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BACKGROUND: The optimal duration of anticoagulation therapy for isolated distal deep vein thrombosis in patients with cancer is clinically relevant, but the evidence is lacking. The prolonged anticoagulation therapy could have a potential benefit for prevention of thrombotic events; however, it could also increase the risk of bleeding. METHODS: In a multicenter, open-label, adjudicator-blinded, randomized clinical trial at 60 institutions in Japan, we randomly assigned patients with cancer with isolated distal deep vein thrombosis, in a 1-to-1 ratio, to receive either a 12-month or 3-month edoxaban treatment. The primary end point was a composite of a symptomatic recurrent venous thromboembolism (VTE) or VTE-related death at 12 months. The major secondary end point was major bleeding at 12 months, according to the criteria of the International Society on Thrombosis and Haemostasis. The primary hypothesis was that a 12-month edoxaban treatment was superior to a 3-month edoxaban treatment with respect to the primary end point. RESULTS: From April 2019 through June 2022, 604 patients were randomized, and after excluding 3 patients who withdrew consent, 601 patients were included in the intention-to-treat population: 296 patients in the 12-month edoxaban group and 305 patients in the 3-month edoxaban group. The mean age was 70.8 years, 28% of the patients were men, and 20% of the patients had symptoms of deep vein thrombosis at baseline. The primary end point of a symptomatic recurrent VTE event or VTE-related death occurred in 3 of the 296 patients (1.0%) in the 12-month edoxaban group and in 22 of the 305 patients (7.2%) in the 3-month edoxaban group (odds ratio, 0.13; 95% CI, 0.03–0.44). The major secondary end point of major bleeding occurred in 28 of the 296 patients (9.5%) in the 12-month edoxaban group and in 22 of the 305 patients (7.2%) in the 3-month edoxaban group (odds ratio, 1.34; 95% CI, 0.75–2.41). The prespecified subgroups did not affect the estimates on the primary end point. CONCLUSIONS: In patients with cancer with isolated distal deep vein thrombosis, 12 months was superior to 3 months for an edoxaban treatment with respect to the composite outcome of a symptomatic recurrent VTE or VTE-related death. [ABSTRACT FROM AUTHOR]

Background: It has not been yet adequately addressed whether the addition of the nonstatin LDL-C (low-density lipoprotein cholesterol)-lowering agents on top of statins has the same magnitude of risk reduction in the cardiovascular events as compared with more-intensive statin therapy.Methods and Results: We performed a systematic review and meta-analysis of RCTs (randomized controlled trials) comparing more- versus less-intensive lipid-lowering therapy (LLT) on clinical outcomes in patients with atherosclerotic cardiovascular risk. We included 23 studies involving 133 037 patients (more-intensive LLT: 67 691 patients and less-intensive LLT: 65 346 patients). We evaluated 3 types of more- versus less-intensive LLT including more versus less statins (57 672 patients), combination therapy of ezetimibe versus statins alone (20 688 patients), or a PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitor with statins versus statins alone (54 677 patients). The odds for major adverse cardiovascular events (MACE; equivalent to the composite of coronary heart death, nonfatal myocardial infarction, stroke, or coronary revascularization) were significantly lower in the more-intensive LLT group compared with the less-intensive LLT group in the entire study population (odds ratio, 0.84; 95% CI, 0.79-0.88; P<0.001), and in all the 3 categories of more-intensive LLT strategies (more-intensive statin therapy: odds ratio, 0.83; 95% CI, 0.76-0.90; P<0.001, ezetimibe: odds ratio, 0.90; 95% CI, 0.85-0.96; P<0.001, and PCSK9 inhibitors: odds ratio, 0.81; 95% CI, 0.73-0.90; P<0.001) with numerically greater relative odds reduction by more-intensive statin therapy and PCSK9 inhibitors than by ezetimibe. Odds reduction for MACE per 20 mg/dL LDL-C reduction was also different across the 3 types of more-intensive LLT (more-intensive statin therapy: 17.4%, ezetimibe: 11.0%, and PCSK9 inhibitors: 6.6%).Conclusions: In this meta-analysis, more-intensive LLT as compared with less-intensive LLT was associated with significant odds reduction for MACE in the entire study population and in all the 3 categories of more-intensive LLT such as more-intensive statin therapy, ezetimibe, and PCSK9 inhibitors. However, overall odds reduction for MACE and odds reduction for MACE per 20 mg/dL LDL-C reduction were different across the 3 types of more-intensive LLT. Registration: URLs: https://www.crd.york.ac.uk/PROSPERO/ and http://www.umin.ac.jp/ctr. Unique identifiers: PROSPERO: CRD42018081196, and UMIN-CTR: R000036229. [ABSTRACT FROM AUTHOR]

BACKGROUND: The optimal cutoff value of fraCTional flow reserve (FFR) derived from coronary computed tomography angiography (FFRCT) remains unclear. METHODS: The current study population consisted of 93 patients with 139 vessels, who had suspeCTed coronary artery disease by computed tomography angiography and underwent invasive FFR. We evaluated diagnostic performance of FFRCT according to different FFRCT cutoff values and FFRCT ranges with invasive FFR ≤0.80 as the reference standard. RESULTS: In per-vessel analysis, median invasive FFR was 0.85 (interquartile range, 0.75-0.90), and 57 out of 139 vessels (41%) showed hemodynamically significant stenosis (≤0.80). Median FFRCT was 0.77 (interquartile range, 0.66-0.84; mean difference [invasive FFR-FFRCT], 0.06±0.11). Per-vessel accuracy, sensitivity, specificity, positive prediCTive value, and negative prediCTive value were 73%, 95%, 59%, 61%, and 94% for the cutoff value of FFRCT ≤0.80, 81%, 86%, 78%, 73%, and 89% for FFRCT ≤0.75, and 83%, 74%, 89%, 82%, and 83% for FFRCT ≤0.70, respeCTively. Per-vessel accuracy across the different ranges of FFRCT ≤0.60, 0.61 to 0.70, 0.71 to 0.80, 0.81 to 0.90, and >0.90 with the cutoff value of FFRCT ≤0.80 were 95%, 74%, 32%, 93%, and 100%, respeCTively. Setting a gray zone of FFRCT 0.71 to 0.80 provided high positive prediCTive value (82%; n=42/51) in the range of FFRCT ≤0.70 and high negative prediCTive value (94%; n=48/51) in FFRCT >0.80. CONCLUSIONS: This study suggested that referral to invasive coronary angiography should be considered individually in the range of FFRCT 0.71 to 0.80, whereas dichotomous decision could be made in FFRCT ≤0.70 and >0.80. Future prospeCTive studies evaluating clinical outcomes are needed to establish optimal FFRCT-based diagnostic algorithm. [ABSTRACT FROM AUTHOR]

Background--There is considerable debate on the management of patients with low-gradient severe aortic stenosis (LG-AS), defined as aortic valve area <1 cm² with peak aortic jet velocity ≤4.0 m/s, and mean aortic pressure gradient ≤40 mm Hg. Methods and Results--In the CURRENT AS registry (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis), there were 2097 patients (initial aortic valve replacement [AVR] strategy: n=977, and conservative strategy: n=1120) with high-gradient severe aortic stenosis (HG-AS) and 1712 patients (initial AVR strategy: n=219, and conservative strategy: n=1493) with LG-AS. AVR was more frequently performed in HG-AS patients than in LG-AS patients (60% versus 28%) during the entire follow-up. In the comparison between the initial AVR and conservative groups, the propensity score-matched cohorts were developed in both HG-AS (n=887 for each group) and LG-AS (n=218 for each group) strata. The initial AVR strategy when compared with the conservative strategy was associated with markedly lower risk for a composite of aortic valve-related death or heart failure hospitalization in both HG-AS and LG-AS strata (hazard ratio, 0.30; 95% confidence interval, 0.25-0.37; P<0.001 and hazard ratio, 0.46; 95% confidence interval, 0.32-0.67; P<0.001, respectively). Among 1358 patients with LG-AS with preserved left ventricular ejection fraction, the initial AVR strategy was associated with a better outcome than the conservative strategy (adjusted hazard ratio, 0.37; 95% confidence interval, 0.23-0.59; P<0.001). Conclusions--The initial AVR strategy was associated with better outcomes than the conservative strategy in both HG-AS and LG-AS patients, although AVR was less frequently performed in LG-AS patients than in HG-AS patients. The favorable effect of initial AVR strategy was also seen in patients with LG-AS with preserved left ventricular ejection fraction. Clinical Trial Registration--URL: http://www.umin.ac.jp/ctr/index.htm. Unique identifier: UMIN000012140. [ABSTRACT FROM AUTHOR]

Background: In patients with ST-segment-elevation acute myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention, long-term risks for cardiac and noncardiac death beyond acute phase of STEMI have not been thoroughly evaluated yet.Methods and Results: We identified 3942 STEMI patients who had primary percutaneous coronary intervention within 24 hours after onset between January 2005 and December 2007 in the CREDO-Kyoto AMI registry (Coronary Revascularization Demonstrating Outcome study in Kyoto Acute Myocardial Infarction) and evaluated their short-term (within 6-month) and long-term (beyond 6-month) incidences and causes of deaths. The cumulative 5-year incidence of all-cause death in the current study population was 20.4% (cardiac death, 12.2% and noncardiac death, 9.4%, respectively). The vast majority of deaths were cardiac in origin within 6-month (cardiac death, 8.0% and noncardiac death, 0.9%), whereas noncardiac death accounted for nearly two thirds of all-cause death beyond 6-month (cardiac death, 4.6% and noncardiac death, 8.5%). In the stratified analysis according to age, the proportion of noncardiac death was similar regardless of age although the absolute mortality rate was higher with increasing age. By the multivariable Cox regression models, the independent risk factors of all-cause death were advanced age, cardiogenic shock, renal dysfunction, large infarct size, and anterior wall infarction within 6 months after STEMI, and advanced age, previous heart failure, renal dysfunction, and liver cirrhosis beyond 6 months after STEMI, respectively.Conclusions: In STEMI patients who underwent primary percutaneous coronary intervention, the long-term risk for cardiac death was relatively low compared with that for noncardiac death, which accounted for nearly two thirds of all-cause death beyond 6 months. [ABSTRACT FROM AUTHOR]

Background: Many of the previous randomized trials comparing percutaneous coronary intervention (PCI) with coronary artery bypass grafting (CABG) in patients with multivessel coronary artery disease reported equivalent or better survival with CABG as compared with PCI at 5-year follow-up. However, 5-year follow-up might be too short to evaluate the true differences in long-term clinical outcomes between PCI and CABG. Methods and Results: Among 8934 patients enrolled in the extended 10- to 14-year follow-up study of the CREDO-Kyoto registry cohort-1 (Coronary Revascularization Demonstrating Outcome study in Kyoto) conducted in the bare-metal stent era, 5152 (PCI: n=3490 and CABG: n=1662) patients had multivessel coronary artery disease without left main disease. Median follow-up duration was 11.2 (interquartile range: 10.2-12.2) years. The cumulative 10-year incidence of all-cause death was not significantly different between PCI and CABG (32.2% versus 31.7%; log-rank P=0.93). After adjusting for confounders, however, the mortality risk of PCI was significantly higher than that of CABG (hazard ratio, 1.19 [95% confidence interval, 1.02-1.39]; P=0.03). Within 5 years after the index procedure, the risk for all-cause death was significantly higher after PCI than after CABG (hazard ratio, 1.41; 95% CI, 1.12-1.79; P=0.004). By a landmark analysis at 5 years, however, the cumulative 10-year incidence of and adjusted risk for all-cause death beyond 5 years were not significantly different between PCI and CABG (19.3% versus 20.0%; log-rank P=0.22 and hazard ratio, 1.02, 95% confidence interval, 0.83-1.26; P=0.82). Conclusions: CABG as compared with PCI was associated with better 10-year survival in patients with multivessel coronary artery disease. However, the benefit of CABG compared with PCI on late mortality beyond 5 years was not observed in this study. [ABSTRACT FROM AUTHOR]

Background--There is a paucity of data reporting the clinical outcomes of biodegradable polymer biolimus-eluting stent (BP-BES) compared with durable polymer everolimus-eluting stent (DP-EES) beyond 1 year after stent implantation when the polymer is fully degraded. Methods and Results--The NOBORI Biolimus-Eluting Versus XIENCE/PROMUS Everolimus-Eluting Stent Trial (NEXT) is a prospective, multicenter, randomized, open-label, noninferiority trial comparing BP-BES with DP-EES in patients scheduled for percutaneous coronary intervention using drug-eluting stent (DES) without any exclusion criteria among 98 participating centers in Japan. The trial was designed to evaluate noninferiority of BP-BES relative to DP-EES in terms of any targetlesion revascularization at 1 year and death or myocardial infarction at 3 years. Between May and October 2011, 3235 patients were randomly assigned to receive either BP-BES (1617 patients) or DP-EES (1618 patients). Complete 3-year follow-up was achieved in 97.6% of patients. At 3 years, the primary safety end point of death or myocardial infarction occurred in 159 patients (9.9%) in the BP-BES group and in 166 patients (10.3%) in the DP-EES group, demonstrating noninferiority of BP-BES relative to DP-EES (P noninferiority<0.0001 and P superiority=0.7). Cumulative incidence of target-lesion revascularization was not significantly different between the 2 groups (7.4% versus 7.1%; P=0.8). By a landmark analysis at 1 year, the cumulative incidences of death or myocardial infarction and target-lesion revascularization were also not significantly different between the 2 groups (4.6% versus 5.2%; P=0.46 and 3.3% versus 2.7%; P=0.39, respectively). Conclusions--Safety and efficacy outcomes of BP-BES were non inferior to those of DP-EES 3 years after stent implantation. [ABSTRACT FROM AUTHOR]