Direct Oral Anticoagulants for Cancer-Associated Venous Thromboembolism.

PURPOSE OF REVIEW: To present the randomized controlled trial (RCT) evidence and highlight the areas of uncertainty regarding direct oral anticoagulants (DOAC) for cancer-associated venous thromboembolism (CAT). RECENT FINDINGS: In the last years, four RCTs have shown that rivaroxaban, edoxaban, and apixaban are at least as effective as low-molecular-weight heparin (LMWH) for the treatment of both incidental and symptomatic CAT. On the other hand, these drugs increase the risk of major gastrointestinal bleeding in patients with cancer at this site. Another two RCTs have demonstrated that apixaban and rivaroxaban also prevent CAT in subjects at intermediate-to-high risk commencing chemotherapy, albeit at the price of higher likelihood of bleeding. By contrast, data are limited about the use DOAC in individuals with intracranial tumors or concomitant thrombocytopenia. It is also possible that some anticancer agents heighten the effects of DOAC via pharmacokinetic interactions, up to making their effectiveness-safety profile unfavorable. Leveraging the results of the aforementioned RCTS, current guidelines recommend DOAC as the anticoagulants of choice for CAT treatment and, in selected cases, prevention. However, the benefit of DOAC is less defined in specific patient subgroups, in which the choice of DOAC over LMWH should be carefully pondered.

Reasons for reperfusion delay in ST-elevation myocardial infarction and their impact on mortality.

AIMS: The impact of reperfusion delay in ST-elevation myocardial infarction (STEMI) is well known. We aimed to describe the specific reasons for delay to primary percutaneous coronary intervention (pPCI), and their impact on mortality after adjusting for confounders, using the first-medical-contact-to-device (FMCTD) time to measure the delay. METHODS: Between January 2006 and December 2019, 2149 STEMI patients underwent pPCI at our centre. Delayed pPCI was defined as FMCTD > 90 min or > 120 min in the case of inter-hospital transfer. The causes of delay were classified as system-related (related to the network organization) or patient-related (related to the clinical condition of the patient). Primary outcome was 1-year all-cause mortality. RESULTS: The pPCI was timely in 69.9% of patients, delayed for system-related causes in 16.4% or for patient-related causes in 13.7%. Different patient-related causes induced variable median FMCTD time (from 114 min for technically difficult pPCI to 159 min for ECG and/or symptom resolution). By multivariable Cox-regression models, the main independent risk factors for mortality were delay due to comorbidities [hazard ratio (HR) 2.19 (1.22-3.91)], or hemodynamic instability [HR 2.05 (1.25-3.38)], after adjusting for Global Registry of Acute Coronary Events risk score tertiles and angiographic success. The difference in risk of mortality is maintained over the entire spectrum of time from symptom onset. CONCLUSIONS: Different causes of delay had different impacts on mortality, generally more important than the length of the delay. Causes of delay such as hemodynamic instability and comorbidities should prompt specific programs of performance improvement. Timely pPCI maintains prognostic advantages after several hours from symptom onset, mandating prompt reperfusion also in late-presenter patients.

INSAID Variant Classification and Eurofever Criteria Guide Optimal Treatment Strategy in Patients with TRAPS: Data from the Eurofever Registry.

BACKGROUND: TNF receptor-associated periodic syndrome (TRAPS) is a rare autoinflammatory disease caused by dominant mutation of the TNF super family receptor 1A (TNFRSF1A) gene. Data regarding long-term treatment outcomes are lacking. OBJECTIVE: To assess correlations of genotype-phenotypes in patients with TRAPS, as defined by the International Study Group for Systemic Autoinflammatory Diseases (INSAID) classification and Eurofever criteria, with treatment responses. METHODS: Data from 226 patients with variants of the TNFRSF1A gene and enrolled in the Eurofever registry were classified according to the INSAID classification in groups A (pathogenic or likely pathogenic variants), B (variants of uncertain significance or not classified variants), and C (benign or likely benign variants) and screened for Eurofever criteria. RESULTS: In group A (127 of 226 patients, 56%), all fulfilled Eurofever criteria and 20 of 127 patients (16%) developed AA amyloidosis. In group B (78 of 226 patients, 35%), 40 of 78 patients (51%) did not fulfill Eurofever criteria, displaying a lower incidence of abdominal pain (P < .02) and higher efficacy rate of on-demand nonsteroidal anti-inflammatory drugs (P < .02) and colchicine (P < .001). Group C (21 of 226 patients, 9%) presented a milder disease (P < .02) and none fulfilled Eurofever criteria. Anti-IL-1 drugs were the most frequently used in patients fulfilling Eurofever criteria, with the highest efficacy rate (>85% complete response). No patients on anti-IL-1 treatments developed AA amyloidosis, and 7 women with a history of failure to conceive had successful pregnancies. CONCLUSION: Anti-IL-1 drugs are the best maintenance treatment in patients with TRAPS. The diagnosis of TRAPS should be considered very carefully in patients of group B not fulfilling Eurofever criteria and group C, and colchicine may be preferable as the first maintenance treatment.

Frequency, predictors and prognostic impact of implantable cardioverter defibrillator shocks in a primary prevention population with heart failure and reduced ejection fraction.

AIMS: The role of the implantable cardioverter defibrillator (ICD) in primary prevention real-world population is debated. We sought to evaluate the incidence, predictors and prognostic impact of ICD shocks in consecutive heart failure patients implanted for primary prevention at our tertiary institution. METHODS AND RESULTS: We retrospectively selected a sample of 497 patients (mean age 64.8 years, 82.1% men, average left ventricular ejection fraction, LVEF, 27.1%). At long-term follow-up (median time 70.4 months), total mortality was 40.8%, and 16.5% of patients had received at least one appropriate shock (3.12%/year). Inappropriate shock [odds ratio (OR) 1.93, 95% confidence interval (95% CI) 1.08-3.47; P = 0.027] and length of follow-up (1 year, OR 1.01, 95% CI 1.00-1.01; P = 0.0031) were associated with the occurrence of appropriate shock, whereas atrial fibrillation (OR 2.65, 95% CI 1.55-4.51, P < 0.001), length of follow-up (1-year OR 1.01, 95% CI 1.00-1.01, P < 0.001) and appropriate shock (OR 1.93, 95% CI 1.08-3.47, P = 0.027) were associated with the occurrence of inappropriate shock. Neither appropriate nor inappropriate shock independently increased mortality risk, whereas older age (hazard ratio 1.05; 95% CI 1.04-1.07; P < 0.001), atrial fibrillation (hazard ratio 2.25; 95% CI 1.67-3.02; P < 0.001) and lower LVEF (hazard ratio 0.97; 95% CI 0.94-0.99; P = 0.004) did. CONCLUSION: Incidence of shocks in real-world primary prevention ICD recipients might be lower than expected, and the association between ICD shocks and prolongation of survival is not as clear-cut as might be perceived. Further investigations from larger real-world samples are warranted.