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There is still a scarcity of data on causes of long-term mortality in patients with venous thromboembolism (VTE).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.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.Cancer was the most common cause of long-term mortality, while non-cardiovascular non-cancer death became most common among patients without active cancer.

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

Background There is a paucity of data on the long-term clinical outcomes according to the severity of pulmonary embolism (PE) at initial diagnosis. Methods The COMMAND VTE Registry is a multicenter registry enrolling 3027 consecutive patients with acute symptomatic venous thromboembolism (VTE). After excluding 1312 patients without PE, the current study population consisted of 1715 patients with PE, who were divided into 3 groups according to the clinical severity; massive PE, sub-massive PE and low-risk PE. Results There were 179 patients (10%) with massive PE, 742 patients (43%) with sub-massive PE, and 794 patients (46%) with low-risk PE. By the landmark analysis at 3 months, the cumulative incidences of recurrent VTE were similar among the 3 groups both within and beyond 3 months (Massive PE: 2.9%, Sub-massive PE: 4.2%, and Low-risk PE: 3.3%, P = 0.61, and 4.3%, 8.8%, and 7.8% at 5 years, P = 0.47, respectively). After adjusting confounders, the risk of massive PE relative to low-risk PE for recurrent VTE beyond 3 months remained insignificant (adjusted HR 0.54, 95% CI: 0.13–1.51, P = 0.27). Patients with massive PE at initial diagnosis more often presented as severe recurrent PE events than those with sub-massive and low-risk PE. Conclusions In the current real-world large registry, the long-term risk of overall recurrent VTE in patients with massive PE at initial diagnosis did not significantly differ from those with sub-massive and low-risk PE beyond 3 months, although patients with massive PE at initial diagnosis more frequently developed recurrent VTE as PE with severe clinical presentation.

Anticoagulation therapy is prescribed for the prevention of recurrence in patients with venous thromboembolism, which could be temporarily interrupted during invasive procedures. The COMMAND VTE Registry is a multicenter registry enrolling 3027 consecutive patients with acute symptomatic VTE in Japan between January 2010 and August 2014. We identified patients who underwent invasive procedures during the entire follow-up period and evaluated periprocedural managements and clinical outcomes at 30 days after invasive procedures. During a median follow-up period of 1213 (IQR: 847–1764) days, 518 patients underwent invasive procedures with the cumulative incidences of 5.8% at 3 months, 11.1% at 1 year, and 24.0% at 5 years. Among 382 patients in high bleeding-risk category of invasive procedures, anticoagulation therapy had been discontinued already in 62 patients (16%) and interrupted temporarily in 288 patients (75%) during the invasive procedures with bridging anticoagulation therapy with heparin in 214 patients (56%). Among 80 patients in low bleeding-risk category, anticoagulation therapy had been already discontinued in 15 patients (19%) and interrupted temporarily in 31 patients (39%) during invasive procedure with bridging anticoagulation therapy with heparin in 17 patients (21%). At 30 days after the invasive procedures, 14 patients (2.7%) experienced recurrent VTE, while 28 patients (5.4%) had major bleeding. This study elucidated the real-world features of peri-procedural management and prognosis in patients with VTE who underwent invasive procedures during follow-up in the large multicenter VTE registry. The 30-day incidence rates of recurrent VTE and major bleeding events were 2.7% and 5.4%.

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 P0.001). 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, P0.001, 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).Compared with men, women had significantly lower adjusted mortality risk after PCI among patients with stable CAD, but not among those with ACS.

The treatment of coronary artery disease has substantially changed over the past two decades. However, it is unknown whether and how much these changes have contributed to the improvement of long-term outcomes after coronary revascularization. We assessed trends in the demographics, practice patterns and long-term outcomes in 24,951 patients who underwent their first percutaneous coronary intervention (PCI) (n = 20,106), or isolated coronary artery bypass grafting (CABG) (n = 4,845) using the data in a series of the CREDO-Kyoto PCI/CABG Registries (Cohort-1 [2000 to 2002]: n = 7,435, Cohort-2 [2005 to 2007]: n = 8,435, and Cohort-3 [2011 to 2013]: n = 9,081). From Cohort-1 to Cohort-3, the patients got progressively older across subsequent cohorts (67.0 ± 10.0, 68.4 ± 9.9, and 69.8 ± 10.2 years, ptrend

Prolonged anticoagulation therapy is recommended for patients with intermediate-risk for recurrence of venous thromboembolism (VTE). The current study aimed to identify risk factors of VTE recurrence and major bleeding in intermediate-risk patients. The COMMAND VTE Registry is a multicenter registry enrolled consecutive 3027 patients with acute symptomatic VTE among 29 centers in Japan. The current study population consisted of 1703 patients with intermediate-risk for recurrence. The primary outcome measure was recurrent VTE during the entire follow-up period, and the secondary outcome measures were recurrent VTE and major bleeding during anticoagulation therapy. In the multivariable Cox regression model for recurrent VTE incorporating the status of anticoagulation therapy as a time-updated covariate, off-anticoagulation therapy was strongly associated with an increased risk for recurrent VTE (HR 9.42, 95% CI 5.97–14.86). During anticoagulation therapy, the independent risk factor for recurrent VTE was thrombophilia (HR 3.58, 95% CI 1.56–7.50), while the independent risk factors for major bleeding were age ≥ 75 years (HR 2.04, 95% CI 1.36–3.07), men (HR 1.52, 95% CI 1.02–2.27), history of major bleeding (HR 3.48, 95% CI 1.82–6.14) and thrombocytopenia (HR 3.73, 95% CI 2.04–6.37). Among VTE patients with intermediate-risk for recurrence, discontinuation of anticoagulation therapy was a very strong independent risk factor of recurrence during the entire follow-up period. The independent risk factors of recurrent VTE and those of major bleeding during anticoagulation therapy were different: thrombophilia for recurrent VTE, and advanced age, men, history of major bleeding, and thrombocytopenia for major bleeding. Unique identifier: UMIN000021132. COMMAND VTE Registry: http://www.umin.ac.jp/ctr/index.htm .

BACKGROUND Data on the clinical outcomes of percutaneous coronary intervention (PCI) for unprotected left main coronary artery (LMCA) in patients with acute coronary syndrome (ACS) are limited. Therefore, this study aimed to assess the clinical outcome of patients with ACS who underwent PCI for LMCA culprit lesion.Methods and Results:Of 1,809 patients enrolled in the Assessing Optimal Percutaneous Coronary Intervention for the LMCA (AOI-LMCA) registry (a retrospective 6-center registry of consecutive patients undergoing LMCA stenting in Japan), the current study population consisited of 1,500 patients with unprotected LMCA stenting for LMCA ACS (ACS with shock: 115 patients, ACS without shock: 281 patients) and stable CAD (1,104 patients). The cumulative 180-day incidence of death was markedly higher in the ACS with shock group than in the other groups (49.5%, 8.6%, and 3.3%, respectively; P

Background The majority of acute pulmonary embolism (PE) is caused by thrombus developed from leg veins. However, impact of concomitant deep venous thrombosis (DVT) on clinical outcomes has not been fully evaluated in patients with acute PE. Methods The COMMAND VTE Registry is a multicenter registry enrolling consecutive 3027 patients with acute symptomatic venous thromboembolism (VTE) in Japan. The current study population consisted of 655 acute PE patients who underwent lower extremities ultrasound examination at diagnosis for the assessment of concomitant DVT status. Results There were 424 patients with proximal DVT (64.7%), 162 patients with distal DVT (24.7%), and 69 patients with no DVT (10.5%). The cumulative 90-day incidence of all-cause death was higher in proximal DVT patients than in distal DVT and no DVT patients (7.9%, 2.5%, and 1.4%, p = 0.01). Regarding the causes of death, the cumulative 90-day incidence of PE-related death was low, and not significantly different across the 3 groups (1.4%, 0.6%, and 1.7%, p = 0.62). The most frequent cause of death was cancer in proximal and distal DVT patients. There were no significant differences in 90-day rates of recurrent VTE and major bleeding, regardless of the status of concomitant DVT (2.9%, 3.2%, and 2.2%, p = 0.79, and 1.5%, 4.4%, and 4.9%, p = 0.46, respectively). Conclusions Acute PE with proximal DVT at diagnosis was associated with a higher risk for short-term mortality than in patients without DVT, while the risk for short-term mortality was not significantly different between distal DVT patients and patients without DVT.

There is a scarcity of data comparing long-term clinical outcomes between percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) in patients with three-vessel coronary artery disease (3VD) in the new-generation drug-eluting stents era. CREDO-Kyoto PCI/CABG registry Cohort-3 enrolled 14927 consecutive patients who had undergone first coronary revascularization with PCI or isolated CABG between January 2011 and December 2013. We identified 2525 patients with 3VD (PCI: n = 1747 [69%], and CABG: n = 778 [31%]). The primary outcome measure was all-cause death. Median follow-up duration was 5.7 (interquartile range: 4.4 to 6.6) years. The cumulative 5-year incidence of all-cause death was significantly higher in the PCI group than in the CABG group (19.8% vs 13.2%, log-rank p = 0.001). After adjusting confounders, the excess risk of PCI relative to CABG for all-cause death remained significant (HR, 1.45; 95% CI, 1.14 to 1.86; p = 0.003), which was mainly driven by the excess risk for non-cardiovascular death (HR, 1.88; 95% CI, 1.30 to 2.79; p = 0.001), while there was no excess risk for cardiovascular death between PCI and CABG (HR, 1.19; 95% CI, 0.87 to 1.64; p = 0.29). There was significant excess risk of PCI relative to CABG for myocardial infarction (HR, 1.77; 95% CI, 1.19 to 2.69; p = 0.006), whereas there was no excess risk of PCI relative to CABG for stroke (HR, 1.24; 95% CI, 0.83 to 1.88; p = 0.30). In conclusion, in the present study population reflecting real-world clinical practice in Japan, PCI compared with CABG was associated with significantly higher risk for all-cause death, while there was no excess risk for cardiovascular death between PCI and CABG.

Diabetes was reported to be associated with an impaired response to clopidogrel.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).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.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]; PClopidogrel 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).

There is a paucity of data on the influence of low body weight on clinical outcomes in patients with acute venous thromboembolism (VTE).The COMMAND VTE registry is a multicenter cohort study enrolling 3027 consecutive patients with acute symptomatic VTE. The current study population consisted of 2778 patients with available body weight value, who were divided into 2 groups; 1705 patients with lower body weight (≤60 kg) and 1073 patients with higher body weight (60 kg).Patients with lower body weight were older (70.8 versus 60.9 years, P 0.001), and more often women (75% versus 38%, P 0.001), and more often had active cancer (27% versus 19%, P 0.001) than those with higher body weight. The cumulative 5-year incidence of recurrent VTE was not significantly different between the 2 groups (10.6% versus 10.7%, P = 0.51). The cumulative 5-year incidences of major bleeding and all-cause death were significantly higher in patients with lower body weight than in those with higher body weight (14.6% versus 9.6%, P 0.001, and 35.8% versus 19.8%, P 0.001, respectively). The excess adjusted risk of patients with lower body weight relative to those with higher body weight remained significant for major bleeding and all-cause death (HR 1.57, 95%CI: 1.16-2.12, P = 0.003, and HR 1.50, 95%CI: 1.24-1.81, P 0.001, respectively).In the current Japanese real-world registry, there were a high proportion of patients with low body weight, who had a higher risk for major bleeding and mortality without significant excess risk for recurrent VTE.

There are uncertainties on the influence of the days of diagnosis in a week (weekends versus weekdays) on clinical outcomes in patients with acute venous thromboembolism (VTE), including pulmonary embolism (PE) and deep vein thrombosis (DVT). The COMMAND VTE registry is a multicenter cohort study enrolling 3027 consecutive patients with acute symptomatic VTE. The current study population consisted of 337 patients diagnosed on weekends and 2690 patients diagnosed on weekdays. We compared the clinical characteristics, management strategies and 30-day outcomes between the 2 groups. The patients diagnosed on weekends more often presented with PE (72% vs. 55%, P

Background The simplified Pulmonary Embolism Severity Index (sPESI) score is a practical score for identification of patients with low-risk pulmonary embolism (PE), although it has not been applied in patients with active cancer. The current study aimed to evaluate the usefulness of the sPESI score in patients with PE and active cancer. Methods The COMMAND VTE Registry is a multicenter registry enrolling consecutive patients with acute symptomatic VTE. The current study population consisted of 368 patients with PE and active cancer. The 30-day clinical outcomes were compared between patients with sPESI score = 1 and patients with sPESI scores ≥ 2. Results Overall, 37 patients (10%) died during the 30 days after diagnosis. The cumulative 30-day incidences of mortality, and PE-related death, were lower in patients with sPESI score = 1 than in patients with sPESI scores ≥ 2 (6.3% vs 13.1%; log-rank P = .03; and 0.7% vs 3.9%; log-rank P = .046). Among patients with sPESI score = 1, the predominant cause of death was cancer. There were no significant differences in the cumulative 30-day incidence of recurrent VTE and major bleeding between the two groups (3.9% vs 5.6%; log-rank P = .46; and 6.4% vs 4.5%; log-rank P = .45). Conclusions Among patients with PE and active cancer, patients with sPESI score = 1 had a lower 30-day mortality rate compared with patients with sPESI scores ≥ 2, and they showed very low PE-related mortality risk, although the overall mortality rate remained high because of cancer-related mortality. They also showed relatively high risks for recurrence and major bleeding, suggesting the need for careful follow-up. Trial Registry UMIN Clinical Trials Registry; No.: UMIN000021132; URL: http://www.umin.ac.jp/ctr/index.htm

The clinical significance of the CHADSsub2/subscore 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 CHADSsub2/subscore 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 CHADSsub2/subscore 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 CHADSsub2/subscore of 2 were numerically comparable to that in patients with AF and a CHADSsub2/subscore 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 CHADSsub2/subscore was significantly associated with the greater prevalence of higher modified Rankin Scale scores (p for trend = 0.03 andlt;0.001, respectively). An increasing CHADSsub2/subscore was associated with an incrementally increased risk for ischemic stroke and greater severity of ischemic stroke in patients with and without AF.

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.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) measurement5 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.The group with TTR ≥70 % based on PT-INR range ≥1.5 and2.0 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).The current VTE registry showed the optimal intensity of VKA therapy was target PT-INR range ≥1.5 and2.0, 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.

Background It remains controversial whether long‐term clinical impact of newly diagnosed atrial fibrillation (AF) in the acute phase of acute myocardial infarction (AMI) is different from that of prior AF diagnosed before the onset of AMI. Methods and Results The current study population from the CREDO‐Kyoto AMI (Coronary Revascularization Demonstrating Outcome Study in Kyoto Acute Myocardial Infarction) Registry Wave‐2 consisted of 6228 patients with AMI who underwent percutaneous coronary intervention. The baseline characteristics and long‐term clinical outcomes were compared according to AF status (newly diagnosed AF: N=489 [7.9%], prior AF: N=589 [9.5%], and no AF: N=5150 [82.7%]). Median follow‐up duration was 5.5 years. Patients with newly diagnosed AF and prior AF had similar baseline characteristics with higher risk profile than those with no AF including older age and more comorbidities. The cumulative 5‐year incidence of all‐cause death was higher in newly diagnosed AF and prior AF than no AF (38.8%, 40.7%, and 18.7%, P P P P P P =0.048, respectively). The higher stroke risk of newly diagnosed AF compared with prior AF was largely driven by the greater risk within 30 days. The higher adjusted HRs of newly diagnosed AF and prior AF relative to no AF were significant for heart failure hospitalization (HR, 1.73; 95% CI, 1.35–2.22; P P P P Conclusions Newly diagnosed AF in AMI had risks for mortality, heart failure hospitalization, and major bleeding higher than no AF, and comparable to prior AF. The risk of newly diagnosed AF for stroke might be higher than that of prior AF.

BACKGROUND Optimal intensity is unclear for P2Y12receptor blocker therapy after percutaneous coronary intervention (PCI) in real-world clinical practice.Methods and Results:From the CREDO-Kyoto Registry, the current study population consisted of 25,419 patients (Cohort-2: n=12,161 and Cohort-3: n=13,258) who underwent their first PCI. P2Y12receptor blocker therapies were reduced dose of ticlopidine (200 mg/day), and global dose of clopidogrel (75 mg/day) in 87.7% and 94.8% of patients in Cohort-2 and Cohort-3, respectively. Cumulative 3-year incidence of GUSTO moderate/severe bleeding was significantly higher in Cohort-3 than in Cohort-2 (12.1% and 9.0%, P

The duration of anticoagulation therapy after venous thromboembolism (VTE) should be based on the balance between risks of recurrent VTE and bleeding. However, there is uncertainty about the impact of these events on subsequent mortality.We evaluated the association of recurrent VTE and major bleeding events with mortality among 3026 patients in the COMMAND VTE Registry. We estimated the risks of the recurrent VTE events and the major bleeding events for subsequent mortality by the time-updated multivariable Cox proportional hazard model.During the median follow-up period of 1218 days, 225 patients developed recurrent VTE events, 274 patients developed major bleeding events, and 763 patients died. The multivariable Cox proportional hazard model revealed that both the recurrent VTE and major bleeding events were strongly associated with subsequent mortality risk (recurrent VTE: HR 3.24, 95%CI 2.57-4.08, P 0.001; major bleeding: HR 3.53, 95%CI 2.88-4.31, P 0.001). Both the recurrent pulmonary embolism (PE) and recurrent deep vein thrombosis (DVT) events were associated with subsequent mortality risk (recurrent PE events: HR 4.42, 95%CI 3.28-5.95, P 0.001; recurrent DVT events: HR 2.42, 95%CI 1.75-3.36, P 0.001).In the real-world patients with VTE, both the recurrent VTE events and the major bleeding events were strongly associated with subsequent mortality risk with the comparable effect size. The recurrent PE and recurrent DVT events were also associated with increased risks for mortality, although the magnitude of the effect on mortality was numerically greater with the recurrent PE events than with the recurrent DVT events.

The relationship between D-dimer level at diagnosis and long-term clinical outcomes has not been fully evaluated in venous thromboembolism (VTE). The COMMAND VTE Registry is a multicenter registry enrolling consecutive acute symptomatic VTE patients in Japan. Patients with available D-dimer levels at diagnosis (N = 2852) were divided into 4 groups according to the D-dimer levels; Quartile 1 (0.0–4.9 µg/mL): N = 682, Quartile 2 (5.0–9.9 µg/mL) N = 694, Quartile 3 (10.0–19.9 µg/mL) N = 710, and Quartile 4 (≥ 20.0 µg/mL): N = 766. The cumulative incidence of all-cause death was higher in Quartile 4 throughout the entire follow-up period (19.9%, 24.9%, 28.8%, and 41.5% at 5-year, P

Background There are limited data assessing the risk for bleeding on anticoagulation therapy beyond the acute phase in patients with venous thromboembolism (VTE). The present study aimed to identify risk factors for major bleeding during prolonged anticoagulation therapy in VTE patients. Patients and Methods The COMMAND VTE Registry is a multicenter registry enrolling 3,027 consecutive patients with acute symptomatic VTE. The current study population consisted of 2,728 patients who received anticoagulation therapy beyond the acute phase, after excluding those patients with major bleeding events (n = 48), death (n = 66), or loss to follow-up (n = 32) during the initial parenteral anticoagulation period within 10 days after diagnosis, and those without anticoagulation therapy beyond 10 days after diagnosis (n = 153). Results During the median follow-up period of 555 days, major bleeding occurred in 189 patients (70 patients within 3 months; 119 patients beyond 3 months) with fatal bleeding in 24 patients (13%). The cumulative incidence of major bleeding was 2.7% at 3 months, 5.2% at 1 year, and 11.8% at 5 years. Active cancer (hazard ratio [HR], 3.06, 95% confidence interval [CI], 2.23–4.18), previous major bleeding (HR, 2.38, 95% CI, 1.51–3.59), anemia (HR, 1.75, 95% CI, 1.27–2.43), thrombocytopenia (HR, 2.11, 95% CI, 1.27–3.33), and age ≥75 years (HR, 1.64, 95% CI, 1.22–2.20) were independently associated with an increased risk for major bleeding by the multivariable Cox regression model. Conclusion Major bleeding events were not uncommon during prolonged anticoagulation therapy in real-world VTE patients. Active cancer, previous major bleeding, anemia, thrombocytopenia, and old age were the independent risk factors for major bleeding.

BACKGROUND Differences in the clinical characteristics and outcomes of venous thromboembolisms (VTEs) based on different clinical situations surrounding the onset might be important for directing appropriate treatment strategies, but have not yet been appropriately evaluated. Methods and Results: The COMMAND VTE Registry is a multicenter registry enrolling 3,027 consecutive patients with acute symptomatic VTEs in Japan between January 2010 and August 2014. We divided the study population into 3 groups: Out-of-hospital onset (n=2,308), In-hospital onset with recent surgery (n=310), and In-hospital onset without recent surgery (n=374). Active cancer was most prevalent in the In-hospital onset without recent surgery group, and least in the Out-of-hospital onset group (Out-of-hospital onset group: 20%, In-hospital onset with recent surgery group: 26%, and In-hospital onset without recent surgery group: 38%, P

Anticoagulation therapy is prescribed for the prevention of recurrence in patients with venous thromboembolism, which could be temporarily interrupted during invasive procedures. The COMMAND VTE Registry is a multicenter registry enrolling 3027 consecutive patients with acute symptomatic VTE in Japan between January 2010 and August 2014. We identified patients who underwent invasive procedures during the entire follow-up period and evaluated periprocedural managements and clinical outcomes at 30 days after invasive procedures. During a median follow-up period of 1213 (IQR: 847-1764) days, 518 patients underwent invasive procedures with the cumulative incidences of 5.8% at 3 months, 11.1% at 1 year, and 24.0% at 5 years. Among 382 patients in high bleeding-risk category of invasive procedures, anticoagulation therapy had been discontinued already in 62 patients (16%) and interrupted temporarily in 288 patients (75%) during the invasive procedures with bridging anticoagulation therapy with heparin in 214 patients (56%). Among 80 patients in low bleeding-risk category, anticoagulation therapy had been already discontinued in 15 patients (19%) and interrupted temporarily in 31 patients (39%) during invasive procedure with bridging anticoagulation therapy with heparin in 17 patients (21%). At 30 days after the invasive procedures, 14 patients (2.7%) experienced recurrent VTE, while 28 patients (5.4%) had major bleeding. This study elucidated the real-world features of peri-procedural management and prognosis in patients with VTE who underwent invasive procedures during follow-up in the large multicenter VTE registry. The 30-day incidence rates of recurrent VTE and major bleeding events were 2.7% and 5.4%.

Diabetes is a well-known risk factor for adverse outcomes after coronary revascularization.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.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.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;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.

Background Heart failure might be an important determinant in choosing coronary revascularization modalities. There was no previous study evaluating the effect of heart failure on long‐term clinical outcomes after percutaneous coronary intervention (PCI) relative to coronary artery bypass grafting (CABG). Methods and Results Among 14 867 consecutive patients undergoing first coronary revascularization with PCI or isolated CABG between January 2011 and December 2013 in the CREDO‐Kyoto PCI/CABG registry Cohort‐3, we identified the current study population of 3380 patients with three‐vessel or left main coronary artery disease, and compared clinical outcomes between PCI and CABG stratified by the subgroup based on the status of heart failure. There were 827 patients with heart failure (PCI: N=511, and CABG: N=316), and 2553 patients without heart failure (PCI: N=1619, and CABG: N=934). In patients with heart failure, the PCI group compared with the CABG group more often had advanced age, severe frailty, acute and severe heart failure, and elevated inflammatory markers. During a median 5.9 years of follow‐up, there was a significant interaction between heart failure and the mortality risk of PCI relative to CABG (interaction P =0.009), with excess mortality risk of PCI relative to CABG in patients with heart failure (HR, 1.75; 95% CI, 1.28–2.42; P P =0.77). Conclusions There was a significant interaction between heart failure and the mortality risk of PCI relative to CABG with excess risk in patients with heart failure and neutral risk in patients without heart failure.

Prolonged anticoagulation therapy is recommended for patients with intermediate-risk for recurrence of venous thromboembolism (VTE). The current study aimed to identify risk factors of VTE recurrence and major bleeding in intermediate-risk patients. The COMMAND VTE Registry is a multicenter registry enrolled consecutive 3027 patients with acute symptomatic VTE among 29 centers in Japan. The current study population consisted of 1703 patients with intermediate-risk for recurrence. The primary outcome measure was recurrent VTE during the entire follow-up period, and the secondary outcome measures were recurrent VTE and major bleeding during anticoagulation therapy. In the multivariable Cox regression model for recurrent VTE incorporating the status of anticoagulation therapy as a time-updated covariate, off-anticoagulation therapy was strongly associated with an increased risk for recurrent VTE (HR 9.42, 95% CI 5.97-14.86). During anticoagulation therapy, the independent risk factor for recurrent VTE was thrombophilia (HR 3.58, 95% CI 1.56-7.50), while the independent risk factors for major bleeding were age ≥ 75 years (HR 2.04, 95% CI 1.36-3.07), men (HR 1.52, 95% CI 1.02-2.27), history of major bleeding (HR 3.48, 95% CI 1.82-6.14) and thrombocytopenia (HR 3.73, 95% CI 2.04-6.37). Among VTE patients with intermediate-risk for recurrence, discontinuation of anticoagulation therapy was a very strong independent risk factor of recurrence during the entire follow-up period. The independent risk factors of recurrent VTE and those of major bleeding during anticoagulation therapy were different: thrombophilia for recurrent VTE, and advanced age, men, history of major bleeding, and thrombocytopenia for major bleeding. CLINICAL TRIAL REGISTRATION: Unique identifier: UMIN000021132. COMMAND VTE Registry: http://www.umin.ac.jp/ctr/index.htm .

BACKGROUND Data evaluating the effects of acute coronary syndrome (ACS) relative to stable coronary artery disease (CAD) on bleeding risk after percutaneous coronary intervention (PCI) are scarce.Methods and Results:From the CREDO-Kyoto Registry Cohort-3, 13,258 patients undergoing first PCI (5,521 ACS; 7,737 stable CAD) were identified. Patients were further stratified according to ACS presentation and Academic Research Consortium High Bleeding Risk (HBR): ACS/HBR: n=2,502; ACS/no-HBR: n=3,019; stable CAD/HBR: n=3,905; and stable CAD/no-HBR: n=3,832. The primary bleeding endpoint was Bleeding Academic Research Consortium 3/5 bleeding, whereas the primary ischemic endpoint was myocardial infarction (MI)/ischemic stroke. Compared with stable CAD, ACS was associated with a significantly higher adjusted risk for bleeding (hazard ratio [HR] 1.85; 95% confidence interval [CI] 1.68-2.03; P

Background The detailed causes of death in non–ST-segment–elevation myocardial infarction (NSTEMI) have not been adequately evaluated compared to those in ST-segment elevation myocardial infarction (STEMI). Methods The study population was 6,228 AMI patients who underwent percutaneous coronary intervention (STEMI: 4,625 patients and NSTEMI: 1,603 patients). The primary outcome was all-cause death. Results Within 6 months after AMI, the adjusted mortality risk was not significantly different between NSTEMI patients and STEMI patients (HR: 0.83, 95%CI: 0.67–1.03, P = 0.09). Regarding the causes of death within 6 months after AMI, mechanical complications more frequently occurred in STEMI patients than in NSTEMI patients, while proportions of post resuscitation status on arrival and heart failure were higher in in NSTEMI patients than in STEMI patients. Beyond 6 months after AMI, the adjusted mortality risk of NSTEMI relative to STEMI was not significantly different. (HR: 1.04, 95%CI: 0.90–1.20, P = 0.59). Regarding causes of death beyond 6 months after AMI, almost half of deaths were cardiovascular causes in both groups, and breakdown of causes of death was similar between NSTEMI and STEMI. Conclusion The mortality risk within and beyond 6 months after AMI were not significantly different between STEMI patients and NSTEMI patients after adjusting confounders. Deaths due to post resuscitation status and heart failure were more frequent in NSTEMI within 6 months after AMI.

Background Impact of ischemic risk (IR) on long term outcomes in patients at high bleeding risk (HBR) after everolimus-eluting stent (EES) implantation remains unclear. Purpose We aimed to evaluate long term bleeding and ischemic events in patient with HBR or IR after EES implantation. Methods The study population comprised 1219 patients treated with EES without in-hospital events between 2010 and 2011. The follow-up period was 2996±433 days. HBR was defined as Academic research consortium. IR defined as high-risk features of stent-driven recurrent ischemic events in Europe society of cardiology guidelines in 2019: prior stent thrombosis on adequate antiplatelet therapy, diffuse multivessel disease especially in diabetic patients, creatinine clearance 60 mm, and treatment of a chronic total occlusion. Major bleeding (MB) was defined as defined as the occurrence of a Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding event. Primary ischemic events included myocardial infarction, definite stent thrombosis, and cardiac death. The Kaplan-Meier method was used for time-to-event analyses. Results Of the 1219 patients, 317 (26.0%) patients had no risk, 114 (9.4%) patients had only HBR, 288 (23.6%) patients had only IR, and 500 (41.0%) patients had both risks. The 81.4% of HBR patients had IR. The figure of Kaplan-Meier showed MB and CE for 7–8 years. Both risk groups had higher bleeding risk and Ischemic events (log rank p=0.0039, 0.0001). Conclusion HBR patients with EES had a high incidence of IR. Patients who had both HBR and IR are especially at risk for both ischemic events and bleeding compared to those who had no or only one risk. Funding Acknowledgement Type of funding source: None

Background Coronary artery embolism (CE) is one of the important causes of acute coronary syndrome (ACS). The feature of CE is that angiographic evidence of coronary artery embolism and thrombosis without atherosclerotic components. However, the prevalence of CE remains unknown because of the diffifulty to diagnose in the acute settings. A recent retrospective analysis suggested that up to 3% of ACS cases may result from CE. Purpose The aim of this study was to elucidate the prevalence, clinical features and long-term outcomes including all-cause and cardiac death. Methods We analysed the consecutive 2695 patients with first AMI performed coronary intervention between January 2004 and July 2017. CE was diagnosed by clinical histories and angiographic findings. We retrospectively evaluated the clinical and lesion characteristics and outcomes including all-cause and cardiac death. Results The prevalence of CE was 2.0% (n=55; CE group and n=2640; non-CE group), including 8 (15%) patients with multivessel CE. The CE group had higher average age (70.8±14.9 vs. 68.4±12.6, p Conclusion Compared with non-CE group, the prevalence of distal infarction site was significantly higher in the CE group, and the incidence of cardiac death is not significantly different. Funding Acknowledgement Type of funding source: None

Background It is yet to be known whether mechanisms underlying restenosis in newer-generation durable-polymer (DP) and biodegradable-polymer (BP) drug-eluting stents (DES) are different. Purpose This study aims to assess the incidences and predictors of early restenosis and late catch-up phenomenon after newer-generation durable-polymer (DP) and biodegradable-polymer (BP) DES. Methods Between 2010 and 2017, 13858 lesions in 6350 patients were treated with DES (4393 BP-DES, 9465 DP-DES). The early-term (within 1 year) and late-term (from 1 to 2 years) follow-up angiographies were scheduled. Late catch-up phenomenon was defined as in-stent restenosis (ISR) in lesions that evaded ISR within 1 year after stent implantation. ISR was defined as angiographic restenosis of more than 50%. Results The mean patient age was 71 years, and 76.7% were male. Early-term angiographies were performed in 10955 lesions (79.0%). Of those without early-term ISR, late-term angiographies were performed in 7771 lesions (56.1%). The incidences of mid-term restenosis and late catch-up phenomenon were 6.6% and 3.9%, respectively. In the multivariate regression analyses, history of diabetes, hemodialysis and previous PCI were independent predictors of both early restenosis and late catch-up phenomenon. Also, some lesion characteristics such as chronic total occlusion, right coronary artery ostial lesion, small vessel (defined as reference diameter 30mm) and treatment of ISR lesion were independent predictors of both early restenosis and late catch-up phenomenon. Bifurcation lesion and heavily calcified lesion treated with rotablator were independent risk of early restenosis. Bypass graft lesion was an independent predictor of late catch-up phenomenon. Early restenosis was observed less frequently in DP-DES than in BP-DES (6.3% versus 7.4%, P=0.012). On the contrary, late catch-up phenomenon was observed more frequently in DP-DES than in BP-DES (4.3% versus 2.9%, P=0.026). Conclusions Some lesion characteristics were independent predictors of early restenosis and late catch-up phenomenon after newer-generation DES implantation. The deployment of BP-DES resulted in more early restenosis and less late catch-up phenomenon compared to that of DP-DES. Early Restenosis and Late Catch-Up Funding Acknowledgement Type of funding source: None

Background Recently, the Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria has been suggested as the standard definition of HBR. Purpose We aimed to investigate the risk stratification based on ARC-HBR Criteria for long-term bleeding event after everolimus-eluting stent implantation Methods The study population comprised 1193 patients treated with EES without in-hospital event between 2010 and 2011. Individual ARC-HBR criteria was retrospectively assessed. Major bleeding were defined as the occurrence of a Bleeding Academic Research Consortium type 3 or 5 bleeding event. The mean follow-up period was 2996±433 days. Results There were 656 patients (55.0%) in HBR-groups. Cumulative incidence of major bleeding was significantly higher in HBR-group (8.1% vs 3.4% at 4 year, and 16.2% vs 5.7% at 8 year, P Conclusion ARC-HBR criteria successfully stratified the long-term bleeding risk after drug-eluting stent implantation in real-world practice. Funding Acknowledgement Type of funding source: None

OBJECTIVES To evaluate utility of the complex percutaneous coronary intervention (PCI) criteria in real-world practice. BACKGROUND Applicability of procedural complexity criteria for risk stratification has not been adequately evaluated in real-world practice. METHODS Among 13,087 patients undergoing first PCI in the CREDO-Kyoto registry cohort-2, the study population consisted of 7,871 patients after excluding patients with acute myocardial infarction and those without stent implantation. Complex PCI was defined as PCI, which fulfills at least one of the followings: three vessels treated, > = 3 stents implanted, > = 3 lesions treated, bifurcation with two stents, >60 mm total stent lengths, and target of chronic total occlusion. RESULTS The cumulative incidences of and adjusted risks for the primary ischemic (myocardial infarction/ischemic stroke), and bleeding (GUSTO moderate/severe) endpoints were significantly higher in patients with complex PCI (N = 2,777 [35%]) than in those with noncomplex PCI (N = 5,094 [65%]) (15.4% vs. 10.9%, log-rank p

Long-term safety of percutaneous coronary intervention (PCI) as compared with coronary artery bypass grafting (CABG) is still controversial in patients with unprotected left main coronary artery disease (ULMCAD), and there is a scarcity of real-world data on the comparative long-term clinical outcomes between PCI and CABG for ULMCAD in new-generation drug-eluting stents era. The CREDO-Kyoto PCI/CABG registry Cohort-3 enrolled 14927 consecutive patients undergoing first coronary revascularization with PCI or isolated CABG between January 2011 and December 2013, and we identified 855 patients with ULMCAD (PCI: N = 383 [45%], and CABG: N = 472 [55%]). The primary outcome measure was all-cause death. Median follow-up duration was 5.5 (interquartile range: 3.9 to 6.6) years. The cumulative 5-year incidence of all-cause death was not significantly different between the PCI and CABG groups (21.9% vs 17.6%, Log-rank p = 0.13). After adjusting confounders, the excess risk of PCI relative to CABG remained insignificant for all-cause death (HR, 1.00; 95% CI, 0.68 to 1.47; p = 0.99). There were significant excess risks of PCI relative to CABG for myocardial infarction and any coronary revascularization (HR, 2.07; 95% CI, 1.30 to 3.37; p = 0.002, and HR, 2.96; 95% CI, 1.96 to 4.46; p0.001), whereas there was no significant excess risk of PCI relative to CABG for stroke (HR, 0.85; 95% CI, 0.50 to 1.41; p = 0.52). In conclusion, there was no excess long-term mortality risk of PCI relative to CABG, while the excess risks of PCI relative to CABG were significant for myocardial infarction and any coronary revascularization in the present study population reflecting real-world clinical practice in Japan.

BACKGROUND Patients with cancer-associated venous thromboembolism (VTE) are at high risk for recurrent VTE and are recommended to receive prolonged anticoagulation therapy if they are at a low risk for bleeding. However, there are no established risk factors for bleeding during anticoagulation therapy.Methods and Results:The COMMAND VTE Registry is a multicenter retrospective registry enrolling 3,027 consecutive patients with acute symptomatic VTE among 29 Japanese centers. The present study population consisted of 592 cancer-associated VTE patients with anticoagulation therapy. We constructed a multivariable Cox proportional hazard model to estimate the hazard ratio (HR) and 95% confidence interval (CI) of the potential risk factors for major bleeding. During a median follow-up period of 199 days, major bleeding occurred in 72 patients. The cumulative incidence of major bleeding was 5.8% at 3 months, 13.8% at 1 year, 17.5% at 2 years, and 28.1% at 5 years. The most frequent major bleeding site was gastrointestinal tract (47%). Terminal cancer (adjusted HR, 4.17; 95% CI, 2.22-7.85, P

There are uncertainties on the influence of the days of diagnosis in a week (weekends versus weekdays) on clinical outcomes in patients with acute venous thromboembolism (VTE), including pulmonary embolism (PE) and deep vein thrombosis (DVT). The COMMAND VTE registry is a multicenter cohort study enrolling 3027 consecutive patients with acute symptomatic VTE. The current study population consisted of 337 patients diagnosed on weekends and 2690 patients diagnosed on weekdays. We compared the clinical characteristics, management strategies and 30-day outcomes between the 2 groups. The patients diagnosed on weekends more often presented with PE (72% vs. 55%, P 0.001), and with more severe hemodynamic condition for PE patients. The patients diagnosed on weekends more often received initial parenteral anticoagulation therapy and thrombolysis than those diagnosed on weekdays. The cumulative 30-day incidence of all-cause death was not significantly different between the two groups among PE patients (diagnosis on weekends: 6.2% vs. diagnosis on weekdays: 6.5%, P = 0.87), as well as among DVT patients (0.0% vs. 1.5%, P = 0.24). The most frequent cause of deaths was fatal PE in both groups among PE patients. The risks for recurrent VTE and major bleeding at 30-day were not significantly different between the 2 groups among PE patients, nor among DVT only patients. In conclusion, the VTE patients diagnosed on weekends presented more often with PE, and with more severe condition for PE patients. Nevertheless, the risk for 30-day mortality was not significantly different between patients diagnosed on weekends and on weekdays.

Introduction The external validation of the modified Ottawa score to predict the risk of recurrence in patients with cancer-associated venous thromboembolism (VTE) has not yet been firmly established. The present study aimed to evaluate the utility and limitations of the modified Ottawa score in the risk stratification of recurrent VTE in patients with cancer-associated VTE. Materials and methods The COMMAND VTE Registry is a multicenter retrospective registry enrolling 3027 consecutive patients with acute symptomatic VTE among 29 Japanese centers. The present study population consisted of 614 cancer-associated VTE patients, who were divided into 3 groups; High-risk group: 202 patients (33%) with a modified Ottawa score ≥ 1, Intermediate-risk group: 269 patients (44%) with a score = 0, and Low-risk group: 143 patients (23%) with a score ≤ −1. Results Recurrent VTE occurred in 39 patients on anticoagulation therapy within 6 months. The cumulative incidence of recurrent VTE substantially increased in the higher risk categories by the modified Ottawa score (high-risk group: 13.6% [95%CI, 8.9%–20.2%], intermediate-risk group: 5.9% [95%CI, 3.5%–9.8%], and low-risk group: 3.0% [95%CI, 1.1%–7.8%], P = .02). The discriminating power of the score was modest with a C-statistic of 0.63. Each score component of the score had a different impact on recurrent events with a variable effect size. Conclusions The risks of recurrence in patients with cancer-associated VTE substantially increased in the higher risk categories by using the modified Ottawa score, but the discriminating power of the score for recurrence was modest with a variable impact of each score component on recurrent events.

Background: The simplified pulmonary embolism severity index (sPESI) score has been reported to be useful in predicting 30-day mortality for patients with pulmonary embolism, which helps the identification of low-risk patients for early hospital discharge or home treatment. However, therapeutic decision-making should also be based on the risks of adverse events other than mortality. Methods: The COMMAND VTE Registry is a multicentre registry enrolling consecutive patients with acute symptomatic venous thromboembolism in Japan between January 2010 and August 2014, and the current study population consisted of 1715 patients with pulmonary embolism. We calculated the sPESI score for each patient, and compared 30-day rates of mortality, recurrent venous thromboembolism and major bleeding between sPESI scores of 0 and 1 or greater. Results: Patients with a sPESI score of 0 accounted for 383 (22%) patients, and 110 (6.4%) patients died within 30 days. The cumulative 30-day incidence of mortality was lower in patients with a sPESI score of 0 than those with a sPESI score of 1 or greater (0.5% vs. 8.1%, log rank PConclusions: In patients with a sPESI score of 0, the 30-day mortality, recurrent venous thromboembolism and major bleeding rates were reasonably low. The sPESI score could be useful to identify candidates for early hospital discharge or home treatment.

Objectives The purpose of this study was to assess neoatherosclerosis in a registry of prospectively enrolled patients presenting with stent thrombosis using optical coherence tomography. Background In-stent neoatherosclerosis was recently identified as a novel disease manifestation of atherosclerosis after coronary stent implantation. Methods Angiography and intravascular optical coherence tomography were used to investigate etiologic factors of neoatherosclerosis in patients presenting with stent thrombosis >1 year after implantation (very late stent thrombosis [VLST]). Clinical data were collected according to a standardized protocol. Optical coherence tomographic acquisitions were analyzed in a core laboratory. Cox regression analysis was performed to identify factors associated with the formation of neoatherosclerosis and plaque rupture as a function of time. Results Optical coherence tomography was performed in 134 patients presenting with VLST. A total of 58 lesions in 58 patients with neoatherosclerosis were compared with 76 lesions in 76 patients without neoatherosclerosis. Baseline characteristics were similar between groups. In-stent plaque rupture was the most frequent cause (31%) in all patients presenting with VLST. In patients with neoatherosclerosis, in-stent plaque rupture was identified as the cause of VLST in 40 cases (69%), whereas uncovered stent struts (n = 22 [29%]) was the most frequent cause in patients without neoatherosclerosis. Macrophage infiltration was significantly more frequent in optical coherence tomographic frames with plaque rupture compared with those without (50.2% vs. 22.2%; p Conclusions Neoatherosclerosis was frequently observed in patients with VLST. Implantation of a drug-eluting stent was significantly associated with neoatherosclerosis formation. In-stent plaque rupture was the prevailing pathological mechanism and often occurred in patients with neoatherosclerosis and previous myocardial infarction at index percutaneous coronary intervention. Increased macrophage infiltration heralded plaque vulnerability in our study and might serve as an important indicator.

Background Drug-eluting stents with biodegradable polymer coatings have shown promising outcomes in randomised studies. Methods We compared neointimal healing patterns including strut coverage and assessed neointimal maturity using a novel algorithm in coronary lesions treated with sirolimus-eluting stents with biodegradable polymer coating (BP-SES) or everolimus eluting stents with permanent polymer coating (PP-EES) using optical coherence tomography after 6months. Results A total of 39 patients were randomised to BP-SES ( n =19) or PP-EES ( n =20) for the treatment of coronary lesions. Of those, 29 patients (14 BP-SES and 15 PP-EES) underwent optical coherence tomography (OCT) and angiography at 6-month follow-up. Tissue coverage and apposition were assessed in a total of 6162 struts (BP-SES, n =2889; PP-EES, n =3273). Neointimal maturity was assessed in 3672 neointimal regions above struts using grey scale intensity analysis. OCT analysis showed neointimal coverage of 2433 (BP-SES) vs. 2702 (PP-EES) struts (84.2% vs. 82.6%, p =0.70), whereas the remainder was uncovered after 6months. Mean neointimal thickness did not differ significantly between groups (54.3±7.8μm vs. 80±14.6μm, p =0.12). The rate of malapposed struts was comparable between groups (1.3% vs. 2.2%, p =0.27). Grey scale signal intensity analysis showed mature tissue coverage of struts in 46.2% in BP-SES vs. 31.8% in PP-EES ( p =0.31) of neointimal regions. Conclusion The present study showed comparable early vascular healing response characterised by neointimal coverage with mainly immature neointima in both BP-SES and PP-EES.

It is still uncertain whether the final kissing balloon technique (FKBT) is mandatory after crossover stenting for the left main coronary artery (LMCA). Assessing Optimal Percutaneous Coronary Intervention for LMCA (AOI-LMCA) registry, a 6-center retrospective registry, enrolled 1809 consecutive patients for LMCA stenting in Japan. In the present analysis, 5-year clinical outcomes were compared between non-FKBT (n = 160) and FKBT (n = 578) groups in patients treated with crossover stenting with drug-eluting stents from the LMCA to the left anterior descending artery. Propensity score-matched analysis was also performed in 160 patient pairs. In the entire study population as well as in the propensity-matched population, the cumulative 5-year incidence of the primary outcome measure (target lesion revascularization: TLR) was not significantly different between the FKBT and non-FKBT groups (10.7 versus 14.3%, P = 0.49, and 11.8 versus 14.3%, P = 0.53, respectively). In the sensitivity analysis by the multivariable Cox proportional hazard model, the effect of FKBT relative to non-FKBT for TLR remained insignificant (adjusted HR 0.89, 95% CI 0.47–1.69, P = 0.72). Regarding the TLR location, there were no significant differences in the cumulative incidences of TLR for LMCA-only, for the main branch, and for the side branch between the 2 groups (2.2 versus 1.3%, P = 0.93, 11.8 versus 9.1%, P = 0.71, and 8.2 versus 7.6%, P = 0.82, respectively). FKBT after a 1-stent strategy for LMCA crossover stenting did not affect TLR and other clinical outcomes during 5-year follow-up.Clinical Trial Registration: Assessing Optimal Percutaneous Coronary Intervention for Left Main Coronary Artery Stenting Registry (AOI LMCA Stenting Registry). http://www.umin.ac.jp/ctr/index/htm/. Unique Identifier: UMIN000014706.

BACKGROUND The effect of diabetes mellitus (DM) status on the long-term risk for heart failure (HF) in patients undergoing coronary revascularization has not been adequately evaluated.Methods and Results:In this study, 15,231 patients who underwent coronary revascularization in the CREDO-Kyoto Registry Cohort-2 were divided into 2 groups according to DM status (DM group: n=5,999; Non-DM group: n=9,232). The DM group was further divided into 2 groups according to insulin treatment (insulin-treated DM [ITDM]: n=1,353; non-insulin-treated DM [NITDM]: n=4,646). The primary outcome measure was HF hospitalization. The cumulative 5-year incidence of HF hospitalization was significantly higher in the DM than non-DM group (11.0% vs. 6.6%, respectively; log-rank P

Background: Recently, the Academic Research Consortium for High Bleeding Risk (ARC-HBR) has been proposed to standardize the definition of HBR, which was arbitrarily defined as a Bleeding Academic Research Consortium 3 or 5 bleeding ≥4% at 1-year. However, the prevalence and the expected bleeding event rate of HBR patients defined by ARC-HBR criteria are currently unknown in the real-world percutaneous coronary intervention practice. Methods: We applied the ARC-HBR criteria in the CREDO-Kyoto (Coronary Revascularization Demonstrating Outcome Study in Kyoto) registry cohort-2, a multicenter registry that enrolled 13 058 consecutive patients who underwent their first percutaneous coronary intervention. The primary bleeding end point was defined as the Global Utilization of Streptokinase and Tissue plasminogen activator for Occluded coronary arteries moderate/severe bleeding. There were 5570 patients (43%) in the HBR group and 7488 patients in the no-HBR group. Results: Cumulative incidence of the primary bleeding end point was much higher in the HBR group than in the no-HBR group (10.4% versus 3.4% at 1-year, and 18.9% versus 6.6% at 5-year, P P Conclusions: ARC-HBR criteria successfully identified those patients with very HBR after percutaneous coronary intervention, who represented 43% of patients in this all-comers registry.

Background It was reported that tissue morphology of in-stent restenosis (ISR) lesions assessed with optical coherence tomography (OCT) had an effect on midterm results including ISR and target lesion revascularization (TLR) rates after percutaneous coronary intervention (PCI). However, little was known about the association between tissue morphology assessed with OCT and late-term results. Methods We performed PCI treated with paclitaxel coated balloon (PCB) or drug-eluting stent (DES) for 452 ISR lesions (260 lesions with fibrous plaque and 192 lesions with lipid-laden plaque) using OCT between May 2008 and July 2016. Six- to eight-month (midterm) angiographic follow-up was performed on 422 of the 452 ISR lesions (follow-up rate: 93.4%). Furthermore, eighteen- to twenty-month (late-term) angiographic follow-up was performed on 337 of the 361 ISR lesions (follow-up rate: 93.4%) which were free from midterm TLR. We examined the association between tissue morphology, midterm-results and late-term results including ISR and TLR rates. Fibrous plaque was defined as homogeneous, signal-rich regions with low attenuation. Lipid-laden plaque was defined as diffuse border, signal poor regions with high attenuation. Results The patients were 353 men and 69 women, and the mean age was 68.8±9.6 years. PCI were performed with PCB in 285 lesions (PCB group) and DES in 137 lesions (DES group). The figure shows the angiographic midterm results of the 422 lesions and late-term results of the 337 lesions with respect to each tissue morphology and each PCI device. There was no difference in ISR and TLR rates of lesions with both fibrous and lipid-laden plaque at midterm between the two groups. ISR and TLR rates of lesions with lipid-laden plaque at late-term were significantly higher in the PCB group than in the DES group, while there was no difference in ISR and TLR rates of lesions with fibrous plaque at late-term between two groups. Figure 1 Conclusion Tissue morphology of ISR lesions might have an impact on outcomes after PCI. Morphological assessment of ISR tissue using OCT might suggest favorable types of PCI for ISR lesions.

Background The incidence of aortic dissection has been reported to be lower in women; however, women have a poor prognosis. Also, the incidence of false lumen thrombosis has been reported to be different between Europe, the United States, and Japan. We aimed to determine gender differences in long-term prognosis of acute type B aortic dissection. Methods We retrospectively reviewed 220 consecutive patients hospitalized for acute type B aortic dissection between January 2012 to December 2017. After exclusion criteria of unknown onset time, >14 days after the onset, in-hospital death, and aortic events requiring additional treatment during hospitalization were applied, 186 patients were analyzed by gender: 133 men and 53 women. The patient background, treatment method, prognosis, and outcome were compared and examined. Results Both the proportions of smoking history and patients receiving oxygen therapy during hospitalization were significantly higher in men (59% vs. 22%, p Picture 1 Conclusion The long-term prognosis of acute type B aortic dissection treated by medical therapy during hospitalization was equivalent in men and women despite gender differences in several background factors.

Background Successful recanalisation of percutaneous coronary intervention for chronic total occlusion lesions has been associated with improved survival. Purpose This study aimed to assess the impact of successful percutaneous coronary intervention for chronic total occlusion lesions on the long-term outcome of patients with impaired and preserved left ventricular ejection fraction (LVEF). Methods The study sample consisted of 842 consecutive patients (928 chronic total occlusion lesions) undergoing percutaneous coronary intervention at our institution between October 2005 and December 2009. We divided them into 3 groups by the degree of LVEF: less than 40% (severely reduced LVEF, n=140), 40% to 59% (moderately reduced LVEF, n=470), and 60% and above (normal LVEF, n=232). We evaluated mortality during the 10-year follow-up period the basis of procedural success and failure. Results The overall procedural success rate was 89.1%. Median follow-up duration was 7.9 years. The 10-year cumulative incidences of cardiac death in each degree of LVEF are shown in the Figure. Conclusions Successful recanalisation for chronic total occlusion lesions in patients with impaired LVEF may be associated with reduced cardiac mortality.

Background Whether preparation techniques during percutaneous coronary intervention (PCI) are associated with restenosis in severely calcified lesions is not well studied. Purpose We aimed to clarify the effects of the preparation techniques during PCI on mid-term outcomes of severely calcified lesions. Methods We examined 2688 consecutive severely calcified lesions (1854 patients) treated by PCI between January 2008 and December 2017, and identified 1789 lesions (66.6%) undergoing routine follow-up angiography within one year postprocedure. The angiographic outcome measure was defined as in-stent restenosis (ISR); ISR was defined as stenosis of ≥50%. We divided the 1789 lesions into two groups on the basis of the presence or absence of ISR: ISR and non-ISR groups. Result ISR was detected in 337 of the 1789 lesions (18.8%). The ISR group, in comparison with the non-ISR group, had more chronic total occlusion lesions (17.9% vs. 12%, p Conclusion Using scoring or cutting balloon is associated with good midterm results of severely calcified lesions treated by PCI.