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

Importance: Among patients undergoing percutaneous coronary intervention (PCI), it remains unclear whether the treatment efficacy of P2Y12 inhibitor monotherapy after a short course of dual antiplatelet therapy (DAPT) depends on the type of P2Y12 inhibitor. Objective: To assess the risks and benefits of ticagrelor monotherapy or clopidogrel monotherapy compared with standard DAPT after PCI. Data Sources: MEDLINE, Embase, TCTMD, and the European Society of Cardiology website were searched from inception to September 10, 2023, without language restriction. Study Selection: Included studies were randomized clinical trials comparing P2Y12 inhibitor monotherapy with DAPT on adjudicated end points in patients without indication to oral anticoagulation undergoing PCI. Data Extraction and Synthesis: Patient-level data provided by each trial were synthesized into a pooled dataset and analyzed using a 1-step mixed-effects model. The study is reported following the Preferred Reporting Items for Systematic Review and Meta-Analyses of Individual Participant Data. Main Outcomes and Measures: The primary objective was to determine noninferiority of ticagrelor or clopidogrel monotherapy vs DAPT on the composite of death, myocardial infarction (MI), or stroke in the per-protocol analysis with a 1.15 margin for the hazard ratio (HR). Key secondary end points were major bleeding and net adverse clinical events (NACE), including the primary end point and major bleeding. Results: Analyses included 6 randomized trials including 25 960 patients undergoing PCI, of whom 24 394 patients (12 403 patients receiving DAPT; 8292 patients receiving ticagrelor monotherapy; 3654 patients receiving clopidogrel monotherapy; 45 patients receiving prasugrel monotherapy) were retained in the per-protocol analysis. Trials of ticagrelor monotherapy were conducted in Asia, Europe, and North America; trials of clopidogrel monotherapy were all conducted in Asia. Ticagrelor was noninferior to DAPT for the primary end point (HR, 0.89; 95% CI, 0.74-1.06; P for noninferiority = .004), but clopidogrel was not noninferior (HR, 1.37; 95% CI, 1.01-1.87; P for noninferiority > .99), with this finding driven by noncardiovascular death. The risk of major bleeding was lower with both ticagrelor (HR, 0.47; 95% CI, 0.36-0.62; P < .001) and clopidogrel monotherapy (HR, 0.49; 95% CI, 0.30-0.81; P = .006; P for interaction = 0.88). NACE were lower with ticagrelor (HR, 0.74; 95% CI, 0.64-0.86, P < .001) but not with clopidogrel monotherapy (HR, 1.00; 95% CI, 0.78-1.28; P = .99; P for interaction = .04). Conclusions and Relevance: This systematic review and meta-analysis found that ticagrelor monotherapy was noninferior to DAPT for all-cause death, MI, or stroke and superior for major bleeding and NACE. Clopidogrel monotherapy was similarly associated with reduced bleeding but was not noninferior to DAPT for all-cause death, MI, or stroke, largely because of risk observed in 1 trial that exclusively included East Asian patients and a hazard that was driven by an excess of noncardiovascular death.

Sex-Based Outcomes of P2Y12 Inhibitor Monotherapy After Three Months of Dual Antiplatelet Therapy in Patients Undergoing Percutaneous Coronary Intervention.

BACKGROUND: In patients undergoing percutaneous coronary intervention (PCI) in the SMART-CHOICE trial, P2Y12 inhibitor monotherapy after three months of dual antiplatelet therapy (DAPT) achieved clinical outcomes comparable to those of 12 months of DAPT. Nonetheless, the effects of sex on these outcomes remain unknown. METHODS: This open-label, non-inferiority, randomized study, conducted in 33 hospitals in South Korea, included 2,993 patients undergoing PCI with drug-eluting stents. Patients were randomly assigned to receive DAPT (aspirin plus a P2Y12 inhibitor) for three months then P2Y12 inhibitor alone for nine months, or DAPT for the entire 12 months. The primary endpoints were major adverse cardiac and cerebrovascular events (a composite of all-cause death, myocardial infarction, or stroke) 12 months after the index procedure. The bleeding endpoints were Bleeding Academic Research Consortium (BARC) bleeding types 2 to 5. RESULTS: Of the patients, 795 (26.6%) were women, who were older and had a higher prevalence of hypertension, diabetes, and dyslipidemia than men. The sexes exhibited comparable primary endpoints (adjusted hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.55-1.55; P = 0.770) and bleeding endpoints (adjusted HR, 1.07; 95% CI, 0.63-1.81; P = 0.811). P2Y12 inhibitor monotherapy vs DAPT was associated with lower risk of BARC type 2 to 5 bleeding in women (adjusted HR, 0.40; 95% CI, 0.16-0.98; P = 0.045) but the difference was not statistically significant when using the Bonferroni correction. The primary endpoints were similar between treatment groups in both sexes. CONCLUSION: In both sexes undergoing PCI, P2Y12 inhibitor monotherapy after three months of DAPT achieved similar risks of the primary endpoints and the bleeding events compared with prolonged DAPT. Therefore, the benefits of early aspirin withdrawal with ongoing P2Y12 inhibitors may be comparable in women and men. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02079194.

Prevalence and Prognostic Implications of Worsening Renal Function After Acute Myocardial Infarction.

We sought to investigate the relation between worsening renal function (WRF) at 1-year follow-up and clinical outcomes at 3 years after acute myocardial infarction (AMI). We analyzed data from 13,104 patients enrolled in the national AMI registry from November 2011 to December 2015. Patients with all-cause death, recurrent myocardial infarction (re-MI), and rehospitalization for heart failure at 1-year follow-up after AMI were excluded. A total of 6,235 patients were extracted and divided into WRF and non-WRF groups. WRF was defined as a ≥25% decrease in estimated glomerular filtration rate (eGFR) from baseline to 1-year follow-up. The primary outcome was 3-year major adverse cardiac events, a composite of all-cause death, re-MI, and rehospitalization for heart failure. On average, a -1.5 ml/min/1.73 m2/y rate of decrease in eGFR was exhibited, and 575 patients (9.2%) exhibited WRF at 1-year follow-up. After multiple adjustments, WRF at 1-year follow-up was independently associated with increased risks of major adverse cardiac events (adjusted hazard ratio 1.498, 95% confidence interval 1.113 to 2.016, p = 0.01), all-cause death, and re-MI at 3-year follow-up. Older age, female, diabetes mellitus, hypertension, non-ST-segment elevation AMI, anterior AMI, anemia, left ventricular ejection fraction <35%, and baseline eGFR <30 ml/min/1.73 m2 were identified as independent predictors of WRF after AMI. In conclusion, WRF at 1-year follow-up after AMI intuitively seems like a risk marker indicating multiple co-morbidities. Monitoring serum creatinine in patients at 1-year follow-up after AMI may help to identify those who are at the highest risk and guide effective long-term therapeutics.

Impact of gender on mid-term prognosis of patients undergoing coronary artery bypass grafting.

OBJECTIVES: We evaluated the impact of sex on mid-term prognosis in patients who underwent coronary artery bypass grafting (CABG). Data on gender differences in current management or clinical outcomes after CABG are controversial, and there have been limited data focusing on them. METHODS: This was a retrospective and prospective, single-center, observational study. Between January 2001 and December 2017, 6613 patients who underwent CABG were enrolled from an institutional registry of Samsung Medical Center, Seoul, Korea (Clinicaltrials.gov, NCT03870815) and divided into two groups according to sex (female group, n = 1679 vs. male group, n = 4934). The primary outcome was cardiovascular death or myocardial infarction (MI) at 5 years. Propensity score matching analysis was performed to reduce confounding factors. RESULTS: During a mean follow-up duration of 54 months, a total of 252 cardiovascular death or MIs occurred (female, 78 [7.5%] vs. male, 174 [5.7%]). Multivariate analysis revealed no significant difference in the incidence of cardiovascular death or MI at 5 years between female and male groups (hazard ratio [HR] 1.05; 95% confidence interval [CI] 0.78 to 1.41; p = 0.735). After propensity score matching, the incidence of cardiovascular death or MI was still similar between the two groups (HR 1.08; 95% CI 0.76 to 1.54; p = 0.666). The similarity of long-term outcomes between the two groups was consistent across various subgroups. There was also no significant difference in the risk of 5-year cardiovascular death or MI between males and females according to age (pre- and postmenopausal status) (p for interaction = 0.437). CONCLUSIONS: After adjusting for baseline differences, sex does not appear to influence long-term risk of cardiovascular death or MI in patients undergoing CABG. CLINICAL TRIALS.GOV NUMBER: NCT03870815.

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

BACKGROUND: It 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). OBJECTIVES: We sought to assess the effects of P2Y12 inhibitor monotherapy after 1-month to 3-month DAPT vs standard DAPT in relation to PCI complexity. METHODS: We 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. RESULTS: Of 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; Pinteraction = 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; Pinteraction = 0.920). CONCLUSIONS: P2Y12 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).

Moderate-Intensity Statins Plus Ezetimibe vs. High-Intensity Statins After Coronary Revascularization: A Cohort Study.

PURPOSE: Whether moderate-intensity statins plus ezetimibe could be an alternative to high-intensity statins in patients with atherosclerotic cardiovascular disease is unclear. We compared the risk of adverse cardiovascular events in patients receiving moderate-intensity statins plus ezetimibe vs. high-intensity statins after a coronary revascularization procedure using data from a large cohort study. METHOD: Population-based cohort study using nationwide medical insurance data from Korea. Study participants (n = 20,070) underwent percutaneous coronary intervention or coronary artery bypass graft surgery between January 1, 2015, and December 31, 2016, and received moderate-intensity statins (atorvastatin 10-20 mg or rosuvastatin 5-10 mg) plus ezetimibe (n = 922) or high-intensity statins (atorvastatin 40-80 mg or rosuvastatin 20 mg; n = 19,148). The primary outcome was a composite of cardiovascular mortality, hospitalization for myocardial infarction (MI), hospitalization for stroke, or revascularization. RESULTS: At 12 months, the incidence rates of the primary outcome were 138.0 vs. 154.0 per 1000 person-years in the moderate-intensity stains plus ezetimibe and the high-intensity statins group, respectively. The fully adjusted hazard ratio [HR] for the primary outcome was 1.11 (95% confidence interval [CI] 0.86-1.42; p = 0.43). The multivariable-adjusted HR for a composite of cardiovascular mortality, hospitalization for MI, or hospitalization for stroke was 1.05 (95% CI 0.74-1.47; p = 0.80). During follow-up, the proportion of patients maintaining their initial lipid-lowering therapy was significantly higher in the moderate-intensity statins plus ezetimibe group than in the high-intensity statins group. CONCLUSIONS: Patients undergoing a coronary revascularization procedure who received moderate-intensity statins plus ezetimibe showed similar rates of major adverse cardiovascular events as patients who received high-intensity statins.

Effects of Statin Intensity on Long-term Outcomes After Coronary Artery Bypass Grafting.

BACKGROUND: The current study sought to investigate the association between statin intensity and long-term clinical outcomes according to initial clinical presentation after coronary artery bypass grafting (CABG). METHODS: The 6531 patients who underwent CABG included in this study were classified into 4 groups according to statin intensity: 731 in the no or low statin group (atorvastatin <10 mg), 2310 in the lower-moderate group (atorvastatin 10-mg equivalent), 2404 in the higher-moderate group (atorvastatin 20-mg equivalent), and 1086 in the high-intensity group (atorvastatin ≥ 40-mg equivalent). The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE) at 5 years. Multivariate Cox and inverse probability weighting methods were performed to adjust for baseline differences. RESULTS: At least moderate-intensity statin use was associated with significantly lower risk of 5-year MACCE compared with no or low-intensity statin use (hazard ratio [HR], 0.694; 95% confidence interval [CI], 0.493-0.977; P = .036). Among patients who were taking at least a moderate-intensity statin, both higher-moderate intensity (HR, 0.622; 95% CI, 0.479-0.807; P < .001) and high-intensity statin (HR, 0.613; 95% CI, 0.421-0.894; P = .011) groups showed significantly lower risks of MACCE than the lower-moderate intensity statin group at 5 years after CABG. There was no significant difference in the risk of MACCE between higher-moderate intensity and high-intensity statin groups (HR, 0.987; 95% CI, 0.661-1.475; P = .950). Multivariable Cox and inverse probability weighting methods yielded similar results. In a subgroup analysis compared with the use of a lower-moderate intensity statin, the use of a higher-moderate or high-intensity statin (equivalent dose with atorvastatin ≥20 mg) was associated with a significantly lower risk of MACCE among CABG patients who presented with acute coronary syndrome but not in those who presented with stable ischemic heart disease (interaction P = .001). CONCLUSIONS: The use of a lower-moderate intensity statin (atorvastatin 10-mg equivalent) was associated with relatively poorer long-term clinical outcomes than the use of higher-moderate or high-intensity statin, especially in acute coronary syndrome patients after CABG.

Coronary Microcirculatory Dysfunction and Acute Cellular Rejection After Heart Transplantation.

BACKGROUND: Acute cellular rejection is a major determinant of mortality and retransplantation after heart transplantation. We sought to evaluate the prognostic implications of coronary microcirculatory dysfunction assessed by index of microcirculatory resistance (IMR) for the risk of acute cellular rejection after heart transplantation. METHODS: The present study prospectively enrolled 154 heart transplant recipients who underwent scheduled coronary angiography and invasive coronary physiological assessment 1 month after transplantation. IMR is microcirculatory resistance under maximal hyperemia. By measuring hyperemic mean transit time using 3 injections (4 mL each) of room-temperature saline under maximal hyperemia, IMR was calculated as hyperemic distal coronary pressure×hyperemic mean transit time. The primary end point was biopsy-proven acute cellular rejection of grade ≥2R during 2 years of follow-up after transplantation and was compared by using multivariable Cox proportional hazards regression according to IMR. The incremental prognostic value of IMR, in addition to the model with clinical factors, was evaluated by comparison of C-index, net reclassification index, and integrated discrimination index. RESULTS: The mean age of recipients was 51.2±13.1 years (81.2% male), and the cumulative incidence of acute cellular rejection was 19.0% at 2 years. Patients with acute cellular rejection had significantly higher IMR values at 1 month than those without acute cellular rejection (23.1±8.6 versus 16.8±11.1, P=0.002). IMR was significantly associated with the risk of acute cellular rejection (per 5-U increase: adjusted hazard ratio, 1.18 [95% CI, 1.04-1.34], P=0.011) and the optimal cutoff value of IMR to predict acute cellular rejection was 15. Patients with IMR≥15 showed significantly higher risk of acute cellular rejection than those with IMR<15 (34.4% versus 3.8%; adjusted hazard ratio, 15.3 [95% CI 3.6-65.7], P<0.001). Addition of IMR to clinical variables showed significantly higher discriminant and reclassification ability for risk of acute cellular rejection (C-index 0.87 versus 0.74, P<0.001; net reclassification index 1.05, P<0.001; integrated discrimination index 0.20, P<0.001). CONCLUSIONS: Coronary microcirculatory dysfunction assessed by IMR measured early after heart transplantation showed significant association with the risk of acute cellular rejection. In addition to surveillance endomyocardial biopsy, early stratification using IMR could be a clinically useful tool to identify patients at higher risk of future acute cellular rejection after heart transplantation. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02798731.

P2Y12 inhibitor monotherapy in complex percutaneous coronary intervention: A post-hoc analysis of SMART-CHOICE randomized clinical trial.

BACKGROUND: It remains unclear whether P2Y12 monotherapy, especially clopidogrel, following short-duration dual antiplatelet therapy (DAPT) is associated with favorable outcomes in patients undergoing complex percutaneous coronary intervention (PCI). Therefore, this study analyzed the efficacy and safety of P2Y12 inhibitor monotherapy, mostly clopidogrel (78%), in complex PCI following short-term DAPT. METHODS: The post-hoc analysis of the SMART-CHOICE trial involving 2,993 patients included 498 cases of complex PCIs, defined by at least one of the following features: 3 vessels treated, ≥ 3 stents implanted, ≥ 3 lesions treated, bifurcation with ≥ 2 stents implanted, and a total stent length of ≥ 60 mm. The primary endpoint was major adverse cardiac and cerebrovascular event (MACCE), defined as the composite of all-cause death, myocardial infarction, and stroke. The primary safety endpoint included bleeding, defined as Bleeding Academic Research Consortium (BARC) types 2 to 5. RESULTS: Complex PCI group had a higher risk of MACCE (4.0% vs. 2.3%, hazard ratio [HR] = 1.74, 95% confidence interval [CI]: 1.05-2.89, p = 0.033) and a similar risk of BARC types 2-5 bleeding (2.6% vs. 2.6%, HR = 1.02, 95% CI: 0.56-1.86, p = 0.939) compared with those without complex PCIs. Patients undergoing complex PCIs, followed by P2Y12 inhibitor monotherapy and 12 months of DAPT exhibited similar rates of MACCE (3.8% vs. 4.2%, HR = 0.92, 95% CI: 0.38-2.21, p = 0.853). CONCLUSIONS: P2Y12 inhibitor monotherapy, mostly clopidogrel, following 3 months of DAPT did not increase ischemic events in patients with complex PCIs.

P2Y12 inhibitor monotherapy or dual antiplatelet therapy after coronary revascularisation: individual patient level meta-analysis of randomised controlled trials.

OBJECTIVE: To assess the risks and benefits of P2Y12 inhibitor monotherapy compared with dual antiplatelet therapy (DAPT) and whether these associations are modified by patients' characteristics. DESIGN: Individual patient level meta-analysis of randomised controlled trials. DATA SOURCES: Searches were conducted in Ovid Medline, Embase, and three websites (www.tctmd.com, www.escardio.org, www.acc.org/cardiosourceplus) from inception to 16 July 2020. The primary authors provided individual participant data. ELIGIBILITY CRITERIA: Randomised controlled trials comparing effects of oral P2Y12 monotherapy and DAPT on centrally adjudicated endpoints after coronary revascularisation in patients without an indication for oral anticoagulation. MAIN OUTCOME MEASURES: The primary outcome was a composite of all cause death, myocardial infarction, and stroke, tested for non-inferiority against a margin of 1.15 for the hazard ratio. The key safety endpoint was Bleeding Academic Research Consortium (BARC) type 3 or type 5 bleeding. RESULTS: The meta-analysis included data from six trials, including 24 096 patients. The primary outcome occurred in 283 (2.95%) patients with P2Y12 inhibitor monotherapy and 315 (3.27%) with DAPT in the per protocol population (hazard ratio 0.93, 95% confidence interval 0.79 to 1.09; P=0.005 for non-inferiority; P=0.38 for superiority; τ2=0.00) and in 303 (2.94%) with P2Y12 inhibitor monotherapy and 338 (3.36%) with DAPT in the intention to treat population (0.90, 0.77 to 1.05; P=0.18 for superiority; τ2=0.00). The treatment effect was consistent across all subgroups, except for sex (P for interaction=0.02), suggesting that P2Y12 inhibitor monotherapy lowers the risk of the primary ischaemic endpoint in women (hazard ratio 0.64, 0.46 to 0.89) but not in men (1.00, 0.83 to 1.19). The risk of bleeding was lower with P2Y12 inhibitor monotherapy than with DAPT (97 (0.89%) v 197 (1.83%); hazard ratio 0.49, 0.39 to 0.63; P<0.001; τ2=0.03), which was consistent across subgroups, except for type of P2Y12 inhibitor (P for interaction=0.02), suggesting greater benefit when a newer P2Y12 inhibitor rather than clopidogrel was part of the DAPT regimen. CONCLUSIONS: P2Y12 inhibitor monotherapy was associated with a similar risk of death, myocardial infarction, or stroke, with evidence that this association may be modified by sex, and a lower bleeding risk compared with DAPT. REGISTRATION: PROSPERO CRD42020176853.

Sex difference in long-term clinical outcomes after percutaneous coronary intervention: A propensity-matched analysis of National Health Insurance data in Republic of Korea.

OBJECTIVE: We investigated the gender difference in the 5-year outcome after percutaneous coronary intervention (PCI) using an unselected population data. BACKGROUND: Sex-specific outcome after percutaneous coronary intervention (PCI) is not consistent among studies. METHODS: A total of 48,783 patients were enrolled from a Korean nationwide cohort of PCI in year 2011. Outcomes adjusted with age and propensity for clinical characteristics were compared. Primary outcome was 5-year cumulative incidence of all-cause death. Nonfatal major adverse clinical event (MACE) consisting of revascularization, shock, or stroke was also assessed. RESULTS: In unadjusted analysis, women were older and had higher frequency of comorbidities including hypertension, hyperlipidemia, and diabetes compared to men (p < .001, all). Women had higher 5-year death risk than men (21.8 vs. 17.3%; hazard ratio [HR] 1.29, 95% confidential interval [CI] 1.23-1.34). In propensity score-matched analysis (N = 28,924), women had lower 5-year death risk (20.2 vs. 26.1%, HR 0.75, 95% CI 0.71-0.78). This lower death risk in women was consistent in subgroup analyses of age, risk factors, and clinical diagnosis including angina or acute myocardial infarction (p < .05, all). CONCLUSIONS: Older age and more common comorbidities in women contributed to the apparent worse outcome after PCI in women. After adjusting these disadvantages, women had better outcome after PCI than men.

Safety of 3-Month Dual Antiplatelet Therapy After Implantation of Ultrathin Sirolimus-Eluting Stents With Biodegradable Polymer (Orsiro): Results From the SMART-CHOICE Trial.

Background This study sought to investigate the safety of 3-month dual antiplatelet therapy (DAPT) in patients receiving ultrathin sirolimus-eluting stents with biodegradable polymer (Orsiro). Methods and Results The SMART-CHOICE (Smart Angioplasty Research Team: Comparison Between P2Y12 Antagonist Monotherapy vs Dual Anti- platelet Therapy in Patients Undergoing Implantation of Coronary Drug-Eluting Stents) randomized trial compared 3-month DAPT followed by P2Y12 inhibitor monotherapy with 12-month DAPT in 2993 patients undergoing percutaneous coronary intervention. The present analysis was a prespecified subgroup analysis for patients receiving Orsiro stents. As a post hoc analysis, comparisons between Orsiro and everolimus-eluting stents were also done among patients receiving 3-month DAPT. Of 972 patients receiving Orsiro stents, 481 patients were randomly assigned to 3-month DAPT and 491 to 12-month DAPT. At 12 months, the target vessel failure, defined as a composite of cardiac death, target vessel-related myocardial infarction, or target vessel revascularization, occurred in 8 patients (1.7%) in the 3-month DAPT group and in 14 patients (2.9%) in the 12-month DAPT group (hazard ratio [HR], 0.58; 95% CI, 0.24-1.39; P=0.22). In whole population who were randomly assigned to receive 3-month DAPT (n=1495), there was no significant difference in the target vessel failure between the Orsiro group and the everolimus-eluting stent group (n=1014) (1.7% versus 1.8%; HR, 0.96; 95% CI, 0.41-2.22; P=0.92). Conclusions In patients receiving Orsiro stents, clinical outcomes at 1 year were similar between the 3-month DAPT followed by P2Y12 inhibitor monotherapy and 12-month DAPT strategies. With 3-month DAPT, there was no significant difference in target vessel failure between Orsiro and everolimus-eluting stents. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02079194.

Practical guidance for P2Y12 inhibitors in acute myocardial infarction undergoing percutaneous coronary intervention.

AIMS: Potent P2Y12 inhibitors for dual antiplatelet therapy (DAPT) is crucial for managing acute myocardial infarction; however, the selection of drugs is based on limited clinical information such as age and body weight. The current study sought to develop and validate a new risk scoring system that can be used to guide the selection of potent P2Y12 inhibitors by balancing ischaemic benefit and bleeding risk. METHODS AND RESULTS: Derivation cohort of 10 687 patients who participated in the Korea Acute Myocardial Infarction Registry-National Institutes of Health study was used to construct a new scoring system. We combined the ischaemic and bleeding models to establish a simple clinical prediction score. Among the low score group (n = 1764), the observed bleeding risk (8.7% vs. 4.4%, P < 0.001) due to potent P2Y12 inhibitors exceeded ischaemic benefit (1.3% vs. 2.2%, P = 0.185) during 12 months. Conversely, the high score group (n = 1898) showed an overall benefit from taking potent P2Y12 inhibitors from the standpoint of observed ischaemic (17.1% vs. 8.6%, P < 0.001) and bleeding events (10.1% vs. 6.8%, P = 0.073). The performance of ischaemic [integrated area under the curve (iAUC) = 0.809] and bleeding model (iAUC = 0.655) was deemed to be acceptable. CONCLUSION: The new scoring system is a useful clinical tool for guiding DAPT by balancing ischaemic benefit and bleeding risk, especially among Asian populations. Further validation studies with other cohorts will be required to verify that the new system meets the needs of real clinical practice.

Differential effects of dual antiplatelet therapy in patients presented with acute coronary syndrome vs. stable ischaemic heart disease after coronary artery bypass grafting.

AIMS: The current study sought to evaluate whether long-term clinical outcomes according to the use of dual antiplatelet therapy (DAPT) or single antiplatelet therapy (SAPT) differed between acute coronary syndrome (ACS) and stable ischaemic heart disease (SIHD) patients who underwent coronary artery bypass grafting surgery (CABG). METHODS AND RESULTS: Between January 2001 and December 2017, 3199 patients with ACS (55.3%) and 2583 with SIHD (44.7%) who underwent isolated CABG were enrolled. The study population was stratified using DAPT or SAPT in ACS patients and SIHD patients. The primary outcome was a cardiovascular death or myocardial infarction (MI) at 5 years. After CABG, DAPT was more frequently used in patients with ACS than in those with SIHD [n = 1960 (61.3%) vs. n = 1313 (50.8%), P < 0.001]. Among patients with ACS, the DAPT group showed a significantly lower risk of cardiovascular death or MI at 5 years than the SAPT group [DAPT vs. SAPT, 4.0% vs. 7.8%, hazard ratio (HR) 0.521, 95% confidence interval (CI) 0.339-0.799; P = 0.003]. In contrast, among patients with SIHD, there was no significant difference in the rate of cardiovascular death or MI at 5 years between the use of DAPT and SAPT (4.0% vs. 4.0%, HR 0.991, 95% CI 0.604-1.626; P = 0.971). These findings were robust to multiple sensitivity analyses and competing risk analysis. In the subgroup analysis, the use of DAPT was associated with a significantly lower risk of cardiovascular death or MI among SIHD patients with a previous percutaneous coronary intervention (PCI), with a significant interaction between the use of DAPT and PCI history (interaction P = 0.011). CONCLUSION: Among ACS patients who underwent CABG, the use of DAPT was associated with lower cardiovascular death or MI than the use of SAPT, but this was not the case in SIHD patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03870815.

Preoperative cardiac troponin below the 99th-percentile upper reference limit and 30-day mortality after noncardiac surgery.

Preoperative high-sensitivity cardiac troponin (hs-cTn) above the 99th-percentile upper reference limit (URL) is associated with mortality after noncardiac surgery. This study aimed to evaluate whether preoperative hs-cTn concentrations above the lowest limit of detection (LOD) but below the 99th-percentile URL can predict mortality after noncardiac surgery.From January 2010 to April 2019, a total of 12,415 noncardiac surgical patients with preoperative hs-cTn I below the 99th-percentile URL were enrolled. The patients were divided into two groups according to preoperative hs-cTn I concentration: (1) [hs-cTn] below the LOD (6 ng/L), and (2) mildly elevated [hs-cTn] but below the 99th-percentile URL (40 ng/L). The primary outcome was 30-day mortality. Of the 12,415 patients enrolled, 7958 (64.1%) were in the LOD group whereas 4457 (35.9%) were in the mild elevation group. The incidence of 30-day mortality was significantly greater in the mild elevation group (2.1% vs. 4.0% hazard ratio [HR] 1.73; 95% confidence interval [CI] 1.39-2.16; p < 0.001) in the multivariate analyses. The propensity score matched analyses also produced a similar result (2.6% vs. 4.2% HR 1.61; 95% CI 1.26-2.07; p < 0.001). The threshold at which the risk of mortality increased corresponded to a preoperative hs-cTn I ≥ 12 ng/L. Patients with preoperative hs-cTn I above the LOD and below the 99th-percentile URL had greater 30-day mortality after noncardiac surgery.

Prognostic Impact of Residual Anatomic Disease Burden After Functionally Complete Revascularization.

BACKGROUND: Prognostic impact of residual anatomic disease burden after functionally complete percutaneous coronary intervention (PCI), defined by post-PCI fractional flow reserve (FFR) >0.80 would be a clinically relevant question. The current study evaluated clinical outcomes at 2 years according to residual Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) score (RSS) in patients who underwent functionally complete revascularization. METHODS: A total of 1910 patients (2095 revascularized vessels) with post-PCI FFR >0.80 were selected from the International Post-PCI FFR Registry. RSS was defined as the SYNTAX score recalculated after PCI, SYNTAX revascularization index was calculated as 100×(1-RSS/pre-PCI SYNTAX score), and post-PCI FFR was measured after completion of PCI. The primary outcome was target vessel failure (TVF; a composite of cardiac death, target vessel-related myocardial infarction, and clinically driven target vessel revascularization) at 2 years, and risk of TVF was compared according to tertile classification of RSS (0, 1-5, and >5) and post-PCI FFR (≥0.94, 0.87-0.93, and ≤0.86). RESULTS: After PCI, SYNTAX score was changed from 10.0 (Q1-Q3, 7.0-16.0) to 0.0 (Q1-Q3, 0.0-5.0) and FFR changed from 0.70±0.12 to 0.90±0.05. TVF at 2 years occurred in 4.9%, and patients with TVF showed higher pre-PCI SYNTAX score and lower post-PCI FFR than those without. However, there were no significant differences in SYNTAX revascularization index and RSS. The risk of TVF was not different according to tertile of RSS (log-rank P=0.851). Conversely, risk of TVF was different according to tertile of post-PCI FFR (log-rank P=0.009). Multivariable model showed the risk of TVF was significantly associated with post-PCI FFR (hazard ratio, 1.091 [95% CI, 1.032-1.153]; P=0.002) but not with RSS (hazard ratio, 0.969 [95% CI, 0.898-1.045]; P=0.417). CONCLUSIONS: Among patients who underwent functionally complete revascularization, residual anatomic disease burden assessed by RSS was not related with occurrence of TVF at 2 years. These results support the importance of functionally complete revascularization rather than angiographic complete revascularization. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT04012281.

Mildly Elevated Cardiac Troponin below the 99th-Percentile Upper Reference Limit after Noncardiac Surgery.

BACKGROUND AND OBJECTIVES: In patients with perioperative cardiac troponin (cTn) I below the 99th-percentile upper range of limit (URL), mortality according to cTn I level has not been fully evaluated. This study evaluated the association between postoperative cTn I level above the lowest limit of detection but within the 99th-percentile URL and 30-day mortality after noncardiac surgery. METHODS: Patients with cTn I values below the 99th-percentile URL during the perioperative period were divided into a no-elevation group with cTn I at the lowest limit of detection (6 ng/L) and a minor elevation group with cTn I elevation below the 99th percentile URL (6 ng/L < cTn I < 40 ng/L). The primary outcome was 30-day mortality. RESULTS: Of the 5,312 study participants, 2,582 (48.6%) were included in the no-elevation group and 2,730 (51.4%) were included in the minor elevation group. After propensity score-matching, the minor elevation group showed significantly increased 30-day mortality (0.5% vs. 2.3%; hazard ratio, 4.30; 95% confidence interval, 2.23-8.29; p<0.001). The estimated cutoff value of cTn I to predict 30-day mortality was 6 ng/L with the area under the receiver operating characteristic curve 0.657. CONCLUSIONS: A mild elevation of cTn I within the 99th-percentile URL after noncardiac surgery was significantly associated with increased 30-day mortality as compared with the lowest limit of detection. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0004244.

Clinical Implications of Early Exercise Treadmill Testing after Percutaneous Coronary Intervention in the Drug-eluting Stent Era.

BACKGROUND: Limited data are available on the clinical meaning of early routine exercise treadmill testing (ETT) after percutaneous coronary intervention (PCI) in the drug-eluting stent era. We aimed to determine the clinical utility and implications of early routine ETT after PCI. METHODS: This was a single-center, prospective cohort study. A total of 776 patients underwent ETT within 3 months after index PCI were analyzed. We classified patients into ETT positive (+) and negative (-) groups and compared major adverse cardiac events (MACE) including all-cause death, myocardial infarction, and coronary revascularization. RESULTS: The median follow-up duration was 19.6 months (interquartile range, 15.4 to 33.5 months). ETT was positive for 63 patients (17.1%) with single-vessel disease (VD) and 150 patients (36.9%) with multi-VD. Previous PCI, absence of thrombotic lesion, multi-VD, and residual Synergy Between PCI With Taxus and Cardiac Surgery (SYNTAX) score > 8 were independent predictors of ETT (+). Compared with the ETT (-) group, the ETT (+) group was associated with increased risk of MACE for patients with single-VD (18.1% vs. 52.3%; adjusted hazard ratio [HR], 2.67; 95% confidence interval [CI], 1.10-6.49; P = 0.03) and residual SYNTAX score ≤ 8 (26.5% vs. 42.1%; adjusted HR, 1.90; 95% CI, 1.09-3.30; P = 0.02), but not for patients with multi-VD and residual SYNTAX score > 8. CONCLUSION: Early routine ETT after PCI might be helpful for predicting clinical outcomes in patients with single-VD and residual SYNTAX score ≤ 8 but not multi-VD and residual SYNTAX score > 8.