous Coronary Intervention: An Emerging Option for Antiplatelet Therapy De-escalation.

Antiplatelet therapy is considered essential for secondary prevention of ischemic heart disease. After percutaneous coronary intervention (PCI), temporary dual antiplatelet therapy (DAPT), a combination consisting of aspirin and an oral P2Y12 receptor blocker, is recommended. In the long term, this strategy results in more bleeding than antiplatelet therapy with aspirin alone. Therefore, to reduce bleeding, an increasing trend has been to keep DAPT as short as clinically acceptable, after which aspirin monotherapy is continued. Another option to diminish bleeding is to discontinue aspirin at the moment of DAPT cessation after PCI, and to continue on P2Y12 blocker monotherapy. This survey reviews the evidence on P2Y12 blocker monotherapy. Some clinical guidance will be provided on when and in whom P2Y12 inhibitor monotherapy may be applied after DAPT cessation following PCI.

Role of platelet function testing in acute coronary syndromes: a meta-analysis.

OBJECTIVE: This meta-analysis aimed to evaluate whether using platelet function testing (PFT) in acute coronary syndromes (ACS) to personalise antiplatelet therapy including a P2Y12 antagonist offers any clinical benefits to indicate incorporation into routine practice. METHODS: A search was conducted on five databases for randomised controlled trials (RCTs) conducted between 1 January 2000 and 17 July 2022, which included an ADP-specific platelet function assays and P2Y12 antagonists as part of dual antiplatelet therapy (DAPT) and have reported the efficacy and/or safety outcomes. The reported event frequencies were used to calculate the risk ratios (RRs) with a 95% CI. The χ2 heterogeneity statistical test and sensitivity analysis were used for heterogeneity assessment. RESULTS: Five RCTs with 7691 patients were included in the analysis. No significant risk reduction was seen in major adverse cardiovascular events (RR=0.95, p=0.42), individual cardiac events (cardiovascular death: RR=0.76, p=0.26; myocardial infarction: RR=0.96, p=0.74; stent thrombosis: RR=0.92, p=0.83; stroke: RR=0.91, p=0.72; target vessel revascularisation: RR=1.06, p=0.47) and overall clinical outcome (RR=0.90, p=0.22). There was also no difference in the rate of bleeding between PFT-guided and standard therapies (major bleeding: RR=0.97, p=0.78, minor bleeding: RR=0.89, p=0.19 and any bleeding: RR=1.04, p=0.33). CONCLUSION: Compared with standard DAPT with P2Y12 antagonists, using PFT to adjust antiplatelet therapy does not improve clinical outcomes. Therefore, the positions of key guidelines on routine testing in ACS should remain unchanged. In addition, the study highlights the need for well-designed and powered RCTs and standardised testing methodologies to provide reliable findings and definitive conclusions.

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

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

Short Duration of DAPT Versus De-Escalation After Percutaneous Coronary Intervention for Acute Coronary Syndromes.

OBJECTIVES: The aim of this study was to compare short dual antiplatelet therapy (DAPT) and de-escalation in a network meta-analysis using standard DAPT as common comparator. BACKGROUND: In patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI), shortening DAPT and de-escalating to a lower potency regimen mitigate bleeding risk. These strategies have never been randomly compared. METHODS: Randomized trials of DAPT modulation strategies in patients with ACS undergoing PCI were identified. All-cause death was the primary outcome. Secondary outcomes included net adverse cardiovascular events (NACE), major adverse cardiovascular events, and their components. Frequentist and Bayesian network meta-analyses were conducted. Treatments were ranked on the basis of posterior probability. Sensitivity analyses were performed to explore sources of heterogeneity. RESULTS: Twenty-nine studies encompassing 50,602 patients were included. The transitivity assumption was fulfilled. In the frequentist indirect comparison, the risk ratio (RR) for all-cause death was 0.98 (95% CI: 0.68-1.43). De-escalation reduced the risk for NACE (RR: 0.87; 95% CI: 0.70-0.94) and increased major bleeding (RR: 1.54; 95% CI: 1.07-2.21). These results were consistent in the Bayesian meta-analysis. De-escalation displayed a >95% probability to rank first for NACE, myocardial infarction, stroke, stent thrombosis, and minor bleeding, while short DAPT ranked first for major bleeding. These findings were consistent in node-split and multiple sensitivity analyses. CONCLUSIONS: In patients with ACS undergoing PCI, there was no difference in all-cause death between short DAPT and de-escalation. De-escalation reduced the risk for NACE, while short DAPT decreased major bleeding. These data characterize 2 contemporary strategies to personalize DAPT on the basis of treatment objectives and risk profile.

Duration of dual antiplatelet therapy and subsequent monotherapy type in patients undergoing drug-eluting stent implantation: a network meta-analysis.

AIMS: To compare the safety and efficacy of very short (≤3 months), short (6 months), standard (12 months), and extended (>12 months) dual antiplatelet therapy (DAPT), and of subsequent monotherapies, after coronary drug-eluting stent (DES) implantation. METHODS AND RESULTS: Twenty-two randomized control trials (n = 110 059 patients/year) were selected and included in a Bayesian network meta-analysis. The primary efficacy endpoint (PEP) was a composite of cardiac death, myocardial infarction (MI), and stent thrombosis (ST), with each of the components of the PEP being a secondary efficacy endpoint. The primary safety endpoint was major bleeding rate. Compared to standard, we found a lower rate of MI [odds ratio (OR) 0.56, 95% confidence interval (CI) 0.44-0.77] in extended, a lower rate of major bleeding (OR 0.61, 95% CI 0.39-0.87) in very short, and a lower rate of any bleeding (OR 0.61, 95% CI 0.38-0.90) in short DAPT. All DAPT durations were comparable regarding the secondary efficacy endpoints. Very short DAPT followed by P2Y12 inhibition was the treatment of choice to reduce both major bleeding and MI. In the ACS subgroup, extended DAPT (as compared to standard) reduced PEP and ST rates (but not MIs). CONCLUSION: The efficacy of short and very short is comparable with that of standard DAPT after DES implantation, whereas extended DAPT reduces MI rate. Very short DAPT is associated with lower haemorrhagic events and, followed by a P2Y12 inhibitor monotherapy, should be preferred in order to pursue a trade-off between major bleeding and ischaemic events.

Update on Cilostazol: A Critical Review of Its Antithrombotic and Cardiovascular Actions and Its Clinical Applications.

Cilostazol, a phosphodiesterase III inhibitor, has vasodilating and antiplatelet properties with a low rate of bleeding complications. It has been used over the past 25 years for improving intermittent claudication in patients with peripheral artery disease (PAD). Cilostazol also has demonstrated efficacy in patients undergoing percutaneous revascularization procedures for both PAD and coronary artery disease. In addition to its antithrombotic and vasodilating actions, cilostazol also inhibits vascular smooth muscle cell proliferation via phosphodiesterase III inhibition, thus mitigating restenosis. Accumulated evidence has shown that cilostazol, due to its "pleiotropic" effects, is a useful, albeit underutilized, agent for both coronary artery disease and PAD. It is also potentially useful after ischemic stroke and is an alternative in those who are allergic or intolerant to classical antithrombotic agents (eg, aspirin or clopidogrel). These issues are herein reviewed together with the pharmacology and pharmacodynamics of cilostazol. Large studies and meta-analyses are presented and evaluated. Current guidelines are also discussed, and the spectrum of cilostazol's actions and therapeutic applications are illustrated.