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Background: Antiplatelet therapy deescalation has been suggested as an alternative to standard treatment with potent dual antiplatelet therapy (DAPT) for 1 year in low bleeding risk patients with acute coronary syndromes undergoing percutaneous coronary intervention to mitigate the increased risk of bleeding. Whether this strategy preserves the ischemic and survival benefits of potent DAPT is uncertain. Methods: We performed a pairwise meta-analysis in patients with acute coronary syndrome undergoing percutaneous coronary intervention treated with either 1-year standard potent DAPT versus deescalation therapy (potent DAPT for 1–3 months followed by either reduced potency DAPT or ticagrelor monotherapy for up to 1 year). Randomized trials comparing standard DAPT versus deescalation therapy in patients with acute coronary syndrome undergoing percutaneous coronary intervention were searched through MEDLINE, EMBASE, Cochrane databases, and proceedings of international meetings. The primary end point was 1-year all-cause mortality. Results: The meta-analysis included 6 trials in which 20 837 patients were randomized to potent DAPT for 1 to 3 months followed by deescalation therapy for up to 1 year (n=10 392) or standard potent DAPT for 1 year (n=10 445). Deescalation therapy was associated with lower 1-year rates of all-cause mortality compared with standard therapy (odds ratio, 0.75 [95% CI, 0.59–0.95]; P =0.02). Deescalation therapy was also associated with lower rates of major bleeding (odds ratio, 0.59 [95% CI, 0.48–0.72]; P <0.0001), with no significant difference in major adverse cardiac events (major adverse cardiovascular events; odds ratio, 0.89 [95% CI, 0.77–1.04]; P =0.14). Conclusions: In low bleeding risk patients with acute coronary syndrome undergoing percutaneous coronary intervention, compared with 1-year of potent DAPT, antiplatelet therapy deescalation therapy after 1 to 3 months was associated with decreased mortality and major bleeding with similar rates of major adverse cardiovascular events. [ABSTRACT FROM AUTHOR]

Background: Large-scale randomized comparison of drug-eluting stents (DES) based on durable polymer versus biodegradable polymer technology is currently insufficient in patients with acute coronary syndrome (ACS). The present study aimed to prove the noninferiority of the durable polymer DES (DP-DES) compared with the biodegradable polymer DES (BP-DES) in such patients.Methods: The HOST-REDUCE-POLYTECH-ACS (Harmonizing Optimal Strategy for Treatment of Coronary Artery Diseases-Comparison of Reduction of Prasugrel Dose or Polymer Technology in ACS Patients) trial is an investigator-initiated, randomized, open-label, adjudicator-blinded, multicenter, noninferiority trial comparing the efficacy and safety of DP-DES and BP-DES in patients with ACS. The primary end point was a patient-oriented composite outcome (a composite of all-cause death, nonfatal myocardial infarction, and any repeat revascularization) at 12 months. The key secondary end point was device-oriented composite outcome (a composite of cardiac death, target-vessel myocardial infarction, or target lesion revascularization) at 12 months.Results: A total of 3413 patients were randomized to receive the DP-DES (1713 patients) and BP-DES (1700 patients). At 12 months, patient-oriented composite outcome occurred in 5.2% in the DP-DES group and 6.4% in the BP-DES group (absolute risk difference, -1.2%; Pnoninferiority<0.001). The key secondary end point, device-oriented composite outcome, occurred less frequently in the DP-DES group (DP-DES vs BP-DES, 2.6% vs 3.9%; hazard ratio, 0.67 [95% CI, 0.46-0.98]; P=0.038), mostly because of a reduction in target lesion revascularization. The rate of spontaneous nonfatal myocardial infarction and stent thrombosis were extremely low, with no significant difference between the 2 groups (0.6% versus 0.8%; P=0.513 and 0.1% versus 0.4%; P=0.174, respectively).Conclusions: In ACS patients receiving percutaneous coronary intervention, DP-DES was noninferior to BP-DES with regard to patient-oriented composite outcomes at 12 months after index percutaneous coronary intervention. Registration: URL: https://wwwclinicaltrials.gov; Unique identifier: NCT02193971. [ABSTRACT FROM AUTHOR]

Opening of mitochondrial permeability transition pore and Ca2+ overload are main contributors to myocardial ischemia-reperfusion injury, which paradoxically causes a wide variety of myocardial damage. We investigated the protective role of a novel necrosis inhibitor (NecroX-7; NecX) against myocardial ischemia-reperfusion injury using in vitro and in vivo models. H9C2 rat cardiomyoblasts and neonatal cardiomyocytes were exposed to hypoxia-reoxygenation stress after pre-treatment with NecX, vitamin C, a combination of vitamin C and E, N-acetylcysteine, an apoptosis inhibitor (Z-VAD-fmk), or cyclosporine A. The main mechanism of cell death after hypoxia-reoxygenation stress was not apoptosis but necrosis, which was prevented by NecX. Protective effect of NecX was based on its potent reactive oxygen species scavenging activity, especially on mitochondrial reactive oxygen species. NecX preserved mitochondrial membrane potential through prevention of Ca2+ influx and inhibition of mitochondrial permeability transition pore opening, which was more potent than that by cyclosporine A. Using Sprague-Dawley rats exposed to myocardial ischemia for 45 minutes followed by reperfusion, we compared therapeutic efficacies of NecX with cyclosporine A, vitamin C, a combination of vitamin C and E, and 5% dextrose, each administered 5 minutes before reperfusion. NecX markedly inhibited myocardial necrosis and reduced fibrotic area to a greater extent than did cyclosporine A and other treated groups. In addition, NecX preserved systolic function and prevented pathological dilatory remodeling of left ventricle. The novel necrosis inhibitor has a significant protective effect against myocardial ischemia-reperfusion injury through inhibition of mitochondrial permeability transition pore opening, indicating that it is a promising candidate for cardioprotective adjunctive measure on top of reperfusion therapy. [ABSTRACT FROM AUTHOR]

Myocardial infarction (MI) is a leading cause of death worldwide. Given that a family history is an independent risk factor for coronary artery disease, genetic variants are thought to contribute directly to the development of this condition. The identification of susceptibility genes for coronary artery disease or MI may thus help to identify high-risk individuals and offer the opportunity for disease prevention.We designed a 5-step protocol, consisting of a genome-wide linkage study followed by association analysis, to identify novel genetic variants that confer susceptibility to coronary artery disease or MI. A genome-wide affected sib-pair linkage study with 221 Japanese families with coronary artery disease yielded a statistically significant logarithm of the odds score of 3.44 for chromosome 2p13 and MI. Further association analysis implicated Alström syndrome 1 gene (ALMS1) as a candidate gene within the linkage region. Validation association analysis revealed that representative single-nucleotide polymorphisms of the ALMS1 promoter region were significantly associated with early-onset MI in both Japanese and Korean populations. Moreover, direct sequencing of the ALMS1 coding region identified a glutamic acid repeat polymorphism in exon 1, which was subsequently found to be associated with early-onset MI.The glutamic acid repeat polymorphism of ALMS1 identified in the present study may provide insight into the pathogenesis of early-onset MI. [ABSTRACT FROM AUTHOR]

The article presents a study which aimed to compare two-year definite stent thrombosis (ST)'s risk between other drug-eluting stents (DES) and everolimus-eluting stents (EES). The study conducted randomized controlled trials' meta-analysis. Results showed the association of EES with definite ST's significant reduction.

Supplemental Digital Content is available in the text. Background: The role of immediate percutaneous coronary intervention (PCI; door-to-balloon time ≤90 minutes) in patients with ST-segment–elevation myocardial infarction who present ≥12 hours after symptom onset is still obscure. We sought to explore the clinical outcomes of immediate PCI in patients with ST-segment–elevation myocardial infarction depending on presentation time. Methods: Using the Korea Acute Myocardial Infarction Registry, a nationwide prospective multicenter registry in the Republic of Korea, we analyzed data from 5968 patients with ST-segment–elevation myocardial infarction. These patients were classified into the following groups: early presenters (n=5104 with symptom onset-to-door time <12 hours), late presenters (n=599 with symptom onset-to-door time 12–48 hours), and very late presenters (n=265 with symptom onset-to-door time ≥48 hours). The primary outcome was major adverse cardiac events, a composite of cardiac death, any myocardial infarction, and clinically driven target lesion revascularization. Results: In early presenters, immediate PCI was significantly associated with a lower rate of major adverse cardiac events compared with delayed PCI (door-to-balloon time >90 minutes; immediate versus delayed PCI, 8.6% versus 17.9%; inverse probability weighting adjusted hazard ratio, 0.63 [95% CI, 0.56–0.71]). In late presenters, immediate PCI was not associated with better major adverse cardiac events outcomes (13.0% versus 14.8%; inverse probability weighting adjusted hazard ratio, 1.05 [95% CI, 0.77–1.44]). The same trend was found for cardiac death (early presenters: immediate versus delayed PCI, 5.6% versus 14.3%; inverse probability weighting adjusted hazard ratio, 0.55 [95% CI, 0.48–0.64]; late presenters: 9.9% versus 9.8%; inverse probability weighting adjusted hazard ratio, 1.25 [95% CI, 0.86–1.82]). Very late presenters also showed the same trends as late presenters. Immediate PCI was an independent predictor of major adverse cardiac events in early presenters but not in late presenters. Conclusions: Immediate PCI, defined by time door-to-balloon time ≤90 minutes, for patients with ST-segment–elevation myocardial infarction who present ≥12 hours after symptom onset is not associated with improved long-term clinical outcomes as compared with delayed PCI (door-to-balloon time >90 minutes). [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text. Background: β-Blockers can improve prognosis after acute myocardial infarction. However, it remains unclear how long β-blockers should be prescribed. Methods: We included patients from the prospective, nationwide Korea Acute Myocardial Infarction Registry-National Institutes of Health registry and collected data on β-blockers and left ventricular ejection fraction (LVEF) at 1-year follow-up. Patients were stratified into 2 groups: 1001 patients with a 1-year LVEF<50% and 3007 patients with a 1-year LVEF≥50%. The primary outcome was 2-year all-cause mortality from the 1-year follow-up. Results: A total of 3177 patients received β-blockers at 1 year, and 151 patients died during the 2-year follow-up from 1 year after index hospitalization. β-Blockers showed survival benefits in patients with a 1-year LVEF<50% (log-rank P =0.001) but not in those with a 1-year LVEF≥50% (log-rank P =0.311). After adjusting covariates, β-blockers were associated with a 51% reduction in mortality in patients with a 1-year LVEF<50% (P =0.020) but not in their counterparts (P =0.322). Indeed, there was a prognostic interaction between the use of β-blockers at 1 year and 1-year LVEF (P for interaction=0.004). Conclusions: Use of β-blockers at 1-year follow-up after acute MI was associated with improved outcomes in patients with an LVEF<50% at 1 year but not in those with an LVEF>50% at 1 year. This study provides valuable information about differential responsiveness to β-blockers according to 1-year LVEF and might suggest the proper duration of β-blockers after acute MI. Registration: URL: http://cris.nih.go.kr/cris/en/; Unique identifier: KCT0000863. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text. Background: Although 1-stent with provisional approach is the preferred strategy for the treatment of bifurcation lesions, the optimal treatment strategy according to lesion location is still debatable. This study aimed to identify whether clinical outcomes according to treatment strategy differed between left main (LM) and non-LM bifurcation lesions in the second-generation drug-eluting stent era. Methods: The Coronary Bifurcation Stenting registry III is a retrospective multicenter registry of 2648 patients with bifurcation lesions who underwent percutaneous coronary intervention with second-generation drug-eluting stent. Among the study population, 935 (35.3%) patients had an LM bifurcation lesion. The primary outcome was target lesion failure, a composite of cardiac death, myocardial infarction, and target lesion revascularization. Results: Median follow-up duration was 53 months. LM bifurcation was associated with a higher risk of target lesion failure (HRadj, 1.846 [95% CI, 1.317–2.588]; P <0.001) than non-LM bifurcation. Two-stent strategy was more frequently applied in patients with LM bifurcation than in patients with non-LM bifurcation (27.1% versus 11.7%; P <0.001). In the LM bifurcation group, compared with the 1-stent strategy, the 2-stent strategy showed a significantly higher risk of target lesion failure (2-stent versus 1-stent, 17.4% versus 10.6%; HRadj, 1.848 [95% CI, 1.045–3.266]; P =0.035), mainly driven by the higher rate of target lesion revascularization (15.3% versus 5.5%; HRadj, 2.698 [95% CI, 1.276–5.706]; P =0.009). However, the risk of cardiac death or myocardial infarction did not differ between the 2 groups (4.4% versus 6.6%; HRadj, 0.694 [95% CI, 0.306–1.572]; P =0.381). For patients with non-LM-bifurcation, there was no significant difference in the rate of target lesion failure between 1-stent and 2-stent strategies (5.6% versus 6.3%; HRadj, 0.925 [95% CI, 0.428–2.001]; P =0.843). Conclusions: Even in the second-generation drug-eluting stent era, the 1-stent strategy, if possible, should initially be considered the preferred approach for the treatment of LM bifurcation lesions. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03068494. [ABSTRACT FROM AUTHOR]

Background: Whether prolonged dual antiplatelet therapy (DAPT) improves clinical outcomes after percutaneous coronary intervention for coronary bifurcation lesion is uncertain. Methods and Results: We evaluated 2082 patients who were treated with drug-eluting stent for bifurcation lesions and were event free (no death, myocardial infarction [MI], cerebrovascular accident, stent thrombosis, or any revascularization) at 12 months after the index procedure. Patients were divided into 2 groups: DAPT ≥12-month group (n=1776) and DAPT <12-month group (n=306). Primary outcome was all-cause death or MI. At 4 years after the index procedure, death or MI occurred less frequently in the DAPT ≥12-month group than the DAPT <12-month group (2.8% versus 12.3%; adjusted hazard ratio, 0.21; 95% confidence interval, 0.13–0.35; P <0.001). After propensity score matching, incidence of death or MI was still lower in the DAPT ≥12-month group than the DAPT <12-month group (2.6% versus 12.3%; adjusted hazard ratio, 0.22; 95% confidence interval, 0.12–0.38; P <0.001). In subgroup analysis, the treatment effect of prolonged DAPT was consistent across subgroups regardless of lesion location, stenting technique, or type of used drug-eluting stent. Conclusions: The risk of all-cause death or MI was significantly lower in the ≥12-month DAPT group than the <12-month DAPT group after percutaneous coronary intervention for bifurcation lesion using drug-eluting stent. Our results suggest that prolonged DAPT may improve long-term clinical outcomes after percutaneous coronary intervention for bifurcation lesions. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01642992 [ABSTRACT FROM AUTHOR]

Background: Latrophilin-2 (Lphn2), an adhesive GPCR (G protein-coupled receptor), was found to be a specific marker of cardiac progenitors during the differentiation of pluripotent stem cells into cardiomyocytes or during embryonic heart development in our previous studies. Its role in adult heart physiology, however, remains unclear., Methods: The embryonic lethality resulting from Lphn2 deletion necessitates the establishment of cardiomyocyte-specific, tamoxifen-inducible Lphn2 knockout mice, which was achieved by crossing Lphn2 flox/flox mice with mice having MerCreMer (tamoxifen-inducible Cre recombinase) under the α-myosin heavy chain promoter., Results: Tamoxifen treatment for several days completely suppressed Lphn2 expression, specifically in the myocardium, and induced the dilated cardiomyopathy (D-CMP) phenotype with serious arrhythmia and sudden death in a short period of time. Transmission electron microscopy showed mitochondrial abnormalities, blurred Z-discs, and dehiscent myofibrils. The D-CMP phenotype, or heart failure, worsened during myocardial infarction. In a mechanistic study of D-CMP, Lphn2 knockout suppressed PGC-1α and mitochondrial dysfunction, leading to the accumulation of reactive oxygen species and the global suppression of junctional molecules, such as N-cadherin (adherens junction), DSC-2 (desmocollin-2; desmosome), and connexin-43 (gap junction), leading to the dehiscence of cardiac myofibers and serious arrhythmia. In an experimental therapeutic trial, activators of p38-MAPK, which is a downstream signaling molecule of Lphn2, remarkably rescued the D-CMP phenotype of Lphn2 knockout in the heart by restoring PGC-1α and mitochondrial function and recovering global junctional proteins., Conclusions: Lphn2 is a critical regulator of heart integrity by controlling mitochondrial functions and cell-to-cell junctions in cardiomyocytes. Its deficiency leads to D-CMP, which can be rescued by activators of the p38-MAPK pathway.

Background: The efficacy and safety of each third-generation drug-eluting stent with ultrathin struts and advanced polymer technology remain unclear. We investigated the clinical outcomes of percutaneous coronary intervention using the Coroflex ISAR polymer-free sirolimus-eluting stent (SES) or Orsiro biodegradable polymer SES., Methods: The HOST-IDEA trial (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis-Coronary Intervention With Next-Generation Drug-Eluting Stent Platforms and Abbreviated Dual Antiplatelet Therapy), initially designed with a 2×2 factorial approach, sought to randomize patients undergoing percutaneous coronary intervention based on dual antiplatelet therapy duration (3 versus 12 months) and stent type (Coroflex ISAR versus Orsiro). Despite randomizing 2013 patients for dual antiplatelet therapy duration, the stent arm transitioned to a registry format during the trial. Among these, 328 individuals (16.3%) were randomized for Coroflex ISAR or Orsiro SES, while 1685 (83.7%) underwent percutaneous coronary intervention without stent-type randomization. In this study, the Coroflex ISAR (n=559) and Orsiro groups (n=1449) were matched using a propensity score. The prespecified primary end point was target lesion failure, a composite of cardiac death, target vessel myocardial infarction, and clinically driven target lesion revascularization at 12 months., Results: The baseline patient and procedural characteristics were well balanced between the Coroflex ISAR and Orsiro groups after propensity score matching (n=559, each group). The Coroflex ISAR group was significantly associated with a higher rate of target lesion failure, mainly driven by clinically driven target lesion revascularization, compared with the Orsiro group (3.4% versus 1.1%; hazard ratio, 3.21 [95% CI, 1.28-8.05]; P =0.01). A higher risk of target lesion failure in the Coroflex ISAR group was consistently observed across various subgroups. The rates of any bleeding (hazard ratio, 0.85 [95% CI, 0.51-1.40]; P =0.52) and major bleeding (hazard ratio, 1.58 [95% CI, 0.61-4.08]; P =0.34) were comparable between the 2 groups., Conclusions: In this propensity score-matched analysis of the stent arm registry from the HOST-IDEA trial, the Orsiro SES was associated with significantly better outcomes in terms of 1-year target lesion failure, mainly driven by clinically driven target lesion revascularization, than the Coroflex ISAR SES., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02601157., Competing Interests: Dr Han reports grants from ChongKunDang and HanMi outside the submitted work. Dr K.W. Park reports speaker fees from Daiichi Sankyo, AstraZeneca, Sanofi, Bristol-Myers Squibb, Bayer, and Pfizer outside the submitted work. Dr H.-S. Kim reports grants or speaker fees from Daiichi Sankyo, Boston Scientific, Terumo, Biotronik, Dio, Medtronic, Abbott Vascular, Edwards Life Science, Amgen, and Behringer Ingelheim outside of the submitted work. The other authors report no conflicts.

Background: There are limited data regarding the safety of deferral of percutaneous coronary intervention based on intravascular ultrasound (IVUS) findings. The current study sought to compare the prognosis between deferred lesions based on IVUS and fractional flow reserve (FFR)-guided treatment decision., Methods: This study is a post hoc analysis of the FLAVOUR randomized trial (Fractional Flow Reserve and Intravascular Ultrasound for Clinical Outcomes in Patients With Intermediate Stenosis) that compared 2-year clinical outcomes between IVUS- and FFR-guided treatment decision on intermediate coronary artery lesions using predefined criteria. In both IVUS and FFR groups, vessels were classified into deferred or revascularized vessels, and patients were classified as those with or without deferred lesions. Vessel-oriented composite outcomes (cardiac death, target vessel myocardial infarction, or target vessel revascularization) in deferred vessels and patient-oriented composite outcomes (death, myocardial infarction, or any revascularization) in patients with deferred lesions were compared between the IVUS and FFR groups., Results: A total of 1682 patients and 1820 vessels were analyzed, of which 922 patients and 989 vessels were deferred. At 2 years, there was no difference in the cumulative incidence of vessel-oriented composite outcomes in deferred vessels between IVUS (n=375) and FFR (n=614) groups (3.8% versus 4.1%; hazard ratio, 0.91 [95% CI, 0.47-1.75]; P =0.77). The risk of vessel-oriented composite outcomes was comparable between deferred and revascularized vessels following treatment decision by IVUS (3.8% versus 3.5%; hazard ratio, 1.09 [95% CI, 0.54-2.19]; P =0.81) and FFR (4.1% versus 3.6%; hazard ratio, 1.14 [95% CI, 0.56-2.32]; P =0.72). In comparison of patient-oriented composite outcomes in patients with deferred lesions, there was no significant difference between the IVUS (n=357) and FFR (n=565) groups (6.2% versus 5.9%; hazard ratio, 1.05 [95% CI, 0.61-1.80]; P =0.86)., Conclusions: In patients with intermediate coronary artery stenosis, deferral of percutaneous coronary intervention based on IVUS-guided treatment decision showed comparable risk of clinical events with FFR-guided treatment decision., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02673424., Competing Interests: Disclosures Dr Lee received an institutional research grant from Abbott Vascular, Boston Scientific, Philips Volcano, Terumo Corporation, Donga-ST, and Zoll Medical. Dr Hahn received an institutional research grant from the National Evidence-Based Healthcare Collaborating Agency, Ministry of Health and Welfare, Republic of Korea, Abbott Vascular, Biosensors, Boston Scientific, Daiichi Sankyo, Donga-ST, Hanmi Pharmaceutical, and Medtronic, Inc. The other authors report no conflicts.

Background: Limited data are available on short-term dual antiplatelet therapy (DAPT) after percutaneous coronary intervention using third-generation drug-eluting stents with ultrathin struts and advanced polymer technology. We investigated whether 3- to 6-month DAPT was noninferior to 12-month DAPT after implantation of drug-eluting stents with ultrathin struts and advanced polymer technology., Methods: We performed an open-label, randomized trial at 37 centers in South Korea. We enrolled patients undergoing percutaneous coronary intervention using the Orsiro biodegradable-polymer sirolimus-eluting stents or the Coroflex ISAR polymer-free sirolimus-eluting stents. Patients with ST-segment-elevation myocardial infarction were excluded. Patients were randomly assigned to receive either 3- to 6-month or 12-month DAPT after percutaneous coronary intervention. The choice of antiplatelet medications was at the physician's discretion. The primary outcome was a net adverse clinical event, a composite of cardiac death, target vessel myocardial infarction, clinically driven target lesion revascularization, stent thrombosis, or major bleeding, defined as Bleeding Academic Research Consortium type 3 or 5 at 12 months. The major secondary outcomes were target lesion failure, a composite of cardiac death, target vessel myocardial infarction, clinically driven target lesion revascularization, and major bleeding., Results: A total of 2013 patients (mean age, 65.7±10.5 years; 1487 males [73.9%]; 1110 [55.1%] presented with acute coronary syndrome) were randomly assigned to 3- to 6-month DAPT (n=1002) or 12-month DAPT (n=1011). The primary outcome occurred in 37 (3.7%) patients in the 3- to 6-month DAPT group and 41 (4.1%) in the 12-month DAPT group. The noninferiority of the 3- to 6-month DAPT group to the 12-month DAPT group was met (absolute risk difference, -0.4% [1-sided 95% CI, -∞% to 1.1%]; P <0.001 for noninferiority). There were no significant differences in target lesion failure (hazard ratio, 0.98 [95% CI, 0.56-1.71], P =0.94) or major bleeding (hazard ratio, 0.82 [95% CI, 0.41-1.61], P =0.56) between the 2 groups. Across various subgroups, the treatment effect of 3- to 6-month DAPT was consistent for net adverse clinical event., Conclusions: Among patients undergoing percutaneous coronary intervention using third-generation drug-eluting stents, 3- to 6-month DAPT was noninferior to 12-month DAPT for net adverse clinical event. Further research is needed to generalize this finding to other populations and to determine the ideal regimen for 3- to 6-month DAPT., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT02601157.

Background: Long-term outcomes of antiplatelet monotherapy in patients who receive percutaneous coronary intervention are unknown. The HOST-EXAM (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis-Extended Antiplatelet Monotherapy) Extended study reports the posttrial follow-up results of the original HOST-EXAM trial., Methods: From March 2014 through May 2018, 5438 patients who maintained dual antiplatelet therapy without clinical events for 12±6 months after percutaneous coronary intervention with drug-eluting stents were randomly assigned in a 1:1 ratio to receive clopidogrel (75 mg once daily) or aspirin (100 mg once daily). The primary end point (a composite of all-cause death, nonfatal myocardial infarction, stroke, readmission attributable to acute coronary syndrome, and Bleeding Academic Research Consortium type 3 or greater bleeding), secondary thrombotic end point (cardiac death, nonfatal myocardial infarction, ischemic stroke, readmission attributable to acute coronary syndrome, and definite or probable stent thrombosis), and bleeding end point (Bleeding Academic Research Consortium type 2 or greater bleeding) were analyzed during the extended follow-up period. Analysis was performed on the per-protocol population (2431 patients in the clopidogrel group and 2286 patients in the aspirin group)., Results: During a median follow-up of 5.8 years (interquartile range, 4.8-6.2 years), the primary end point occurred in 12.8% and 16.9% in the clopidogrel and aspirin groups, respectively (hazard ratio, 0.74 [95% CI, 0.63-0.86]; P <0.001). The clopidogrel group had a lower risk for the secondary thrombotic end point (7.9% versus 11.9%; hazard ratio, 0.66 [95% CI, 0.55-0.79]; P <0.001) and secondary bleeding end point (4.5% versus 6.1%; hazard ratio, 0.74 [95% CI, 0.57-0.94]; P =0.016). There was no significant difference in the incidence of all-cause death between the 2 groups (6.2% versus 6.0%; hazard ratio, 1.04 [95% CI, 0.82-1.31]; P =0.742). Landmark analysis at 2 years showed that the beneficial effect of clopidogrel was consistent throughout the follow-up period., Conclusions: During an extended follow-up of >5 years after randomization, clopidogrel monotherapy compared with aspirin monotherapy was associated with lower rates of the composite net clinical outcome in patients without clinical events for 12±6 months after percutaneous coronary intervention with drug-eluting stents., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT02044250.

Background: The clinical outcome after percutaneous coronary intervention (PCI) is affected by various clinical and procedural risk factors. We investigated the relative impact of clinical and procedural risks on clinical outcomes after PCI., Methods: A total of 13 172 patients were enrolled from the Grand-DES registry. The population was grouped into tertiles (high-, intermediate-, low-risk) according to the number of prespecified clinical and procedural risk factors, respectively. The primary end point was major adverse cardiac and cerebrovascular events (MACCE) at 3 years post-PCI., Results: MACCE occurred in 1109 (8.4%) patients during the follow-up period (median duration: 1126 days). Compared with procedural risk, clinical risk showed superior predictive power (area under the curve: 0.678 versus 0.570, P <0.001, for clinical and procedural risks, respectively) and greater magnitude of effect in the multivariate analysis for MACCE (Clinical risk: hazard ratio, 1.953 [95% CI, 1.809-2.109], P <0.001; procedural risk: hazard ratio, 1.240 [95% CI, 1.154-1.331], P <0.001). In subgroup analyses within each clinical risk tertile, procedural risk had no significant impact on MACCE in the lowest clinical risk tertile. An annual landmark analysis revealed that clinical and procedural risks were both significant predictors of MACCE, which occurred within the first and second year post-PCI. However, for MACCE occurring in the third year post-PCI, only clinical risk but not procedural risk was a significant predictor of events., Conclusions: Clinical and procedural risks were both significant predictors for ischemic clinical events in patients undergoing PCI. However, clinical risk had a greater and more prolonged effect on outcomes than procedural risk. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03507205.

Background: The prognostic value of angiographic complete revascularization in patients with chronic kidney disease (CKD) has not been thoroughly investigated, especially for contemporary coronary stents. We compared the clinical outcomes of complete and incomplete revascularization with second-generation drug-eluting stent, according to the presence of CKD., Methods: From the Grand Drug-Eluting Stent Registry (N=17 286) in Korea, we selected 8471 patients, who were treated with second-generation drug-eluting stent and had glomerular filtration rate and quantitative coronary angiography data (3014 [35.6%] patients with CKD and 5457 (64.4%) patients with preserved renal function). Angiographic complete revascularization was defined as a residual SYNTAX score (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) of 0. The primary outcome was the patient-oriented composite outcome at 3 years, including all-cause death, any myocardial infarction, and any revascularization., Results: The patient-oriented composite outcome rate after complete revascularization was significantly lower than that after incomplete revascularization in patients with CKD (14.6% versus 21.8%; adjusted hazard ratio, 0.79; 95% CI, 0.64-0.96; P=0.020) and in patients with preserved renal function (8.0% versus 12.0%; adjusted hazard ratio 0.77; 95% CI, 0.63-0.94; P=0.011). The cutoff values of residual SYNTAX scores for predicting better patient-oriented composite outcomes were different according to the presence of CKD, that is, <3 and <8 in patients with CKD and with preserved renal function, respectively., Conclusions: Angiographic complete revascularization led to better clinical outcomes in patients with CKD and with preserved renal function. However, the residual SYNTAX score to achieve a better outcome was lower in patients with CKD than with preserved renal function, favoring more aggressive revascularization in patients with CKD.

Background: Data examining the impact of diabetes mellitus (DM) on ischemic risk after percutaneous coronary intervention in women are limited as most clinical trial participants are male. We evaluated (1) the impact of DM on ischemic outcomes in women undergoing drug-eluting stent (DES) implantation and (2) whether the outcomes of new- versus early-generation DES vary by DM status., Methods and Results: We pooled patient-level data of 10 448 women undergoing percutaneous coronary intervention with DES from 26 randomized trials. Baseline characteristics and 3-year clinical outcomes were stratified according to DM status (noninsulin-dependent and insulin-dependent) and DES generation. The primary end point was the composite of all-cause death or myocardial infarction. Secondary end points were definite or probable stent thrombosis and target lesion revascularization. Compared with women without DM (n=7154, 68.5%), adjusted risks (adjusted hazard ratios [95% CI]) for death or myocardial infarction among women with noninsulin-dependent DM (n=2241, 21.4%) and insulin-dependent DM (n=1053, 10.1%) were 1.30 (1.11-1.53) and 1.71 (1.41-2.07), respectively ( P trend <0.001). Similar trends were observed for def/prob stent thrombosis and target lesion revascularization. Compared with early-generation DES, use of newer-generation DES was associated with significant reductions in death or myocardial infarction in the absence of DM whereas differences were nonsignificant in the presence of DM, with similar findings for def/prob stent thrombosis and target lesion revascularization., Conclusions: The presence of DM is associated with substantial, graded, and durable risks for ischemic events among women undergoing percutaneous coronary intervention with DES. The safety and efficacy profile of newer-generation DES is preserved among women without DM, while benefits are nonsignificant among women with DM.

Background: The Korean chronic total occlusion (CTO) registry was collected prospectively from 26 cardiovascular centers since May 2007. The aim of this study is to investigate the impact of a successful staged percutaneous coronary intervention (PCI) of CTO lesions in acute myocardial infarction (AMI) patients on clinical outcomes., Patients and Methods: Among 2813 patients who underwent a staged PCI because of CTO lesions, 422 (15%) patients underwent primary PCI because of AMI. Among 422 patients, successful staged CTO-PCI was performed in 76%. The clinical outcomes were compared between the successful CTO-PCI group (n=321) and the failed CTO-PCI group (n=101). To adjust for potential confounders, a propensity score matching (PSM) analysis was carried out using the logistic regression model., Results: After the PSM analysis, two propensity-matched groups (85 pairs, n=170) were generated and the baseline characteristics were balanced. The incidence of total death (P=0.029) and non-ST-segment elevation myocardial infarction (NSTEMI, P=0.043) at 1 year was higher in the failed CTO-PCI group. Multivariate regression showed that successful CTO-PCI was an independent predictor of preventing mortality (hazard ratio, 0.21, P=0.048). In the subgroup analysis, the Kaplan-Meier curve showed that successful CTO-PCI had a lower incidence of total death (log-rank=0.004) and cardiac death (log-rank=0.005) up to 1 year in NSTEMI patients. Cox-proportional analysis showed that successful CTO-PCI was beneficial in patients with NSTEMI, hypertension, and non-left-anterior descending artery lesion for preventing mortality., Conclusion: In this study, a staged successful CTO-PCI in AMI patients was associated with improved 1-year survival in the Korean population.

Background: There are limited data on the frequency of and factors associated with quantitative coronary angiography (QCA)-defined longitudinal stent deformation (LSD) in various contemporary drug-eluting stents platforms. This study sought to evaluate the predictors of LSD and its long-term clinical implication., Methods and Results: A patient-level pooled analysis was performed with 7350 lesions in 5871 patients treated with platinum-chromium-based everolimus-eluting stent (Promus Element), cobalt-chromium-based everolimus-eluting stent (Promus/Xience V), or cobalt-chromium-based zotarolimus-eluting stent (Endeavor Resolute). QCA was performed to analyze differences of stent length between immediate post-deployment and final post-procedure. Independent factors associated with LSD were identified. Clinical outcomes at 3 years were compared between those with and without QCA-based LSD. The frequency of QCA-based LSD was 1.12% (82 cases). Nine of these cases were angiographically overt. Left main or ostial lesion, bifurcation treatment with provisional side branch stenting or ballooning, additional downstream intervention of a distal lesion, intravascular ultrasound use, and adjunctive post-dilatation were independently associated with QCA-based LSD. The type of stent was not associated with QCA-based LSD. Rates of target lesion failure were nominally higher in lesions with QCA-based LSD than in those without (8.97% versus 5.88%; hazard ratio, 1.415; 95% confidence interval, 0.631-3.175; P =0.399)., Conclusions: LSD is uncommon with contemporary drug-eluting stents, regardless of the type of stent platform. LSD is mainly associated with procedural factors, especially with additional downstream procedures which require the passage of devices through the stent. Careful manipulation of poststent imaging or procedural devices is required to prevent LSD. More data are needed to clarify the impact of LSD on clinical events., (© 2017 American Heart Association, Inc.)

The phenomenon of obesity paradox after acute myocardial infarction (AMI) has been reported under strong recommendation of statin therapy. However, the impact of statin therapy on this paradox has not been investigated. This study investigated the impact of statin therapy on 1-year mortality according to obesity after AMI. A total of 2745 AMI patients were included from the Korea Acute Myocardial Infarction Registry after 1:4 propensity score matching analysis (n = 549 for nonstatin group and n = 2196 for statin group). Primary and secondary outcomes were all-cause and cardiac death, respectively. During 1-year follow-up, the incidence of all-cause (8.4% vs 3.7%) and cardiac (6.2% vs 2.3%) death was higher in nonstatin group than in statin (P < .001, respectively). In nonstatin group, the incidence of all-cause (7.2% vs 9.0%) and cardiac (5.5% vs 6.5%) death did not differ significantly between obese and nonobese patients. However, in statin group, obese patients had lower 1-year rate of all-cause (1.7% vs 4.8%) and cardiac (1.2% vs 2.9%) death (P < .05, respectively), and lower cumulative rates by Kaplan-Meier analysis of all-cause and cardiac death compared with nonobese patients (log-rank P < .05, respectively). The overall risk of all-cause death was significantly lower in obese than in nonobese patients only in statin group (hazard ratio: 0.35; P = .001). After adjusting for confounding factors, obesity was independently associated with decreased risk of all-cause death in statin group. In conclusion, the greater benefit of statin therapy for survival in obese patients is further confirmation of the obesity paradox after AMI.

Background: The aim of this study was to identify the prognostic predictors for the worse clinical outcomes after a successful chronic total occlusion (CTO) intervention with drug-eluting stents., Patients and Results: A total of 2334 patients in the multicenter Korean CTO registry who underwent a successful CTO intervention with drug-eluting stents (first generation, 1367, new generation, 967) were enrolled. The primary endpoint was the composite of cardiac death, myocardial infarction, and stent thrombosis.The cumulative incidence of the primary endpoint was 2.5% (median follow-up duration: 22 months). In multivariate analysis, age above 65 years [hazard ratio (HR)=1.769, 95% confidence interval (CI)=1.025-3.052, P=0.041], heart failure (HR=4.242, 95% CI=2.335-7.705, P<0.001), and diabetes (HR=1.773, 95% CI=1.043-3.012, P=0.034) were the significant predictors. The cumulative incidence of the primary endpoint was significantly higher in patients with three risk factors (19.1%) than in those with one (2.2%) or two (3.0%) risk factors (P=0.001). The cumulative target-vessel revascularization rate was 8.4%, with the significant predictors being a diffuse long lesion (HR=1.626, 95% CI=1.129-2.340, P=0.009) and at least three implanted stents (HR=1.964, 95% CI=1.301-2.965, P=0.001)., Conclusion: Clinical parameters such as age, diabetes, and heart failure were independent predictors of the composite of cardiac death, myocardial infarction, and stent thrombosis, whereas angiographic or procedural parameters such as lesion length and number of implanted stents were predictors of target-vessel revascularization. Clinical outcomes after CTO intervention were worse in patients with multiple risk factors.