Seasonal variation and prognosis in patients with acute myocardial infarction complicated by cardiogenic shock.

Background: Little is known about the association between seasonal variation and prognosis in patients with CS caused by AMI. Objectives: We investigated the 12-month clinical outcomes in patients treated with percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) complicated by cardiogenic shock (CS) according to season. Methods: A total of 695 patients undergoing PCI for AMI complicated by CS was enrolled from 12 centers in South Korea. The study patients were divided into four groups according to season in which the AMI with CS occurred (spring, n = 178 vs. summer, n = 155 vs. autumn, n = 182 vs. winter, n = 180). We compared major adverse cardiovascular events (MACEs; the composite of cardiac death, myocardial infarction, re-hospitalization due to heart failure, and any revascularization) between the four groups. Results: The risk of MACE during the 12 months after CS was similar in the four groups: spring, 68 patients, vs. summer, 69, vs. autumn, 73, vs. winter, 68 (p = 0.587). Multivariate Cox-regression analysis revealed no significant difference in 12-month MACE among groups compared to the spring group after inverse probability of treatment weighting adjustment (summer, HR 1.40, 95 % CI 0.98-1.99, p = 0.062; autumn, HR 1.26, 95 % CI 0.89-1.80, p = 0.193; winter, HR 1.18, 95 % CI 0.83-1.67, p = 0.356). The similarity of MACE between the four groups was consistent across a variety of subgroups. Conclusions: After adjusting for baseline differences, seasonal variation seems not to influence the mid-term risk of 12-month MACE in patients treated with PCI for AMI complicated by CS. Condensed abstract: Data are limited regarding the association between seasonal variation and prognosis in patients with cardiogenic shock (CS) caused by AMI. This study divided patients undergoing PCI for AMI complicated by CS into four groups based on the season of occurrence and found no significant differences in 12-month MACE between the groups after adjusting for bias and confounding factors. Multivariate analysis revealed consistent MACE similarity across subgroups. The study suggests that seasonal variation has no impact on the mid-term risk of 12-month MACE in patients with CS caused by AMI, after adjusting for baseline differences. Trial registration: ClinicalTrials.gov NCT02985008RESCUE (REtrospective and prospective observational Study to investigate Clinical oUtcomes and Efficacy of left ventricular assist device for Korean patients with cardiogenic shock), NCT02985008, Registered December 5, 2016 - retrospectively and prospectively. Irb information: This study was approved by the institutional review board of Samsung Medical Center (Reference number: 2016-03-130).

Efficacy and safety of durable versus biodegradable polymer drug-eluting stents in patients with acute myocardial infarction complicated by cardiogenic shock.

The clinical impact of different polymer technologies in newer-generation drug-eluting stents (DESs) for patients with acute myocardial infarction (AMI) complicated by cardiogenic shock (CS) remains poorly understood. We investigated the efficacy and safety of durable polymer DESs (DP-DESs) compared with biodegradable polymer DESs (BP-DESs). A total of 620 patients who underwent percutaneous coronary intervention with newer-generation DESs for AMI complicated by CS was divided into two groups based on polymer technology: the DP-DES group (n = 374) and the BP-DES group (n = 246). The primary outcome was target vessel failure (TVF) during a 12-month follow-up, defined as a composite of cardiac death, myocardial infarction, or target vessel revascularization. Both the DP-DES and BP-DES groups exhibited low stent thrombosis rates (1.3% vs. 1.6%, p = 0.660). The risk of TVF did not significantly differ between the two groups (34.2% vs. 28.5%, hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.69-1.29, p = 0.721). This finding remained consistent after adjustment with inverse probability of treatment weighting (28.1% vs. 25.1%, HR 0.98, 95% CI 0.77-1.27, p = 0.899). In AMI patients complicated by CS, the risk of a composite of cardiac death, myocardial infarction, or target vessel revascularization was not significantly different between those treated with DP-DESs and those treated with BP-DESs.Trial registration: RESCUE registry, https://clinicaltrials.gov/ct2/show/NCT02985008 , NCT02985008.

Prognostic effect of sex according to shock severity in patients with acute myocardial infarction complicated by cardiogenic shock.

BACKGROUND: Sex disparities in cardiogenic shock (CS) treatment are controversial, and the prognostic implications of sex remain unclear in CS caused by acute myocardial infarction (AMI). OBJECTIVES: This study aimed to evaluate the prognostic effect of sex according to the severity of CS in patients undergoing percutaneous coronary intervention (PCI) for AMI complicated by CS. METHODS: We assessed 695 patients from 12 tertiary centers in South Korea who underwent PCI for AMI complicated by CS, and analyzed outcomes by sex (female [n = 184] vs. male [n = 511]). We compared a 12-month patient-oriented composite endpoint (POCE, defined as a composite of all-cause mortality, myocardial infarction, re-hospitalization due to heart failure, and repeat revascularization) between the sexes, respective of SCAI shock stage C&D or E. Propensity score-matched analysis was performed to reduce bias. RESULTS: We found that the female group was older and had higher vasoactive-inotropic and IABP-SHOCK II scores than the male group, with findings consistent across SCAI shock stages. During the 12-month follow-up period, multivariate analysis revealed no significant differences in POCE (HR 1.01, 95% CI 0.67-1.53, p = 0.963 for SCAI stage C&D, HR 1.24, 95% CI 0.84-1.84, p = 0.286 for SCAI stage E) between females and males. After propensity score matching, the incidence of POCE (HR 1.47, 95% CI 0.79-2.72, p = 0.220 for SCAI stage C&D, HR 0.88, 95% CI 0.49-1.57, p = 0.665 for SCAI stage E) was similar between sexes. CONCLUSIONS: Sex does not appear to influence the risk of 12-month POCE in patients treated with PCI for CS caused by AMI, irrespective of shock severity. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT02985008. RESCUE (REtrospective and prospective observational Study to investigate Clinical oUtcomes and Efficacy of left ventricular assist device for Korean patients with cardiogenic shock), NCT02985008, Registered December 5, 2016 - retrospectively and prospectively. IRB INFORMATION: This study was approved by the institutional review board of Samsung Medical Center (Reference number: 2016-03-130).

Association of Prophylactic Distal Perfusion Cannulation With Mortality in Patients Receiving Venoarterial Extracorporeal Membrane Oxygenation.

Prophylactic distal perfusion cannulation (PDPC) is protectively associated with limb ischemia in patients with cardiogenic shock (CS) receiving femoral venoarterial extracorporeal membrane oxygenation (VA-ECMO). However, evidence supporting its benefits beyond limb ischemia reduction is scarce. We aimed to investigate whether PDPC, compared with no-PDPC, is associated with a lower risk of mortality in patients receiving VA-ECMO. From a multicenter registry, we identified 479 patients who underwent VA-ECMO support for refractory CS. The association of PDPC with 30-day mortality was assessed using multiple methods, including instrumental variable analysis, overlap weighting, and propensity score matching. Of the 479 patients, 154 (32.2%) received PDPC. The 30-day mortality rate was 33.1% in the PDPC group and 53.2% in the no-PDPC group. The instrumental variable analysis showed a protective association of PDPC with 30-day mortality (absolute risk difference -16.7%, 95% confidence interval -31.3% to -2.1%; relative risk 0.68, 95% confidence interval 0.40 to 0.96). The findings were consistent in the overlap-weighted analysis (hazard ratio 0.68, 95% confidence interval 0.48 to 0.98) and in the propensity score-matched analysis (hazard ratio 0.67, 95% confidence interval 0.45 to 1.00). There were no significant differences in safety outcomes, including stroke, ECMO site bleeding, gastrointestinal bleeding, and sepsis, between PDPC and no-PDPC. In conclusion, PDPC was associated with a lower risk of mortality at 30 days in patients with CS receiving VA-ECMO. The efficacy and safety of PDPC merit evaluation in future randomized studies. Clinical trial registration: ClinicalTrials.gov; NCT02985008.

Impact of Acute Myocardial Infarction Type on Prognosis in Female Patients With Cardiogenic Shock.

There are limited data about mid-term prognosis according to acute myocardial infarction (AMI) type in female patients with AMI complicated by cardiogenic shock (CS). In this study, we evaluated the impact of AMI type on prognosis in female patients who underwent percutaneous coronary intervention (PCI) for AMI complicated by CS. A total of 184 female patients who underwent PCI for AMI complicated by CS were enrolled from 12 centers in the Republic of Korea. Patients were divided into 2 groups according to AMI type: the ST-segment elevation myocardial infarction (n = 114) and the non-ST-segment elevation myocardial infarction (n = 70) group. Primary outcome was a major adverse cardiac event (MACE) (defined as a composite of cardiac death, myocardial infarction, or repeat revascularization). Propensity-score matching analysis was performed to reduce selection bias and potential confounding factors. During 12-month follow-up, a total of 73 MACEs occurred (ST-segment elevation myocardial infarction group, 47 [41.2%] vs non-ST-segment elevation myocardial infarction group, 26 [37.1%], p = 0.643). Multivariate analysis revealed no significant difference in the incidence of MACE at 12 months between the 2 groups (adjusted hazard ratio 1.16, 95% confidence interval 0.70 to 2.37, p = 0.646). After propensity-score matching, the incidence of MACE at 12 months remained similar between the 2 groups (hazard ratio 1.31, 95% confidence interval 0.69 to 2.52, p = 0.413). The similarity in MACEs between the 2 groups was consistent across a variety of subgroups. In conclusion, after adjusting for baseline differences, AMI clinical type did not appear to increase the risk of MACEs at 12 months in female patients who underwent emergency PCI for AMI complicated by CS.

Aspirin vs Clopidogrel for Long-term Maintenance After Coronary Stenting in Patients With Diabetes: A Post Hoc Analysis of the HOST-EXAM Trial.

Importance: Selecting the optimal antiplatelet agent in patients who have received percutaneous coronary intervention is especially important in those with diabetes due to the heightened risk of ischemic events in this population. Studies on the efficacy and safety of clopidogrel vs aspirin for long-term maintenance after percutaneous coronary intervention in patients with diabetes are lacking. Objective: To investigate cardiovascular outcomes with clopidogrel vs aspirin in patients with and without diabetes. Design, Setting, and Participants: This was a post hoc analysis of the HOST-EXAM randomized clinical trial, an investigator-initiated, prospective, randomized, open-label, multicenter trial performed at 37 centers in Korea. Patients who received dual antiplatelet therapy without clinical events for 6 to 18 months after percutaneous coronary intervention with drug-eluting stents were enrolled from March 2014 to May 2018 with follow-up at 6, 12, 18, and 24 months. All 5438 patients in the original trial were included in this analysis, which was conducted from June to October 2021. Interventions and Exposures: Enrolled patients were randomized 1:1 to clopidogrel or aspirin monotherapy. Subgroup analyses were performed by the presence of diabetes. Main Outcomes and Measures: The main outcome was primary composite end point of all-cause death, nonfatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and major bleeding (Bleeding Academic Research Consortium type 3 or 5) at 24-month follow-up. Results: Of 5438 patients (mean [SD] age, 63.5 [10.7] years; 1384 [25.5%] female), 1860 (34.2%) had diabetes (925 in the clopidogrel arm and 935 in the aspirin arm), and 5338 (98.2%) completed follow-up. The rate of the primary composite end point was significantly lower in the clopidogrel group compared to the aspirin group in patients with diabetes (6.3% vs 9.2%; hazard ratio [HR], 0.69; 95% CI, 0.49-0.96; P = .03; absolute risk difference [ARD], 2.7%; number needed to treat [NNT], 37) and without diabetes (5.3% vs 7.0%; HR, 0.76; 95% CI, 0.58-1.00; P = .046; ARD, 1.6%, NNT, 63; P for interaction = .65). The presence of diabetes was not associated with a difference in benefit observed with clopidogrel monotherapy over aspirin for the thrombotic composite end point (HR, 0.68; 95% CI, 0.45-1.04 for patients with diabetes vs HR, 0.68; 95% CI, 0.49-0.93 for those without; P for interaction = .99) and any bleeding with Bleeding Academic Research Consortium 2, 3, or 5 (HR, 0.65; 95% CI, 0.39-1.09 for patients with diabetes vs HR, 0.74; 95% CI, 0.48-1.13 for those without; P for interaction = .71). Conclusion and Relevance: In this study, clopidogrel monotherapy was associated with a lower rate of the primary composite end point compared to aspirin monotherapy as long-term maintenance therapy after dual antiplatelet therapy for coronary stenting in both patients with and without diabetes. Clopidogrel might thus be considered rather than aspirin in patients who have undergone coronary stenting and successfully completed dual antiplatelet therapy, regardless of diabetes status. Trial Registration: ClinicalTrials.gov Identifier: NCT02044250.

Non-culprit left main coronary artery disease in acute myocardial infarction complicated by cardiogenic shock.

OBJECTIVES: We evaluated the clinical impact of residual non-culprit left main coronary artery disease (LMCAD) on prognosis in patients undergoing emergent percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) complicated by cardiogenic shock (CS). METHODS: A total of 429 patients who underwent PCI for AMI complicated by CS was enrolled from 12 centers in the Republic of Korea. The patients were divided into two groups according to presence of non-culprit LMCAD or not: the LMCAD non-culprit group (n = 43) and the no LMCAD group (n = 386). Primary outcome was major adverse cardiac event (MACE, defined as a composite of cardiac death, myocardial infarction, or repeat revascularization). Propensity score matching analysis was performed to reduce selection bias and potential confounding factors. RESULTS: During a 12-month follow-up, a total of 168 MACEs occurred (LMCAD non-culprit group, 17 [39.5%] vs. no LMCAD group, 151 [39.1%]). Multivariate analysis revealed no significant difference in the incidence of MACE at 12 months between the LMCAD non-culprit and no LMCAD groups (adjusted hazard ratio [HR] 0.97, 95% confidence interval [CI] 0.58 to 1.62, p = 0.901). After propensity score matching, the incidence of MACE was still similar between the two groups (HR 0.64; 95% CI 0.33 to 1.23; p = 0.180). The similarity of MACEs between the two groups was consistent across a variety of subgroups. CONCLUSIONS: After adjusting for baseline differences, residual non-culprit LMCAD does not appear to increase the risk of MACEs at 12 months in patients undergoing emergent PCI for AMI complicated by CS.

Safety and Efficacy of Everolimus-Eluting Bioresorbable Vascular Scaffold Versus Second-Generation Drug-Eluting Stents in Real-World Practice.

BACKGROUND: The risk of device thrombosis and device-oriented clinical outcomes with bioresorbable vascular scaffold (BVS) was reported to be significantly higher than with contemporary drug-eluting stents (DESs). However, optimal device implantation may improve clinical outcomes in patients receiving BVS. The current study evaluated mid-term safety and efficacy of Absorb BVS with meticulous device optimization under intravascular imaging guidance. METHODS: The SMART-REWARD and PERSPECTIVE-PCI registries in Korea prospectively enrolled 390 patients with BVS and 675 patients with DES, respectively. The primary endpoint was target vessel failure (TVF) at 2 years and the secondary major endpoint was patient-oriented composite outcome (POCO) at 2 years. RESULTS: Patient-level pooled analysis evaluated 1,003 patients (377 patients with BVS and 626 patients with DES). Mean scaffold diameter per lesion was 3.24 ± 0.30 mm in BVS group. Most BVSs were implanted with pre-dilatation (90.9%), intravascular imaging guidance (74.9%), and post-dilatation (73.1%) at proximal to mid segment (81.9%) in target vessel. Patients treated with BVS showed comparable risks of 2-year TVF (2.9% vs. 3.7%, adjusted hazard ratio [HR], 1.283, 95% confidence interval [CI], 0.487-3.378, P = 0.615) and 2-year POCO (4.5% vs. 5.9%, adjusted HR, 1.413, 95% CI, 0.663-3.012, P = 0.370) than those with DES. The rate of 2-year definite or probable device thrombosis (0.3% vs. 0.5%, P = 0.424) was also similar. The sensitivity analyses consistently showed comparable risk of TVF and POCO between the 2 groups. CONCLUSION: With meticulous device optimization under imaging guidance and avoidance of implantation in small vessels, BVS showed comparable risks of 2-year TVF and device thrombosis with DES. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02601404, NCT04265443.

Long-term Effects of P2Y12 Inhibitor Monotherapy After Percutaneous Coronary Intervention: 3-Year Follow-up of the SMART-CHOICE Randomized Clinical Trial.

Importance: Although P2Y12 inhibitor monotherapy after a minimum period of dual antiplatelet therapy (DAPT) is a well-known way to reduce the risk of bleeding after percutaneous coronary intervention (PCI), data comparing long-term clinical outcomes between P2Y12 inhibitor monotherapy and extended DAPT in patients undergoing PCI have been unavailable. Objective: To identify the long-term safety and efficacy of P2Y12 inhibitor monotherapy following 3 months of DAPT after PCI. Design, Setting, and Participants: The Smart Angioplasty Research Team: Comparison Between P2Y12 Antagonist Monotherapy and Dual Antiplatelet Therapy in Patients Undergoing Implantation of Coronary Drug-Eluting Stents (SMART-CHOICE) trial was an open-label, noninferiority, randomized clinical trial, enrolling patients who underwent PCI with drug-eluting stent at 33 hospitals in Korea from March 2014 through July 2017. Clinical follow-up was extended to 3 years and completed in August 2020. Interventions: Patients were randomly assigned to either P2Y12 inhibitor monotherapy after 3 months of DAPT or DAPT for 12 months or longer. Main Outcomes and Measures: The primary end point was major adverse cardiac and cerebrovascular events (a composite of all-cause death, myocardial infarction, or stroke) at 3 years. The secondary end points included the components of the primary end point, bleeding (defined as Bleeding Academic Research Consortium [BARC] types 2-5), and major bleeding (BARC types 3-5). Results: In total, 2993 patients were randomly assigned to receive P2Y12 inhibitor monotherapy after 3 months of DAPT (1495 patients [50%]; mean [SD] age, 64.6 [10.7] years; 1087 [72.7%] male) or prolonged DAPT (1498 patients [50%]; mean [SD] age, 64.6 [10.7] years; 1111 [74.2%] male) after PCI. At 3 years, the primary end point occurred in 87 individuals (6.3%) in the P2Y12 inhibitor monotherapy group and 83 (6.1%) in the prolonged DAPT group (hazard ratio [HR], 1.06 [95% CI, 0.79-1.44]; P = .69). P2Y12 inhibitor monotherapy significantly reduced the risk of bleeding (BARC types 2-5: 112 [3.2%] vs 44 [8.2%]; HR, 0.39 [95% CI, 0.28-0.55]; P < .001) and major bleeding (BARC types 3-5; 17 [1.2%] vs 31 [2.4%]; HR, 0.56 [95% CI, 0.31-0.99]; P = .048), compared with prolonged DAPT. The landmark analyses between 3 months and 3 years and per-protocol analyses showed consistent results. Conclusions and Relevance: Among patients who underwent PCI and completed 3-month DAPT, P2Y12 inhibitor monotherapy was associated with a lower risk of clinically relevant major bleeding than prolonged DAPT. Although the 3-year risk of ischemic cardiovascular events was comparable between the 2 groups, this result should be interpreted with caution owing to the limited number of events and sample size. Trial Registration: ClinicalTrials.gov Identifier: NCT02079194.

Clinical Significance of Serum Lactate in Acute Myocardial Infarction: A Cardiac Magnetic Resonance Imaging Study.

Little is known about causality and the pathological mechanism underlying the association of serum lactate with myocardial injury in patients with acute myocardial infarction (AMI). We evaluated data from 360 AMI patients undergoing percutaneous coronary intervention (PCI) using cardiovascular magnetic resonance imaging (CMR). Of these, 119 patients had serum lactate levels > 2.5 mmol/L on admission (high serum lactate group), whereas 241 patients had serum lactate levels ≤ 2.5 mmol/L (low serum lactate group). We compared the myocardial infarct size assessed by CMR between the two groups and performed inverse probability of treatment weighting (IPTW). In CMR analysis, myocardial infarct size was significantly greater in the high serum lactate group than in the low serum lactate group (22.0 ± 11.4% in the high serum lactate group vs. 18.9 ± 10.5% in the low serum lactate group; p = 0.011). The result was consistent after IPTW adjustment (21.5 ± 11.1% vs. 19.2 ± 10.4%; p = 0.044). In multivariate analysis, high serum lactate was associated with larger myocardial infarct (odds ratio 1.59; 95% confidence interval 1.00-2.51; p = 0.048). High serum lactate could predict advanced myocardial injury in AMI patients undergoing PCI.

Clinical significance of lactate clearance in patients with cardiogenic shock: results from the RESCUE registry.

BACKGROUND: Limited data are available on the clinical significance of lactate clearance (LC) in patients with cardiogenic shock (CS). This study investigated the prognostic role of LC in CS patients. METHODS: We analyzed data from 628 patients in the RESCUE registry, a multicenter, observational cohort enrolled between January 2014 and December 2018. Univariable logistic regression analysis was performed to determine the prognostic implications of 24 h LC, and then patients were divided into two groups according to the cut-off value of 24 h LC (high lactate clearance [HLC] group vs. low lactate clearance [LLC] group). The primary outcome was in-hospital mortality. We also assessed all-cause mortality at 12 month follow-up and compared the prognostic performance of 24 h LC according to initial serum lactate level. RESULTS: In the univariable logistic regression analysis, 24 h LC was associated with in-hospital mortality (odds ratio 0.989, 95% confidence interval [CI] 0.985-0.993, p < 0.001), and the cut-off value for the LC of the study population was 64%. The HLC group (initial 24 h LC ≥ 64%, n = 333) had a significantly lower incidence of in-hospital death than the LLC group (n = 295) (25.5% in the HLC group vs. 42.7% in the LLC group, p < 0.001). During 12 months of follow-up, the cumulative incidence of all-cause death was significantly lower in the HLC group than in the LLC group (33.0% vs. 48.8%; hazard ratio 0.55; 95% CI 0.42-0.70; p < 0.001). In subgroup analysis, 24 h LC predicted in-hospital mortality better in patients with initial serum lactate > 5 mmol/L than in those with serum lactate ≤ 5 mmol/L (c-statistics of initial serum lactate > 5 mmol/L = 0.782 vs. c-statistics of initial serum lactate ≤ 5 mmol/L = 0.660, p = 0.011). CONCLUSIONS: Higher LC during the early phase of CS was associated with reduced risk of in-hospital and 12 month all-cause mortalities. Patients with LC ≥ 64% during the 24 h after CS onset could expect a favorable prognosis, especially those with an initial serum lactate > 5 mmol/L. TRIAL REGISTRATION: RESCUE (REtrospective and prospective observational Study to investigate Clinical oUtcomes and Efficacy of left ventricular assist device for Korean patients with cardiogenic shock), NCT02985008, Registered December 5, 2016-retrospectively and prospectively registered, https://clinicaltrials.gov/ct2/show/record/NCT02985008.

Old Age and Myocardial Injury in ST-Segment Elevation Myocardial Infarction.

BACKGROUND: Little is known about the causality and pathological mechanism underlying the association between old age and myocardial injury in patients with ST-segment elevation myocardial infarction (STEMI). We evaluated the association between old age and myocardial injury in STEMI patients undergoing primary percutaneous coronary intervention (PCI) using cardiovascular magnetic resonance imaging (CMR). METHODS: A total of 279 patients with STEMI who underwent primary PCI and CMR were enrolled. Of these, 52 patients were over the age of 70 years (18.6%, Age ≥70 group) and 227 patients were under the age of 70 years (81.4%, Age <70 group) at STEMI occurrence. We compared myocardial infarct size on CMR according to age at STEMI occurrence and performed inverse probability of treatment weighting. RESULTS: On CMR analysis, myocardial infarct size on CMR tended to be greater in the Age ≥70 group than in the Age <70 group (21.2 ± 10.2% versus 19.5 ± 11.1%; p = 0.072). After performing inverse probability of treatment weighting adjustment, myocardial infarct size was significantly greater in the Age ≥70 group compared with the Age <70 group (22.6 ± 10.4% versus 19.6 ± 11.1%; p = 0.001). Subgroup analysis of patients older than 70 years revealed no significant difference in myocardial infarct size according to sex (20.1 ± 11.5% in females versus 20.4 ± 9.9% in males; p = 0.901). CONCLUSIONS: Despite appropriate coronary revascularization, old age was associated with greater extent of myocardial injury in STEMI patients.

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.

Association between polyvascular disease and clinical outcomes in patients with cardiogenic shock: Results from the RESCUE registry.

BACKGROUND: Clinical implications of systemic atherosclerosis in patients with cardiogenic shock (CS) remain unclear. This study investigated the association between polyvascular disease (PVD) and clinical outcome in CS patients. METHODS: A total of 1247 CS patients was enrolled from the RESCUE registry, a multicenter, observational cohort between January 2014 and December 2018. They were divided into two groups according to presence of PVD, defined as ≥2 coexistence of coronary artery disease, peripheral arterial disease, or cerebrovascular disease. Primary outcome was all-cause death during 12 months of follow-up. RESULTS: 136 (10.9%) patients were diagnosed with PVD. The risk of 12-month all-cause death was significantly higher in the PVD group than in the non-PVD group (54.4% versus 40.4%, adjusted hazard ratio [HR] 1.31, 95% confidence interval [CI] 1.02-1.69, p = 0.034). There was a significant interaction between PVD and vasoactive inotropic score (VIS) (p for interaction = 0.014). Among the 945 patients with VIS <84, PVD was associated with a higher risk of 12-month all-cause death (unadjusted HR 1.77, 95% CI 1.30-2.41, p = 0.030); among the 302 patients with VIS ≥84, the incidence of 12-month all-cause death was similar between the PVD and non-PVD groups (unadjusted HR 1.03, 95% CI 0.68-1.56, p = 0.301). CONCLUSIONS: Presence of PVD was associated with 12-month all-cause mortality in patients with CS, especially for less severe forms of CS patients with VIS <84. Clinicaltrials.govnumber:NCT02985008.

P2Y12 Inhibitor Monotherapy Versus Conventional Dual Antiplatelet Therapy or Aspirin Monotherapy in Acute Coronary Syndrome: A Pooled Analysis of the SMART-DATE and SMART-CHOICE Trials.

Controversy remains regarding the optimal antiplatelet regimen in patients with acute coronary syndrome (ACS). This study sought to investigate the efficacy and safety of P2Y12 inhibitor monotherapy compared with conventional dual antiplatelet therapy (DAPT) and aspirin monotherapy in patients with ACS undergoing percutaneous coronary intervention. Data on 4,453 patients were pooled from SMART-DATE and SMART-CHOICE randomized trials. Antiplatelet therapy regimens were categorized as P2Y12 inhibitor monotherapy (P2Y12 inhibitor monotherapy after 3-month DAPT), conventional DAPT (12-month or longer DAPT), and aspirin monotherapy (aspirin monotherapy after 6-month DAPT). The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE, a composite of all-cause death, myocardial infarction, and stroke). Inverse-probability of treatment-weighted (IPTW) analysis was performed. At 1 year, patients in the P2Y12 inhibitor monotherapy had a comparable risk of MACCE compared with those in the conventional DAPT (IPTW-adjusted hazard ratio [HR], 0.655; 95% confidence interval [CI] 0.393 to 1.094; p = 0.106), and tended to have a lower risk of MACCE than those in the aspirin monotherapy (IPTW-adjusted HR, 0.606; 95% CI, 0.347 to 1.058; p = 0.078). The adjusted hazard for the Bleeding Academic Research Consortium (BARC) type 2 to 5 bleeding was significantly lower in P2Y12 inhibitor monotherapy than in conventional DAPT (IPTW-adjusted HR, 0.341; 95% CI, 0.190 to 0.614; p < 0.001) and in aspirin monotherapy (IPTW-adjusted HR, 0.359; 95% CI, 0.182 to 0.708; p = 0.003). In conclusion, among patients with ACS undergoing PCI, P2Y12 inhibitor monotherapy after 3-month DAPT reduced risk of bleeding compared with conventional DAPT and aspirin monotherapy after 6-month DAPT without increasing MACCE.

P2Y12 inhibitor monotherapy after coronary stenting according to type of P2Y12 inhibitor.

OBJECTIVE: To compare P2Y12 inhibitor monotherapy after 3-month dual antiplatelet therapy (DAPT) with 12-month DAPT according to the type of P2Y12 inhibitor in patients undergoing percutaneous coronary intervention (PCI). METHODS: The Smart Angioplasty Research Team: Comparison Between P2Y12 Antagonist Monotherapy vs Dual Antiplatelet Therapy in Patients Undergoing Implantation of Coronary Drug-Eluting Stents (SMART-CHOICE) randomised trial compared 3-month DAPT followed by P2Y12 inhibitor monotherapy with 12-month DAPT. In this trial, 2993 patients undergoing successful PCI with drug-eluting stent were enrolled in Korea. As a prespecified analysis, P2Y12 inhibitor monotherapy after 3-month DAPT versus 12-month DAPT were compared among patients receiving clopidogrel and those receiving potent P2Y12 inhibitor (ticagrelor or prasugrel), respectively. The primary endpoint was a composite of all-cause death, myocardial infarction or stroke at 12 months after the index procedure. RESULTS: Among 2993 patients (mean age 64 years), 58.2% presented with acute coronary syndrome. Clopidogrel was prescribed in 2312 patients (77.2%) and a potent P2Y12 inhibitor in 681 (22.8%). There were no significant differences in the primary endpoint between the P2Y12 inhibitor monotherapy group and the DAPT group among patients receiving clopidogrel (3.0% vs 3.0%; HR: 1.02; 95% CI 0.64 to 1.65; p=0.93) as well as among patients receiving potent P2Y12 inhibitors (2.4% vs 0.7%; HR: 3.37; 95% CI 0.77 to 14.78; p=0.11; interaction p=0.1). Among patients receiving clopidogrel, P2Y12 inhibitor monotherapy compared with DAPT showed consistent treatment effects across various subgroups for the primary endpoint. Among patients receiving potent P2Y12 inhibitors, the rate of bleeding (Bleeding Academic Research Consortium types 2- 5) was significantly lower in the P2Y12 inhibitor monotherapy group than in the DAPT group (1.5% vs 5.0%; HR: 0.33; 95% CI 0.12 to 0.87; p=0.03). CONCLUSIONS: Compared with 12-month DAPT, clopidogrel monotherapy after 3-month DAPT showed comparable cardiovascular outcomes in patients undergoing PCI. TRIAL REGISTRATION NUMBER: NCT02079194.

Pharmacodynamic Profile and Prevalence of Bleeding Episode in East Asian Patients with Acute Coronary Syndromes Treated with Prasugrel Standard-Dose versus De-escalation Strategy: A Randomized A-MATCH Trial.

Compared with Caucasian patients, East Asian patients have the unique risk-benefit trade-off and different responsiveness to antithrombotic regimens. The aim of this study was to compare pharmacodynamic profile in East Asian patients with acute coronary syndromes (ACSs) treated with prasugrel standard-dose versus a de-escalation strategy. Before discharge, ACS patients with age <75 years or weight ≥60 kg (n = 255) were randomly assigned to the standard-dose (10-mg group) or de-escalation strategy (5-mg group or platelet function test [PFT]-guided group). After 1 month, VerifyNow P2Y12 assay-based platelet reactivity (P2Y12 reaction unit [PRU]) and bleeding episodes were evaluated. Primary endpoint was the percentage of patients with the therapeutic window (85 ≤ PRU ≤ 208). The 250 patients completed 1-month treatment. The percentage of patients within the therapeutic window was significantly lower in the 10-mg group (n = 85) compared with the 5-mg (n = 83) and PFT-guided groups (n = 82) (35.3 vs. 67.5 vs. 65.9%) (odds ratio [OR]: 3.80 and 3.54; 95% confidence interval [CI]: 2.01-7.21 and 1.87-6.69, respectively). Compared with the 10-mg group, the bleeding rate was tended to be lower with de-escalation strategies (35.3 vs. 24.1% vs. 23.2%) (hazard ratio [HR]: 0.58 and 0.55; 95% CI: 0.30-1.14 and 0.28-1.09, respectively). "PRU < 127" was the optimal cut-off for predicting 1-month bleeding events (area under the curve: 0.616; 95% CI: 0.543-0.689; p = 0.005), which criteria was significantly associated with early discontinuation of prasugrel treatment (HR: 2.00; 95% CI: 1.28-3.03; p = 0.001). In conclusion, compared with the standard-dose prasugrel, the prasugrel de-escalation strategy in East Asian patients presented with ACS showed a higher chance within the therapeutic window and a lower tendency toward bleeding episodes. REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier:NCT01951001.

Effects of Prolonged Dual Antiplatelet Therapy in ST-Segment Elevation vs. Non-ST-Segment Elevation Myocardial Infarction.

BACKGROUND: The benefits and risks of prolonged dual antiplatelet therapy (DAPT) have not been studied extensively across a broad spectrum of acute coronary syndromes. In this study we investigated whether treatment effects of prolonged DAPT were consistent in patients presenting with ST-segment elevation myocardial infarction (STEMI) vs. non-STEMI (NSTEMI).Methods and Results:As a post hoc analysis of the SMART-DATE trial, effects of ≥12 vs. 6 months DAPT were compared among 1,023 patients presenting with STEMI and 853 NSTEMI patients. The primary outcome was a composite of recurrent myocardial infarction (MI) or stent thrombosis at 18 months after the index procedure. Compared with the 6-month DAPT group, the rate of the composite endpoint was significantly lower in the ≥12-month DAPT group (1.2% vs. 3.8%; hazard ratio [HR] 0.31, 95% confidence interval [CI] 0.12-0.77; P=0.012). The treatment effect of ≥12- vs. 6-month DAPT on the composite endpoint was consistent among NSTEMI patients (0.2% vs. 1.2%, respectively; HR 0.20, 95% CI 0.02-1.70; P=0.140; Pinteraction=0.718). In addition, ≥12-month DAPT increased Bleeding Academic Research Consortium (BARC) Type 2-5 bleeding among both STEMI (4.4% vs. 2.0%; HR 2.18, 95% CI 1.03-4.60; P=0.041) and NSTEMI (5.1% vs. 2.2%; HR 2.37, 95% CI 1.08-5.17; P=0.031; Pinteraction=0.885) patients. CONCLUSIONS: Compared with 6-month DAPT, ≥12-month DAPT reduced recurrent MI or stent thrombosis regardless of the type of MI at presentation.

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.

A randomised comparison of coronary stents according to short or prolonged durations of dual antiplatelet therapy in patients with acute coronary syndromes: a pre-specified analysis of the SMART-DATE trial.

BACKGROUND: Data on direct comparison between various drug-eluting stents with short duration dual antiplatelet therapy (DAPT) are limited, especially in patients with acute coronary syndrome (ACS). AIMS: We sought to compare biodegradable polymer biolimus-eluting stents (BP-BES) with durable polymer everolimus-eluting (DP-EES) and zotarolimus-eluting stents (DP-ZES) in patients with ACS according to different durations of DAPT. METHODS: In the SMART-DATE trial, 2,712 patients with ACS underwent randomisation for allocation of DAPT (6 months [n=1,357] or 12 months or longer [n=1,355]) and type of stent (BP-BES [n=901]), DP-EES [n=904], or DP-ZES [n=907]). The primary endpoint was a composite of cardiac death, myocardial infarction, or stent thrombosis. RESULTS: At 18 months, the primary endpoint was attained by 2.6% with BP-BES, 2.0% with DP-EES, and 2.1% with DP-ZES (HR 1.29, 95% CI: 0.70-2.39, p=0.42 for BP-BES vs DP-EES and HR 1.23, 95% CI: 0.67-2.26, p=0.50 for BP-BES vs DP-ZES). The treatment effect of BP-BES for the primary endpoint was consistent among patients receiving 6-month DAPT as well as those receiving 12-month or longer DAPT (BP-BES vs. DP-EES, pinteraction=0.48 and BP-BES vs DP-ZES, pinteraction=0.87). After excluding 179 patients (101 in the BP-BES group) who did not receive allocated DES, the per-protocol analysis showed similar results. CONCLUSIONS: The risk of a composite of cardiac death, myocardial infarction, or stent thrombosis was not significantly different between patients receiving BP-BES versus DP-EES or DP-ZES across a short or prolonged duration of DAPT after ACS.