Prognostic significance of baseline low-density lipoprotein cholesterol in patients undergoing coronary revascularization; a report from the CREDO-Kyoto registry.

BACKGROUND: The impact of very low baseline levels of low-density lipoprotein cholesterol (LDL-C) on patients with coronary artery disease remains unclear. METHOD: We enrolled 39,439 patients of the pooled population from the CREDO-Kyoto registries Cohorts 1, 2, and 3. The study population consisted of 33,133 patients who had undergone their first coronary revascularization. We assessed the risk for mortality and cardiovascular events according to quintiles of the baseline LDL-C levels. RESULTS: Patients in the very low LDL-C quintile (<85 mg/dL) had more comorbidities than those in the other quintiles. Lower LDL-C levels were strongly associated with anemia, thrombocytopenia, and end-stage renal disease. The cumulative 4-year incidence of all-cause death increased as LDL-C levels decreased (very low: 19.4 %, low: 14.5 %, intermediate: 11.1 %, high: 10.0 %, and very high: 9.2 %; p < 0.001), which was driven by both the early and late events. After adjusting for baseline characteristics, the adjusted risks of the very low and low LDL-C quintiles relative to the intermediate LDL-C quintile remained significant for all-cause death (very low: HR 1.29, 95 % CI 1.16-1.44, p < 0.001; low: HR 1.15, 95 % CI 1.03-1.29, p = 0.01). The excess adjusted risks of the lowest LDL-C quintile relative to the intermediate LDL-C quintile were significant for clinical outcomes such as cardiovascular death (HR 1.17, 95 % CI 1.01-1.35), non-cardiovascular death (HR 1.35, 95 % CI 1.15-1.60), sudden death (HR 1.44, 95 % CI 1.01-2.06), and heart failure admission (HR 1.11 95 % CI 1.01-1.22), while there was no excess risk for the lowest LDL-C quintile relative to the intermediate LDL-C quintile for myocardial infarction and stroke. CONCLUSIONS: Lower baseline LDL-C levels were associated with more comorbidities and a significantly higher risk of death, regardless of cardiovascular or non-cardiovascular causes, in patients who underwent coronary revascularization.

Concomitant Mitral Regurgitation in Severe Aortic Stenosis　- Insights From the CURRENT AS Registry-2.

BACKGROUND: Data on concomitant mitral regurgitation (MR) in patients with severe aortic stenosis (AS) are scarce.Methods and Results: We investigated the risk of concomitant MR in patients with severe AS in the CURRENT AS Registry-2 according to initial treatment strategy (transcatheter aortic valve implantation [TAVI], surgical aortic valve replacement [SAVR], or conservative). Among 3,365 patients with severe AS, 384 (11.4%) had moderate/severe MR (TAVI: n=126/1,148; SAVR: n=68/591; conservative: n=190/1,626). The cumulative 3-year incidence for death or heart failure (HF) hospitalization was significantly higher in the moderate/severe than no/mild MR group in the entire population (54.6% vs. 34.3%, respectively; P<0.001) and for each treatment strategy (TAVI: 45.0% vs. 31.8% [P=0.006]; SAVR: 31.9% vs. 18.7% [P<0.001]; conservative: 67.8% vs. 41.6% [P<0.001]). The higher adjusted risk of moderate/severe MR relative to no/mild MR for death or HF hospitalization was not significant in the entire population (hazard ratio [HR] 1.15; 95% confidence interval [CI] 0.95-1.39; P=0.15); however, the risk was significant in the SAVR (HR 1.92; 95% CI 1.04-3.56; P=0.04) and conservative (HR 1.30; 95% CI 1.02-1.67; P=0.04) groups, but not in the TAVI group (HR 1.03; 95% CI 0.70-1.52; P=0.86), despite no significant interaction (Pinteraction=0.37). CONCLUSIONS: Moderate/severe MR was associated with a higher risk for death or HF hospitalization in the initial SAVR and conservative strategies, while the association was less pronounced in the initial TAVI strategy.

[Evaluation of Changes in Membranous Septum Length during the Cardiac Cycle and by Measurement Methods Using the Preoperative CT for Transcatheter Aortic Valve Replacement: A Single-center Cross-sectional Study].

PURPOSE: The purpose of this study was to evaluate the changes in membranous septum (MS) length during the cardiac cycle and by measurement methods using the preoperative computed tomography (CT) images for transcatheter aortic valve replacement (TAVR). METHOD: Among 34 consecutive patients who underwent preoperative contrast-enhanced CT for TAVR, we measured MS lengths by three measurement methods (coronal, stretched, and reformatted coronal view method) at 10% intervals in the cardiac cycle. RESULT: MS lengths differed between the three measurement methods in all cardiac phases. Moderate correlations were observed between the MS lengths measured by the coronal view method and the other two methods. In contrast, strong correlations were observed between the MS lengths measured by the stretched view method and the reformatted coronal view method. The frequencies of the minimum and maximum MS lengths during the cardiac cycle tended to be highest at R-R 90% and R-R 30%, respectively. The median MS lengths at R-R 90% were smaller than those at R-R 30% in all measurement methods. CONCLUSION: The MS length in patients undergoing contrast-enhanced CT for TAVR varies notably depending on the cardiac cycle and measurement methods. When evaluating MS length, it is crucial to consider the measurement method and to perform measurements during diastole in order to evaluate the minimum value during the cardiac cycle.

In-hospital outcomes after SAVR or TAVI in patients with severe aortic stenosis.

There were no data comparing the in-hospital outcomes after transcatheter aortic valve implantation (TAVI) with those after surgical aortic valve replacement (SAVR) in Japan. Among consecutive patients with severe AS between April 2018 and December 2020 in the CURRENT AS Registry-2, we identified 1714 patients who underwent aortic valve replacement (TAVI group: 1134 patients, and SAVR group: 580 patients). Patients in the TAVI group were much older (84.4 versus 73.6 years, P < 0.001) and more often had comorbidities than those in the SAVR group. In-hospital death rate was numerically lower in the TAVI group than in the SAVR group (0.6% versus 2.2%). After excluding patients with dialysis, in-hospital death rate was very low and comparable in the TAVI and SAVR groups (0.6% versus 0.8%). The rates of major bleeding and new-onset atrial fibrillation during index hospitalization were higher after SAVR than after TAVI (72% versus 20%, and 26% versus 4.6%, respectively), while the rate of pacemaker implantation was higher after TAVI than after SAVR (8.1% versus 2.4%). Regarding the echocardiographic data at discharge, the prevalence of patient-prosthesis mismatch was lower in the TAVI group than in the SAVR group (moderate: 9.0% versus 26%, and severe: 2.6% versus 4.8%). In this real-world data in Japan, TAVI compared with SAVR was chosen in much older patients with more comorbidities with severe AS. In-hospital death rate was numerically lower in the TAVI group than in the SAVR group.

A snare maneuver to reposition self-expandable aortic valve after transcatheter replacement of surgically implanted valve.

In this case, we successfully repositioned the transcatheter heart valve (THV) by pulling it with a snare inserted via the right brachial artery. Attempting to pull the THV via the femoral approach was not successful, due to the vector of the pulling force not being coaxial. Changing the direction of the force by switching to an approach from the right brachial artery successfully prevented perivalvular leakage. While there are previous case reports of repositioning an implanted transcatheter valve in a native valve using a gooseneck snare, to our knowledge, this is the first case of successfully repositioning an implanted transcatheter valve in a valve-in-valve procedure using the precise assessment that can be achieved with intra-procedural transesophageal echocardiography. Learning objective: Perivalvular leakage (PVL) is a major problem after transcatheter aortic valve replacement. In this case, we experienced PVL after implantation of self-expandable transcatheter heart valve (THV) inside the previously inserted Mosaic bioprosthetic valve. Depth of the implanted valve was too low into left ventricle accessed with transesophageal echocardiogram. It is barely known whether THV in surgical implanted aortic valve could be repositioned using snare maneuver, but we successfully pulled the valve via brachial artery and PVL was controlled.

Effects of peripheral artery disease on long-term outcomes after percutaneous coronary intervention versus coronary artery bypass grafting in patients with severe coronary artery disease.

BACKGROUND: There is a scarcity of data evaluating the effect of peripheral artery disease (PAD) on long-term mortality after percutaneous coronary intervention (PCI) relative to coronary artery bypass grafting (CABG) in patients with severe coronary artery disease in real-world practice. METHODS: Among 14,867 consecutive patients who underwent their first coronary revascularization with PCI or isolated CABG between 2011 and 2013 in the CREDO-Kyoto PCI/CABG registry Cohort-3, the current study population consisted of 3380 patients with three-vessel coronary artery disease or left main coronary artery disease. Long-term clinical outcomes were compared between PCI and CABG stratified by the presence or absence of PAD. Median clinical follow-up was 5.9 (IQR: 5.1-6.8) years. RESULTS: There were 461 patients with PAD (PCI: N = 307, CABG: N = 154), and 2919 patients without PAD (PCI: N = 1823, CABG: N = 1096). The cumulative 5-year mortality after coronary revascularization was 31.2 % in patients with PAD and 16.2 % in those without PAD (p < 0.0001). There was a higher risk of PCI relative to CABG for all-cause death in patients with and without PAD (adjusted HR, 1.59; 95%CI, 0.99-2.53; p = 0.054, and HR, 1.25; 95%CI, 1.01-1.56; p = 0.04) without interaction (p interaction p = 0.48); Nevertheless, there was no excess risk of PCI relative to CABG for cardiovascular death regardless of PAD. CONCLUSIONS: The long-term mortality after coronary revascularization was significantly higher in severe CAD patients with PAD than those without PAD. There was a higher mortality risk of PCI relative to CABG in patients with and without PAD without interaction, which was mainly driven by excess non-cardiovascular deaths.

Statin Discontinuation After Coronary Revascularization.

There is a scarcity of studies evaluating statin discontinuation in patients with coronary artery disease in real-world practice. In 11,144 patients who underwent first coronary revascularization and taking statins in the CREDO-Kyoto Registry Cohort-3, we evaluated the incidence of statin discontinuation, defined as stopping statins for at least 2 months. The reasons for statin discontinuation included nonadherence, side effects, worsening co-morbidities, surgery, prescription error, and direction by physicians for other reasons. During a median 6 years of follow-up, the cumulative incidence of statin discontinuation was 6.1% at 1 year, 12.4% at 3 years, 17.4% at 5 years, and 21.4% at 7 years. The major components of the reasons for statin discontinuation were nonadherence, side effects, and worsening co-morbidities. Compared with patients with statin discontinuation because of other reasons, patients with statin discontinuation because of nonadherence more often had younger age, men, acute coronary syndrome, and current smoking; patients with statin discontinuation because of side effects more often had liver cirrhosis; and patients with statin discontinuation because of worsening co-morbidities more often had advanced age and co-morbidities such as malignancy. Statin discontinuation was strongly associated with subsequent mortality (hazard ratio [HR] 3.54; 95% confidence interval [CI] 3.18 to 3.94, p <0.001), which was consistent, regardless of the reasons, except for the small group of patients with prescription error (nonadherence: HR 2.35, 95% CI 1.69 to 3.27, p <0.001; side effects: HR 2.48, 95% CI 1.84 to 3.34, p <0.001; worsening co-morbidities: HR 22.08, 95% CI 18.55 to 26.29, p <0.001). In conclusion, in real-world practice, approximately 1 in 5 patients discontinued statins after coronary revascularization during a median of 6 years of follow-up. Statin discontinuation was associated with subsequent mortality.

The characteristics and outcomes in patients with acute heart failure who used tolvaptan: from KCHF registry.

AIMS: The use of tolvaptan is increasing in clinical practice in Japan. However, the characteristics of patients who used tolvaptan and the timing of its use in patients with acute heart failure (AHF) are not fully elucidated. METHODS AND RESULTS: Among consecutive 4056 patients in the Kyoto Congestive Heart Failure registry, we analysed 3802 patients after excluding patients on dialysis, prior or unknown tolvaptan use at admission, and unknown timing of tolvaptan use, and we divided them into two groups: tolvaptan use (N = 773) and no tolvaptan use (N = 3029). The prevalence of tolvaptan use varied widely from 48.7% to 0% across the participating centres. Factors independently associated with tolvaptan use were diabetes, poor medical adherence, oedema, pleural effusion, hyponatraemia, estimated glomerular filtration rate < 30 mL/min/1.73 m2 , moderate/severe tricuspid regurgitation, dobutamine infusion within 24 h, and additional inotropes infusion beyond 24 h after admission. The mortality rate at 90 days after admission was significantly higher in the tolvaptan use group than in the no tolvaptan use group (14.3% vs. 8.6%, P = 0.049). However, after adjustment, the excess mortality risk of tolvaptan use relative to no tolvaptan use was no longer significant (hazard ratio = 1.53, 95% confidence interval = 0.77-3.02, P = 0.22). Patients with tolvaptan use had a longer hospital stay [median (interquartile range): 22 (15-34) days vs. 15 (11-21) days, P < 0.0001] and a higher prevalence of worsening renal failure (47.0% vs. 31.8%, P < 0.0001) and worsening heart failure (24.8% vs. 14.4%, P < 0.0001) than those without. CONCLUSIONS: AHF patients with tolvaptan use had more congestive status with poorer in-hospital outcomes and higher short-term mortality than those without tolvaptan use. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02334891 (NCT02334891) and https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000017241 (UMIN000015238).

The Impact of Mitral Regurgitation on Long-Term Outcomes in Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention.

It is important to clarify the precise impact of mitral regurgitation (MR) on long-term outcomes in acute myocardial infarction (AMI) patients who underwent percutaneous coronary intervention (PCI). In the Coronary Revascularization Demonstrating Outcome study in Kyoto Acute Myocardial Infarction (CREDO-Kyoto AMI) Registry Wave-2, the study population consisted of 5,266 patients with AMI who underwent PCI. The clinical outcomes of all-cause death, cardiovascular death, and hospitalization for heart failure (HF) were compared according to the severity of MR. Mild and moderate/severe MR were identified in 2,112 (40%) and 531 patients (10%), respectively. Patients with greater severity of MR were more likely to be old, had more co-morbidities, and more often presented with large myocardial infarction with HF. During median follow-up duration of 5.6 (interquartile range: 4.2 to 6.6) years, as the MR severity increased from no, mild, to moderate/severe MR, the cumulative 5-year incidences of all-cause death, cardiovascular death and hospitalization for HF incrementally increased ([15.3%, 19.6%, 33.3%], [8.9%, 11.7%, 21.0%] and [5.9%, 12.4%, 23.9%], respectively, P for all<0.001). After adjusting for confounders, however, mild and moderate/severe MR were not independently associated with the higher risks for all-cause death (hazard ratio [95% confidence interval]:1.05 [0.92 to 1.19], p = 0.51, and 1.10 [0.92 to 1.32], p = 0.28) and cardiovascular death (1.01 [0.85 to 1.21], p = 0.89, and 0.93 [0.73 to 1.18], p = 0.54) as compared with no MR. Both mild and moderate/severe MR were independently associated with the higher risks for hospitalization for HF (1.73 [1.42 to 2.11], p <0.001, and 2.23 [1.73 to 2.87], p <0.001). In a large population of patients with AMI who underwent PCI, MR was not independently associated with higher long-term mortality risk but was independently associated with higher risk for hospitalization for HF.

Age and long-term outcomes of patients with venous thromboembolism: From the COMMAND VTE Registry.

BACKGROUND: There is still a scarcity of data on the relation between age and long-term clinical outcomes of patients with venous thromboembolism (VTE). METHODS: The COMMAND VTE Registry was a multicenter registry enrolling 3027 consecutive patients with acute symptomatic VTE in Japan between January 2010 and August 2014. We divided the entire cohort into 3 groups: patients aged <65 years (N = 1100, 36.7%), patients aged 65 ≤ and ≤ 80 years (N = 1314, 43.4%), and patients aged >80 years (N = 603, 19.9%). RESULTS: Discontinuation of anticoagulation therapy during the follow-up period was most frequent in patients aged <65 years (44%, 38% and 33%, P < 0.001). The cumulative 5-year incidences were 12.7%, 9.8% and 7.4% for recurrent VTE, 10.8%, 12.2% and 14.9% for major bleeding, and 23.0%, 31.4%, and 38.6% for all-cause death. Adjusting for cofounders and taking into account the competing risk of all-cause death, the lower risk of patients aged >80 years, and those aged 65 ≤ and ≤ 80 years relative to those aged <65 years remained significant for recurrent VTE (65 ≤ age ≤ 80 years, HR: 0.71, 95%CI: 0.53-0.94, P = 0.02; age > 80 years, HR: 0.59, 95%CI: 0.39-0.89, P = 0.01), and the risk remained insignificant for major bleeding (65 ≤ age ≤ 80 years, HR: 1.00, 95%CI: 0.76-1.31, P = 0.98; age > 80 years, HR: 1.17, 95%CI: 0.83-1.65, P = 0.37). CONCLUSIONS: In the current real-world VTE registry, there was no significant difference in the risk of major bleeding depending on different age groups, while younger patients showed an excess risk for recurrent VTE compared with older patients.

Clopidogrel Monotherapy After 1-Month Dual Antiplatelet Therapy in Patients With Diabetes Undergoing Percutaneous Coronary Intervention.

BACKGROUND: Diabetes was reported to be associated with an impaired response to clopidogrel. OBJECTIVES: The aim of this study was to evaluate the safety and efficacy of clopidogrel monotherapy after very short dual antiplatelet therapy (DAPT) in patients with diabetes undergoing percutaneous coronary intervention (PCI). METHODS: A subgroup analysis was conducted on the basis of diabetes in the STOPDAPT-2 (Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent-2) Total Cohort (N = 5,997) (STOPDAPT-2, n = 3,009; STOPDAPT-2 ACS [Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent-2 for the Patients With ACS], n = 2,988), which randomly compared 1-month DAPT followed by clopidogrel monotherapy with 12-month DAPT with aspirin and clopidogrel after cobalt-chromium everolimus-eluting stent implantation. The primary endpoint was a composite of cardiovascular (cardiovascular death, myocardial infarction, definite stent thrombosis, or stroke) or bleeding (TIMI [Thrombolysis In Myocardial Infarction] major or minor) endpoints at 1 year. RESULTS: There were 2,030 patients with diabetes (33.8%) and 3967 patients without diabetes (66.2%). Regardless of diabetes, the risk of 1-month DAPT relative to 12-month DAPT was not significant for the primary endpoint (diabetes, 3.58% vs 4.12% [HR: 0.87; 95% CI: 0.56-1.37; P = 0.55]; nondiabetes, 2.46% vs 2.49% [HR: 0.99; 95% CI: 0.67-1.48; P = 0.97]; Pinteraction = 0.67) and for the cardiovascular endpoint (diabetes, 3.28% vs 3.05% [HR: 1.10; 95% CI: 0.67-1.81; P = 0.70]; nondiabetes, 1.95% vs 1.43% [HR: 1.38; 95% CI: 0.85-2.25; P = 0.20]; Pinteraction = 0.52), while it was lower for the bleeding endpoint (diabetes, 0.30% vs 1.50% [HR: 0.20; 95% CI: 0.06-0.68; P = 0.01]; nondiabetes, 0.61% vs 1.21% [HR: 0.51; 95% CI: 0.25-1.01; P = 0.054]; Pinteraction = 0.19). CONCLUSIONS: Clopidogrel monotherapy after 1-month DAPT compared with 12-month DAPT reduced major bleeding events without an increase in cardiovascular events regardless of diabetes, although the findings should be considered as hypothesis generating, especially in patients with acute coronary syndrome, because of the inconclusive result in the STOPDAPT-2 ACS trial. (Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent-2 [STOPDAPT-2], NCT02619760; Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent-2 for the Patients With ACS [STOPDAPT-2 ACS], NCT03462498).

Prevalence and Effects of High-Intensity Statins for Japanese Patients Presenting With Acute Coronary Syndrome　- A Post Hoc Secondary Analysis of STOPDAPT-2 ACS.

BACKGROUND: The REAL-CAD trial, reported in 2017, demonstrated a significant reduction in cardiovascular events with high-intensity statins in patients with chronic coronary syndrome. However, data are scarce on the use of high-intensity statins in Japanese patients with acute coronary syndrome (ACS).Methods and Results: In STOPDAPT-2 ACS, which exclusively enrolled ACS patients between March 2018 and June 2020, 1,321 (44.2%) patients received high-intensity statins at discharge, whereas of the remaining 1,667 patients, 96.0% were treated with low-dose statins. High-intensity statins were defined as the maximum approved doses of strong statins in Japan. The incidence of the cardiovascular composite endpoint (cardiovascular death, myocardial infarction, definite stent thrombosis, stroke) was significantly lower in patients with than without high-intensity statins (1.44% vs. 2.69% [log-rank P=0.025]; adjusted hazard ratio [aHR] 0.48, 95% confidence interval [CI] 0.24-0.94, P=0.03) and the effect was evident beyond 60 days after the index percutaneous coronary intervention (log-rank P=0.01; aHR 0.38, 95% CI 0.17-0.86, P=0.02). As for the bleeding endpoint, there was no significant difference between the 2 groups (0.99% vs. 0.73% [log-rank P=0.43]; aHR 0.96, 95% CI 0.35-2.60, P=0.93). CONCLUSIONS: The prevalence of high-intensity statins has increased substantially in Japan. The use of the higher doses of statins in ACS patients recommended in the guidelines was associated with a significantly lower risk of the primary cardiovascular composite endpoint compared with lower-dose statins.

Sex Differences in Clinical Outcomes After Percutaneous Coronary Intervention.

BACKGROUND: There is a scarcity of studies comparing the clinical outcomes after percutaneous coronary intervention (PCI) for women and men stratified by the presentation of acute coronary syndromes (ACS) or stable coronary artery disease (CAD).Methods and Results: The study population included 26,316 patients who underwent PCI (ACS: n=11,119, stable CAD: n=15,197) from the CREDO-Kyoto PCI/CABG registry Cohort-2 and Cohort-3. The primary outcome was all-cause death. Among patients with ACS, women as compared with men were much older. Among patients with stable CAD, women were also older than men, but with smaller difference. The cumulative 5-year incidence of all-cause death was significantly higher in women than in men in the ACS group (26.2% and 17.9%, log rank P<0.001). In contrast, it was significantly lower in women than in men in the stable CAD group (14.2% and 15.8%, log rank P=0.005). After adjusting confounders, women as compared with men were associated with significantly lower long-term mortality risk with stable CAD but not with ACS (hazard ratio [HR]: 0.75, 95% confidence interval [CI]: 0.69-0.82, P<0.001, and HR: 0.92, 95% CI: 0.84-1.01, P=0.07, respectively). There was a significant interaction between the clinical presentation and the mortality risk of women relative to men (interaction P=0.002). CONCLUSIONS: Compared with men, women had significantly lower adjusted mortality risk after PCI among patients with stable CAD, but not among those with ACS.

Clinical characteristics, management strategies and outcomes of patients with recurrent venous thromboembolism in the real world.

There is a paucity of data on management strategies and clinical outcomes after recurrent venous thromboembolism (VTE). In a multicenter registry enrolling 3027 patients with acute symptomatic VTE, the current study population was divided into the following 3 groups: (1) First recurrent VTE during anticoagulation therapy (N = 110); (2) First recurrent VTE after discontinuation of anticoagulation therapy (N = 116); and (3) No recurrent VTE (N = 2801). Patients with first recurrent VTE during anticoagulation therapy more often had active cancer (45, 25 and 22%, P < 0.001). Among 110 patients with first recurrent VTE during anticoagulation therapy, 84 patients (76%) received warfarin at recurrent VTE with the median prothrombin time-international normalized ratio (PT-INR) value at recurrent VTE of 1.6, although patients with active cancer had a significantly higher median PT-INR value at recurrent VTE compared with those without active cancer (2.0 versus 1.4, P < 0.001). Within 90 days after recurrent VTE, 23 patients (20.9%) during anticoagulation therapy and 24 patients (20.7%) after discontinuation of anticoagulation therapy died. Active cancer was a major cause of recurrent VTE during anticoagulation therapy as a patient-related factor, while sub-optimal intensity of anticoagulation therapy was a major cause of recurrent VTE during anticoagulation therapy as a treatment-related factor, particularly in patients without active cancer.

Modifiers of the Risk of Diabetes for Long-Term Outcomes After Coronary Revascularization: CREDO-Kyoto PCI/CABG Registry.

Background: Diabetes is a well-known risk factor for adverse outcomes after coronary revascularization. Objectives: This study sought to determine high-risk subgroups in whom the excess risks of diabetes relative to nondiabetes are particularly prominent and thus may benefit from more aggressive interventions. Methods: The study population consisted of 39,427 patients (diabetes: n = 15,561; nondiabetes: n = 23,866) who underwent first percutaneous coronary intervention (n = 33,144) or coronary artery bypass graft (n = 6,283) in the pooled CREDO-Kyoto PCI/CABG (Coronary Revascularization Demonstrating Outcome Study in Kyoto Percutaneous Coronary Intervention/Coronary Artery Bypass Graft) registry. The primary outcome measure was major adverse cardiovascular and cerebral endpoints (MACCE), which was defined as a composite of all-cause death, myocardial infarction, and stroke. Results: With median follow-up of 5.6 years, diabetes was associated with significantly higher adjusted risks for MACCE. The excess adjusted risks of diabetes relative to nondiabetes for MACCE increased with younger age (≤64 years: adjusted HR: 1.30; 95% CI: 1.19-1.41; P < 0.001; 64-73 years: adjusted HR: 1.24; 95% CI: 1.16-1.33; P < 0.001; >73 years: adjusted HR: 1.17; 95% CI: 1.10-1.23; P < 0.001; P interaction < 0.001), mainly driven by greater excess adjusted mortality risk of diabetes relative to nondiabetes in younger tertile. No significant interaction was observed between adjusted risk of diabetes relative to nondiabetes for MACCE and other subgroups such as sex, mode of revascularization, and clinical presentation of acute myocardial infarction. Conclusions: The excess risk of diabetes relative to nondiabetes for MACCE was profound in the younger population. This observation suggests more aggressive interventions for secondary prevention in patients with diabetes might be particularly relevant in younger patients.

Causes of long-term mortality in patients with venous thromboembolism in the real world: From the COMMAND VTE registry.

INTRODUCTION: There is still a scarcity of data on causes of long-term mortality in patients with venous thromboembolism (VTE). MATERIALS AND METHODS: The COMMAND VTE Registry is a physician-initiated, retrospective, multicenter cohort study in which consecutive 3027 patients with acute symptomatic VTE among 29 centers in Japan were included between January 2010 and August 2014. We investigated detailed causes and risk factors for long-term mortality. RESULTS: During a median observation period of 1218 days, a total of 764 patients died, and the prevalence of active cancer was higher in patients who died than in patients alive (61 % versus 10 %, P < 0.001). The cumulative incidences of cardiac death, pulmonary embolism (PE)-related death, bleeding death, cancer death, and non-cardiovascular non-cancer death were 2.2 %, 2.9 %, 2.0 %, 16.1 %, and 6.7 % at 5 years, respectively. The incidence of cancer death increased gradually, which was the most common cause of long-term death. Among patients without active cancer, the incidence of PE-related death increased rapidly and became a plateau beyond the acute phase, whereas the incidence of non-cardiovascular non-cancer death kept increasing, which became most common in the long term. The separate multivariable analysis among patient with and without active cancer identified independent risk factors of all-cause death including a few patient characteristics among patients with active cancer and several patient characteristics among patients without active cancer. CONCLUSIONS: Cancer was the most common cause of long-term mortality, while non-cardiovascular non-cancer death became most common among patients without active cancer.

Percutaneous coronary intervention using new-generation drug-eluting stents versus coronary arterial bypass grafting in stable patients with multi-vessel coronary artery disease: From the CREDO-Kyoto PCI/CABG registry Cohort-3.

AIMS: There is a scarcity of studies comparing percutaneous coronary intervention (PCI) using new-generation drug-eluting stents (DES) with coronary artery bypass grafting (CABG) in patients with multi-vessel coronary artery disease. METHODS AND RESULTS: The CREDO-Kyoto PCI/CABG registry Cohort-3 enrolled 14927 consecutive patients who underwent first coronary revascularization with PCI or isolated CABG between January 2011 and December 2013. The current study population consisted of 2464 patients who underwent multi-vessel coronary revascularization including revascularization of left anterior descending coronary artery (LAD) either with PCI using new-generation DES (N = 1565), or with CABG (N = 899). Patients in the PCI group were older and more often had severe frailty, but had less complex coronary anatomy, and less complete revascularization than those in the CABG group. Cumulative 5-year incidence of a composite of all-cause death, myocardial infarction or stroke was not significantly different between the 2 groups (25.0% versus 21.5%, P = 0.15). However, after adjusting confounders, the excess risk of PCI relative to CABG turned to be significant for the composite endpoint (HR 1.27, 95%CI 1.04-1.55, P = 0.02). PCI as compared with CABG was associated with comparable adjusted risk for all-cause death (HR 1.22, 95%CI 0.96-1.55, P = 0.11), and stroke (HR 1.17, 95%CI 0.79-1.73, P = 0.44), but with excess adjusted risk for myocardial infarction (HR 1.58, 95%CI 1.05-2.39, P = 0.03), and any coronary revascularization (HR 2.66, 95%CI 2.06-3.43, P<0.0001). CONCLUSIONS: In this observational study, PCI with new-generation DES as compared with CABG was associated with excess long-term risk for major cardiovascular events in patients who underwent multi-vessel coronary revascularization including LAD.

Stroke Risk Stratification With the CHADS2 Score in Patients Without Atrial Fibrillation Who Underwent Percutaneous Coronary Intervention.

The clinical significance of the CHADS2 score remains unclear in patients with coronary artery disease (CAD) without atrial fibrillation (AF). Therefore, the purpose of this study was to evaluate the association between the CHADS2 score and the long-term risk of ischemic stroke and its severity in patients with CAD with and without AF. Using the CREDO (Coronary Revascularization Demonstrating Outcome study)-Kyoto Registry Cohort-3, the present study population consisted of 11,516 patients with CAD who underwent percutaneous coronary intervention without oral anticoagulants at discharge. We divided the patients into 2 groups according to the presence (n = 721) or absence (n = 10,795) of AF. As the CHADS2 score increased from 0 or 1 to 6, the cumulative 5-year incidence of ischemic stroke incrementally increased from 2.1% to 17.1% in patients without AF and from 4.2% to 40.7% in patients with AF. The cumulative 5-year incidence of ischemic stroke in patients without AF and a CHADS2 score of 2 were numerically comparable to that in patients with AF and a CHADS2 score of 1 (3.4% and 3.7%). In the 423 patients who developed ischemic stroke, the modified Rankin Scale score was not significantly different between patients with and without AF (p for trend = 0.12). In patients with and without AF, the increase in the CHADS2 score was significantly associated with the greater prevalence of higher modified Rankin Scale scores (p for trend = 0.03 and <0.001, respectively). An increasing CHADS2 score was associated with an incrementally increased risk for ischemic stroke and greater severity of ischemic stroke in patients with and without AF.

Optimal quality of vitamin K antagonist therapy in Japanese patients with venous thromboembolism.

BACKGROUND: Vitamin K antagonist (VKA) remains an essential option for venous thromboembolism (VTE), although direct oral anticoagulants have become available. However, there is a paucity of data on the optimal intensity and quality of control for VKA in Japanese. METHODS: The COMMAND VTE Registry is a multicenter registry enrolling consecutive 3027 patients with acute symptomatic VTE among 29 centers in Japan. The current study population consisted of 1938 patients who received VKA with prothrombin time-international normalized ratio (PT-INR) measurement >5 times. The primary outcome measure was a composite of symptomatic VTE recurrence or major bleeding at 1 year. The presumed optimal quality of VKA therapy was defined as the combination of PT-INR range and time in therapeutic range (TTR) with the numerically lowest event rate. RESULTS: The group with TTR ≥70 % based on PT-INR range ≥1.5 and <2.0 showed the lowest cumulative incidence rate. The cumulative 1-year incidence and the adjusted risk for the primary outcome measure were significantly lower in the optimal quality group than in the non-optimal quality group (5.2 % vs. 11.7 %, p = 0.001, and HR 0.49, 95%CI 0.28-0.81). Similarly, the cumulative 1-year incidences of a recurrent VTE, major bleeding, and all-cause death were significantly lower in the optimal quality group (recurrent VTE: 2.5 % vs. 6.0 %, p = 0.02; major bleeding: 2.8 % vs. 7.0 %, p = 0.008; and all-cause death: 2.8 % vs. 12.6 %, p < 0.0001). The lower risk of the optimal quality group relative to non-optimal quality group for the clinical outcomes was consistent regardless of the etiology of VTE (active cancer, transient risk factor, and unprovoked). CONCLUSIONS: The current VTE registry showed the optimal intensity of VKA therapy was target PT-INR range ≥1.5 and <2.0, which could support the current Japanese guideline recommendation, and the good quality of control for VKA therapy of TTR ≥70 % was independently associated with better outcomes.