Aplicabilidad de los criterios de alto riesgo hemorrágico del Academic Research Consortium al síndrome coronario agudo sometido a intervención coronaria percutánea

Introduction and objectivesThe recent Academic Research Consortium for High Bleeding Risk (ARC-HBR) proposal did not consider acute coronary syndrome (ACS), by consensus, a bleeding criterion per se despite being a high bleeding risk (HBR) scenario. We investigated the applicability of the ARC-HBR classification and criteria in ACS patients.MethodsPatients with ACS undergoing coronary stenting between 2012 and 2018 at a tertiary hospital were retrospectively classified as being at HBR if they met ≥ 1 major or ≥ 2 minor ARC-HBR criteria. The primary endpoint was the 1-year cumulative incidence of Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding.ResultsAmong 4412 patients, 29.5% were at HBR. The incidence of bleeding was higher in the HBR group than in the non-HBR group (9.4% vs 1.3%; P < .01). The rates of in-hospital periprocedural and postdischarge bleeding were also higher in the HBR group (4.3% vs 0.5% and 5.3% vs 0.9%, respectively; P < .01). Bleeding risk gradually increased with increasing ARC-HBR criteria: 1.8%, 5.0%, 9.4%, 16.8%, 25.2%, and 25.9% for 1 isolated minor criterion, ≥ 2 isolated minor criteria, 1 major criterion (isolated or plus 1 minor criterion), 1 major plus ≥ 2 minor criteria, ≥ 2 major criteria (isolated or plus 1 minor criterion), and ≥ 2 major plus ≥ 2 minor criteria, respectively. Sixteen (80%) out of 20 ARC-HBR criteria satisfied the ARC-HBR predefined cutoffs for BARC 3 or 5 bleeding risk.ConclusionsThis study supports the use of the ARC-HBR classification and criteria in the ACS setting. The ARC-HBR classification provides an accurate major bleeding risk estimate and it seems suitable for the identification and management of patients at HBR.Full English text available from:www.revespcardiol.org/en     

Validation of the Academic Research Consortium High Bleeding Risk Definition in Contemporary PCI Patients

BackgroundBleeding following percutaneous coronary intervention has important prognostic implications. The Academic Research Consortium (ARC) recently proposed a list of clinical criteria to define patients at high bleeding risk (HBR).ObjectivesThis study sought to validate the ARC definition for HBR patients in a contemporary real-world cohort.MethodsPatients undergoing coronary stenting between 2014 and 2017 at a tertiary-care center were defined as HBR if they met at least 1 major or 2 minor ARC-HBR criteria. To account for the presence of multiple criteria, patients were further stratified by the number of times they fulfilled the ARC-HBR definition. The primary endpoint was a composite of peri-procedural in-hospital or post-discharge bleeding at 1 year. Secondary endpoints included individual components of the primary bleeding endpoint, myocardial infarction, and all-cause mortality.ResultsAmong 9,623 patients, 4,278 (44.4%) qualified as HBR. Moderate or severe anemia was the most common major criterion (33.2%); age ≥75 years was the most frequent minor criterion and the most common overall (46.8%). The rate of the primary bleeding endpoint at 1 year was 9.1% in HBR patients compared with 3.2% in non-HBR patients (p < 0.001), with a stepwise increase in bleeding risk corresponding to the number of times the ARC-HBR definition was fulfilled. HBR patients also experienced significantly higher rates of all secondary endpoints.ConclusionsThis study validates the ARC-HBR definition in a contemporary group of patients who underwent percutaneous coronary intervention. The ARC-HBR definition identified patients at increased risk not only for bleeding but also for thrombotic events, including all-cause mortality. Coexistence of multiple ARC-HBR criteria showed additive prognostic value.     

Comparative Outcomes After Percutaneous Coronary Intervention in Unconscious and Conscious Patients With Out-of-Hospital Cardiac Arrest

BackgroundUp to 70% of out-of-hospital cardiac arrest (OHCA) patients have a relevant coronary stenosis which may need revascularization. The short- and long-term ischemic and bleeding risk of unconscious and conscious OHCA patients undergoing percutaneous coronary intervention (PCI) is largely unknown.ObjectivesThis study sought to compare the occurrence of 1-year outcomes after PCI between OHCA patients, stratified on the basis of state of consciousness, with patients with acute coronary syndrome (ACS) not preceded by OHCA.MethodsThe study assessed the unadjusted and adjusted risk of cardiovascular events in a prospective single-center cohort of 9,303 consecutive PCI patients.ResultsAt 1 year, all-cause mortality was higher in unconscious (49.5%) but not in conscious OHCA (8.9%) patients than in ACS patients (8.0%), and both unconscious and conscious OHCA patients were more likely than ACS patients to experience definite stent thrombosis (4.4% and 3.5% vs 1.3%) and Bleeding Academic Research Consortium 3 or 5 bleeding (17.8% and 9.0% vs 5.1%). The higher hazards were largely determined by events occurring in the first 30 days. After multivariable adjustment, only unconscious OHCA patients remained at increased risk of death (adjusted HR: 3.27; 95% CI: 2.65-4.05), definite stent thrombosis (adjusted HR: 2.40; 95% CI: 1.30-4.43), and Bleeding Academic Research Consortium 3 or 5 bleeding (adjusted HR: 2.51; 95% CI: 1.82-3.47) at 1 year.ConclusionsAt 1 year after PCI, unconscious OHCA patients were at higher risk of death, definite stent thrombosis, and bleeding, while conscious OHCA patients had similar hazards compared with an all-comer ACS population without OHCA. Dedicated PCI strategies for OHCA patients taking into account their state of consciousness after resuscitation are warranted.     

DAPT Score and the Impact of Ticagrelor Monotherapy During the Second Year After PCI

ObjectivesThis study assessed the ability of the dual-antiplatelet therapy (DAPT) score in stratifying ischemic and bleeding risk in a contemporary percutaneous coronary intervention (PCI) population.BackgroundThe DAPT score is recommended by guidelines as a tool to stratify ischemic and bleeding risk. Its utility in contemporary PCI is unknown.MethodsThe study studied patients in GLOBAL LEADERS (A Clinical Study Comparing Two Forms of Anti-platelet Therapy After Stent Implantation) who were free of major ischemic and bleeding events and adhered to antiplatelet strategy during the first year after PCI. The primary ischemic endpoint was the composite of myocardial infarction or stent thrombosis. The primary bleeding endpoint was Bleeding Academic Research Consortium type 3 or 5. Outcomes from 12 to 24 months after PCI were compared according to the DAPT score.ResultsOf 11,289 patients that were event-free after the first year, 6,882 and 4,407 patients had low (<2) and high (≥2) DAPT scores, respectively. Compared with a low DAPT score, patients with a high DAPT score had a higher rate of the composites of myocardial infarction or stent thrombosis (0.70% vs. 1.55%; p < 0.0001). The rate of Bleeding Academic Research Consortium type 3 or 5 bleeding was 0.54% and 0.30% in the low and high DAPT score groups, respectively (p = 0.058). The effect of ticagrelor versus aspirin monotherapy on primary ischemic and bleeding endpoints during the second year were no different among the 2 groups.ConclusionsThe DAPT score can stratify ischemic but not bleeding risk in a contemporary PCI population during the second year. The score did not provide additional value for selection of antiplatelet strategy beyond the first year.     

Ticagrelor With or Without Aspirin in High-Risk Patients With Diabetes Mellitus Undergoing Percutaneous Coronary Intervention

BackgroundP2Y₁₂ inhibitor monotherapy with ticagrelor after a brief period of dual antiplatelet therapy can reduce bleeding without increasing ischemic harm after percutaneous coronary intervention (PCI). The impact of this approach among patients with diabetes mellitus (DM) remains unknown.ObjectivesThe purpose of this study was to examine the effect of ticagrelor monotherapy versus ticagrelor plus aspirin among patients with DM undergoing PCI.MethodsThis was a pre-specified analysis of the DM cohort in the TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk Patients after Coronary Intervention) trial. After 3 months of ticagrelor plus aspirin, patients were maintained on ticagrelor and randomized to aspirin or placebo for 1 year. The primary endpoint was Bleeding Academic Research Consortium 2, 3, or 5 bleeding. The composite ischemic endpoint was all-cause death, myocardial infarction, or stroke.ResultsPatients with DM comprised 37% (n = 2,620) of the randomized cohort and were characterized by more frequent comorbidities and a higher prevalence of multivessel disease. The incidence of Bleeding Academic Research Consortium 2, 3, or 5 bleeding was 4.5% and 6.7% among patients with DM randomized to ticagrelor plus placebo versus ticagrelor plus aspirin (hazard ratio: 0.65; 95% confidence interval: 0.47 to 0.91; p = 0.012). Ticagrelor monotherapy was not associated with an increase in ischemic events compared with ticagrelor plus aspirin (4.6% vs. 5.9%; hazard ratio: 0.77; 95% confidence interval: 0.55 to 1.09; p = 0.14). In the overall trial population, there was no significant interaction between DM status and treatment group for the primary bleeding or ischemic endpoints.ConclusionsCompared with ticagrelor plus aspirin, the effect of ticagrelor monotherapy in reducing the risk of clinically relevant bleeding without any increase in ischemic events was consistent among patients with or without DM undergoing PCI. (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention [TWILIGHT]; NCT02270242)     

Cancer Patients Have a Higher Risk of Thrombotic and Ischemic Events After Percutaneous Coronary Intervention

ObjectivesThis study sought to define the risk of stent thrombosis (ST) and myocardial infarction (MI) in cancer patients compared with noncancer patients after percutaneous coronary intervention (PCI).BackgroundCancer patients are considered to be at high thrombotic risk, but data on whether this is the case after PCI remain inconclusive.MethodsCancer patients undergoing PCI at Mayo Clinic Rochester from January 1, 2003, to December 31, 2013, were identified by cross-linking institutional cancer and PCI databases and by propensity score matching to noncancer patients. The combined primary endpoint was all-cause mortality, MI, and revascularization rate at 5-year follow-up. Secondary endpoints were the individual primary endpoint components, cause of mortality, ST, and Bleeding Academic Research Consortium 2+ bleeding.ResultsThe primary endpoint occurred in 48.6% of 416 cancer and in 33.0% of 768 noncancer patients (p < 0.001). In competing risk analyses, cancer patients had a higher rate of noncardiac death (24.0% vs. 10.5%; p < 0.001) and a lower rate of cardiac death (5.0% vs. 11.7%; p < 0.001). Cancer patients had a higher rate of MI (16.1% vs. 8.0%; p < 0.001), ST (6.0% vs. 2.3%; p < 0.001), repeat revascularization (21.2% vs. 10.0%; p < 0.001), and bleeding (6.7% vs. 3.9%; p = 0.03). The most critical period for ST in cancer patients was in the first year after PCI. The dual antiplatelet therapy score was predictive of thrombotic and ischemic events in both groups.ConclusionsCancer patients have a higher risk of thrombotic and ischemic events after PCI, identifiable by a high dual antiplatelet therapy score. These findings have important implications for antiplatelet therapy decisions.     

Ticagrelor Monotherapy Versus Dual-Antiplatelet Therapy After PCI: An Individual Patient-Level Meta-Analysis

ObjectivesThe aim of this study was to compare ticagrelor monotherapy with dual-antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) with drug-eluting stents.BackgroundThe role of abbreviated DAPT followed by an oral P2Y₁₂ inhibitor after PCI remains uncertain.MethodsTwo randomized trials, including 14,628 patients undergoing PCI, comparing ticagrelor monotherapy with standard DAPT on centrally adjudicated endpoints were identified, and individual patient data were analyzed using 1-step fixed-effect models. The protocol was registered in PROSPERO (CRD42019143120). The primary outcomes were the composite of Bleeding Academic Research Consortium type 3 or 5 bleeding tested for superiority and, if met, the composite of all-cause death, myocardial infarction, or stroke at 1 year, tested for noninferiority against a margin of 1.25 on a hazard ratio (HR) scale.ResultsBleeding Academic Research Consortium type 3 or 5 bleeding occurred in fewer patients with ticagrelor than DAPT (0.9% vs. 1.7%, respectively; HR: 0.56; 95% confidence interval [CI]: 0.41 to 0.75; p < 0.001). The composite of all-cause death, myocardial infarction, or stroke occurred in 231 patients (3.2%) with ticagrelor and in 254 patients (3.5%) with DAPT (HR: 0.92; 95% CI: 0.76 to 1.10; p < 0.001 for noninferiority). Ticagrelor was associated with lower risk for all-cause (HR: 0.71; 95% CI: 0.52 to 0.96; p = 0.027) and cardiovascular (HR: 0.68; 95% CI: 0.47 to 0.99; p = 0.044) mortality. Rates of myocardial infarction (2.01% vs. 2.05%; p = 0.88), stent thrombosis (0.29% vs. 0.38%; p = 0.32), and stroke (0.47% vs. 0.36%; p = 0.30) were similar.ConclusionsTicagrelor monotherapy was associated with a lower risk for major bleeding compared with standard DAPT, without a concomitant increase in ischemic events.     

Prevalence and Impact of High Bleeding Risk in Patients Undergoing Left Main Artery Disease PCI

ObjectivesThe aim of this study was to determine the prevalence and prognostic impact of high bleeding risk (HBR), as determined by the Academic Research Consortium HBR criteria, in real-world patients undergoing left main (LM) percutaneous coronary intervention (PCI).BackgroundLM PCI is often reserved for patients at increased risk for periprocedural adverse events. Patients at HBR represent a relevant percentage of this cohort, but their outcomes after LM PCI are still poorly investigated.MethodsAll patients undergoing LM PCI between 2014 and 2017 at a tertiary care center were prospectively enrolled. Patients were defined as having HBR if they met at least 1 major or 2 minor Academic Research Consortium HBR criteria. The primary endpoint was the composite of all-cause death, myocardial infarction (MI), or stroke at 12 months.ResultsAmong 619 enrolled patients, 55.3% were at HBR. The rate of the primary endpoint was 4-fold higher in patients at HBR compared with those without HBR (20.5% vs 4.9%; HR: 4.43; 95% CI: 2.31-8.48), driven by an increased risk for all-cause death (HR: 3.88; 95% CI: 1.88-8.02) and MI (HR: 6.18; 95% CI: 1.83-20.9). Rates of target vessel or lesion revascularization and stent thrombosis were comparable in the 2 groups. Bleeding occurred more frequently in patients at HBR (HR: 3.77; 95% CI: 1.83-7.76). Consistent findings were observed after Cox multivariable regression adjustment.ConclusionsAmong patients undergoing LM PCI, those with HBR are at increased risk for all-cause death, MI, and bleeding. Conversely, rates of repeat revascularization and stent thrombosis were comparable, suggesting frailty and comorbidities as primary causes of worse outcomes in patients at HBR.     

Ticagrelor With or Without Aspirin After Complex PCI

BackgroundWhether a regimen of ticagrelor monotherapy attenuates bleeding complications without increasing ischemic risk in patients undergoing complex percutaneous coronary intervention (PCI) is unknown.ObjectivesThe purpose of this study was to evaluate the effect of ticagrelor monotherapy versus ticagrelor plus aspirin in patients undergoing complex PCI from the randomized, double-blind, placebo-controlled TWILIGHT (Ticagrelor with Aspirin or Alone in High-Risk Patients after Coronary Intervention) trial.MethodsIn the TWILIGHT trial, after 3 months of ticagrelor plus aspirin, event-free and adherent patients remained on ticagrelor and were randomly assigned to receive aspirin or placebo for 1 year. Complex PCI was defined as any of the following: 3 vessels treated, ≥3 lesions treated, total stent length >60 mm, bifurcation with 2 stents implanted, atherectomy device use, left main PCI, surgical bypass graft or chronic total occlusion as target lesions. Bleeding and ischemic endpoints were evaluated at 1 year after randomization.ResultsAmong 7,119 patients randomized in the main trial, complex PCI was performed in 2,342 patients. Compared to ticagrelor plus aspirin, ticagrelor plus placebo resulted in significantly lower rates of Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding (4.2% vs. 7.7%; hazard ratio [HR]: 0.54; 95% confidence interval [CI]: 0.38 to 0.76). BARC type 3 or 5 bleeding was also significantly reduced (1.1% vs. 2.6%; HR: 0.41; 95% CI: 0.21 to 0.80). There were no significant between-group differences in death, myocardial infarction, or stroke (3.8% vs. 4.9%; HR: 0.77; 95% CI: 0.52 to 1.15), nor in stent thrombosis.ConclusionsAmong patients undergoing complex PCI who initially completed 3 months of ticagrelor plus aspirin, continuation of ticagrelor monotherapy was associated with lower incidence of bleeding without increasing the risk of ischemic events compared to continuing ticagrelor plus aspirin. (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention [TWILIGHT]; NCT02270242)     

Aspirin-Free Prasugrel Monotherapy Following Coronary Artery Stenting in Patients With Stable CAD: The ASET Pilot Study

ObjectivesThe aim of this study was to evaluate the hypothesis that prasugrel monotherapy following successful everolimus-eluting stent implantation is feasible and safe in patients with stable coronary artery disease (CAD).BackgroundRecent studies have suggested that short dual-antiplatelet therapy strategies may provide an adequate balance between ischemic and bleeding risks. However, the complete omission of aspirin immediately after percutaneous coronary intervention (PCI) has not been tested so far.MethodsThe study was a multicenter, single-arm, open-label trial with a stopping rule based on the occurrence of definite stent thrombosis (if >3, trial enrollment would be terminated). Patients undergoing successful everolimus-eluting stent implantation for stable CAD with SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) scores <23 were included. All participants were on standard dual-antiplatelet therapy at the time of index PCI. Aspirin was discontinued on the day of the index procedure but given prior to the procedure; prasugrel was administered in the catheterization laboratory immediately after the successful procedure, and aspirin-free prasugrel became the therapy regimen from that moment. Patients were treated solely with prasugrel for 3 months. The primary ischemic endpoint was the composite of cardiac death, spontaneous target vessel myocardial infarction, or definite stent thrombosis, and the primary bleeding endpoint was Bleeding Academic Research Consortium types 3 and 5 bleeding up to 3 months.ResultsFrom February 22, 2018, to May 7, 2019, 201 patients were enrolled. All patients underwent PCI for stable CAD. Overall, 98.5% of patients were adherent to prasugrel at 3-month follow-up. The primary ischemic and bleeding endpoints occurred in 1 patient (0.5%). No stent thrombosis events occurred.ConclusionsAspirin-free prasugrel monotherapy following successful everolimus-eluting stent implantation demonstrated feasibility and safety without any stent thrombosis in selected low-risk patients with stable CAD. These findings may help underpin larger randomized controlled studies to evaluate the aspirin-free strategy compared with traditional dual-antiplatelet therapy following PCI. (Acetyl Salicylic Elimination Trial: The ASET Pilot Study [ASET]; NCT03469856)     

P2Y12 Inhibitor Monotherapy or Dual Antiplatelet Therapy After Complex Percutaneous Coronary Interventions

BackgroundIt remains unclear whether P2Y₁₂ inhibitor monotherapy preserves ischemic protection while limiting bleeding risk compared with dual antiplatelet therapy (DAPT) after complex percutaneous coronary intervention (PCI).ObjectivesWe sought to assess the effects of P2Y₁₂ inhibitor monotherapy after 1-month to 3-month DAPT vs standard DAPT in relation to PCI complexity.MethodsWe pooled patient-level data from randomized controlled trials comparing P2Y₁₂ inhibitor monotherapy and standard DAPT on centrally adjudicated outcomes after coronary revascularization. Complex PCI was defined as any of 6 criteria: 3 vessels treated, ≥3 stents implanted, ≥3 lesions treated, bifurcation with 2 stents implanted, total stent length >60 mm, or chronic total occlusion. The primary efficacy endpoint was all-cause mortality, myocardial infarction, and stroke. The key safety endpoint was Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding.ResultsOf 22,941 patients undergoing PCI from 5 trials, 4,685 (20.4%) with complex PCI had higher rates of ischemic events. The primary efficacy endpoint was similar between P2Y₁₂ inhibitor monotherapy and DAPT among patients with complex PCI (HR: 0.87; 95% CI: 0.64-1.19) and noncomplex PCI (HR: 0.91; 95% CI: 0.76-1.09; P_interaction = 0.770). The treatment effect was consistent across all the components of the complex PCI definition. Compared with DAPT, P2Y₁₂ inhibitor monotherapy consistently reduced BARC 3 or 5 bleeding in complex PCI (HR: 0.51; 95% CI: 0.31-0.84) and noncomplex PCI patients (HR: 0.49; 95% CI: 0.37-0.64; P_interaction = 0.920).ConclusionsP2Y₁₂ inhibitor monotherapy after 1-month to 3-month DAPT was associated with similar rates of fatal and ischemic events and lower risk of major bleeding compared with standard DAPT, irrespective of PCI complexity. (PROSPERO [P2Y12 Inhibitor Monotherapy Versus Standard Dual Antiplatelet Therapy After Coronary Revascularization: Individual Patient Data Meta-Analysis of Randomized Trials]; CRD42020176853)     

Ticagrelor Monotherapy After PCI in High-Risk Patients With Prior MI: A Prespecified TWILIGHT Substudy

ObjectivesThe aim of this study was to evaluate if patients with prior myocardial infarction (MI) could benefit from ticagrelor monotherapy in terms of bleeding reduction without any compromise in ischemic event prevention.BackgroundPatients with history of MI who undergo percutaneous coronary intervention (PCI) remain at risk for recurrent ischemic events. The optimal antithrombotic strategy for this cohort remains debated.MethodsIn this prespecified analysis of the randomized TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk Patients after Coronary Intervention) trial, the authors evaluated the impact of history of MI on treatment effect of ticagrelor monotherapy versus ticagrelor plus aspirin in patients undergoing PCI with drug-eluting stent with at least 1 clinical and 1 angiographic high-risk feature and free from adverse events at 3 months after index PCI. The primary endpoint was Bleeding Academic Research Consortium type 2, 3, or 5 bleeding, and the key secondary endpoint was the composite of all-cause death, MI, or stroke, both at 12 months after randomization.ResultsA total of 1,937 patients (29.7%) with and 4,595 patients (70.3%) without prior MI were randomized to ticagrelor and placebo or ticagrelor and aspirin. At 1 year after randomization, patients with prior MI experienced higher rates of death, MI, or stroke (5.7% vs 3.2%; P < 0.001) but similar BARC types 2 to 5 bleeding (5.0% vs 5.5%; P = 0.677) compared with patients without prior MI. Ticagrelor monotherapy consistently reduced the risk for the primary bleeding outcome in patients with (3.4% vs 6.7%; HR: 0.50; 95% CI: 0.33-0.76) and without (4.2% vs 7.0%; HR: 0.58; 95% CI: 0.45-0.76; P_interaction = 0.54) prior MI. Rates of the key secondary ischemic outcome were not significantly different between treatment groups irrespective of history of MI (prior MI, 6.0% vs 5.5% [HR: 1.09; 95% CI: 0.75-1.58]; no prior MI, 3.1% vs 3.3% [HR: 0.92; 95% CI: 0.67-1.28]; P_interaction = 0.52).ConclusionsTicagrelor monotherapy is associated with significantly lower risk for bleeding events compared with ticagrelor plus aspirin, without any compromise in ischemic prevention, among high-risk patients with history of MI undergoing PCI. (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention [TWILIGHT]; NCT02270242)     

Impact of Age on the Safety and Efficacy of Ticagrelor Monotherapy in Patients Undergoing PCI

ObjectivesThe aim of this study was to assess the impact of age on the safety and efficacy of ticagrelor monotherapy after percutaneous coronary intervention (PCI).BackgroundAs the risk for bleeding and ischemic complications after PCI increases with age, the authors conducted a pre-specified analysis of the TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention) trial to evaluate the possible benefits of ticagrelor monotherapy according to age.MethodsThe TWILIGHT trial enrolled patients undergoing PCI with drug-eluting stents who fulfilled at least 1 clinical and 1 angiographic high-risk criterion. Age ≥65 years was a clinical entry criterion. After 3 months of dual-antiplatelet therapy with ticagrelor, event-free patients were randomized to ticagrelor plus placebo or ticagrelor plus aspirin for an additional 12 months. The primary endpoint was Bleeding Academic Research Consortium type 2, 3, or 5 bleeding. The key secondary endpoint was the composite of all-cause death, myocardial infarction, or stroke.ResultsA total of 3,113 patients (47.7%) were ≥65 years of age. At 1 year after randomization, ticagrelor monotherapy significantly reduced BARC type 2, 3, or 5 bleeding (4.5% vs. 8.2%; hazard ratio: 0.53; 95% confidence interval: 0.40 to 0.71) without increasing ischemic events (4.2% vs. 4.4%; hazard ratio: 0.96; 95% confidence interval: 0.68 to 1.35) compared with ticagrelor plus aspirin among patients ≥65 years of age. These findings were consistent in patients <65 years of age with respect to the primary (p_interaction = 0.62) and key secondary (p_interaction = 0.77) endpoints and across different age categories.ConclusionsA strategy of ticagrelor monotherapy following 3 months of dual-antiplatelet therapy significantly reduced clinically relevant bleeding compared with ticagrelor plus aspirin without an increase in ischemic events, irrespective of age.     

Validation of High-Risk Features for Stent-Related Ischemic Events as Endorsed by the 2017 DAPT Guidelines

ObjectivesThis study sought to validate European Society of Cardiology guideline-endorsed high-risk features of stent-related recurrent ischemic events for the prediction of ischemic and bleeding outcomes including a stratification according to the PRECISE-DAPT score estimated bleeding risk.BackgroundThe 2017 European Society of Cardiology–focused update on dual-antiplatelet therapy endorsed high-risk features of stent-related recurrent ischemic events. Because patients with high ischemic risk also have an increased bleeding risk, appropriate risk stratification for ischemic and bleeding events is crucial.MethodsBetween January 2009 and December 2015, a total of 10,236 consecutive patients undergoing clinically indicated percutaneous coronary intervention were prospectively included in the Bern PCI Registry. Guideline-endorsed high-risk features were retrospectively assessed. The primary ischemic endpoint was device-oriented composite endpoint (DOCE) (cardiac death, target-vessel myocardial infarction, and target lesion revascularization) at 1 year, and the primary bleeding endpoint was Bleeding Academic Research Consortium (BARC) 3–5 at 1 year.ResultsA total of 5,323 (52.0%) patients had at least 1 high-risk feature. Among patients with high-risk features, DOCE (12.3% vs. 5.5%; p < 0.001) and BARC 3–5 bleeding (4.9% vs. 2.2%; p < 0.001) occurred more frequently compared with those without. There was a graded risk increase for DOCE (0: 5.5%; 1 to 2: 11.3%; and ≥3: 16.7%; p < 0.001) and BARC 3–5 bleeding (0: 2.2%; 1 to 2: 4.5%; and ≥3: 6.6%; p < 0.001) as the number of high-risk features increased. High-PRECISE-DAPT score (≥25) was associated with an increased risk of DOCE and BARC 3–5 bleeding, irrespective of number of high-risk features.ConclusionsThe European Society of Cardiology guideline-endorsed high-risk features were associated with increased ischemic and bleeding risks following percutaneous coronary intervention in routine clinical practice. (CARDIOBASE Bern PCI Registry; NCT02241291)     

Access-Site Crossover in Patients With Acute Coronary Syndrome Undergoing Invasive Management

ObjectivesThe aim of this study was to assess the impact of access-site crossover in patients with acute coronary syndrome undergoing invasive management via radial or femoral access.BackgroundThere are limited data on the clinical implications of access-site crossover.MethodsIn the MATRIX (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox)–Access trial, 8,404 patients with acute coronary syndrome were randomized to radial or femoral access. Patients undergoing access-site crossover or successful access site were investigated. Thirty-day coprimary outcomes were a composite of death, myocardial infarction, or stroke (major adverse cardiovascular events [MACE]) and a composite of MACE or Bleeding Academic Research Consortium type 3 or 5 bleeding (net adverse clinical events [NACE]).ResultsAccess-site crossover occurred in 183 of 4,197 patients (4.4%) in the radial group (mainly to femoral access) and 108 of 4,207 patients (2.6%) in the femoral group (mainly to radial access). In multivariate analysis, the risk for coprimary outcomes was not significantly higher with radial crossover compared with successful radial (MACE: adjusted rate ratio [adjRR]: 1.25; 95% confidence interval [CI]: 0.81 to 1.93; p = 0.32; NACE: adjRR: 1.40; 95% CI: 0.94 to 2.06; p = 0.094) or successful femoral access (MACE: adjRR: 1.17; 95% CI: 0.76 to 1.81; p = 0.47; NACE: adjRR: 1.26; 95% CI: 0.86 to 1.86; p = 0.24). Access site–related Bleeding Academic Research Consortium type 3 or 5 bleeding was higher with radial crossover than successful radial access. Femoral crossover remained associated with higher risks for MACE (adjRR: 1.84; 95% CI: 1.18 to 2.87; p = 0.007) and NACE (adjRR: 1.69; 95% CI: 1.09 to 2.62; p = 0.019) compared with successful femoral access. Results remained consistent after excluding patients with randomized access not attempted.ConclusionsCrossover from radial to femoral access abolishes the bleeding benefit offered by the radial over femoral artery but does not appear to increase the risk for MACE or NACE compared with successful radial or femoral access. (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox [MATRIX]; NCT01433627)     

Impacts of geriatric nutritional risk index on prognosis of patients with non-ST-segment elevation acute coronary syndrome: Results from an observational cohort study in China

Background and aimsIt is recognized that malnutrition increases risk of worse prognosis in patients with various diseases. The present study investigated if poor nutritional status predicts adverse outcomes in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) undergoing percutaneous coronary intervention (PCI).Methods and resultsThe study enrolled 2299 patients (mean age: 60.01 ± 8.95 years; 71.8% male) with NSTE-ACS who underwent PCI at Beijing Anzhen Hospital from January to December 2015. The entire cohort was divided into training set (n = 1519) and testing set (n = 780) at a ratio of approximate 2 : 1. Nutritional status was assessed by geriatric nutritional risk index (GNRI). The primary endpoint was a composite of adverse events as follows: all-cause death, non-fatal myocardial infarction (MI) and any revascularization. Multivariate Cox analysis showed that GNRI significantly associated with primary endpoint, independent of other risk factors [hazard ratio (HR) 1.159 per 1-point decrease of GNRI, 95% confidence interval (CI) 1.130–1.189, p < 0.001]. The addition of GNRI to a baseline model had an incremental effect on the predictive value for adverse prognosis in training set [AUC: from 0.821 to 0.873, p < 0.001; category-free net reclassification improvement (NRI): 0.313, p < 0.001; integrated discrimination improvement (IDI): 0.108, p < 0.001]. The incremental effect of GNRI was further validated and confirmed in testing set.ConclusionLower GNRI is a significant predictor of adverse prognosis in patients with NSTE-ACS undergoing PCI. Further studies need to be performed to determine whether nutritional interventions have a positive impact on improving clinical prognosis.     

3- or 1-Month DAPT in Patients at High Bleeding Risk Undergoing Everolimus-Eluting Stent Implantation

ObjectivesThe aim of this study was to evaluate 2 abbreviated dual-antiplatelet therapy (DAPT) regimens in patients at high bleeding risk (HBR) undergoing percutaneous coronary intervention (PCI).BackgroundCurrent-generation drug-eluting stents are preferred over bare-metal stents for HBR patients, but their optimal DAPT management remains unknown.MethodsThe XIENCE Short DAPT program included 3 prospective, multicenter, single-arm studies enrolling HBR patients who underwent successful PCI with a cobalt-chromium everolimus-eluting stent. After 1 month (XIENCE 28 USA and XIENCE 28 Global) or 3 months (XIENCE 90) of DAPT, event-free patients discontinued the P2Y₁₂ inhibitor. The postmarketing approval XIENCE V USA study was used as historical control in a propensity score–stratified analysis.ResultsA total of 3,652 patients were enrolled. The propensity-adjusted rate of the primary endpoint of all-cause mortality or myocardial infarction was 5.4% among 1,693 patients on 3-month DAPT versus 5.4% in the 12-month DAPT historical control (P_{noninferiority} = 0.0063) and 3.5% among 1,392 patients on 1-month DAPT versus 4.3% in the 6-month DAPT historical control (P_{noninferiority} = 0.0005). Bleeding Academic Research Consortium (BARC) types 2 to 5 bleeding was not significantly lower with 3- or 1-month DAPT, while BARC types 3 to 5 bleeding was reduced in both experimental groups. The rate of definite or probable stent thrombosis was 0.2% in XIENCE 90 (P < 0.0001 for the performance goal of 1.2%) and 0.3% in XIENCE 28.ConclusionsAmong HBR patients undergoing PCI with cobalt-chromium everolimus-eluting stents, DAPT for 1 or 3 months was noninferior to 6 or 12 months of DAPT for ischemic outcomes and may be associated with less major bleeding and a low incidence of stent thrombosis.     

Ticagrelor or Prasugrel in Patients With Acute Coronary Syndromes and Diabetes Mellitus

ObjectivesThe aim of this study was to assess the efficacy and safety of ticagrelor versus prasugrel in patients with diabetes mellitus (DM) presenting with acute coronary syndromes (ACS) in whom invasive therapy was planned.BackgroundThe efficacy and safety of ticagrelor versus prasugrel in patients with ACS with DM undergoing invasive treatment remain unknown.MethodsThis pre-specified analysis of the ISAR-REACT (Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment) 5 trial included 892 patients with ACS with DM and 3,124 patients with ACS without DM randomized to prasugrel or ticagrelor. The primary endpoint was a composite of death, myocardial infarction, or stroke; the safety endpoint was Bleeding Academic Research Consortium types 3 to 5 bleeding (both assessed 12 months after randomization).ResultsThe primary endpoint occurred in 51 patients (11.2%) in the ticagrelor group and 55 patients (13.0%) in the prasugrel group in the DM cohort (hazard ratio: 0.84; 95% confidence interval: 0.58 to 1.24; p = 0.383) and in 132 patients (8.6%) in the ticagrelor group and 81 patients (5.2%) in the prasugrel group in the non-DM cohort (hazard ratio: 1.70; 95% confidence interval: 1.29 to 2.24; p < 0.001). There was a significant treatment arm–by–diabetic status interaction (p_int = 0.0035). Bleeding Academic Research Consortium types 3 to 5 bleeding occurred in 27 patients (6.9%) in the ticagrelor group and 19 patients (5.5%) in the prasugrel group (p = 0.425) in the DM cohort and in 68 patients (5.2%) in the ticagrelor group and 60 patients (4.6%) in the prasugrel group in the non-DM cohort (p = 0.500).ConclusionsDM seems to affect the efficacy of ticagrelor and prasugrel in patients with ACS. In patients with DM, the efficacy of ticagrelor was comparable with that of prasugrel. (Prospective, Randomized Trial of Ticagrelor Versus Prasugrel in Patients With Acute Coronary Syndrome [ISAR-REACT 5]; NCT01944800)     

Development and Validation of a Practical Model to Identify Patients at Risk of Bleeding After TAVR

ObjectivesNo standardized algorithm exists to identify patients at risk of bleeding after transcatheter aortic valve replacement (TAVR). The aim of this study was to generate and validate a useful predictive model.BackgroundBleeding events after TAVR influence prognosis and quality of life and may be preventable.MethodsUsing machine learning and multivariate regression, more than 100 clinical variables from 5,185 consecutive patients undergoing TAVR in the prospective multicenter RISPEVA (Registro Italiano GISE sull’Impianto di Valvola Aortica Percutanea; NCT02713932) registry were analyzed in relation to Valve Academic Research Consortium-2 bleeding episodes at 1 month. The model’s performance was externally validated in 5,043 TAVR patients from the prospective multicenter POL-TAVI (Polish Registry of Transcatheter Aortic Valve Implantation) database.ResultsDerivation analyses generated a 6-item score (PREDICT-TAVR) comprising blood hemoglobin and serum iron concentrations, oral anticoagulation and dual antiplatelet therapy, common femoral artery diameter, and creatinine clearance. The 30-day area under the receiver-operating characteristic curve (AUC) was 0.80 (95% confidence interval [CI]: 0.75–0.83). Internal validation by optimism bootstrap-corrected AUC was 0.79 (95% CI: 0.75–0.83). Score quartiles were in graded relation to 30-day events (0.8%, 1.1%, 2.5%, and 8.5%; overall p <0.001). External validation produced a 30-day AUC of 0.78 (95% CI: 0.72–0.82). A simple nomogram and a web-based calculator were developed to predict individual patient probabilities. Landmark cumulative event analysis showed greatest bleeding risk differences for top versus lower score quartiles in the first 30 days, when most events occurred. Predictivity was maintained when omitting serum iron values.ConclusionsPREDICT-TAVR is a practical, validated, 6-item tool to identify patients at risk of bleeding post-TAVR that can assist in decision making and event prevention.     

Ticagrelor or Prasugrel in Patients With Acute Coronary Syndrome in Relation to Estimated Glomerular Filtration Rate

ObjectivesThe aim of this study was to assess the safety and efficacy of ticagrelor versus prasugrel for patients with acute coronary syndrome (ACS) according to their estimated glomerular filtration rates (eGFRs).BackgroundThe outcomes of ticagrelor versus prasugrel in patients with ACS according to eGFR have not been defined.MethodsPatients (n = 4,012) were categorized into 3 groups: low eGFR (<60 mL/min/1.73 m²), intermediate eGFR (≥60 and <90 mL/min/1.73 m²), and high eGFR (≥90 mL/min/1.73 m²). The primary endpoint was a composite of all-cause death, myocardial infarction, and stroke; the secondary safety endpoint was Bleeding Academic Research Consortium types 3 to 5 bleeding, both at 1 year.ResultsPatients with low eGFRs had a higher risk for the primary endpoint compared with patients with intermediate eGFRs (adjusted HR: 1.89; 95% CI: 1.46-2.46]) and those with high eGFRs (adjusted HR: 2.33; 95% CI: 1.57-3.46). A risk excess for low eGFR was also observed for bleeding (adjusted HR: 1.55 [95% CI: 1.12-2.13] vs intermediate eGFR; adjusted HR: 1.59 [95% CI: 1.01-2.50] vs high eGFR). However, eGFR did not affect the relative efficacy and safety of ticagrelor versus prasugrel. In patients with low eGFR, the primary endpoint occurred in 20.5% with ticagrelor and in 14.7% with prasugrel (HR: 1.47; 95% CI: 1.04-2.08; P = 0.029); there was no significant difference in bleeding.ConclusionsThese results show that among patients with ACS, reduction of eGFR is associated with increased risk for ischemic and bleeding events but has no significant impact on the relative efficacy and safety of ticagrelor versus prasugrel. (Prospective, Randomized Trial of Ticagrelor Versus Prasugrel in Patients With Acute Coronary Syndrome [ISAR-REACT 5]; NCT01944800)