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.

Sex differences in myocardial injury after non-cardiac surgery and postoperative mortality.

BACKGROUND: Myocardial injury after non-cardiac surgery (MINS) has recently been accepted as a predictor of mortality. However, sex differences in the incidence of MINS and survival thereafter are not fully understood. This study aimed to compare the incidence of MINS and mortality among male and female patients. METHODS: This single-center study was conducted using the database of a large tertiary referral hospital. Consecutive patients with cardiac troponin (cTn) detected within 30 days after non-cardiac surgery performed between January 2010 and June 2019 were grouped according to sex. The incidence of MINS and mortality of patients with MINS were compared between men and women. RESULTS: Of the 33,311 patients, 18,546 (55.7%) were men and 14,765 (44.3%) were women. In a multivariable analysis, women showed a significantly lower incidence of MINS than did men (17.9% vs. 14.2%; odds ratio, 0.76; 95% confidence interval [CI], 0.71-0.81; P < 0.001). In patients with MINS, the propensity-score-matched analysis showed that 30-day mortality did not differ according to sex, but mortality in females was significantly lower than that in males during the overall follow-up (33.0% vs. 25.7%; hazard ratio, 0.75; 95% CI, 0.66-0.84; P < 0.001). CONCLUSION: The incidence of MINS was lower in women than in men. In patients with MINS, female sex may be associated with a survival benefit. Further studies are needed to confirm these findings.

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.

Impact of Clinical and Lesion Features on Outcomes After Percutaneous Coronary Intervention in Bifurcation Lesions.

Background: Bifurcation percutaneous coronary intervention (PCI) is associated with higher risk of clinical events. Objectives: This study aimed to determine clinical and lesion features that predict adverse outcomes, and to evaluate the differential prognostic impact of these features in patients undergoing PCI for bifurcation lesions. Methods: We analyzed 5,537 patients from the BIFURCAT (comBined Insights From the Unified RAIN and COBIS bifurcAtion regisTries) registry. The primary outcome was major adverse cardiac events (MACE) at 2-year follow-up; secondary outcomes included hard endpoints (all-cause death, myocardial infarction) and lesion-oriented clinical outcomes (LOCO) (target-vessel myocardial infarction, target lesion revascularization). The least absolute shrinkage and selection operator (LASSO) model was used for feature selection. Results: During the 2-year follow-up period, MACE occurred in 492 patients (8.9%). The LASSO model identified 5 clinical features (old age, chronic renal disease, diabetes mellitus, current smoking, and left ventricular dysfunction) and 4 lesion features (left main disease, proximal main branch disease, side branch disease, and a small main branch diameter) as significant features that predict MACE. A combination of all 9 features improved the predictive value for MACE compared with clinical and lesion features (area under the receiver-operating characteristics curve: 0.657 vs 0.636 vs 0.581; P < 0.001). For secondary endpoints, the clinical features had a higher impact than lesion features on hard endpoints, whereas lesion features had a higher impact than clinical features on LOCO. Conclusions: In bifurcation PCI, 9 features were associated with MACE. Clinical features were predominant predictors for hard endpoints, and lesion features were predominant for predicting LOCO. Clinical and lesion features have distinct values, and both should be considered in bifurcation PCI.

P2Y12 inhibitor monotherapy in patients undergoing percutaneous coronary intervention.

For 20 years, dual antiplatelet therapy (DAPT), consisting of the combination of aspirin and a platelet P2Y12 receptor inhibitor, has been the gold standard of antithrombotic pharmacology after percutaneous coronary intervention (PCI). In the past 5 years, several investigations have challenged this paradigm by testing the efficacy and safety of P2Y12 inhibitor monotherapy (that is, without aspirin) following a short course of DAPT. Collectively, these studies suggested a reduction in the risk of major bleeding and no significant increase in thrombotic or ischaemic events compared with guideline-recommended DAPT. Current recommendations are evolving to inform clinical practice on the ideal candidates for P2Y12 inhibitor monotherapy after PCI. Generalizing the results of studies of P2Y12 inhibitor monotherapy requires a thorough understanding of their design, populations, interventions, comparators and results. In this Review, we provide an up-to-date overview on the use of P2Y12 inhibitor monotherapy after PCI, including supporting pharmacodynamic and clinical evidence, practical recommendations and future directions.

The current status and outcomes of in-hospital P2Y12 receptor inhibitor switching in Korean patients with acute myocardial infarction.

BACKGROUND/AIMS: While switching strategies of P2Y12 receptor inhibitors (RIs) have sometimes been used in acute myocardial infarction (AMI) patients, the current status of in-hospital P2Y12RI switching remains unknown. METHODS: Overall, 8,476 AMI patients who underwent successful revascularization from Korea Acute Myocardial Infarction Registry-National Institute of Health (KAMIR-NIH) were divided according to in-hospital P2Y12RI strategies, and net adverse cardiovascular events (NACEs), defined as a composite of cardiac death, non-fatal myocardial infarction (MI), stroke, or thrombolysis in myocardial infarction (TIMI) major bleeding during hospitalization were compared. RESULTS: Patients with in-hospital P2Y12RI switching accounted for 16.5%, of which 867 patients were switched from clopidogrel to potent P2Y12RI (C-P) and 532 patients from potent P2Y12RI to clopidogrel (P-C). There were no differences in NACEs among the unchanged clopidogrel, the unchanged potent P2Y12RIs, and the P2Y12RI switching groups. However, compared to the unchanged clopidogrel group, the C-P group had a higher incidence of non-fatal MI, and the P-C group had a higher incidence of TIMI major bleeding. In clinical events of in-hospital P2Y12RI switching, 90.9% of non-fatal MI occurred during pre-switching clopidogrel administration, 60.7% of TIMI major bleeding was related to pre-switching P2Y12RIs, and 71.4% of TIMI major bleeding was related to potent P2Y12RIs. Only 21.6% of the P2Y12RI switching group switched to P2Y12RIs after a loading dose (LD); however, there were no differences in clinical events between patients with and without LD. CONCLUSION: In-hospital P2Y12RI switching occurred occasionally, but had relatively similar clinical outcomes compared to unchanged P2Y12RIs in Korean AMI patients. Non-fatal MI and bleeding appeared to be mainly related to pre-switching P2Y12RIs.

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.

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

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

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.

Incidence and Predictors of Stent Thrombosis in Patients Treated with Stents for Coronary Bifurcation Narrowing (From the BIFURCAT Registry).

Percutaneous coronary interventions performed at coronary bifurcations yield high rates of stent thrombosis (ST). The aim of the present study was to investigate the predictors of ST in contemporary coronary bifurcation percutaneous coronary interventions. We retrospectively investigated the BIFURCAT (comBined Insights From the Unified RAIN and COBIS bifurcAtion regisTries) registry on coronary bifurcations to assess the incidence and predictors of definite ST, which were the study primary endpoints. Predictors of ST among patients on dual antiplatelet therapy (DAPT) were also examined. A total of 5330 patients were included. After a mean 2-years follow-up, 64 (1.2%) patients experienced ST. 42 (65.6%) ST patients were on DAPT. At multivariable analysis, age (HR 1.02, CI 1.01 to 1.05, p = 0,027), smoking status (HR 2.57, CI 1.49 to 4.44, p = 0.001), chronic kidney disease (HR 2.26, CI 1.24 to 4.12, p = 0.007) and a 2-stent strategy (HR 2.38, CI 1.37 to 4.14, p = 0.002) were independent predictors of ST, whereas intracoronary imaging (HR 0.42, CI 0.23 to 0.78, p = 0.006) and final kissing balloon (FKB) (HR 0.48, CI 0.29 to 0.82, p = 0.007) were protective against ST. Among patients on DAPT, smoking status and a 2-stent strategy significantly increased the risk of ST, while intracoronary imaging and FKB reduced the risk. In conclusion, age, smoking status, chronic kidney disease and a 2-stent strategy were significant predictors of ST, whereas intracoronary imaging use and FKB had a protective effect. Only smoking status and a 2-stent strategy significantly predicted ST in DAPT subgroup, while intracoronary imaging and FKB had a protective role.

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.

Prognosis of Myocardial Injury After Non-Cardiac Surgery in Adults Aged Younger Than 45 Years.

BACKGROUND: This study compared myocardial injury after non-cardiac surgery (MINS) and mortalities between patients under and over the age of 45 years.Methods and Results:From January 2010 and June 2019, patients with cardiac troponin measurement within 30 days after non-cardiac surgery were enrolled and divided into groups according to age: >45 (≥45 years) and <45 (<45 years). Further analyses were conducted only in patients who were diagnosed with MINS. The outcomes were MINS and 30-day mortality. Of the 35,223 patients, 31,161 (88.5%) patients were in the >45-year group and 4,062 (11.5%) were in the <45-year group. After adjustment with inverse probability of weighting, the <45-years group showed a lower incidence of MINS and cardiovascular mortality (16.6% vs. 11.7%; odds ratio, 0.77; 95% confidence interval [CI], 0.69-0.84; P<0.001 and 0.4% vs. 0.2%; hazard ratio [HR], 0.41; 95% CI, 0.19-0.88; P=0.02, respectively). In a comparison of only the <45-years group, MINS was associated with increased 30-day mortality (0.7% vs. 10.3%; HR, 10.48; 95% CI, 6.18-17.78; P<0.001), but the mortalities of patients with MINS did not differ according to age. CONCLUSIONS: MINS has a comparable prognostic impact in patients aged under and over 45 years; therefore, future studies need to also consider patients aged <45 years regarding risk factors of MINS and screening of perioperative troponin elevation.

Smoking may be more harmful to vasospastic angina patients who take antiplatelet agents due to the interaction: Results of Korean prospective multi-center cohort.

BACKGROUND: The interaction between smoking and the use of antiplatelet agents on the prognosis of vasospastic angina (VA) is rarely investigated. METHODS: VA-Korea is a nation-wide multi-center registry with prospective design (n = 1812). The primary endpoint was the composite occurrence of acute coronary syndrome (ACS), symptomatic arrhythmia, and cardiac death. Log-rank test and Cox proportional hazard model were for statistical analysis. Also, we conducted interaction analysis in both additive and multiplicative scales between smoking and antiplatelet agents among VA patients. For additive scale interaction, relative excess risk due to interaction (RERI) was calculated and for multiplicative scale interaction, the ratio of hazard ratio (HR) was calculated. All statistical analysis conducted by Stata Ver 16.1. RESULTS: Patients who were smoking and using antiplatelet agents had the highest incidence rate in the primary composite outcome. The incidence rate was 3.49 per 1,000 person-month (95% CI: 2.30-5.30, log-rank test for primary outcome p = 0.017) and HR of smoking and using antiplatelet agents was 1.66 (95%CI: 0.98-2.81). The adjusted RERI of smoking and using antiplatelet agents was 1.10 (p = 0.009), and the adjusted ratio of HR of smoking and using antiplatelet agents was 3.32 (p = 0.019). The current study observed the interaction between smoking and using antiplatelet agents in both additive and multiplicative scales. CONCLUSIONS: Smoking was associated with higher rates of unfavorable clinical outcomes among VA patients taking antiplatelet agents. This suggested that VA patients, especially those using antiplatelet agents should quit smoking.

Associations Between Preoperative Glucose and Hemoglobin A1c Level and Myocardial Injury After Noncardiac Surgery.

Background Perioperative blood glucose level has shown an association with postoperative outcomes. We compared the incidences of myocardial injury after noncardiac surgery (MINS) and 30-day mortality, according to preoperative blood glucose and hemoglobin A1c (HbA1c) levels. Methods and Results The patients were divided according to blood glucose level within 1 day before surgery. The hyperglycemia group was defined with fasting glucose >140 mg/dL or random glucose >180 mg/dL. In addition, we compared the outcomes according to HbA1c >6.5% among patients with available HbA1c within 3 months before surgery. The primary outcome was MINS, and 30-day mortality was also compared. A total of 12 304 patients were enrolled and divided into 2 groups: 8324 (67.7%) in the normal group and 3980 (32.3%) in the hyperglycemia group. After adjustment with inverse probability of weighting, the hyperglycemia group exhibited significantly higher incidences of MINS and 30-day mortality (18.7% versus 27.6%; odds ratio, 1.29; 95% CI, 1.18-1.42; P<0.001; and 2.0% versus 5.1%; hazard ratio, 2.00; 95% CI, 1.61-2.49; P<0.001, respectively). In contrast to blood glucose, HbA1c was not associated with MINS or 30-day mortality. Conclusions Preoperative hyperglycemia was associated with MINS and 30-day mortality, whereas HbA1c was not. Immediate glucose control may be more crucial than long-term glucose control in patients undergoing noncardiac surgery. Registration URL: https://www.cris.nih.go.kr; Unique identifier: KCT0004244.

Intraoperative blood loss may be associated with myocardial injury after non-cardiac surgery.

BACKGROUND: This study aimed to evaluate the association between intraoperative blood loss and myocardial injury after non-cardiac surgery (MINS), which is a severe and common postoperative complication. METHODS: We compared the incidence of MINS based on significant intraoperative bleeding, defined as an absolute hemoglobin level < 7 g/dL, a relative hemoglobin level less than 50% of the preoperative measurement, or need for packed red cell transfusion. We also estimated a threshold for intraoperative hemoglobin level associated with MINS. RESULTS: We stratified a total of 15,926 non-cardiac surgical patients with intraoperative hemoglobin and postoperative cardiac troponin (cTn) measurements according to the occurrence of significant intraoperative bleeding; 13,416 (84.2%) had no significant bleeding while 2,510 (15.8%) did have significant bleeding. After an adjustment with inverse probability weighting, the incidence of MINS was higher in the significant bleeding group (35.2% vs. 16.4%; odds ratio, 1.58; 95% confidence interval, 1.43-1.75; p < 0.001). The threshold of intraoperative hemoglobin associated with MINS was estimated to be 9.9 g/dL with an area under the curve of 0.643. CONCLUSION: Intraoperative blood loss appeared to be associated with MINS. Further studies are needed to confirm these findings. CLINICAL REGISTRATION: The cohort was registered before patient enrollment at https://cris.nih.go.kr (KCT0004244).