Myocardial Infarction Major Bleeding Research Articles

Clinical outcomes of adjusted-dose versus standard-dose prasugrel in East Asian patients with acute myocardial infarction

BackgroundThe comparative efficacy and safety of adjusted- and standard-dose prasugrel in East Asian patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI) remain unclear. This study aimed to comparatively assess the ischaemic and bleeding outcomes of adjusted-dose (maintenance dose: 3.75 mg) and standard-dose (maintenance dose: 10 mg) prasugrel in East Asian patients with AMI undergoing PCI. MethodsFrom a combined dataset sourced from nationwide AMI registries in Japan and South Korea (n = 17,118), patients treated with either adjusted- or standard-dose prasugrel were identified. Patients who did not undergo emergent PCI, those on oral anticoagulants, and those meeting the criteria of contraindication of prasugrel in South Korea (age ≥ 75 years, body weight < 60 kg, or history of stroke) were excluded. Major adverse cardiovascular events (MACE) and Thrombolysis in Myocardial Infarction (TIMI) major bleeding events were compared between the adjusted-dose (n = 1160) and standard-dose (n = 1086) prasugrel groups. ResultsWithin the propensity-matched cohort (n = 702 in each group), no significant difference was observed in the in-hospital MACE between the adjusted- and standard-dose prasugrel groups (1.85% vs. 2.71%, odds ratio [OR] 0.68, 95% confidence interval [CI] 0.33–1.38, p = 0.286). However, the incidence of in-hospital major bleeding was significantly lower in the adjusted-dose prasugrel group than in the standard-dose group (0.43% vs. 1.71%, OR 0.25, 95% CI 0.07–0.88, p = 0.031). The cumulative 12-month incidence of MACE was equivalent in both groups (4.70% vs. 4.70%, OR 1.00, 95% CI 0.61–1.64, p = 1.000). ConclusionsAmong East Asian patients with AMI undergoing PCI, those administered adjusted-dose prasugrel exhibited a lower risk of in-hospital bleeding events than those administered standard-dose prasugrel, while maintaining a comparable 1-year incidence of MACE.

One-Month Dual Antiplatelet Therapy Followed by P2Y12 Inhibitor Monotherapy After Biodegradable Polymer Drug-Eluting Stent Implantation - The REIWA Region-Wide Registry.

The safety and feasibility of using 1-month dual antiplatelet therapy (DAPT) followed by P2Y12inhibitor monotherapy for patients after percutaneous coronary intervention (PCI) with thin-strut biodegradable polymer drug-eluting stents (BP-DES) in daily clinical practice remain uncertain.Methods and Results: The REIWA region-wide registry is a prospective study conducted in 1 PCI center and 9 local hospitals in northern Japan. A total of 1,202 patients who successfully underwent final PCI using BP-DES (Synergy: n=400; Ultimaster: n=401; Orsiro: n=401), were enrolled in the registry, and received 1-month DAPT followed by P2Y12inhibitor (prasugrel 3.75 mg/day or clopidogrel 75 mg/day) monotherapy. The primary endpoint was a composite of cardiovascular and bleeding events at 12 months, including cardiovascular death, myocardial infarction (MI), definite stent thrombosis (ST), ischemic or hemorrhagic stroke, and Thrombolysis in Myocardial Infarction (TIMI) major or minor bleeding. Based on the results of a previous study, we set the performance goal at 5.0%. Over the 1-year follow-up, the primary endpoint occurred in 3.08% of patients, which was lower than the predefined performance goal (Pnon-inferiority<0.0001). Notably, definite ST occurred in only 1 patient (0.08%) within 1 year (at 258 days). No differences were observed in the primary endpoint between stent types. The REIWA region-wide registry suggests that 1-month DAPT followed by P2Y12inhibitor monotherapy is safe and feasible for Japanese patients with BP-DES.

Streptokinase-Based Pharmacoinvasive Strategy Versus Primary Percutaneous Coronary Intervention: A Propensity Score Matching Analysis from the Siriraj STEMI Network

Objective: To investigate the efficacy and safety of pharmacoinvasive (PI) strategy compared to primary percutaneous coronary intervention (PPCI) in the setting of a real-world ST-elevation myocardial infarction (STEMI) network where streptokinase (SK) is predominantly prescribed. Materials and Methods: The authors analyzed 325 STEMI patients who participated in The Siriraj STEMI network between July 2015 and October 2020. The primary efficacy endpoint was the incidence of cumulative major adverse cardiovascular and cerebrovascular events (MACCE) at one month, which were the composite of death, myocardial infarction, stroke, and non-coronary artery bypass graft (CABG)-related thrombolysis in myocardial infarction (TIMI) major or minor bleeding. The safety endpoint was non-CABG-related TIMI major or minor bleeding during the index hospitalization. Cox regression was performed for survival analysis. The authors applied propensity score matching to reduce the bias of the confounding variables. Results: Two hundred four patients received fibrinolytic therapy, 191 (93.6%) obtained SK, and 121 participants underwent PPCI. After propensity score matching analysis, the incidence of cumulative MACCE at one-month follow-up was not significantly different between the PI and the PPCI group (p=0.726) as well as the incidence of bleeding endpoint (p=0.446). In the subgroup analysis of the 191 patients who received SK (SK-PI), there was no statistical difference in the occurrence of cumulative MACCE compared to PPCI (p=0.136). Killip classification class III (hazard ratio [HR] 7.50, 95% confidence interval [CI] 3.25 to 17.31, p&lt;0.001), and class IV (HR 9.78, 95% CI 4.31 to 22.21, p&lt;0.001) were independent risk factors for developing MACCE. Conclusion: The streptokinase-based pharmacoinvasive strategy is non-statistically different in terms of efficacy and safety compared to PPCI. This evidence supports the utilization of the SK-PI approach in low- to middle-income countries where the availability of fibrin-specific fibrinolytic agents is often limited. Keywords: Revascularization strategy; Acute coronary syndrome; Fibrinolytic therapy

Sex‐Based Differences in Outcomes Following Peripheral Artery Revascularization: Insights From VOYAGER PAD

BackgroundDespite high female prevalence of peripheral artery disease (PAD), little is known about sex‐based outcomes after lower extremity revascularization (LER) for symptomatic PAD. The effects of rivaroxaban according to sex following LER have not been fully reported.Methods and ResultsIn VOYAGER PAD (Vascular Outcomes Study of ASA [acetylsalicylic acid] Along with Rivaroxaban in Endovascular or Surgical Limb Revascularization for Peripheral Artery Disease), low‐dose rivaroxaban versus placebo on a background of aspirin reduced the composite primary efficacy outcome of cardiovascular and limb events in patients with PAD undergoing LER. Unplanned index limb revascularization was prespecified and prospectively ascertained. The primary safety outcome was Thrombolysis in Myocardial Infarction major bleeding. Analyses of outcomes and treatment effects by sex were performed using Cox proportional hazards models. Among 6564 randomly assigned patients followed for a median of 28 months, 1704 (26.0%) were women. Among patients administered placebo, women were at similar risk for the primary efficacy outcome (hazard ratio [HR], 0.90; [95% CI, 0.74–1.09]; P=0.29) as men, while female sex was associated with a trend toward higher risk of unplanned index limb revascularization (HR, 1.18; [95% CI, 1.00–1.40]; P=0.0499). Irrespective of sex, effects of rivaroxaban were consistent for the primary efficacy outcome (P‐interaction=0.22), unplanned index limb revascularization (P‐interaction=0.64), and bleeding (P‐interaction=0.61). Women were more likely than men to discontinue study treatment (HR, 1.13; [95% CI, 1.03–1.25]; P=0.0099).ConclusionsAmong >1700 women with PAD undergoing LER, women and men were at similar risk for the primary outcome, but a trend for greater risk of unplanned index limb revascularization among women was observed. Effects of rivaroxaban were consistent by sex, though women more often discontinued treatment. Better understanding of sex‐based outcomes and treatment adherence following LER is needed.RegistrationURL: http://clinicaltrials.gov; Unique identifier: NCT02504216.

The Incidence and Impact of In-Hospital Bleeding in Patients with Acute Coronary Syndrome during the COVID-19 Pandemic.

Background: The COVID-19 pandemic increased the complexity of the clinical management and pharmacological treatment of patients presenting with an Acute Coronary Syndrome (ACS). Aim: to explore the incidence and prognostic impact of in-hospital bleeding in patients presenting with ACS before and during the COVID-19 pandemic. Methods: We evaluated in-hospital Thrombolysis In Myocardial Infarction (TIMI) major and minor bleeding among 2851 patients with ACS from 17 Italian centers during the first wave of the COVID-19 pandemic (i.e., March–April 2020) and in the same period in the previous two years. Results: The incidence of in-hospital TIMI major and minor bleeding was similar before and during the COVID-19 pandemic. TIMI major or minor bleeding was associated with a significant threefold increase in all-cause mortality, with a similar prognostic impact before and during the COVID-19 pandemic. Conclusions: the incidence and clinical impact of in-hospital bleeding in ACS patients was similar before and during the COVID-19 pandemic. We confirmed a significant and sizable negative prognostic impact of in-hospital bleeding in ACS patients.

Effect of Platelet Inhibition by Cangrelor Among Obese Patients Undergoing Coronary Stenting: Insights From CHAMPION.

In randomized trials, cangrelor reduced periprocedural ischemic events related to percutaneous coronary intervention without increasing GUSTO severe bleeding. However, some antiplatelet agents have shown a differential treatment effect by body mass index (BMI). Patients from the 3 CHAMPION trials (Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition) who were randomized to cangrelor versus clopidogrel during percutaneous coronary intervention were stratified by BMI. The primary efficacy end point was a composite of death, myocardial infarction, ischemia-driven revascularization, or stent thrombosis within 48 hours. The principal safety outcome was GUSTO moderate or severe bleeding at 48 hours, although more sensitive bleeding measures such as Thrombolysis in Myocardial Infarction major bleeding were also assessed. We examined obese patients (defined as BMI≥30) versus nonobese patients. There were 24 893 patients, with 8979 (36.1%) having BMI of ≥30. There was no significant difference in the primary efficacy end point among obese versus nonobese patients (4.3% versus 4.2%; rate ratio, 1.01 [95% CI, 0.89-1.15]; P=0.82). There was a consistent benefit in the primary efficacy end point in patients who received cangrelor versus placebo who were obese (3.9% versus 4.7%, rate ratio, 0.83 [95% CI, 0.68-1.02]; P=0.07) and not obese (3.8% versus 4.7%; rate ratio, 0.81 [95% CI, 0.69-0.94]; P=0.0053); interaction P=0.77. There was no difference in GUSTO moderate or severe bleeding among patients who received cangrelor versus placebo who were obese (0.6% versus 0.6%; rate ratio, 0.99 [95% CI, 0.58-1.67]; P=0.96). Cangrelor at the time of percutaneous coronary intervention is effective and safe in obese and nonobese patients. There was no difference in short-term efficacy between obese and nonobese patients. Periprocedural cangrelor is an effective and safe antiplatelet agent, irrespective of BMI. URL: https://www. gov; Unique identifier: NCT01156571, NCT00385138, NCT00305162.

Network meta-analysis and trial sequential analysis for atrial fibrillation patients receiving PCI or with ACS.

In patients with atrial fibrillation (AF) and acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI), choosing the most appropriate antithrombotic treatment remains a dilemma. We aimed to compare the relative efficacy and safety outcomes of antithrombotic drugs in patients with AF after undergoing PCI or ACS. Randomized controlled trials were systematically searched on PubMed, EMBASE, and the Cochrane Library. Five studies (11,532 patients) were included in the network meta-analysis. Trial sequential analysis (TSA) was performed to assess the reliability and conclusiveness of the meta-analysis comparing the dual antithrombotic therapy strategies with the triple antithrombotic therapy strategy. Compared with vitamin K antagonist + dual antiplatelet therapy, novel oral anticoagulant (NOAC) + P2Y12 inhibitor was associated with a significantly better trial-defined primary safety outcome (odds ratio: 0.53; 95% CI, 0.31-0.90) and the lowest probability of thrombolysis in myocardial infarction major bleeding and intracranial hemorrhage using the cumulative ranking technique. In patients omitting aspirin, TSA demonstrated conclusive evidence with significant decreases in all safety outcomes and inconclusive evidence with a nonsignificant increase in in-stent thrombosis (risk ratio: 1.32; TSA-adjusted 95% CI, 0.54-3.24) and myocardial infarction (risk ratio: 1.19; TSA-adjusted 95% CI, 0.84-1.68). In patients with AF receiving PCI or with ACS, NOAC + P2Y12 inhibitor was associated with the lowest bleeding risk but resulted in a statistically nonsignificant, numerically greater risk for stent thrombosis and myocardial infarction, suggesting that triple antithrombotic therapy should still be an option for certain patients at a high risk of stent thrombosis or myocardial infarction.

Revascularisation for Symptomatic Peripheral Artery Disease: External Applicability of the VOYAGER PAD Trial

In the VOYAGER PAD trial, rivaroxaban 2.5 mg plus aspirin significantly reduced the primary composite efficacy outcome of acute limb ischaemia, major amputation, myocardial infarction, ischaemic stroke, or cardiovascular death compared with aspirin alone. However, patients enrolled in the trial may not reflect patients encountered in daily clinical practice. This study described the proportion of patients eligible for VOYAGER PAD within the nationwide Danish Vascular Registry (DVR), reasons for ineligibility, and outcomes according to eligibility. In total, 32 911 patients who underwent lower extremity revascularisation for symptomatic peripheral arterial disease (PAD) in the DVR (2000-2016) were identified. Trial inclusion and exclusion criteria were applied, and the three year cumulative incidence of primary and secondary trial outcomes was estimated. Altogether, 27.1% of patients with PAD in the DVR were "VOYAGER eligible". Of those not included, 30.7% had at least one exclusion criterion ("VOYAGER excluded"), and an additional 42.3% did not fulfil the inclusion criteria ("VOYAGER not included"). The main reasons for exclusion were atrial fibrillation (32.3%), poorly regulated hypertension (20.6%), requirement for long term dual antiplatelet therapy (10.9%), cytochrome P450 inhibitors or inducers (9.7%), and renal failure (9.3%). The three year rate of the primary efficacy outcome was 10.08 per 100 person years among the "VOYAGER eligible", 16.32 among "VOYAGER excluded", and 6.98 among the "VOYAGER not included". For the primary safety outcome of thrombolysis in myocardial infarction (TIMI) major bleeding, rates were 2.24, 3.76, and 1.17, respectively. Rates of secondary endpoints were also consistently lower for patients who did not meet the inclusion criteria (predominantly due to central aorto-iliac procedures) and highest for "VOYAGER excluded" patients. "VOYAGER eligible" patients experienced a higher cumulative incidence of most endpoints than patients enrolled in the control arm of the VOYAGER PAD trial. Among patients in routine clinical practice, 27.1% were eligible for the VOYAGER PAD trial. These patients were older, had more severe vascular symptoms, higher bleeding risk, and worse prognosis than trial participants.

Safety and Effectiveness of Paclitaxel Drug-Coated Devices in Peripheral Artery Revascularization: Insights From VOYAGER PAD

BackgroundPaclitaxel drug-coated devices (DCDs) were developed to improve lower extremity revascularization (LER) patency in peripheral artery disease (PAD) but have been associated with long-term mortality. ObjectivesThis study assessed DCD safety and effectiveness in LER for PAD. MethodsVOYAGER PAD (Vascular Outcomes Study of ASA [acetylsalicylic acid] Along with Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD) randomized patients with PAD who underwent LER to rivaroxaban or placebo. The primary VOYAGER PAD study efficacy and safety outcomes were composite cardiovascular and limb events and Thrombolysis In Myocardial Infarction major bleeding. For prespecified DCD analyses, primary safety and effectiveness outcomes were mortality and unplanned index limb revascularization (UILR). Major adverse limb events (MALE) were a secondary outcome. Inverse probability treatment weighting was used to account for each subject's propensity for DCD treatment. Effects of rivaroxaban were assessed with Cox proportional hazards models. ResultsAmong 4,316 patients who underwent LER, 3,478 (80.6%) were treated for claudication, and 1,342 (31.1%) received DCDs. Median follow-up was 31 months, vital status was ascertained in 99.6% of patients, and there were 394 deaths. After weighting, DCDs were not associated with mortality (HR: 0.95; 95% CI: 0.83-1.09) or MALE (HR: 1.08; 95% CI: 0.90-1.30) but were associated with reduced UILR (3-year Kaplan-Meier: 21.5% vs 24.6%; HR: 0.84; 95% CI: 0.76-0.92). Irrespective of DCD use, consistent benefit of rivaroxaban for composite cardiovascular and limb events (Pinteraction = 0.88) and safety of rivaroxaban with respect to bleeding (Pinteraction = 0.57) were observed. ConclusionsIn >4,000 patients with PAD who underwent LER, DCDs were not associated with mortality or MALE but were associated with persistent reduction in UILR. These findings provide insight into the safety and effectiveness of DCDs in PAD. (Vascular Outcomes Study of ASA [acetylsalicylic acid] Along with Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD [VOYAGER PAD]; NCT02504216)

Low-dose rivaroxaban plus aspirin in older patients with peripheral artery disease undergoing acute limb revascularization: insights from the VOYAGER PAD trial.

In this secondary analysis of the VOYAGER trial, rivaroxaban 2.5 mg twice/day plus aspirin 100 mg/day was assessed in older adults. Advanced age is associated with elevated bleeding risk and unfavourable net benefit for dual antiplatelet therapy in chronic coronary artery disease. The risk-benefit of low-dose rivaroxaban in patients ≥75 years with peripheral artery disease (PAD) after lower extremity revascularization (LER) has not been described. The primary endpoint was a composite of acute limb ischaemia, major amputation, myocardial infarction, ischaemic stroke, or cardiovascular death. The principal safety outcome was thrombolysis in myocardial infarction (TIMI) major bleeding analysed by the pre-specified age cut-off of 75 years. Of 6564 patients randomized, 1330 (20%) were >75 years. Absolute 3-year Kaplan-Meier cumulative incidence rates for primary efficacy (23.4% vs. 19.0%) and safety (3.5% vs. 1.5%) endpoints were higher in elderly vs. non-elderly patients. Efficacy of rivaroxaban (P-interaction 0.83) and safety (P-interaction 0.38) was consistent irrespective of age. The combination of intracranial and fatal bleeding was not increased in patients >75 years (2 rivaroxaban vs. 8 placebo). Overall, benefits (absolute risk reduction 3.8%, number needed to treat 26 for the primary endpoint) exceeded risks (absolute risk increase 0.81%, number needed to harm 123 for TIMI major bleeding). Patients ≥75 years with PAD are at both heightened ischaemic and bleeding risk after LER. No excess harm with respect to major, intracranial or fatal bleeding was seen in older patients yet numerically greater absolute benefits were observed. This suggests that low-dose rivaroxaban combined with aspirin should be considered in PAD after LER regardless of age.

Long-Term Ticagrelor in Patients With Prior Coronary Stenting in the PEGASUS-TIMI 54 Trial.

BackgroundCoronary stent type and risk of stent thrombosis remain important factors affecting recommended duration of dual antiplatelet therapy. We investigated the efficacy and safety of long‐term ticagrelor in patients with prior coronary stenting enrolled in the PEGASUS‐TIMI 54 (Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin–Thrombolysis in Myocardial Infarction 54) trial.Methods and ResultsPatients in PEGASUS‐TIMI 54 had a myocardial infarction 1 to 3 year prior and were randomized 1:1:1 to ticagrelor 60 or 90 mg BID or placebo. The primary end point was a composite of cardiovascular death, myocardial infarction, or stroke (major adverse cardiovascular events). Stent thrombosis was prospectively adjudicated (Academic Research Consortium definition). Baseline characteristics were compared by most recent stent type (bare metal versus drug‐eluting stent and first‐ versus later‐generation drug‐eluting stent). Treatment arms were compared using Cox proportional hazards models. Of 21 162 patients randomized, 80% (n=16 891) had prior coronary stenting. Following randomization, myocardial infarction was the most frequent ischemic event in patients with prior stenting in the placebo arm, occurring in 5.2% of patients (Type 1: 4.1%), followed by cardiovascular death (2.3%), stroke (1.7%), and stent thrombosis (0.9%). Ticagrelorpooled reduced major adverse cardiovascular events (7.0% versus 8.0%; hazard ratio [HR], 0.85; 95% CI, 0.75–96) regardless of stent type (bare metal stent versus drug‐eluting stent: pinteraction=0.767; first versus later generation: pinteraction=0.940). The rate of any stent thrombosis was numerically lower with ticagrelorpooled (0.7% versus 0.9%; HR, 0.73; 95% CI, 0.50–1.05) and Thrombolysis in Myocardial Infarction major bleeding was increased (HR, 2.65; 95% CI, 1.90–3.68).ConclusionsLong‐term ticagrelor reduces major adverse cardiovascular events in patients with prior myocardial infarction and coronary stenting regardless of stent type, with the benefit driven predominantly by reduction in de novo events. Nonfatal major bleeding is increased with ticagrelor.Registration Informationclinicaltrials.gov. Identifier: NCT01225562.

Effect of Rivaroxaban and Aspirin in Patients With Peripheral Artery Disease Undergoing Surgical Revascularization: Insights From the VOYAGER PAD Trial.

Patients with peripheral artery disease requiring lower extremity revascularization (LER) are at high risk of adverse limb and cardiovascular events. The VOYAGER PAD trial (Vascular Outcomes Study of ASA [Acetylsalicylic Acid] Along With Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD) demonstrated that rivaroxaban significantly reduced this risk. The efficacy and safety of rivaroxaban has not been described in patients who underwent surgical LER. The VOYAGER PAD trial randomized patients with peripheral artery disease after surgical and endovascular LER to rivaroxaban 2.5 mg twice daily plus aspirin or matching placebo plus aspirin and followed for a median of 28 months. The primary end point was a composite of acute limb ischemia, major vascular amputation, myocardial infarction, ischemic stroke, or cardiovascular death. The principal safety outcome was Thrombolysis in Myocardial Infarction major bleeding. International Society on Thrombosis and Haemostasis bleeding was a secondary safety outcome. All efficacy and safety outcomes were adjudicated by a blinded independent committee. Of the 6564 randomized, 2185 (33%) underwent surgical LER and 4379 (67%) endovascular. Compared with placebo, rivaroxaban reduced the primary end point consistently regardless of LER method (P-interaction, 0.43). After surgical LER, the primary efficacy outcome occurred in 199 (18.4%) patients in the rivaroxaban group and 242 (22.0%) patients in the placebo group with a cumulative incidence at 3 years of 19.7% and 23.9%, respectively (hazard ratio, 0.81 [95% CI, 0.67-0.98]; P=0.026). In the overall trial, Thrombolysis in Myocardial Infarction major bleeding and International Society on Thrombosis and Haemostasis major bleeding were increased with rivaroxaban. There was no heterogeneity for Thrombolysis in Myocardial Infarction major bleeding (P-interaction, 0.17) or International Society on Thrombosis and Haemostasis major bleeding (P-interaction, 0.73) on the basis of the LER approach. After surgical LER, the principal safety outcome occurred in 11 (1.0%) patients in the rivaroxaban group and 13 (1.2%) patients in the placebo group; 3-year cumulative incidence was 1.3% and 1.4%, respectively (hazard ratio, 0.88 [95% CI, 0.39-1.95]; P=0.75) Among surgical patients, the composite of fatal bleeding or intracranial hemorrhage (P=0.95) and postprocedural bleeding requiring intervention (P=0.93) was not significantly increased. The efficacy of rivaroxaban is associated with a benefit in patients who underwent surgical LER. Although bleeding was increased with rivaroxaban plus aspirin, the incidence was low, with no significant increase in fatal bleeding, intracranial hemorrhage, or postprocedural bleeds requiring intervention. Registration: URL: http://www.clinicaltrials.gov; Unique Identifier: NCT02504216.

Optimisation of oral anticoagulants for patients with atrial fibrillation within 12 months after percutaneous coronary intervention: A meta-analysis and systematic review.

The optimal antithrombotic strategy, especially regarding oral anticoagulants (OACs) for atrial fibrillation (AF) patients with bleeding and thrombosis risk after percutaneous coronary intervention (PCI), remains unknown. This study explored the optimal oral anticoagulants for AF patients after PCI using a meta-analysis. Randomised controlled trials were identified from PubMed, Embase, and the Cochrane Library through December 2020. Risk ratios, 95% confidence intervals, and random-effects models were used to compare different antithrombotic strategies through network meta-analysis, and the combination of antithrombotic agents was ranked according to the surface under the cumulative ranking curve and rankograms. Interval plots were drawn to observe pairwise comparisons between the different strategies. Five studies of 11,532 patients were included. Factor IIa inhibitor 110 mg bid plus a P2Y12 inhibitor had the greatest advantage for reducing Thrombolysis In Myocardial Infarction (TIMI) major or minor bleeding; Factor Xa inhibitor plus a P2Y12 inhibitor had the greatest advantage for reducing International Society on Thrombosis and Hemostasis major bleeding. For patients at risk of stroke plus all-cause death, factor IIa inhibitor 150 mg bid plus a P2Y12 inhibitor should be prioritised, and for those at risk of myocardial infarction and stent thrombosis, vitamin K antagonists plus a P2Y12 inhibitor were preferred. Factor IIa inhibitor 110 mg, factor IIa inhibitor 150 mg, factor Xa inhibitor and vitamin K antagonists should be selected in different situations.

Patient Selection and Clinical Outcomes in the STOPDAPT-2 Trial: An All-Comer Single-Center Registry During the Enrollment Period of the STOPDAPT-2 Randomized Controlled Trial.

We sought to evaluate the impact of patient selection for the STOPDAPT-2 trial (Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent-2) on clinical outcomes in a registry from a single center that participated in the STOPDAPT-2 trial. Among 2190 consecutive patients who underwent percutaneous coronary intervention using stent in Kokura Memorial Hospital during the enrollment period of the STOPDAPT-2 trial, 521 patients had exclusion criteria such as in-hospital major complications, anticoagulant use, or prior intracranial bleeding (ineligible group). Among 1669 patients who met the eligibility criteria (eligible group), 582 were enrolled (enrolled group) and 1087 were not enrolled (nonenrolled group) in the STOPDAPT-2 trial. The primary outcome measure was defined as a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, stroke, or Thrombolysis in Myocardial Infarction major and minor bleeding. Compared with the enrolled group, patients in the nonenrolled group more often had high bleeding risk according to the Academic Research Consortium for High Bleeding Risk definition (52.6% versus 41.2%; P<0.001) and were frailer according to the Canadian Study of Health and Aging Clinical Frailty Scale (intermediate, 21.4% versus 14.1%; high, 6.4% versus 2.1%; P<0.001). The cumulative 1-year incidences of the primary outcome measure, all-cause death, and major bleeding were significantly higher in the nonenrolled group than in the enrolled group (7.2% versus 4.5%, P=0.03; 4.1% versus 0.9%, P<0.001; and 4.3% versus 2.1%, P=0.03, respectively) and in the ineligible group than in the eligible group (21.2% versus 6.3%, P<0.001; 9.9% versus 3.0%, P<0.001; and 13.5% versus 3.5%, P<0.001, respectively). Patients who were ineligible, eligible but not enrolled, and enrolled in the STOPDAPT-2 trial had different risk profiles and clinical outcomes, suggesting important implications in applying the trial results in daily clinical practice.

Prevalence, clinical determinants and prognostic implications of coronary procedural complications of percutaneous coronary intervention in non-ST-segment elevation myocardial infarction: Insights from the contemporary multinational TAO trial

Few data are available on procedural complications of percutaneous coronary intervention (PCI) in the setting of acute coronary syndrome in the contemporary era. We sought to describe the prevalence of procedural complications of PCI in a non-ST-segment elevation acute coronary syndrome (NSTE ACS) cohort, and to identify their clinical characteristics and association with clinical outcomes. Patients randomized in TAO (Treatment of Acute coronary syndrome with Otamixaban), an international randomized controlled trial (ClinicalTrials.gov Identifier: NCT01076764) that compared otamixaban with unfractionated heparin plus eptifibatide in patients with NSTE ACS who underwent PCI, were included in the analysis. Procedural complications were collected prospectively, categorized and adjudicated by a blinded Clinical Events Committee, with review of angiograms. A multivariable model was constructed to identify independent clinical characteristics associated with procedural complications. A total of 8656 patients with NSTE ACS who were enrolled in the TAO trial underwent PCI, and 451 (5.2%) experienced at least one complication. The most frequent complications were no/slow reflow (1.5%) and dissection with decreased flow (1.2%). Procedural complications were associated with the 7-day ischaemic outcome of death, myocardial infarction or stroke (24.2% vs. 6.0%, odds ratio 5.01, 95% confidence interval 3.96-6.33; P<0.0001) and with Thrombolysis In Myocardial Infarction major and minor bleeding (6.2% vs. 2.3%, odds ratio 2.79, 95% confidence interval 1.86-4.2; P<0.0001). Except for previous coronary artery bypass grafting, multivariable analysis did not identify preprocedural clinical predictors of complications. In a contemporary NSTE ACS population, procedural complications with PCI remain frequent, are difficult to predict based on clinical characteristics, and are associated with worse ischaemic and haemorrhagic outcomes.

Sex Differences in Ischemic and Bleeding Outcomes in Patients With Non-ST-Segment-Elevation Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: Insights From the TAO Trial.

Previous studies have observed poorer outcomes in females with myocardial infarction, but older age and lower use of percutaneous coronary intervention in females are factors that potentially explain the worse outcome. This study sought to determine if female sex is an independent factor of ischemic and bleeding outcomes in non-ST-segment-elevation acute coronary syndrome treated with a systematic invasive approach. The TAO trial (Treatment of Acute Coronary Syndrome With Otamixaban) randomized patients with non-ST-segment-elevation acute coronary syndrome treated invasively to heparin plus eptifibatide versus otamixaban. In this post hoc analysis, the primary ischemic end point (all-cause death, myocardial infarction within 180 days) and the primary safety end point (Thrombolysis in Myocardial Infarction major or minor bleeding within 30 days) were analyzed according to sex. Of 13 229 randomized patients, 3980 (30.1%) were females and 9249 (69.9%) were males. Females were older (64.8±11.0 versus 60.7±11.1 years), had more comorbidities, received less peri-procedural antithrombotic therapy, and underwent less frequently revascularization. Overall, females experienced a higher risk of ischemic (10.2% versus 9.1%; odds ratio [OR], 1.15 [1.01-1.30]) and bleeding events (4.2% versus 3.4%; OR, 1.23 [1.02-1.49]) than males. After multivariate analysis, the risk of ischemic outcomes (OR, 1.04 [0.90-1.19]), death (OR, 1.00 [0.75-1.23]), or bleeding (OR, 1.05 [0.85-1.28]), were similar between females and males. Only, noncoronary artery bypass graft related Thrombolysis in Myocardial Infarction major bleeding were increased in females (OR, 1.69 [1.11-2.56]). In patients with non-ST-segment-elevation acute coronary syndrome with systematic invasive management, ischemic outcomes, bleeding events, and mortality were higher in females. After multivariate analyses, female sex was not an independent predictor of ischemic and bleeding events although noncoronary artery bypass graft related Thrombolysis in Myocardial Infarction major bleeding was higher in females. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01076764.

Clinical Outcomes of Ticagrelor in Korean Patients with Acute Myocardial Infarction without High Bleeding Risk.

BackgroundAlthough ticagrelor is known to increase the bleeding risk compared to clopidogrel in East Asian patients, its clinical benefits in patients with acute myocardial infarction (AMI) without high bleeding risk (HBR) remains unknown.MethodsA total of 7,348 patients who underwent successful percutaneous coronary intervention (PCI) from the Korea Acute Myocardial Infarction Registry-National Institute of Health (KAMIR-NIH), between November 2011 and December 2015, were divided into two groups according to the Academic Research Consortium for HBR criteria (KAMIR-HBR, 2,469 patients; KAMIR-non HBR, 4,879 patients). We compared in-hospital major adverse cardiovascular events (MACEs, defined as a composite of cardiac death, non-fatal myocardial infarction, or stroke), and the thrombolysis in myocardial infarction (TIMI) major bleeding between ticagrelor and clopidogrel in the KAMIR-HBR and the KAMIR-non HBR groups, respectively.ResultsAfter propensity score matching, ticagrelor had a higher incidence of in-hospital TIMI major bleeding than clopidogrel in all patients (odds ratio [OR], 1.683; 95% confidence interval [CI], 1.010–2.805; P = 0.046) and the KAMIR-HBR group (OR, 3.460; 95% CI, 1.374–8.714; P = 0.008). However, there was no significant difference in in-hospital TIMI major bleeding between ticagrelor and clopidogrel in the KAMIR-non HBR group (OR, 1.436; 95% CI, 0.722–2.855; P = 0.303). No differences were observed in the cumulative incidences of in-hospital and 6-month MACEs between ticagrelor and clopidogrel in both groups.ConclusionsThe bleeding risk of ticagrelor was attenuated in Korean patients with AMI without HBR. Appropriate patient selection could reduce in-hospital bleeding complications associated with ticagrelor in Korean patients with AMI who underwent successful PCI.

Efficacy and safety of newer P2Y12 inhibitors for acute coronary syndrome: a network meta-analysis

Whether newer P2Y12 inhibitors are more efficacious and safer than clopidogrel and whether there is a superior one remain uncertain. We compared the effect of P2Y12 inhibitors on clinical outcomes in patients with acute coronary syndrome (ACS). Randomized controlled trials comparing clopidogrel, prasugrel, ticagrelor, or cangrelor, in combination with aspirin were searched. Sixteen trials with altogether 77,896 patients were included. Compared to clopidogrel, cardiovascular mortality was reduced with prasugrel (OR 0.85, 95% CI 0.75–0.97) and ticagrelor (0.82, 0.73–0.93). Myocardial infarction (0.75, 0.63–0.89) and major adverse cardiovascular events (0.80, 0.69–0.94) were reduced by prasugrel. Stent thrombosis was reduced by prasugrel (0.49, 0.38–0.63), ticagrelor (0.72, 0.57–0.90), and cangrelor (0.59, 0.43–0.81). It was reduced more by prasugrel than ticagrelor (0.69, 0.51–0.93). There were more major bleeds with prasugrel (1.24, 1.05–1.48). Thrombolysis in Myocardial Infarction (TIMI) major bleeding was increased with prasugrel compared to clopidogrel (1.36, 1.11–1.66) and ticagrelor (1.33, 1.06–1.67). TIMI minor bleeding was increased with prasugrel (1.44, 1.16–1.77) and cangrelor (1.47, 1.01–2.16) compared to clopidogrel while it was increased with prasugrel compared to ticagrelor (1.32, 1.01–1.72). Prasugrel is preferable to those ACS patients at low bleeding risk to reduce cardiovascular events whereas ticagrelor is a relatively safe antiplatelet drug of choice for most patients.

Sarcopenia Index as a Predictor of Clinical Outcomes in Older Patients with Coronary Artery Disease.

To demonstrate the association of the serum creatinine/serum cystatin C ratio (sarcopenia index, SI) with clinical outcomes including cardiovascular and bleeding risk in older patients who underwent percutaneous coronary intervention (PCI), we analyzed a multicenter nation-wide pooled registry. A total of 1086 older patients (65 years or older) who underwent PCI with second-generation drug-eluting stents (DES) were enrolled. The total population was divided into quartiles according to the SI, stratified by sex. The primary clinical outcomes were major adverse cardiovascular events (MACE, all-cause death, myocardial infarction and target lesion revascularization) and thrombolysis in myocardial infarction major and minor bleeding during a 3-year follow-up period. In the total population, MACE occurred within 3 years in 154 (14.2%) patients. The lowest SI quartile group (Q1) had a significantly higher 3-year MACE rate (Q1 vs. Q2–4; 23.1% vs. 11.2%, p < 0.001), while bleeding event rates were similar between the groups (Q1 vs. Q2–4; 2.6% vs. 2.2%, p = 0.656). The Cox proportional hazard model showed that lower SI is an independent predictor for MACE events (HR 2.23, 95% CI 1.62–3.07, p < 0.001). The SI, a surrogate for the degree of muscle mass, is associated with cardiovascular and non-cardiovascular death, but not with bleeding in older patients who underwent PCI.

Platelet Reactivity in Hepatitis C Virus-Infected Patients on Dual Antiplatelet Therapy for Acute Coronary Syndrome.

BackgroundCoronary artery disease (CAD) has been recognized as a serious and potentially life‐threatening complication of Hepatitis C Virus (HCV) infection. High on‐treatment platelet reactivity has been associated with high risk of ischemic events in patients with CAD, but data regarding the association with HCV infection are still lacking. This post hoc analysis aims to assess high on‐treatment platelet reactivity, severity of CAD, and long‐term outcomes of patients with acute coronary syndrome (ACS) who were infected with HCV.Methods and ResultsPatients with ACS who were infected with HCV (n=47) were matched to patients with ACS and without HCV (n=137) for age, sex, diabetes mellitus, hypertension, and renal function. HCV‐infected patients with ACS had higher levels of platelet reactivity (ADP10–light transmittance aggregometry, 56±18% versus 44±22% [P=0.002]; arachidonic acid–light transmittance aggregometry, 25±21% versus 16±15% [P=0.011]) and higher rates of high on‐treatment platelet reactivity on clopidogrel and aspirin compared with patients without HCV. Moreover, HCV‐infected patients with ACS had higher rates of multivessel disease (53% versus 30%; P=0.004) and 3‐vessel disease (32% versus 7%; P<0.001) compared with patients without HCV. At long‐term follow‐up, estimated rates of major adverse cardiovascular events (cardiac death, nonfatal myocardial infarction, and ischemia‐driven revascularization) were 57% versus 34% (P=0.005) in HCV‐ and non–HCV‐infected patients with ACS, respectively. In addition, thrombolysis In Myocardial Infarction (TIMI) major bleeding rates were higher in HCV‐infected patients (11% versus 3%; P=0.043) compared with noninfected patients. Multivariable analysis demonstrated that HCV infection was an independent predictor of high on‐treatment platelet reactivity, severity of CAD, and long‐term outcome.ConclusionsIn this hypothesis‐generating study, patients with ACS and HCV infection showed increased on‐treatment platelet reactivity, more severe CAD, and worse prognosis compared with patients without HCV.