Trends in Dual Antiplatelet Therapy of Aspirin and Clopidogrel and Outcomes in Ischemic Stroke Patients Noneligible for POINT/CHANCE Trial Treatment.

BACKGROUND: Recent clinical trials established the benefit of dual antiplatelet therapy with aspirin and clopidogrel (DAPT-AC) in early-presenting patients with minor ischemic stroke. However, the impact of these trials over time on the use and outcomes of DAPT-AC among the patients with nonminor or late-presenting stroke who do not meet the eligibility criteria of these trials has not been delineated. METHODS AND RESULTS: In a multicenter stroke registry, this study examined yearly changes from April 2008 to August 2022 in DAPT-AC use for stroke patients ineligible for CHANCE/POINT (Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events/Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke) clinical trials due to National Institutes of Health Stroke Scale >4 or late arrival beyond 24 hours of onset. A total of 32 118 patients (age, 68.1±13.1 years; male, 58.5%) with National Institutes of Health Stroke Scale of 4 (interquartile range, 1-7) were analyzed. In 2008, DAPT-AC was used in 33.0%, other antiplatelets in 62.7%, and no antiplatelet in 4.3%. The frequency of DAPT-AC was relatively unchanged through 2013, when the CHANCE trial was published, and then increased steadily, reaching 78% in 2022, while other antiplatelets decreased to 17.8% in 2022 (Ptrend<0.001). From 2011 to 2022, clinical outcomes nonsignificantly improved, with an average relative risk reduction of 2%/y for the composite of stroke, myocardial infarction, and all-cause mortality, both among patients treated with DAPT-AC and patients treated with other antiplatelets. CONCLUSIONS: Use of DAPT-AC in stroke patients with stroke ineligible for recent DAPT clinical trials increased markedly and steadily after CHANCE publication in 2013, reaching deployment in nearly 4 of every 5 patients by 2022. The secondary prevention in patients with ischemic stroke seems to be gradually improving, possibly due to the enhancement of risk factor control.

Prognostic Impact of CYP2C19 Genotypes on Long-Term Clinical Outcomes in Older Patients After Percutaneous Coronary Intervention.

BACKGROUND: Carriers of CYP2C19 loss-of-function alleles have increased adverse events after percutaneous coronary intervention, but limited data are available for older patients. We aimed to evaluate the prognostic impact of CYP2C19 genotypes on clinical outcomes in older patients after percutaneous coronary intervention. METHODS AND RESULTS: The study included 1201 older patients (aged ≥75 years) who underwent percutaneous coronary intervention and received clopidogrel-based dual antiplatelet therapy in South Korea. Patients were grouped on the basis of CYP2C19 genotypes. The primary outcome was 3-year major adverse cardiac events, defined as a composite of cardiac death, myocardial infarction, and stent thrombosis. Older patients were grouped into 3 groups: normal metabolizer (36.6%), intermediate metabolizer (48.1%), and poor metabolizer (15.2%). The occurrence of the primary outcome was significantly different among the groups (3.1, 7.0, and 6.2% in the normal metabolizer, intermediate metabolizer, and poor metabolizer groups, respectively; P=0.02). The incidence rate of all-cause death at 3 years was greater in the intermediate metabolizer and poor metabolizer groups (8.1% and 9.2%, respectively) compared with that in the normal metabolizer group (3.5%, P=0.03) without significant differences in major bleeding. In the multivariable analysis, the intermediate metabolizer and poor metabolizer groups were independent predictors of 3-year clinical outcomes. CONCLUSIONS: In older patients, the presence of any CYP2C19 loss-of-function allele was found to be predictive of a higher incidence of major adverse cardiac events within 3 years following percutaneous coronary intervention. This finding suggests a need for further investigation into an optimal antiplatelet strategy for older patients. REGISTRATION: URL: https://clinicaltrials.gov. Identifier: NCT04734028.

Safety of Clopidogrel vs. Ticagrelor in Dual Antiplatelet Therapy Regimens for High-Bleeding Risk Acute Coronary Syndrome Patients: A Comprehensive Meta-analysis of Adverse Outcomes.

INTRODUCTION: Patients of acute coronary syndrome (ACS) at a high-bleeding risk (HBR) often require dual antiplatelet therapy (DAPT) to reduce the risk of recurrent cardiovascular events. Clopidogrel and ticagrelor are the most commonly used antiplatelet agents in DAPT regimens. However, the safety profiles of these drugs in ACS patients at HBR remain a subject of ongoing debate. AIM: To investigate any difference between the safety of clopidogrel and ticagrelor used as a part of DAPT regimen in ACS patients at HBR. METHODS: A systematic search on PubMed, Cochrane Library, and Google Scholar was conducted to identify experimental and observational studies published up to the knowledge cutoff date in September 2023. Studies comparing the safety of clopidogrel and ticagrelor in ACS patients at HBR were included for analysis. The primary outcomes assessed were major bleeding events, stroke, and myocardial infarction (MI), while secondary outcomes included all-cause mortality, major adverse cardiac and cerebrovascular events (MACCE), and net adverse clinical and cerebral events (NACCE). RESULTS: We included a total of 8 observational studies in our meta-analysis. The pooled analysis revealed a statistically significant increase in the risk of MI (pooled RR = 1.43; 95% CI 1.12-1.83; P = 0.005) in the patients using clopidogrel. There were no statistically significant differences in major bleeding events (pooled RR = 0.94; 95% CI 0.82-1.09; P = 0.44), stroke (pooled RR = 1.36; 95% CI 0.86-2.14; P = 0.18), all-cause mortality (pooled RR = 1.17; 95% CI 0.97-1.41; P = 0.10), MACCE (pooled RR = 1.07; 95% CI 0.76-1.50; P = 0.69) and NACCE (pooled RR = 0.95; 95% CI 0.66-1.37; P = 0.78) between the two groups. Subgroup analyses based on region were performed. CONCLUSION: Both drugs are generally safe for treating ACS patients with HBR at baseline, although a higher risk of MI was observed with the use of clopidogrel. Nevertheless, drug choice should factor in regional variations, patient-specific characteristics, cost, accessibility, and potential drug interactions.

Efficacy and safety of proton pump inhibitors on cardiovascular events and inflammatory factors in patients with upper gastrointestinal bleeding undergoing dual antiplatelet therapy.

BACKGROUND: This work evaluated the effects of proton pump inhibitors (PPIs) on cardiovascular events (CVEs) and inflammatory factors in patients with upper gastrointestinal bleeding (UGIB) undergoing dual antiplatelet therapy (DAPT) after percutaneous coronary intervention. Clinical data from these patients were analysis, intending to provide relevant theoretical evidence for clinical practice. MATERIALS AND METHODS: Data of 166 patients who underwent percutaneous coronary intervention and developed UGIB while on DAPT at The First People' Hospital of Linping District from April 2021 to April 2023 were retrospectively analyzed. The patients were rolled into two groups: those who received PPI treatment and those who did not, namely, PPI and non-PPI group, respectively. Furthermore, occurrence of CVEs and the levels of inflammatory factors of patients in all groups were statistically analyzed. RESULTS: In patients with UGIB, melena is a common presentation. The incidence of CVE in the PPI group showed no statistically significant difference compared to the control group, and there was no significant variance observed in the distribution of CVE incidence among different PPIs. However, levels of C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α) were significantly lower in the PPI group compared to the non-PPI group (P < 0.05). CONCLUSION: Melena was the most frequent clinical manifestation in UGIB patients. The use of PPIs did not increase the risk of CVEs, and different PPI drugs did not affect the occurrence of CVEs. Furthermore, PPIs lowered CRP and TNF-α levels in serum of these patients.

Net clinical benefit of extended dual pathway inhibition according to baseline risk in patients with chronic coronary syndrome: a COMPASS substudy.

AIMS: Guidelines recommend extended dual pathway inhibition (DPI) with aspirin and rivaroxaban in patients with chronic coronary syndrome (CCS) at high ischaemic risk. The CHADS-P2A2RC score improves risk prediction and enables antithrombotic treatment allocation in these patients. This study evaluated the net clinical benefit of DPI treatment according to baseline risk as classified by the CHADS-P2A2RC score in patients with CCS included in the COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial. METHODS AND RESULTS: COMPASS patients with CCS (n = 14 670), randomized to aspirin alone or DPI, were stratified according to cardiovascular risk using the CHADS-P2A2RC score. Endpoints were major adverse cardiovascular events (MACE), all-cause death, fatal/critical organ bleeding, and composite adverse events (MACE and bleeding). Net clinical benefit was the 30-month risk difference of MACE and bleeding. Thirty-month incidences of MACE [7.9% vs. 3.9%, hazard ratio (HR) 2.01, 95% confidence interval (CI) 1.83-2.18] and fatal/critical organ bleeding (1.2% vs. 0.8%, HR 1.49, 95% CI 1.06-1.92) were higher in high-risk (CHADS-P2A2RC ≥ 4) than in low/moderate-risk (CHADS-P2A2RC < 4) patients. DPI reduced MACE (low/moderate risk: HR 0.62, 95% CI 0.47-0.82; high risk: HR 0.82, 95% CI 0.68-0.99, P for interaction 0.09) and all-cause death (low/moderate risk: HR 0.65, 95% CI 0.46-0.91; high risk: HR 0.81, 95% CI 0.65-1.00, P for interaction 0.29), without substantially increasing fatal/critical organ bleeding (low/moderate risk: HR 1.35, 95% CI 0.72-2.53; high risk: HR 1.18, 95% CI 0.73-1.90, P for interaction 0.73). DPI provided net clinical benefit of similar magnitude in low/moderate-risk (-1.81%, 95% CI -3.00 to -0.62) and high-risk (-1.96%, 95% CI -3.60 to -0.33) CCS patients. CONCLUSION: As classified by the CHADS-P2A2RC score, low/moderate- and high-risk patients with CCS derived similar net clinical benefit and reduction in all-cause death from DPI treatment.

Association of antiplatelet therapy with clinical outcomes in patients with peripheral artery disease.

BACKGROUND: The beneficial role of dual anti-platelet therapy (DAPT) in coronary artery disease is well established. However, there is limited data describing the effects of DAPT in patients with atherosclerotic peripheral artery disease (PAD). The aim of this meta-analysis is to compare clinical outcomes associated with DAPT versus single anti-platelet therapy (SAPT) in patients with symptomatic PAD. METHODS: We performed a literature search for studies assessing the risk of adverse cardiovascular and limb events in cohorts receiving either DAPT or SAPT. The primary endpoint was all cause mortality. The secondary endpoints included graft failure, amputation, total bleeding, severe bleeding and fatal bleeding. The search included the following databases: Ovid MEDLINE, EMBASE, Web of Science, and Google Scholar. The search was not restricted to time or publication status. RESULTS: A total of 11 studies with 54,331 participants (24,449 on SAPT and 29,882 on DAPT) were included. Patients with PAD treated with SAPT had higher all-cause mortality compared to patients treated with DAPT (OR 1.37, 95 % CI 1.09-1.74; p < 0.01). There was no difference in risk of graft failure or amputation between patients treated with SAPT or DAPT (OR 0.9, 95 % CI 0.77-1.06; p = 0.19; OR 1.11, 95 % CI 0.88-1.41; p = 0.37). Patients treated with SAPT had lower total bleeds compared to patients treated with DAPT (OR 0.53, 95 % CI 0.36-0.77; p < 0.01). However, For SAPT plus AC vs SAPT, a total of 8 studies with 17,100 participants (3447 with SAPT plus AC and 8619 with only SAPT) were included. Patients on SAPT plus AC did not have a statistically significant difference in risk for all-cause mortality, (OR 0.91, 95 % CI 0.67-1.24; p = 0.56). SAPT plus AC had significantly lower risk of MI (OR 0.82, 95 % CI 0.69-0.97; p = 0.02), amputation (OR 0.72, 95 % CI 0.53-0.97; p = 0.03), and graft failure (OR 0.66, 95 % CI 0.48-0.93; p = 0.02). There was no significant different in risk of fatal bleeding be-tween the two groups (OR 1.60, 95 % CI 0.76-3.35; p = 0.22). CONCLUSIONS: In patients with symptomatic PAD, a strategy of DAPT may confer a mortality benefit when compared to SAPT without significantly increasing the risk of serious bleeding events.

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.

One year clinical outcome of dual anti-platelet therapy with the Novel Ticagrelor plus Aspirin versus Clopidogrel plus Aspirin for Endovascular Intervention of patients with Intracranial Aneurysm: A meta-analysis.

BACKGROUND: The use of stents to treat un-ruptured intracranial aneurysms was first approved in the year 2002 in the United States as a Humanitarian Device Exemption. Antiplatelet therapy is mandatory following stent placement. Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel has been the first line agents for the prevention of thromboembolic events following neuro-endovascular procedures. However, clopidogrel hypo-responsiveness has often been observed. In this analysis, we aimed to systematically compare one year clinical outcome of DAPT with the Novel Ticagrelor plus Aspirin versus Clopidogrel plus Aspirin for Endovascular Intervention of patients with Intracranial Aneurysm. METHODS: Online electronic databases were searched from June 2023 till July 2023 for relevant studies which compared DAPT with ticagrelor or clopidogrel for endovascular intervention in patients with intracranial aneurysm. The endpoints which were analyzed were classified into thromboembolic and hemorrhagic events. A fixed and a random effect statistical model were used during data analysis respectively. Risk ratio (RR) with 95 % confidence interval (CI) was used to represent the data following analysis. RESULTS: Five studies with a total number of 893 participants were included in this analysis. Three hundred and fifty eight (358) participants were assigned to the ticagrelor group whereas 535 participants were assigned to clopidogrel group. Participants' enrollment period ranged from the year 2009 to 2019. Our results showed that during a mean follow-up time period of one year, DAPT with ticagrelor was associated with significantly lower thromboembolic events with RR: 0.33, 95 % CI: 0.16 - 0.68; P = 0.003. In addition, at one year, DAPT with ticagrelor was not associated with any increase in hemorrhagic events (RR: 0.66, 95 % CI: 0.29 - 1.50; P = 0.32) when compared to DAPT with clopidogrel. CONCLUSION: At one year, DAPT with ticagrelor was associated with significantly lower thromboembolic events without any increase in hemorrhagic events when compared to clopidogrel associated DAPT for endovascular intervention of patients with intracranial aneurysm. However, even though ticagrelor-associated DAPT use appeared to be more effective and safe, this hypothesis should only be confirmed in larger upcoming trials.

Validation of prediction tools for GI bleeding in patients on dual anti-platelet therapy after percutaneous coronary intervention.

BACKGROUND AND AIMS: The management of dual anti-platelet therapy after percutaneous coronary intervention (PCI) and GI bleeding (GIB) remains a clinical dilemma. We sought to identify predictors of GIB and recurrent bleeding and to determine whether recurrent bleeding increases the risk of major adverse cardiovascular events (MACEs). METHODS: In this single-center retrospective study, patients undergoing PCI were identified. The primary and secondary endpoints were GIB at 180 days and recurrent bleeding or MACE at 365 days. Logistic regression was used to identify predictors of GIB and recurrent bleeding. Cox proportional hazards modeling was used to determine whether recurrent bleeding can predict a MACE. RESULTS: Five hundred thirty-six patients were included. On multivariable analysis, PCI for acute coronary syndrome was associated with a 95% increased odds of GIB (P < .001). The P2Y12 inhibitor was continued in >90% of patients, which trended toward significance for recurrent bleeding (P < .10). The HAS-BLED score (Hypertension, Abnormal renal and liver function, Stroke, Bleeding tendency or predisposition, Labile INRs, Elderly, Drugs), including a labile international normalized ratio and prior major bleeding, was strongly associated with recurrent bleeding (P ≤ .009). Recurrent bleeding was associated with a 115% increased risk of MACEs (P = .02). We derived a novel risk score, named the SIGE score ([S]TEMI at PCI, having a labile [I]NR at PCI, index [G]IB within 180 days of PCI, and previous precatheterization [E]ndoscopy within 6 months), to predict recurrent bleeding at 365 days with a high predictive accuracy (area under the curve, .773; 95% confidence interval, .702-.845). CONCLUSIONS: The SIGE score may help to predict recurrent bleeding, which was shown to be associated with an increased risk of MACEs. Further external validation is needed.

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.

Temporal variations in ischemic and bleeding event risks after acute coronary syndrome during dual antiplatelet therapy.

BACKGROUND: This study estimates the temporal risk variations of ischemic and bleeding events during dual antiplatelet therapy (DAPT) among patients stratified according to the Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria, suggesting the optimal period for DAPT after acute coronary syndrome (ACS). METHODS: A total of 1264 ACS patients receiving either clopidogrel or prasugrel with aspirin were classified by ARC-HBR; HBR (n = 574) and non-HBR groups (n = 690). This study was designed as a multicenter observation to evaluate the primary endpoints of ischemic, including cardiovascular death, myocardial infarction, or ischemic stroke, and bleeding events, defined as Bleeding Academic Research Consortium type 3/5. The temporal risk variations were estimated using the Cox hazard and Royston-Parmar models. RESULTS: Ischemic and bleeding events were observed in 9.4% and 7.4%, respectively, during an average observation period of 313 days. The HBR group had a higher incidence of both events than the non-HBR group (15.3% vs. 4.5%, P < 0.01 for ischemic; 11.9% vs. 3.8%, P < 0.01 for bleeding). The estimated risk curves for both events revealed peaks and steep declines in the first few days, followed by constant declines. The peak of risk was higher for bleeding than for ischemic events, but this relationship reversed early, with ischemic events displaying a higher risk in both the HBR and non-HBR groups until at least 60 days. CONCLUSIONS: A 60-day period of DAPT is appropriate to balance the risks of adverse events after ACS, regardless of ARC-HBR criteria.

Defining Strategies of Modulation of Antiplatelet Therapy in Patients With Coronary Artery Disease: A Consensus Document from the Academic Research Consortium.

Antiplatelet therapy is the mainstay of pharmacologic treatment to prevent thrombotic or ischemic events in patients with coronary artery disease treated with percutaneous coronary intervention and those treated medically for an acute coronary syndrome. The use of antiplatelet therapy comes at the expense of an increased risk of bleeding complications. Defining the optimal intensity of platelet inhibition according to the clinical presentation of atherosclerotic cardiovascular disease and individual patient factors is a clinical challenge. Modulation of antiplatelet therapy is a medical action that is frequently performed to balance the risk of thrombotic or ischemic events and the risk of bleeding. This aim may be achieved by reducing (ie, de-escalation) or increasing (ie, escalation) the intensity of platelet inhibition by changing the type, dose, or number of antiplatelet drugs. Because de-escalation or escalation can be achieved in different ways, with a number of emerging approaches, confusion arises with terminologies that are often used interchangeably. To address this issue, this Academic Research Consortium collaboration provides an overview and definitions of different strategies of antiplatelet therapy modulation for patients with coronary artery disease, including but not limited to those undergoing percutaneous coronary intervention, and consensus statements on standardized definitions.

Outcomes with P2Y12 inhibitor monotherapy after PCI according to bleeding risk: A Bayesian meta-analysis.

BACKGROUND: P2Y12 inhibitor monotherapy is a promising novel strategy to reduce bleeding complications compared to dual antiplatelet therapy (DAPT) in patients undergoing percutaneous coronary intervention (PCI). In order to personalise treatment with DAPT based on patients' bleeding risk, we compared outcomes after PCI between P2Y12 inhibitor monotherapy and DAPT according to bleeding risk. METHODS: A search for randomized clinical trials (RCTs) comparing P2Y12 inhibitor monotherapy after a short period of DAPT to standard DAPT after PCI was performed. Outcome differences between treatment groups regarding major bleedings, major adverse cardiac and cerebral events (MACCE) and net adverse clinical events (NACE) were assessed with hazard ratios (HRs) and corresponding credible intervals (CrI) according a Bayesian random effects model in patients with and without high bleeding risk (HBR). RESULTS: Five RCTs including 30,084 patients were selected. P2Y12 inhibitor monotherapy compared to DAPT reduced major bleedings in the total population (HR: 0.65, 95 % CrI: 0.44 to 0.92). The HRs of the HBR and non-HBR subgroups showed a similar reduction of bleedings for monotherapy (HBR: HR 0.66, 95 % CrI: 0.25 to 1.74; non-HBR: HR 0.63, 95 % CrI: 0.36 to 1.09). No notable differences between treatments on MACCE and NACE were observed in either sub-group or in the total population. CONCLUSIONS: Regardless of bleeding risk, P2Y12 inhibitor monotherapy is the favourable choice after PCI regarding major bleedings and does not increase ischemic events compared to DAPT. This suggests that bleeding risk is not decisive when considering P2Y12 inhibitor monotherapy.

Five-Year Prognostic Value of DAPT Score in Older Patients undergoing Percutaneous Coronary Intervention: A Large-Sample Study in the Real World.

AIM: The dual-antiplatelet therapy (DAPT) score is recommended for predicting the risk of ischemia and bleeding for patients undergoing percutaneous coronary intervention (PCI). This study aimed to investigate the long-term prognostic value of the DAPT score in older PCI patients. METHODS: This study enrolled 10,724 consecutive patients who underwent PCI from January 2013 to December 2013 in Fu Wai hospital, among whom 2,981 (27.8%) were aged ≥ 65 years. The ischemic endpoint was major adverse cardiovascular and cerebrovascular events (MACCE, including myocardial infarction, all-cause death, and stroke). The bleeding endpoint was Bleeding Academic Research Consortium (BARC) 2, 3, or 5 bleeding. RESULTS: After a 5-year follow-up, 256 (12.0%) MACCEs and 53 (2.5%) BARC 2, 3, or 5 bleeding occurred. The patients were divided into two groups according to the DAPT score: the low-score (＜2, n=1,646) and high-score (≥ 2, n=485) group. Multivariate Cox regression revealed that the risk of MACCE was similar between the two groups [hazard ratio (HR): 1.214, 95% confidence interval (CI): 0.916-1.609, P=0.178], whereas the risk of bleeding was significantly higher in the high-score group than in the low-score group (HR: 2.447, 95% CI: 1.407-4.257, P=0.002). The DAPT score did not show prognostic value in MACCE [area under the receiver operating characteristic curve (AUROC), 0.534; 95% CI: 0.496-0.572, P=0.079]; however, it demonstrated a certain prognostic value in BARC 2, 3, or 5 bleeding (AUROC, 0.646; 95% CI: 0.573-0.719, P＜0.001). CONCLUSION: This study suggested that in older PCI patients, the DAPT score did not show predictive value for MACCE; however, it had a certain predictive value for 5-year BARC 2, 3, or 5 bleeding.

Comparison of De-escalation of DAPT Intensity or Duration in East Asian and Western Patients with ACS Undergoing PCI: A Systematic Review and Meta-analysis.

BACKGROUND: Guideline-recommended dual antiplatelet therapy (DAPT; aspirin plus prasugrel/ticagrelor) for 12 months in acute coronary syndrome (ACS) patients increases bleeding, with East Asians (EAs) exhibiting higher bleeding and lower ischemic risk, compared with non-East Asians (nEAs). We sought to compare DAPT "de-escalation" strategies in EA and nEA populations. METHODS: A systematic review and meta-analysis of randomized controlled trials assessing reduction of DAPT intensity or duration in ACS patients undergoing percutaneous coronary intervention, in EA and nEA, was performed using a random-effects model. RESULTS: Twenty-three trials assessed reduction of DAPT intensity (n = 12) or duration (n = 11). Overall, reduced DAPT intensity attenuated major bleeding (odds ratio [OR]: 0.78, 95% confidence interval [CI]: 0.65-0.94, p = 0.009), without impacting net adverse cardiovascular events (NACE) or major adverse cardiovascular events (MACE). In nEA, this increased MACE (OR: 1.20, 95% CI: 1.09-1.31, p < 0.0001) without impacting NACE or bleeding; while in EA, it reduced major bleeding (OR: 0.71, 95% CI: 0.53-0.95, p = 0.02) without affecting NACE or MACE. Overall, abbreviation of DAPT duration reduced NACE (OR: 0.90, 95% CI: 0.82-0.99, p = 0.03) due to major bleeding (OR: 0.69, 95% CI: 0.53-0.99, p = 0.006), without impacting MACE. In nEA, this strategy did not impact NACE, MACE, or major bleeding; while in EA, it reduced major bleeding (OR: 0.60, 95% CI: 0.4-0.91, p = 0.02) without impacting NACE or MACE. CONCLUSION: In EA, reduction of DAPT intensity or duration can minimize bleeding, without safety concerns. In nEA, reduction of DAPT intensity may incur an ischemic penalty, while DAPT abbreviation has no overall benefit.

Role of platelet function and genetic testing in patients undergoing percutaneous coronary intervention.

Dual antiplatelet therapy (DAPT) represents the standard of care for patients undergoing percutaneous coronary intervention (PCI). Increasing evidence indicates that a "one-size-fits-all" approach with the use of a standard DAPT regimen for all patients undergoing PCI could lead to either suboptimal efficacy or prohibitively high bleeding in specific cohorts of patients. Moreover, the broad interindividual variability in response to P2Y12 inhibitors can impact outcomes and resource utilization. Among the strategies proposed to provide a more balanced trade-off between bleeding and ischemic events at a single patient level, a guided selection of P2Y12 inhibitors, by using platelet function or genetic testing, has shown promising results. In this review, we provide a focused summary of the rationale and evidence on the use of platelet function and genetic testing-guided antiplatelet therapy, and we explore the implications for their use in the modern setting of patients undergoing 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.

Risk of Postdischarge Bleeding From Dual Antiplatelet Therapy After Percutaneous Coronary Intervention Among US Black and White Adults.

Background Dual antiplatelet therapy after percutaneous coronary intervention reduces myocardial infarctions but increases bleeding. The risk of bleeding may be higher among Black patients for unknown reasons. Bleeding risk scores have not been validated among Black patients. We assessed the difference in bleeding risk between Black and White patients along with the performance of the Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Anti Platelet Therapy, Patterns of Nonadherence to Antiplatelet Regimens in Stented Patients, and Academic Research Consortium for High Bleeding Risk scores among both groups. Methods and Results This was a single-center prospective study of patients who underwent percutaneous coronary intervention (2014-2019) and were followed for 1 year. The outcome was postdischarge Bleeding Academic Research Consortium 2 to 5 bleeding. Incidence rates were reported. Cox proportional hazards models measured the effect of self-reported Black race on bleeding and determined the predictors of bleeding among 19 a priori variables. The 3 risk scores were assessed among Black and White patients separately using the Harrell concordance index. Of 1529 included patients, 342 (22.4%) self-reported as being Black race. Unadjusted bleeding rates were 22.7 per 100 person-years among Black patients versus 16.3 among White patients (hazard ratio, 1.41 [95% CI, 1.00-2.00], P=0.052). Predictors of bleeding were age, glomerular filtration rate <30 mL/min per 1.73 m2, prior bleeding, ticagrelor or prasugrel use, and anticoagulant use. Among Black and White patients, respectively, the C-indexes were the following: 0.644 versus 0.600 for Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Anti Platelet Therapy (P<0.001 for both), 0.620 versus 0.612 for Patterns of Nonadherence to Antiplatelet Regimens in Stented Patients (P=0.003 and P<0.001, respectively), and 0.600 versus 0.598 for Academic Research Consortium for High Bleeding Risk (P=0.006 and P<0.001, respectively). Conclusions The risk of dual antiplatelet therapy-associated postdischarge Bleeding Academic Research Consortium 2 to 5 bleeding was not significantly different between self-reported Black and White patients. Bleeding risk scores performed similarly among both groups.