The Conundrum of Occult Cancer Screening in Venous Thromboembolism: Lessons from the REMOTEV Registry.

(1) Background and Objectives: Venous thromboembolism (VTE) is strongly associated with cancer, and may be the first event revealing occult neoplasia. Nonetheless, the reasonable extent of the etiological assessment after an unprovoked VTE event remains debated. The main objective of this study was to evaluate the incidence of occult neoplasia one year after an episode of VTE, in consecutively hospitalized patients for VTE from the REMOTEV registry. The secondary objectives were to assess the performance of the various tests used for occult cancer screening in a real-life setting and analyze the risk factors associated with the discovery of cancer and the 1-year prognosis. (2) Methods: REMOTEV is a prospective, non-interventional cohort study of patients with acute VTE. Patients included in the registry from 23 October 2013 to 28 July 2018 were analyzed after a follow-up of 12 months. Cancer detection was performed according to local practices and consisted of a limited strategy to which an abdominal ultrasound was added. In the presence of suggestive clinical manifestations, further examinations were performed on an individual basis. (3) Results: A total of 993 patients were included in the study. At 1 year, the incidence of newly diagnosed cancer was low (5.3%). Half of the detected cancers were metastatic at discovery (51%) and had a poor global prognosis (32% of mortality at 1 year). Admission pulmonary CT scans as well as (thoracic)-abdomino-pelvic CT scans (when performed) were responsible for the majority of detected cancers. Age over 65 years and the concomitant presence of an unusual site and lower-limb deep vein thrombosis were the only factors associated with occult neoplasia in this cohort. After 1-year FU, mortality was higher in cancer patients (HR 6.0 (CI 95% 3.5−10.3, p < 0.0001)), and cancer evolution was the leading cause of death in the cancer group. (4) Conclusions: In REMOTEV, VTE-revealed occult cancer prevalence was low, but similar to recent reports and associated with higher age, multiple thrombotic sites and worse prognosis.

The Effect of Transoesophageal Echocardiography on Treatment Change in a High-Volume Stroke Unit.

Background and purpose-current guidelines recommend the use of transesophageal echocardiography (TEE) in relation to cardio-embolic sources of stroke. Methods-by using an hospital-based cohort, we retrospectively analyzed consecutive patients with acute ischemic stroke (AIS), acute hemorrhagic stroke (AHS) and transient ischemic attack (TIA) who were admitted in Strasbourg Stroke Center, France between November 2017 to December 2018. TEE reports were screened for detection of potential cardiac sources of embolism and the subsequent change in medical management. We performed univariate and multivariate analyses to identify predictors of relevant TEE findings. Results-out of the 990 patients admitted with confirmed stroke, 432 patients (42.6%) underwent TEE. Patients with TEE were younger (62.8 ± 14.8 vs. 73.8, p < 0.001), presented less comorbidities and lower stroke severity assessed by lower NIHSS (2 IQR (0-4) vs. 3 IQR (0-10), p < 0.01) and Modified Rankin Scale (1 IQR (0-1) vs. 1 (0-3), p < 0.01). A total of 227 examinations (52.5%) demonstrated abnormal findings considered as potential cardiac sources of embolism and 31 examinations (7.1%) were followed by subsequent change in medical management. Age (HR: 0.948, 95% CI 0.923 to 0.974; p < 0.001), previous AIS (HR: 3.542, 95% CI 1.290 to 9.722; p = 0.01), previous TIA (HR: 7.830, CI 95% 2214 to 27,689; p = 0.001) and superficial middle cerebral artery territory infarction (HR: 2.774, CI 95% 1.168-6.589; p = 0.021) were strong independent predictors with change in medical management following TEE. Conclusions-additional TEE changed the medical course of stroke patients in 7.1% in a French high-volume stroke unit.

Prognostic Value of Troponin Elevation in COVID-19 Hospitalized Patients.

(1) Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) penetrates the respiratory epithelium through angiotensin-converting enzyme-2 (ACE2) binding. Myocardial and endothelial expression of ACE2 could account for the growing body of reported evidence of myocardial injury in severe forms of Human Coronavirus Disease 2019 (COVID-19). We aimed to provide insight into the impact of troponin (hsTnI) elevation on SARS-CoV-2 outcomes in patients hospitalized for COVID-19. (2) Methods: This was a retrospective analysis of hospitalized adult patients with the SARS-CoV-2 infection admitted to a university hospital in France. The observation period ended at hospital discharge. (3) Results: During the study period, 772 adult, symptomatic COVID-19 patients were hospitalized for more than 24 h in our institution, of whom 375 had a hsTnI measurement and were included in this analysis. The median age was 66 (55-74) years, and there were 67% of men. Overall, 205 (55%) patients were placed under mechanical ventilation and 90 (24%) died. A rise in hsTnI was noted in 34% of the cohort, whereas only three patients had acute coronary syndrome (ACS) and one case of myocarditis. Death occurred more frequently in patients with hsTnI elevation (HR 3.95, 95% CI 2.69-5.71). In the multivariate regression model, a rise in hsTnI was independently associated with mortality (OR 3.12, 95% CI 1.49-6.65) as well as age ≥ 65 years old (OR 3.17, 95% CI 1.45-7.18) and CRP ≥ 100 mg/L (OR 3.62, 95% CI 1.12-13.98). After performing a sensitivity analysis for the missing values of hsTnI, troponin elevation remained independently and significantly associated with death (OR 3.84, 95% CI 1.78-8.28). (4) Conclusion: Our study showed a four-fold increased risk of death in the case of a rise in hsTnI, underlining the prognostic value of troponin assessment in the COVID-19 context.

Outcomes of COVID-19 Hospitalized Patients Previously Treated with Renin-Angiotensin System Inhibitors.

(1) Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) penetrates respiratory epithelium through angiotensin-converting enzyme-2 binding, raising concerns about the potentially harmful effects of renin-angiotensin system inhibitors (RASi) on Human Coronavirus Disease 2019 (COVID-19) evolution. This study aimed to provide insight into the impact of RASi on SARS-CoV-2 outcomes in patients hospitalized for COVID-19. (2) Methods: This was a retrospective analysis of hospitalized adult patients with SARS-CoV-2 infection admitted to a university hospital in France. The observation period ended at hospital discharge. (3) Results: During the study period, 943 COVID-19 patients were admitted to our institution, of whom 772 were included in this analysis. Among them, 431 (55.8%) had previously known hypertension. The median age was 68 (56-79) years. Overall, 220 (28.5%) patients were placed under mechanical ventilation and 173 (22.4%) died. According to previous exposure to RASi, we defined two groups, namely, "RASi" (n = 282) and "RASi-free" (n = 490). Severe pneumonia (defined as leading to death and/or requiring intubation, high-flow nasal oxygen, noninvasive ventilation, and/or oxygen flow at a rate of ≥5 L/min) and death occurred more frequently in RASi-treated patients (64% versus 53% and 29% versus 19%, respectively). However, in a propensity score-matched cohort derived from the overall population, neither death (hazard ratio (HR) 0.93 (95% confidence interval (CI) 0.57-1.50), p = 0.76) nor severe pneumonia (HR 1.03 (95%CI 0.73-1.44), p = 0.85) were associated with RASi therapy. (4) Conclusion: Our study showed no correlation between previous RASi treatment and death or severe COVID-19 pneumonia after adjustment for confounders.

Pulmonary Embolism and Coexisting Deep Vein Thrombosis: A Detrimental Association?

BACKGROUND: The prognostic significance of coexisting deep vein thrombosis (DVT) in acute pulmonary embolism (PE) is controversial. This study aimed to provide routine patient care data on the impact of this association on PE severity and 3-month outcomes in a population presenting with symptomatic venous thromboembolism (VTE) from the REMOTEV registry. METHODS AND RESULTS: REMOTEV is a prospective, non-interventional study of patients with acute symptomatic VTE, treated with direct oral anticoagulants (DOACs) or standard anticoagulation (vitamin K antagonists (VKA) or parenteral heparin/fondaparinux alone) for at least 3 months. From 1 November 2013 to 28 February 2018, among 1241 consecutive patients included, 1192 had a follow-up of at least 3 months and, among them, 1037 had PE with (727) or without DVT (310). The median age was 69 (55-80, 25th-75th percentiles). Patients with PE-associated DVT had more severe forms of PE (p < 0.0001) and, when DVT was present, proximal location was significantly correlated to PE severity (p < 0.01). However, no difference in all-cause mortality rate (hazard ratio (HR) 1.36 (CI 95% 0.69-2.92)), nor in the composite criterion of all-cause mortality and recurrence rate (HR 1.56 (CI 95% 0.83-3.10)) was noted at 3 months of follow-up. CONCLUSION: In REMOTEV, coexisting DVT was associated with a higher severity of PE, with no impact on short-term prognosis.

Rifampicin reverses nicardipine effect inducing uncontrolled essential hypertension.

Dihydropyridine calcium-channel blockers are a known substrate for the cytochrome P450 isoform 3A4. Rifampicin, an antitubercular agent, is one of the most potent inducers of hepatic and intestinal CYP3A4 thus increasing dihydropyridine metabolism. We report a case of a 67-year-old hypertensive female treated with a four-drug antihypertensive regimen including a dihydropyridine (nicardipine 50 mg bid), who was admitted for septic arthritis of the knee requiring antibiotic treatment with teicoplanin 400 mg od and rifampicin 600 mg bid. Six days after rifampicin initiation, she presented with Posterior Reversible Encephalopathy Syndrome due to uncontrolled hypertension. We hypothesized that disequilibrium of previously controlled hypertension was partially due to nicardipine ineffectiveness. Plasma nicardipine concentration was assessed through high-performance liquid chromatography 5 hours after coadministration of the two drugs and proved undetectable.

Rivaroxaban versus standard anticoagulation for symptomatic venous thromboembolism (REMOTEV observational study): Analysis of 6-month outcomes.

BACKGROUND: This study aimed to provide safety and efficacy data of rivaroxaban in routine patient care in a non-selected symptomatic venous thromboembolism (VTE) population. METHODS AND RESULTS: REMOTEV is a prospective, non-interventional study of patients with acute symptomatic VTE, treated with oral rivaroxaban, VKA or parenteral heparin/fondaparinux alone for at least 3months and who are followed up for 6months. From Nov. 2013 to July 2015, 499 consecutive patients were retained for baseline analysis and 445 for safety analysis. The mean age was 65.1years, 7.6% had previously known active cancer, 18.6% had creatinine clearance 30≤CrCl<60mL/min, and 87.8% had pulmonary embolism with or without deep venous thrombosis. The major and clinically relevant bleeding rate was 5.4% (15/280) in the rivaroxaban group, 9.4%/(9/96) in the VKA group and 7.2% (5/69) in the heparin/fondaparinux group. The recurrent VTE rate was 1.4% (4/280) in the rivaroxaban group, 3.1% (3/96) in the VKA group and 11.6% (8/69) in the heparin/fondaparinux group. In the propensity score-adjusted samples, major and clinically relevant non-major bleeding (HR 0.37 [95% CI, 0.15 to 0.93], p<0.05), all-cause death (HR 0.21 [95% CI, 0.06 to 0.66], p<0.01) and the composite of recurrent VTE, major and clinically relevant non-major bleeding and all-cause mortality (HR 0.35 [95% CI, 0.17 to 0.71], p<0.01), were significantly lower in the rivaroxaban group compared to the VKA group. CONCLUSION: In REMOTEV 6-month outcomes are consistent with the findings of the phase 3 randomized trials and post-marketing data, with low rates of major bleeding and symptomatic recurrent VTE.

Place of non-vitamin K antagonist oral anticoagulants in anticoagulant-antiplatelet combinations in peripheral artery disease.

Non-vitamin K antagonist oral anticoagulants are becoming increasingly important in the prophylaxis and treatment of thrombosis in atrial fibrillation and venous thromboembolism. Antiplatelets are widely prescribed in the primary and secondary prevention of cardiac and vascular diseases. There are potentially numerous situations where anticoagulants and antiplatelets may be combined; these combinations have been explored in coronary artery disease, and some have been included in updated recommendations. Is it legitimate to transpose these recommendations to the management of peripheral artery disease? The specific characteristics of the treated vessels, the stents used, the respective frequencies of stent thrombosis and its effect on the target organ are probably different, and explain why opinions differ. However, because of a lack of evidence, empirical behaviours are being established without scientific validation. This review of the literature details the situations in which combinations of an anticoagulant and an antiplatelet have been explored in peripheral artery disease. We discuss the issue of antithrombotic combinations in stable peripheral artery disease and for vascular or endovascular surgery.

Statins and prevention of venous thromboembolism: Myth or reality?

The pleiotropic effects of statins, beyond their cholesterol-lowering properties, are much debated. In primary prevention, several observational cohort and case-control studies appear to show that statins reduce the incidence of venous thromboembolism by about 30%. In a single randomized placebo-controlled clinical trial (JUPITER), which included 17,000 patients, rosuvastatin 20mg/day reduced the risk of venous thromboembolism by 43%. However, these patients were at low risk of venous thromboembolism, and the frequency of the event was, in principle, low. In secondary prevention, several observational studies and post-hoc analyses of randomized clinical trials have suggested that statins may prevent recurrence of venous thromboembolism. However, none of these studies had enough scientific weight to form the basis of a recommendation to use statins for secondary prevention. The putative preventive effect of statins appears to be independent of plasma cholesterol concentration and could be a pharmacological property of the statin class, although a dose-effect relationship has not been demonstrated. The mechanism through which statins might prevent venous thrombosis is thought to involve their anti-inflammatory and antioxidant effects or perhaps a more specific action, by blocking the degradation of antithrombotic proteins. A mechanism involving the action of statins on interactions between risk factors for atherosclerosis and venous thromboembolism is supported by some studies, but not all. In the absence of firm evidence, statins cannot currently be recommended for primary or secondary prevention of venous thromboembolism.