Abdominal aortic mural thrombus in association with active ulcerative colitis.

Aortic mural thrombus (AMT) in the absence of aneurysm or atherosclerosis is a rare clinical finding and an uncommon cause of peripheral arterial embolization. AMT in a normal artery is usually attributed to systemic hypercoagulability. We describe a case of subacute lower limb ischemia due to AMT associated with active ulcerative colitis (UC). A 46-year-old man with active UC was referred to our hospital for the evaluation and treatment of left leg pain. Ultrasound and contrast computed tomography showed occlusion of the left popliteal artery, and an AMT in the abdominal aorta between the inferior mesenteric artery and the aortic bifurcation. We started anticoagulant therapy, intravenous infliximab, and cytapheresis. Four weeks after initiating anticoagulation therapy, we were able to successfully treat the AMT with anticoagulation therapy without surgical thrombectomy. The inflammatory status of ulcerative colitis was also under control, and AMT had not recurred at 1 year after treatment. Invasive therapies are often selected to treat AMT. However, if a patient's hypercoagulable state is controlled, AMT can safely be treated with anticoagulation therapy alone without recurrence. Learning objective: Aortic mural thrombus (AMT) in the absence of aneurysm or atherosclerosis is a rare clinical finding and an uncommon cause of peripheral arterial embolization. AMT in a normal artery is usually attributed to systemic hypercoagulability. We describe a case of subacute lower limb ischemia due to AMT associated with active ulcerative colitis. We controlled the ulcerative colitis condition and successfully treated the AMT with anticoagulation therapy alone.

Subclass phenotypes in patients with unprovoked venous thromboembolisms using a latent class analysis.

BACKGROUND: Patients with unprovoked venous thromboembolisms (VTEs) can be sub-classified based on the different phenotypes using a latent class analysis (LCA), which might be useful for selecting individual management strategies. METHODS: In the COMMAND VTE Registry-2 database enrolling 5197 VTE patients, the current derivation cohort consisted of 1556 patients with unprovoked VTEs. We conducted clustering with an LCA, and the patients were classified into subgroups with the highest probability. We compared the clinical characteristics and outcomes among the developed subgroups. RESULTS: This LCA model proposed 3 subgroups based on 8 clinically relevant variables, and classified 592, 813, and 151 patients as Class I, II, and III, respectively. Based on the clinical features, we named Class I the younger, Class II the older with a few comorbidities, and Class III the older with many comorbidities. The cumulative 3-year anticoagulation discontinuation rate was highest in the older with many comorbidities (Class III) (39.9 %, 36.1 %, and 48.4 %, P = 0.02). There was no significant difference in the cumulative 5-year incidence of recurrent VTEs among the 3 classes (12.8 %, 11.1 %, and 4.0 % P = 0.20), whereas the cumulative 5-year incidence of major bleeding was significantly higher in the older with many comorbidities (Class III) (7.8 %, 12.7 %, and 17.8 %, P = 0.04). CONCLUSION: The current LCA revealed that patients with unprovoked VTEs could be sub-classified into further phenotypes depending on the patient characteristics. Each subclass phenotype could have different clinical outcomes risks especially a bleeding risk, which could have a potential benefit when considering the individual anticoagulation strategies. CLINICAL TRIAL REGISTRATION: URL: http://www.umin.ac.jp/ctr/index.htm COMMAND VTE Registry-2: Unique identifier, UMIN000044816 COMMAND VTE Registry: Unique identifier, UMIN000021132.

Edoxaban, Rivaroxaban or Apixaban for Cancer-Associated Venous Thromboembolism in the Real World: Insights from the COMMAND VTE Registry-2.

BACKGROUND: Real-world data on clinical characteristics and outcomes related to the use of different direct oral anticoagulants (DOACs) for cancer-associated venous thromboembolism (VTE) is lacking. METHODS: The COMMAND VTE Registry-2 is a multicenter registry enrolling 5,197 consecutive patients with acute symptomatic VTE from 31 centers in Japan from January 2015-August 2020. Our study population comprised 1,197 patients with active cancer who were divided into the edoxaban (N=643, 54%), rivaroxaban (N=297, 25%), and apixaban (N=257, 22%) groups. RESULTS: The cumulative 5-year incidence of recurrent VTE (9.3%, 10.2%, and 8.5%, respectively, P=0.82) and all-cause death (67.5%, 66.8%, and 63.8%, respectively, P=0.22) did not differ among the groups. Despite adjusting for confounders, the risks of recurrent VTE and all-cause death did not differ significantly among the groups. The cumulative 5-year incidence of major and clinically relevant bleeding was significantly lower in the rivaroxaban group than those in the other groups (22.6%, 14.0%, and 22.8%, P=0.04; and 37.6%, 26.8%, and 38.3%, P=0.01, respectively). After adjusting for confounders, in the rivaroxaban group, the risk for major bleeding was numerically lower (HR: 0.65, 95% CI: 0.40-1.01) and that of clinically relevant all bleeding was significantly lower (HR: 0.67, 95% CI: 0.48-0.92) than those in the edoxaban group. CONCLUSIONS: The risks of recurrent VTE and all-cause death did not differ significantly among the different DOACs ; however, the risk of bleeding events could differ, with a potentially lower risk of bleeding with rivaroxaban.

Home Treatment for Active Cancer Patients With Low-Risk Pulmonary Embolism　- A Predetermined Companion Report From the ONCO PE Trial.

BACKGROUND: Patients with appropriately selected low-risk pulmonary embolism (PE) can be treated at home, although it has been controversial whether applies to patients with cancer, who are considered not to be at low risk.Methods and Results: The current predetermined companion report from the ONCO PE trial evaluated the 3-month clinical outcomes of patients with home treatment and those with in-hospital treatment. The ONCO PE trial was a multicenter, randomized clinical trial among 32 institutions in Japan investigating the optimal duration of rivaroxaban treatment in cancer-associated PE patients with a score of 1 using the simplified version of the Pulmonary Embolism Severity Index (sPESI). Among 178 study patients, there were 66 (37%) in the home treatment group and 112 (63%) in the in-hospital treatment group. The primary endpoint of a composite of PE-related death, recurrent venous thromboembolism (VTE) and major bleeding occurred in 3 patients (4.6% [0.0-9.6%]) in the home treatment group and in 2 patients (1.8% [0.0-4.3%]) in the in-hospital treatment group. In the home treatment group, there were no cases of PE-related death or recurrent VTE, but major bleeding occurred in 3 patients (4.6% [0.0-9.6%]), and 2 patients (3.0% [0.0-7.2%]) required hospitalization due to bleeding events. CONCLUSIONS: Active cancer patients with PE of sPESI score=1 could be potential candidates for home treatment.

Fragility and long-term clinical outcomes in patients with venous thromboembolism receiving direct oral anticoagulants: From the COMMAND VTE REGISTRY-2.

INTRODUCTION: There is limited data on the safety of direct oral anticoagulants (DOACs) in fragile patients with venous thromboembolism (VTE). MATERIALS AND METHODS: We used the COMMAND VTE Registry-2 enrolling patients with acute symptomatic VTE. The study population consisted of 3928 patients receiving DOACs, who were divided into fragile (2136 patients) and non-fragile groups (1792 patients). Fragility was defined as patients of age ≥ 75 years, creatinine clearance level ≤ 50 ml/min, and/or body weight ≤ 50 kg. RESULTS: The fragile group significantly more often received reduced doses of DOACs compared to the non-fragile group (51 % and 19 %, P < 0.001). The cumulative 5-year incidence of major bleeding was numerically higher in the fragile group than the non-fragile group (15.0 % and 11.1 %, P = 0.052), even with no significant excess risk after adjusting for confounders (HR 1.03, 95%CI 0.81-1.31, P = 0.78). The cumulative 5-year incidence of clinically relevant bleeding was significantly higher in the fragile group than the non-fragile group (28.6 % and 19.6 %, P < 0.001), even after adjusting for confounders (HR 1.28, 95%CI 1.08-1.53, P = 0.005). There was no significant difference in cumulative 5-year incidence of recurrent VTE between the groups (9.6 % and 8.9 %, P = 0.68), which was consistent after adjusting for confounders (HR 1.13, 95%CI 0.84-1.51, P = 0.41). CONCLUSIONS: Among VTE patients receiving DOACs, fragile patients were associated with a numerically higher rate of major bleeding and a significantly increased risk of clinically relevant bleeding, but not an increased risk of recurrent VTE.

Cancer-associated venous thromboembolism in the direct oral anticoagulants era: Insight from the COMMAND VTE Registry-2.

BACKGROUND: There is a paucity of data on real-world management strategies and clinical outcomes of cancer-associated venous thromboembolism (VTE) in the direct oral anticoagulants (DOACs) era. OBJECTIVES: To investigate the status of cancer-associated VTE in the DOAC era. METHODS: This multicenter, retrospective cohort study among 31 centers in Japan between 2015 and 2020 enrolled 5197 consecutive patients with acute symptomatic VTE, who were divided into 1507 patients (29 %) with active cancer and 3690 patients (71 %) without. RESULTS: The cumulative 3-year rate of anticoagulation discontinuation was significantly higher in patients with active cancer than in those without (62.7 % vs. 59.1 %, P < 0.001). The cumulative 5-year incidence of recurrent VTE was higher in patients with active cancer than in those without (10.1 % vs. 9.1 %, P = 0.01), however, after adjusting for the confounders and competing risk of mortality, the excess risk of the active cancer group relative to the no active cancer group was no longer significant (HR: 0.95, 95 % CI: 0.73-1.24). The cumulative 5-year incidence of major bleeding was much higher in the active cancer group (20.4 % vs. 11.6 %, P < 0.001). Even after adjusting for the confounders and competing risk of mortality, the risk of the active cancer group relative to the no active cancer group remained significant (HR: 1.36, 95 % CI: 1.11-1.66). CONCLUSIONS: The current large real-world registry revealed that the risk of major bleeding was still higher in patients with active cancer than in those without, leading to the frequent anticoagulation discontinuation, which has been still a huge challenge to overcome in the DOAC era.

Application of the RIETE score to identify low-risk patients with pulmonary embolism: From the COMMAND VTE Registry.

BACKGROUND: The RIETE score could be specifically useful for identification of low-risk pulmonary embolism (PE) patients for home treatment. However, the external validation of the RIETE score has been limited. METHODS: The COMMAND VTE Registry is a multicenter registry enrolling consecutive patients with acute symptomatic venous thromboembolism (VTE). The current study population consisted of 1479 patients with acute PE, who were divided into 2 groups; RIETE scores of 0 (N = 260) and ≥ 1 (N = 1219). RESULTS: The cumulative 10-day and 30-day incidences of a composite endpoint of all-cause death, recurrent PE, or major bleeding were lower in patients with the RIETE score of 0 than in those with the RIETE score of ≥1 (10-day: 0.4 % vs. 6.7 %, P < 0.001, and 30-day: 0.4 % vs. 10.0 %, P < 0.001). The area under the receiver-operating characteristic curve (AUC) in the RIETE score for the 10-day composite endpoint showed numerically better predictive ability than that in the sPESI score (0.77 vs. 0.73, P = 0.07), and the AUC in the RIETE score for the 30-day composite endpoint showed significantly better predictive ability than that in the sPESI score (0.77 vs. 0.71, P = 0.003). CONCLUSIONS: The RIETE score was well validated in the current large real-world registry. The RIETE score of 0 could identify patients with reasonably low risks of the 10-day and 30-day composite endpoint of all-cause death, recurrent PE, or major bleeding.

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.

Validation of the Academic Research Consortium High Bleeding Risk (ARC-HBR) criteria in patients undergoing peripheral endovascular interventions.

BACKGROUND: It remains unclear whether the Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria could apply to peripheral artery disease (PAD) patients undergoing endovascular therapy (EVT). AIMS: We sought to evaluate the application of the ARC-HBR criteria to PAD patients undergoing EVT with contemporary drug-coated devices (DCD) for femoropopliteal artery lesions. METHODS: Between May 2012 and December 2019, 542 consecutive patients undergoing EVT with DCD for femoropopliteal artery lesions were retrospectively analysed. The primary study endpoint was major bleeding events, defined as Bleeding Academic Research Consortium type 3 or 5. RESULTS: Of 542 patients, 435 (80.3%) were stratified into the HBR group. The cumulative 5-year incidence of major bleeding events was significantly higher in the HBR group than in the non-HBR group (31.9% vs 2.3%; p<0.001). The 5-year major bleeding event rate gradually increased with the number of ARC-HBR criteria (≥2 major criteria: 48.6%, 1 major: 33.1%, ≥2 minor: 12.9%, and non-HBR: 2.3%; p<0.001). Major bleeding events were associated with a 5.4-fold increased risk of mortality (adjusted hazard ratio: 5.42, 95% confidence interval: 2.91-10.1; p<0.001). Severe chronic kidney disease, heart failure, and severe anaemia were predictors of major bleeding events. CONCLUSIONS: 80.3% of PAD patients undergoing EVT for femoropopliteal artery lesions with contemporary drug-coated devices met the ARC-HBR criteria. Given that major bleeding events remarkably increased the risk of mortality after EVT, the ARC-HBR criteria might be helpful for the risk stratification of PAD patients who undergo EVT with contemporary DCD.

Impact of Heart Rate at Diagnosis on Clinical Outcomes in Patients With Acute Pulmonary Embolism.

Data on the impact of heart rate (HR) at diagnosis on clinical outcomes in patients with acute pulmonary embolism (PE) remain scarce. The present study population consisted of 1,532 patients with PE; the patients were divided into 4 groups, including (1) HR <80 beats/min (n = 451, 29%), (2) 80 ≤HR <100 beats/min (n = 620, 40%), (3) 100 ≤HR <110 beats/min (n = 215, 14%), and (4) HR ≥110 beats/min (n = 246, 16%). The cumulative 30-day incidences of all-cause death were significantly higher in the 100 ≤HR <110 and HR ≥110 beats/min groups than in the HR <80 beats/min group. Incidences were 2.7%, 3.6%, 6.6%, and 5.7% (p = 0.04) in the HR <80 beats/min, 80 ≤HR <100 beats/min, 100 ≤HR <110 beats/min, and HR ≥110 beats/min groups, respectively. With the HR <80 beats/min group as reference, the 100 ≤HR <110 and HR ≥110 groups, but not the 80 ≤HR <100 group, were significantly associated with an increased risk of 30-day all-cause death. Hazard ratio was 2.53 (95% confidence interval [CI] 1.17 to 5.56, p = 0.02) for the 80 ≤HR <100 beats/min group, 2.20 (95% CI 1.02 to 4.84, p = 0.046) for the 100 ≤HR <110 beats/min group, and 1.34 (95% CI 0.67 to 2.79, p = 0.41) for the HR ≥110 beats/min group. The cumulative 30-day incidences of all-cause death in patients with simplified Pulmonary Embolism Severity Index score = 0 were 0.6%, 0.3%, and 0.7% when based on cut-off values of HR ≥110 beats/min, HR ≥100 beats/min, and ≥80 beats/min, respectively. Patients with moderate tachycardia (100 ≤HR <110) seemed to be at comparable risk of 30-day all-cause death to those with HR ≥110 beats/min and at higher risk of 30-day all-cause death than those with HR <80 beats/min; this may suggest a potential benefit of the alternative cut-off value of HR ≥100 beats/min in the simplified Pulmonary Embolism Severity Index score for identification of low-risk patients.

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.

Percutaneous transluminal renal artery stenting using digital subtraction angiography with diluted contrast medium in a patient with severe chronic kidney disease.

Atherosclerotic renal artery stenosis (ARAS) is associated with ischemic nephropathy, kidney failure, and secondary hypertension. Percutaneous transluminal renal artery stenting (PTRAS) is required for patients with hemodynamically significant ARAS. However, PTRAS can be problematic in patients with chronic kidney disease (CKD) because the use of a large amount of iodinated contrast medium is associated with an increased risk of contrast-induced nephropathy. We describe a case of PTRAS with successful revascularization by using digital subtraction angiography (DSA) with diluted contrast medium (1:10 dilution). An 89-year-old man with resistant hypertension and CKD was hospitalized in our institution for acute coronary syndrome. During hospitalization, the patient's blood pressure was extremely high (180-200/70-90 mmHg), despite the use of four antihypertensive agents. We examined the cause of hypertension and detected significant right renal artery stenosis and left kidney atrophy with renal artery obstruction. We performed PTRAS on the right renal artery by using DSA with a diluted contrast medium. Revascularization was successful using only 3 mL of the contrast medium. PTRAS using DSA with diluted contrast medium can be an effective technique for treating ARAS in patients with CKD to preserve renal function. Learning objectives: Atherosclerotic renal artery stenosis (ARAS) is associated with ischemic nephropathy, kidney failure, and secondary hypertension. Percutaneous transluminal renal artery stenting (PTRAS) is required for patients with hemodynamically significant ARAS. However, PTRAS can be problematic in patients with chronic kidney disease because of the increased risk of contrast-induced nephropathy. We describe a technique of PTRAS using digital subtraction angiography with a diluted contrast medium to achieve a successful revascularization.

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.

Impact of High Lipoprotein(a) Levels on Clinical Outcomes Following Peripheral Endovascular Therapy.

BACKGROUND: Elevated lipoprotein(a) (Lp[a]) levels are an independent risk factor for the development of atherosclerotic diseases, including peripheral artery disease (PAD). However, their prognostic impact in patients with PAD remains unknown. OBJECTIVES: The aim of this study was to examine the prognostic impact of elevated Lp(a) levels in patients with PAD undergoing endovascular therapy (EVT). METHODS: In total, 1,169 patients who underwent successful EVT for symptomatic PAD between September 2016 and August 2021 were included in this study. High Lp(a) levels were defined as >30 mg/dL. The associations of high Lp(a) levels with incident major adverse cardiovascular events (MACE) (all-cause death, myocardial infarction, and stroke) and major adverse limb events (MALE) (repeat revascularization for target limb and major amputation) were analyzed. RESULTS: During a median follow-up period of 1.7 years (IQR: 0.6-3.0 years), 230 MACE (210 deaths, 15 myocardial infarctions, and 22 strokes) and 263 MALE (219 reinterventions and 36 major amputations) were observed. The cumulative incidence rate of MACE (48.1% vs 27.3%) and MALE (67.9% vs 27.2%) was significantly higher in patients with high Lp(a) levels (P < 0.001 for both). The adjusted HR were 1.93 (95% CI: 1.44-2.59; P < 0.001) for MACE and 4.15 (95% CI: 3.14-5.50; P < 0.001) for MALE. These associations were not influenced by low-density lipoprotein cholesterol levels or statin administration (P for interaction >0.05 for all). CONCLUSIONS: Elevated Lp(a) levels were independently associated with incident MACE and MALE in patients with PAD treated with revascularization irrespective of low-density lipoprotein cholesterol level and statin administration.

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.

Periprocedural management and clinical outcomes of invasive procedures after venous thromboembolism: from the COMMAND VTE registry.

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%.

Use of Proprotein Converse Subtilisin/Kexin Type 9 Inhibitor to Treat Cholesterol Crystal Embolisms after Catheterization: A Report of Three Cases.

Cholesterol crystal embolism (CCE) is a serious complication that occurs after cardiac and vascular procedures. CCE involves multiple organs, and the prognosis and renal function of patients is poor. Although the efficacy of steroid, statin, and low-density lipoprotein apheresis has been reported, no definitive treatment has been established. We herein report three consecutive cases treated with conventional steroid therapy with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor after catheterization. The renal function was preserved, steroid therapy was stopped, and wound healing of blue toes was achieved. PCSK9 inhibitor therapy was safe in the present patient and may be a potential treatment option for CCE.

Risk factors of thrombotic recurrence and major bleeding in patients with intermediate-risk for recurrence of venous thromboembolism.

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 .

Severity of pulmonary embolism at initial diagnosis and long-term clinical outcomes: From the COMMAND VTE Registry.

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.

Temporal Course of Vascular Response After Fluoropolymer Paclitaxel-Eluting Stent Implantation for Femoropopliteal Artery Lesions.

BACKGROUND: Limited data are available regarding the vascular response after fluoropolymer paclitaxel-eluting stent (FP-PES) implantation. This study sought to assess the vascular response at 6 and 12 months after FP-PES implantation for femoropopliteal artery lesions using serial optical coherence tomography (OCT) examination.Methods and Results:From the IMPERIAL trial, this study evaluated 10 de novo femoropopliteal lesions treated with FP-PES. The primary study endpoint was neointimal tissue coverage at a 6- and 12-month follow up, as assessed by serial OCT examination. The incidence of peri-strut low-intensity area (PLIA) and extra-stent lumen (ESL) was also assessed. A total of 203 matched cross-sectional images were evaluated at 6 and 12 months (5,615 and 5,763 struts, respectively). From 6 to 12 months, the mean neointimal thickness tended to increase from 198 µm to 233 µm, with a significant reduction in the incidence of malapposed struts (0.59% vs. 0.28%, P=0.039). Conversely, uncovered struts and PLIA were more frequently observed at 12 months (4.4% vs. 7.8%, P=0.01; 12.7% vs. 21.0%, P<0.001, respectively). The ESL area significantly increased over time without any difference in its incidence (0.24±0.32 mm2vs. 0.38±0.36 mm2, P=0.009). CONCLUSIONS: Neointimal proliferation was markedly inhibited from 6 to 12 months after FP-PES implantation, whereas the incidence of uncovered struts and PLIA significantly increased over time with the enlargement of ESL.