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)     

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)     

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)     

Bleeding and Ischemic Outcomes With Ticagrelor Monotherapy According to Body Mass Index

BackgroundThere is a paucity of data regarding the safety and efficacy of different antiplatelet regimens according to standardized body mass index (BMI) categories.ObjectivesThe aim of this study was to investigate bleeding and ischemic outcomes according to BMI in the TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention) trial.MethodsThe TWILIGHT trial randomized high-risk patients to ticagrelor plus aspirin or ticagrelor plus placebo at 3 months after percutaneous coronary intervention. In this secondary analysis, patients were stratified by standard BMI categories, as recommended by the European Society of Cardiology Working Group on Thrombosis (normal weight [BMI 18.5-24.99 kg/m²], overweight [BMI 25-29.99 kg/m²], and obese [BMI ≥30 kg/m²]) and by median BMI, as prespecified in the protocol.ResultsAmong 7,038 patients randomized and with available BMI, 1,807 (25.7%) were normal weight, 2,927 (41.6%) were overweight, and 2,304 (32.7%) were obese. In normal-weight, overweight, and obese patients, ticagrelor monotherapy, compared with ticagrelor plus aspirin, reduced the primary endpoint of Bleeding Academic Research Consortium type 2, 3, or 5 bleeding (normal weight: HR: 0.48 [95% CI: 0.32-0.73]; overweight: HR: 0.57 [95% CI: 0.41-0.78]; obese: HR: 0.63 [95% CI: 0.44-0.91]; P for interaction = 0.627), without any increase in the composite ischemic endpoint of all-cause death, myocardial infarction, or stroke (normal weight: HR: 1.36 [95% CI: 0.84-2.19]; overweight: HR: 0.92 [95% CI: 0.63-1.35]; obese: HR: 0.84 [95% CI: 0.56-1.25]; P for interaction = 0.290). These findings were consistent with the prespecified analysis by median BMI.ConclusionsAmong high-risk patients undergoing percutaneous coronary intervention, ticagrelor monotherapy, compared with ticagrelor plus aspirin, reduced bleeding events without any increase in ischemic risk across different BMI categories.     

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 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.     

Ticagrelor With or Without Aspirin After PCI: The TWILIGHT Platelet Substudy

BackgroundAn evolving strategy in the setting of percutaneous coronary intervention (PCI) involves withdrawal of acetylsalicylic acid (ASA), or aspirin, while maintaining P2Y₁₂ inhibition. However, the pharmacodynamic effects of this approach on blood thrombogenicity and platelet reactivity remain unknown.ObjectivesThis study sought to compare the antithrombotic potency of ticagrelor alone versus ticagrelor plus ASA among high-risk patients undergoing PCI with drug-eluting stents.MethodsThis was a mechanistic substudy within the TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention) trial, which randomized patients undergoing PCI to ticagrelor plus placebo versus ticagrelor plus ASA following 3 months of dual antiplatelet therapy. Substudy participants were enrolled after randomization, at which time ex vivo assays to quantify thrombus size under dynamic flow conditions and platelet reactivity were performed. Pharmacodynamic assessments were repeated 1 to 6 months thereafter. The primary endpoint was thrombus size at the post-randomization visit with platelet reactivity following stimuli to arachidonic acid, collagen, adenosine diphosphate, and thrombin as secondary endpoints. Results were analyzed using analysis of covariance.ResultsA total of 51 patients were enrolled, among whom 42 underwent perfusion assays at baseline and follow-up with a median time between studies of 1.5 months. The adjusted mean difference in post-randomization thrombus area was similar between groups: −218.2 μm² (95% confidence interval [CI]: −575.9 to 139.9 μm²; p = 0.22). Markers sensitive to cyclo-oxygenase-1 blockade, including platelet reactivity in response to arachidonic acid (mean difference: 10.9 U; 95% CI: 1.9 to 19.9 U) and collagen (mean difference: 9.8 U; 95% CI: 0.8 to 18.8 U) stimuli were higher among patients receiving placebo, whereas levels of platelet reactivity were similar with adenosine diphosphate and thrombin.ConclusionsAmong high-risk patients receiving drug-eluting stents, the antithrombotic potency of ticagrelor monotherapy is similar to that of ticagrelor plus ASA with respect to ex vivo blood thrombogenicity, whereas markers sensitive to cyclo-oxygenase-1 blockade are increased in the absence of ASA. (Platelet Substudy of the TWILIGHT Trial; NCT04001374).     

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)     

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)     

Diabetes-Related Factors and the Effects of Ticagrelor Plus Aspirin in the THEMIS and THEMIS-PCI Trials

BackgroundTHEMIS (The Effect of Ticagrelor on Health Outcomes in Diabetes Mellitus Patients Intervention Study) (n = 19,220) and its pre-specified THEMIS-PCI (The Effect of Ticagrelor on Health Outcomes in Diabetes Mellitus Patients Intervention Study-Percutaneous Coronary Intervention) (n = 11,154) subanalysis showed, in individuals with type 2 diabetes mellitus (median duration 10.0 years; HbA_1c 7.1%) and stable coronary artery disease without prior myocardial infarction (MI) or stroke, that ticagrelor plus aspirin (compared with placebo plus aspirin) produced a favorable net clinical benefit (composite of all-cause mortality, MI, stroke, fatal bleeding, and intracranial bleeding) if the patients had a previous percutaneous coronary intervention.ObjectivesIn these post hoc analyses, the authors examined whether the primary efficacy outcome (cardiovascular death, MI, stroke: 3-point major adverse cardiovascular events [MACE]), primary safety outcome (Thrombolysis In Myocardial Infarction–defined major bleeding) and net clinical benefit varied with diabetes-related factors.MethodsOutcomes were analyzed across baseline diabetes duration, HbA_1c, and antihyperglycemic medications.ResultsIn THEMIS, the incidence of 3-point MACE increased with diabetes duration (6.7% for ≤5 years, 11.1% for >20 years) and HbA_1c (6.4% for ≤6.0%, 11.8% for >10.0%). The relative benefits of ticagrelor plus aspirin on 3-point MACE reduction (hazard ratio [HR]: 0.90; p = 0.04) were generally consistent across subgroups. Major bleeding event rate (overall: 1.6%) did not vary by diabetes duration or HbA_1c and was increased similarly by ticagrelor across all subgroups (HR: 2.32; p < 0.001). These findings were mirrored in THEMIS-PCI. The efficacy and safety of ticagrelor plus aspirin did not differ by baseline antihyperglycemic therapy. In THEMIS-PCI, but not THEMIS, ticagrelor generally produced favorable net clinical benefit across diabetes duration, HbA_1c, and antihyperglycemic medications.ConclusionTicagrelor plus aspirin yielded generally consistent and favorable net clinical benefit across the diabetes-related factors in THEMIS-PCI but not in the overall THEMIS population.     

Ticagrelor Monotherapy Versus Ticagrelor With Aspirin in Patients With ST-Segment Elevation Myocardial Infarction

ObjectivesThe aim of this study was to assess whether the effects of ticagrelor monotherapy after 3-month dual-antiplatelet therapy (DAPT) are consistent among patients presenting with ST-segment elevation myocardial infarction (STEMI), non–ST-segment elevation myocardial infarction, and unstable angina treated with drug-eluting stents.BackgroundTicagrelor monotherapy after short-term DAPT has not been investigated in patients with STEMI.MethodsThis was a pre-specified, stratified, subgroup analysis of the STEMI cohort from the TICO (Ticagrelor Monotherapy After 3 Months in the Patients Treated With New Generation Sirolimus Stent for Acute Coronary Syndrome) trial, which constituted 36% of the total population. The primary outcome was a composite of major bleeding and major adverse cardiac and cerebrovascular events (MACCE; death, myocardial infarction, stent thrombosis, stroke, or target vessel revascularization). The secondary outcomes were major bleeding and MACCE.ResultsThe incidence of the primary outcome was 4.4% in patients with STEMI (n = 1,103), 6.0% in those with non–ST-segment elevation myocardial infarction (n = 1,027), and 4.1% in those with unstable angina (n = 926), without statistical significance (p = 0.09). Compared with ticagrelor-based 12-month DAPT, ticagrelor monotherapy after 3-month DAPT showed consistent effects on the primary outcome across clinical presentations (p for interaction [p_int] = 0.64). Furthermore, the effect of ticagrelor monotherapy on the reduction of major bleeding was consistent across clinical presentations (p_int = 0.36). The effect of ticagrelor monotherapy on MACCE was also consistent in patients with STEMI, without evidence of a higher risk for MACCE (p_int = 0.14).ConclusionsThis pre-specified subgroup analysis revealed no heterogeneity in the effects of ticagrelor monotherapy after 3-month DAPT, compared with 12-month DAPT, for the primary outcome, major bleeding, and MACCE across clinical presentations including STEMI, though larger studies are needed to demonstrate these findings with adequate power. (Ticagrelor Monotherapy After 3 Months in the Patients Treated With New Generation Sirolimus Stent for Acute Coronary Syndrome [TICO Study]; NCT02494895)     

1-Month Dual-Antiplatelet Therapy Followed by Aspirin Monotherapy After Polymer-Free Drug-Coated Stent Implantation: One-Month DAPT Trial

ObjectivesThe aim of this study was to determine whether 1 month of dual-antiplatelet therapy (DAPT) followed by aspirin monotherapy after polymer-free drug-coated stent (PF-DCS) implantation is noninferior to 6 to 12 months of DAPT after biodegradable-polymer drug-eluting stent (BP-DES) implantation.BackgroundIt is necessary to determine the optimal minimal duration of DAPT followed by aspirin monotherapy after percutaneous coronary intervention (PCI).MethodsIn this trial, 3,020 patients with coronary artery disease considered for PCI for noncomplex lesions were randomized to 1-month DAPT after PF-DCS (n = 1,507) or 6- to 12-month DAPT after BP-DES (n = 1,513). The primary endpoint was the 1-year composite of cardiac death, nonfatal myocardial infarction, target vessel revascularization, stroke, or major bleeding (noninferiority hypothesis margin of 3%).ResultsThe primary endpoint occurred in 88 patients (5.9%) in the 1-month DAPT after PF-DCS group and 98 patients (6.5%) in the 6- to 12-month DAPT after BP-DES group (absolute difference −0.7%; upper limit of 1-sided 97.5% confidence interval: 1.33%; P < 0.001 for noninferiority). The occurrence of major bleeding was not different (1.7% vs 2.5%; P = 0.136). There was no difference in the occurrence of stent thrombosis (0.7% vs 0.8%; P = 0.842).ConclusionsAmong patients who underwent PCI for noncomplex lesions, 1-month DAPT followed by aspirin monotherapy after PF-DCS implantation was noninferior to 6- to 12-month DAPT after BP-DES implantation for the 1-year composite of cardiovascular events or major bleeding. The present findings need to be interpreted in the setting of different types of stents according to antiplatelet strategy. (A Randomized Controlled Comparison Between One Versus More Than Six Months of Dual Antiplatelet Therapy After Biolimus A9-Eluting Stent Implantation; NCT02513810)     

Clopidogrel Monotherapy After 1-Month Dual Antiplatelet Therapy in Patients With Diabetes Undergoing Percutaneous Coronary Intervention

BackgroundDiabetes was reported to be associated with an impaired response to clopidogrel.ObjectivesThe aim of this study was to evaluate the safety and efficacy of clopidogrel monotherapy after very short dual antiplatelet therapy (DAPT) in patients with diabetes undergoing percutaneous coronary intervention (PCI).MethodsA subgroup analysis was conducted on the basis of diabetes in the STOPDAPT-2 (Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent–2) Total Cohort (N = 5,997) (STOPDAPT-2, n = 3,009; STOPDAPT-2 ACS [Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent–2 for the Patients With ACS], n = 2,988), which randomly compared 1-month DAPT followed by clopidogrel monotherapy with 12-month DAPT with aspirin and clopidogrel after cobalt-chromium everolimus-eluting stent implantation. The primary endpoint was a composite of cardiovascular (cardiovascular death, myocardial infarction, definite stent thrombosis, or stroke) or bleeding (TIMI [Thrombolysis In Myocardial Infarction] major or minor) endpoints at 1 year.ResultsThere were 2,030 patients with diabetes (33.8%) and 3967 patients without diabetes (66.2%). Regardless of diabetes, the risk of 1-month DAPT relative to 12-month DAPT was not significant for the primary endpoint (diabetes, 3.58% vs 4.12% [HR: 0.87; 95% CI: 0.56-1.37; P = 0.55]; nondiabetes, 2.46% vs 2.49% [HR: 0.99; 95% CI: 0.67-1.48; P = 0.97]; P_interaction = 0.67) and for the cardiovascular endpoint (diabetes, 3.28% vs 3.05% [HR: 1.10; 95% CI: 0.67-1.81; P = 0.70]; nondiabetes, 1.95% vs 1.43% [HR: 1.38; 95% CI: 0.85-2.25; P = 0.20]; P_interaction = 0.52), while it was lower for the bleeding endpoint (diabetes, 0.30% vs 1.50% [HR: 0.20; 95% CI: 0.06-0.68; P = 0.01]; nondiabetes, 0.61% vs 1.21% [HR: 0.51; 95% CI: 0.25-1.01; P = 0.054]; P_interaction = 0.19).ConclusionsClopidogrel monotherapy after 1-month DAPT compared with 12-month DAPT reduced major bleeding events without an increase in cardiovascular events regardless of diabetes, although the findings should be considered as hypothesis generating, especially in patients with acute coronary syndrome, because of the inconclusive result in the STOPDAPT-2 ACS trial. (Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent–2 [STOPDAPT-2], NCT02619760; Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent–2 for the Patients With ACS [STOPDAPT-2 ACS], NCT03462498)     

Ticagrelor vs Prasugrel in a Contemporary Real-World Cohort Undergoing Percutaneous Coronary Intervention

BackgroundPotent P2Y₁₂ agents such as ticagrelor and prasugrel are increasingly utilized across the clinical spectrum of patients undergoing percutaneous coronary intervention (PCI). There is a paucity of data supporting their use in a patient population inclusive of both acute coronary syndrome (ACS) and chronic coronary syndrome (CCS) patients.ObjectivesThe authors compared the efficacy and safety of ticagrelor and prasugrel in a real-world contemporary PCI cohort.MethodsConsecutive patients undergoing PCI between 2014 and 2019 discharged on either prasugrel or ticagrelor were included from the prospectively collected institutional PCI registry. Primary endpoint was the composite of death and myocardial infarction (MI), with secondary outcomes including rates of bleeding, stroke, and target vessel revascularization at 1 year.ResultsOverall, 3,858 patients were included in the study (ticagrelor: n = 2,771; prasugrel: n = 1,087), and a majority (48.4%) underwent PCI in the context of CCS. Patients prescribed ticagrelor were more likely to be female, have a history of cerebrovascular disease, and have ACS presentation, while those receiving prasugrel were more likely to be White with a higher prevalence of prior revascularization. No difference in the risk of death or MI was noted across the groups (ticagrelor vs prasugrel: 3.3% vs 3.1%; HR: 0.88; 95% CI: 0.54-1.43; P = 0.59). Rates of target vessel revascularization were significantly lower in the ticagrelor cohort (9.3% vs 14.0%; adjusted HR: 0.71; 95% CI: 0.55-0.91; P = 0.007) with no differences in stroke or bleeding. The results were consistent in patients with CCS (HR: 0.84; 95% CI: 0.46-1.54) and ACS (HR: 1.18; 95% CI: 0.46-1.54), without evidence of interaction (P = 0.37), and confirmed across multivariable adjustment and propensity score stratification analysis.ConclusionsIn this contemporary patient population undergoing PCI, prasugrel and ticagrelor were associated with similar 1-year efficacy and safety.     

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.     

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)     

No Antithrombotic Therapy After Transcatheter Aortic Valve Replacement: Insight From the OCEAN-TAVI Registry

BackgroundSeveral trials demonstrated that aspirin monotherapy compared with aspirin plus clopidogrel is associated with a lower incidence of bleeding without an increased risk of ischemic events in patients after transcatheter aortic valve replacement (TAVR); however, there remains a paucity of data to prove the necessity of even aspirin monotherapy.ObjectivesThis study aimed to compare clinical outcomes and valve performance of the 3 different antithrombotic strategies post-TAVR from the OCEAN-TAVI (Optimized transCathEter vAlvular iNtervention) registry.MethodsPatients who received anticoagulation or had procedural complications were excluded. The remaining patients were classified into 3 groups according to the antithrombotic regimen at discharge: 1) nonantithrombotic therapy (None); 2) single-antiplatelet therapy (SAPT); and 3) dual-antiplatelet therapy (DAPT). The primary outcome was the incidence of net adverse clinical events (NACEs) (ie, cardiovascular death, stroke, myocardial infarction, and life-threatening or major bleeding).ResultsOverall, 3,575 TAVR patients were included (None, 293; SAPT, 1,354; DAPT, 1,928). The median follow-up period was 841 days (IQR: 597-1,340 days). The incidence of NACEs did not differ between the groups (None vs SAPT: adjusted HR [aHR]: 1.18; P = 0.45; None vs DAPT: aHR: 1.09; P = 0.67). There was a lower incidence of all bleeding in patients with no antithrombotics (None vs SAPT: aHR: 0.63; P = 0.12; None vs DAPT: aHR: 0.51; P = 0.04). The valve performance was similar among the groups. Leaflet thrombosis was detected in 8.5% of the nonantithrombotic group.ConclusionsCompared with SAPT/DAPT, the nonantithrombotic strategy was not associated with an increased risk of NACEs and potentially reduced the risk of bleeding events. The nonantithrombotic strategy may be an acceptable alternative to SAPT/DAPT in selected patients with TAVR.     

Effect of CYP2C19 Genotype on Ischemic Outcomes During Oral P2Y12 Inhibitor Therapy: A Meta-Analysis

ObjectivesThe aim of this study was to examine the effect of CYP2C19 genotype on clinical outcomes in patients with coronary artery disease (CAD) who predominantly underwent percutaneous coronary intervention (PCI), comparing those treated with ticagrelor or prasugrel versus clopidogrel.BackgroundThe effect of CYP2C19 genotype on treatment outcomes with ticagrelor or prasugrel compared with clopidogrel is unclear.MethodsDatabases through February 19, 2020, were searched for studies reporting the effect of CYP2C19 genotype on ischemic outcomes during ticagrelor or prasugrel versus clopidogrel treatment. Study eligibility required outcomes reported for CYP2C19 genotype status and clopidogrel and alternative P2Y₁₂ inhibitors in patients with CAD with at least 50% undergoing PCI. The primary analysis consisted of randomized controlled trials (RCTs). A secondary analysis was conducted by adding non-RCTs to the primary analysis. The primary outcome was a composite of cardiovascular death, myocardial infarction, stroke, stent thrombosis, and severe recurrent ischemia. Meta-analysis was conducted to compare the 2 drug regimens and test interaction with CYP2C19 genotype.ResultsOf 1,335 studies identified, 7 RCTs were included (15,949 patients, mean age 62 years; 77% had PCI, 98% had acute coronary syndromes). Statistical heterogeneity was minimal, and risk for bias was low. Ticagrelor and prasugrel compared with clopidogrel resulted in a significant reduction in ischemic events (relative risk: 0.70; 95% confidence interval: 0.59 to 0.83) in CYP2C19 loss-of-function carriers but not in noncarriers (relative risk: 1.0; 95% confidence interval: 0.80 to 1.25). The test of interaction on the basis of CYP2C19 genotype status was statistically significant (p = 0.013), suggesting that CYP2C19 genotype modified the effect. An additional 4 observational studies were found, and adding them to the analysis provided the same conclusions (p value of the test of interaction <0.001).ConclusionsThe effect of ticagrelor or prasugrel compared with clopidogrel in reducing ischemic events in patients with CAD who predominantly undergo PCI is based primarily on the presence of CYP2C19 loss-of-function carrier status. These results support genetic testing prior to prescribing P2Y₁₂ inhibitor therapy.     

Evaluation of Dual Versus Triple Therapy by Landmark Analysis in the RE-DUAL PCI Trial

ObjectivesThe aim of this study was to explore the early versus late benefits and risks of dabigatran dual therapy versus warfarin triple therapy in the RE-DUAL PCI (Randomized Evaluation of Dual Antithrombotic Therapy With Dabigatran Versus Triple Therapy With Warfarin in Patients With Nonvalvular Atrial Fibrillation Undergoing Percutaneous Coronary Intervention) trial.BackgroundPatients with atrial fibrillation who undergo percutaneous coronary intervention are at increased risk for both bleeding and thrombotic events.MethodsA total of 2,725 patients with atrial fibrillation underwent percutaneous coronary intervention and were randomized to receive dabigatran 110 mg, or dabigatran 150 mg plus a P2Y₁₂ inhibitor (and no aspirin), or warfarin plus a P2Y₁₂ inhibitor plus aspirin. Landmark analysis was performed at 30 and 90 days.ResultsThere was a consistent and large reduction in major or clinically relevant nonmajor bleeding in patients randomized to dual therapy during the first 30 days (110 mg: hazard ratio [HR]: 0.45; 95% confidence interval [CI]: 0.31 to 0.66; p < 0.0001; 150 mg: HR: 0.46; 95% CI: 0.30 to 0.72; p = 0.0006) compared with warfarin triple therapy. There was early net clinical benefit in both dabigatran groups versus warfarin (110 mg: HR: 0.65; 95% CI: 0.47 to 0.88; p = 0.0062; 150 mg: HR: 0.54; 95% CI: 0.37 to 0.79; p = 0.0015), due to larger reductions in bleeding than increased thrombotic events for dabigatran 110 mg and bleeding reduction without increased thrombotic risk for dabigatran 150 mg dual therapy versus warfarin triple therapy. After the removal of aspirin in the warfarin group, bleeding remained lower with dabigatran 110 mg and was similar with dabigatran 150 mg versus warfarin.ConclusionsIn RE-DUAL PCI, in which patients in the dual-therapy arms were treated with aspirin for an average of only 1.6 days, there was early net clinical benefit with both doses of dabigatran dual therapy, without an increase in thrombotic events with dabigatran 150 mg. This could be helpful in the subset of patients with elevated risk for both bleeding and thrombotic events.     

P2Y12 Inhibitor or Aspirin Following Dual Antiplatelet Therapy After Percutaneous Coronary Intervention: A Network Meta-Analysis

BackgroundIt is still unknown which antiplatelet monotherapy should be continued after a period of dual antiplatelet therapy (DAPT) in patients undergoing percutaneous coronary intervention (PCI).ObjectivesThe aim of this study was to compare aspirin vs P2Y₁₂ inhibitor (P2Y₁₂-I) monotherapy after dual antiplatelet therapy (DAPT) discontinuation in patients undergoing percutaneous coronary intervention (PCI).MethodsRandomized studies enrolling patients undergoing PCI with second-generation drug-eluting stents and comparing aspirin or P2Y₁₂-I monotherapy after DAPT discontinuation vs prolonged DAPT or aspirin vs P2Y₁₂-I monotherapy after DAPT were included. Primary efficacy and safety endpoints were myocardial infarction (MI) and major bleeding (MB), respectively. Point estimates for dichotomous outcomes were pooled using frequentist and Bayesian frameworks. Sensitivity analyses and treatment hierarchy were performed.ResultsNineteen studies encompassing 73,126 patients were included. The transitivity assumption was met. Under the frequentist framework, patients receiving aspirin had a significantly higher risk for MI compared with P2Y₁₂-I monotherapy (risk ratio: 1.32; 95% CI: 1.08-1.62). Compared with DAPT, both monotherapies reduced MB, but only P2Y₁₂-I showed equivalent efficacy in preventing MI. No significant differences in MB, death, and other thrombotic outcomes were observed. However, point estimates for the risk for stent thrombosis and stroke favored P2Y₁₂-I monotherapy. Consistent results were found in a fixed-effects model and the Bayesian framework, with all models having adequate convergence. P2Y₁₂-I vs aspirin monotherapy had the highest probability of being ranked first for reduction of all assessed outcomes.ConclusionsP2Y₁₂-I monotherapy following DAPT discontinuation after PCI is associated with a significantly lower risk for MI and similar risk for MB, suggesting a potentially relevant net clinical benefit vs aspirin monotherapy. These findings strengthen the rationale for further studies directly comparing the 2 monotherapies after DAPT in PCI patients.