Abstract
Given the aging population, the burden of age-dependent diseases is growing. Despite this, elderly patients are often underrepresented in clinical trials and little data are available on ...current anticoagulant management and outcomes in this unique population, especially those aged 90 years or older. There is uncertainty, and a fear of “doing harm,” that often leads to de-prescription of antithrombotic agents in nonagenarian patients. Decision-making concerning the use of anticoagulant treatment needs to balance the risk of thrombotic events against the risk of major bleeding, especially intracranial hemorrhage. In this perspective, the development of direct oral anticoagulants (DOACs), acting as direct and selective inhibitors of a specific step or enzyme of the coagulation cascade, has dramatically changed oral anticoagulant treatment. In fact, given the lower incidence of intracranial hemorrhage, the favorable overall efficacy and safety, and the lack of routine monitoring, DOACs are the currently recommended anticoagulant agents for the treatment of both atrial fibrillation and venous thromboembolism even in very elderly patients. However, given the limited data available on the management of anticoagulation in nonagenarians, a few unanswered questions remain. In this review, we focused on recent evidence for anticoagulant treatment in atrial fibrillation and venous thromboembolism along with management of anticoagulation-related bleeding in nonagenarians.
Abstract It is still uncertain whether direct oral anticoagulants (DOACs) perform better than vitamin K antagonists (VKAs) in subjects with non-valvular atrial fibrillation (NVAF) and advanced ...chronic kidney disease (CKD). The aim of the study was to compare safety and effectiveness of DOACs and VKAs in patients with NVAF and stage 4 CKD (creatinine clearance 15–29 mL/min). We searched the hospital databases of two academic centers to retrospectively identify patients with stage 4 CKD who were on treatment with DOACs or VKAs for NVAF. Safety was the primary outcome of the study and was assessed in terms of incidence of major bleeding (MB). Secondary outcomes were clinically relevant non-major bleeding (CRNMB) and death for any cause. A total of 176 patients (102 on DOACs and 74 on VKAs) were found and included in the analysis. The incidence rate of MB was not statistically different between groups (8.6 per 100 patients-year in the DOAC group and 5.6 per 100 patients-year in the VKA group). Rates of IS/SSE and CRNMB were statistically similar in the two treatment groups, as well. There were less deaths for any cause in the DOAC group than in the VKA group (8.6 and 15.8 per 100 patients-year, respectively), but the difference was not statistically significant. This study found no difference in terms of safety and effectiveness between patients with NVAF and stage 4 CKD treated with DOACs and VKAs. Larger prospective or randomized studies are needed to confirm these findings.
•Selection of lower rather than higher dose DOAC better protects against the risk of all-cause mortality in patients with established atherosclerosis and with indication for antiplatelets or oral ...anticoagulants.•Benefit of lower dose DOAC selection evidenced across variable clinical manifestations (acute coronary syndrome, stable coronary or peripheral artery disease, with or without atrial fibrillation).•Benefit of lower dose selection manifest at antithrombotic and anticoagulant DOAC regimens.
Antithrombotic/anticoagulation effects of direct oral anticoagulants (DOACs) are dose-dependent. However, recent observations suggest that administering lower dose DOACs may better protect against all-cause mortality. We investigated whether, in patients with established atherosclerosis, DOAC dose selection would affect the risk of all-cause mortality.
We performed a structured literature research for controlled trials allowing random assignment to a lower dose DOAC, a higher dose DOAC, or control therapy in patients with established atherosclerosis. Pooled risk ratios (RRs) of all-cause mortality in lower and higher dose DOACs versus control therapy were estimated using a random-effect model.
Atherosclerosis manifested as acute coronary syndrome (n=17,220), stable coronary (CAD) and/or peripheral artery disease (PAD) (n=27,395) or CAD associated with atrial fibrillation (n=4,510). Antithrombotic doses of rivaroxaban (2.5 mg or 5.0 mg BID) or dabigatran (50 mg, 75 mg, 110 mg, or 150 mg, BID) were tested in three trials versus single or dual antiplatelet control therapy, whereas anticoagulation doses of edoxaban (30 mg or 60 OD) were tested versus warfarin in one trial. Compared to control, patients receiving lower dose (RR 0.80, 95% CI 0.73-0.89, p<0.0001, I²=0%), but not those receiving higher dose DOACs (RR 0.95, 95% CI 0.87-1.05, p=0.3074, I²=0%), had a significant reduction of all-cause mortality. Benefit from lower dose DOACs remained after sensitivity analysis or direct comparison with higher dose DOACs (RR 0.84, 95% CI 0.76-0.93, p=0.0009, I²=0%).
Within antithrombotic/anticoagulation regimens of DOAC administration, selection of lower dose appears to protect from all-cause mortality in patients with established atherosclerosis.
•1155 patients with cancer-associated VTE receiving dalteparin or apixaban from the randomized Caravaggio study.•Recurrent VTE occurred in 78 patients (6.8%) and major bleeding in 45 ...(3.9%).•Pancreatic or hepatobiliary cancer, increase in creatinine clearance, ECOG status of at least 1, index DVT and anti-cancer treatment were independent predictors for recurrent VTE.•ECOG status of 2, genitourinary cancer, upper and non-resected luminal gastrointestinal cancer were independent predictors of major bleeding.
Risks of recurrence and treatment-emergent bleeding are high in patients with cancer-associated venous thromboembolism (VTE) but factors associated with these risks remain substantially undefined.
The aim of this analysis in patients with cancer-associated VTE included in the Caravaggio study was to identify risk factors for recurrent VTE and major bleeding. Variables potentially predictive for recurrent VTE or major bleeding were evaluated in a Cox proportional hazard multivariable analysis with backward variable selection.
Recurrent VTE occurred in 78 patients (6.8%) and major bleeding in 45 (3.9%). Independent risk factors for recurrent VTE were deep vein thrombosis (DVT) as index event (Hazard ratio (HR) 1.84, 95% CI 1.17–2.88), ECOG status of 1 or more (HR 1.95, 95% CI 1.11–3.43), pancreatic or hepatobiliary cancer site (HR 2.20, 95% CI 1.19–4.06), concomitant anti-cancer treatment (HR 1.98, 95% CI 1.03–3.81) and creatinine clearance (HR 1.10, 95% CI 1.00–1.20 for every 10 ml/min absolute increase). Independent risk factors for major bleeding were ECOG status of 2 (HR 2.31, 95% CI 1.24–4.29), genitourinary cancer site (HR 2.72, 95% CI 1.28–5.77), upper gastrointestinal cancer site (HR 3.17, 95% CI 1.22–8.23), and non-resected luminal gastrointestinal cancer (HR 2.77, 95% CI 1.38–5.56).
This analysis of the Caravaggio study in patients with cancer-associated VTE who were on standardized anticoagulant treatment identified five independent predictors for recurrent VTE and four independent predictors of treatment-emergent major bleeding. Considering these risks could help clinicians to optimize the anticoagulant treatment in patients with cancer-associated VTE.
•Women and men have different prevalence of risk factors for venous thromboembolism.•Understanding these differences may help to predict sex-related risk of recurrence.•Women and men had similar ...rates of one year recurrent venous thromboembolism (VTE).•Women had lower quality of life and treatment satisfaction after the first VTE.
Sex and the presence of specific provoking risk factors, along with age, influence the presentation and prognosis of venous thromboembolism (VTE). We investigated the presentation, course and quality of life in women and men with acute VTE classified according to their VTE provoking factors.
PREFER in VTE is an international, non-interventional registry of patients with a first episode of acute symptomatic VTE. Baseline provoking factors were classified as follows: major transient, minor transient, active cancer, and none identifiable. The primary outcome was recurrent VTE. Quality of life and treatment satisfaction were secondary outcomes.
Of 3,455 patients with acute VTE, 1,623 (47%) were women. The mean age at the time of VTE was 61 (SD 18) in women, 60 (SD 15) in men. The distribution of provoking risk factors was similar between sexes, despite a tendency for higher frequency of minor and major transient risk factors in women, and cancer or unprovoked VTE in men. At 12-month follow-up, VTE recurrence was reported in 74 (6.5%) women and 80 (6.4%) men (absolute risk difference -0.1%, 95% CI -1.9%; +2.1%). In patients with unprovoked VTE, the VTE recurrence rate was 38/612 (6.2%) in women and 53/798 (6.6%) in men (absolute risk difference -0.4, 95% CI -3.0; +2.1%). Multivariable Cox regressions confirmed the absence of sex differences. Quality of life and treatment satisfaction scores one year after VTE were lower in women than in men irrespective of the provoking risk factors (p<0.001 for both scores).
Despite differences in the provoking risk factors for VTE, women and men had a similar rate VTE recurrence at one year. After acute VTE, women had lower quality of life and treatment satisfaction scores.
The Padua prediction score (PPS) has been suggested as the best available model for the assessment of the risk of venous thromboembolism (VTE) in hospitalized medical patients. The impact of its use ...in clinical practice has never been prospectively evaluated. According to a quasi-randomized study design, consecutive patients admitted to Internal Medicine Section 1 were allocated to a PPS-based decisional strategy suggesting thromboprophylaxis in patients with PPS score ≥4, and those admitted to Section 2 to a clinical judgment-based strategy. Study patients underwent complete compression ultrasonography of the lower limbs at discharge. The primary outcome was symptomatic or asymptomatic VTE during hospital stay. Secondary outcomes were VTE excluding isolated distal deep vein thrombosis, bleedings, and appropriate thromboprophylaxis. 628 patients were included in the analysis, 235 in the PPS group, and 393 in the clinical judgment group. The two groups differed for length of hospital stay, prevalence of recent trauma or surgery, and stroke. Compared with control, the PPS group had a significantly lower incidence of VTE (8.5 vs. 15.5 %, OR 0.51, 95 % CI 0.30–0.86), also after adjusting for thromboprophylaxis use and patient PPS-risk category (OR 0.54, 95 % CI 0.31–0.94). In conclusion, the use of PPS was associated with a higher rate of appropriate thromboprophylaxis prescription; no significant differences were found in the other secondary outcomes. The use of PPS for the assessment of risk for VTE is associated with a reduced incidence of VTE compared with the clinical judgment. These result needs to be confirmed in future studies.
The infection by the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated with significant cardiovascular morbidity and mortality. Cardiac events require ...prompt diagnosis and management, also in the SARS-CoV-2 era. A 58-year-old male, heavy smoker and with known SARS-CoV-2 infection, abruptly developed severe hypotension and asthenia. At patients' home, emergency physicians found hemodynamic compromise with diffuse ST-elevation at electrocardiography. The patient was rapidly moved to the cardiac catheterization laboratory, and any contact with other health-care workers was avoided. Coronary angiography excluded coronary artery disease. At admission to the coronavirus disease-2019 unit, an increase in inflammatory markers and liver enzymes with normal troponin levels were observed. Bedside lung ultrasonography showed interstitial syndrome and bilateral pleural effusion, whereas echocardiography showed large and diffuse pericardial effusion with a swinging heart. The hemodynamic status improved after gentle fluid therapy such suggesting potential concomitant sepsis and pericardiocentesis was not performed. At this time, a computed tomography scan showed a widespread neoplasm in the right lung involving the subclavian artery and vein and the thoracic lymph nodes. The histology confirmed the diagnosis of a locally advanced pulmonary adenocarcinoma. One week after admission, the patient died for worsening respiratory failure. Not delayed primary PCI remains the standard of care for patients with suspected ST-elevation myocardial infarction (STEMI) in the SARS-CoV-2 era. A diagnostic deepening for potential STEMI-mimicker (known to be associated with SARS-CoV-2 infection and to patients' comorbidities) should be considered, and a multidisciplinary approach is needed in these patients.
Patients with brain cancer have been excluded or were underrepresented in studies on the treatment of venous thromboembolism (VTE), mainly due to the fear of intracranial hemorrhage (ICH).
The aim of ...this study was to provide data on the risk of ICH, recurrent VTE, and major bleeding in patients with active brain cancer.
This was a multicenter, international cohort study at participating sites of the Registro Informatizado Enfermedad Tromboembólica Registry. Patients included in this study were classified as having known active brain cancer, active nonbrain cancer, or without active cancer. ICH at 3 months was the primary study outcome.
Overall, 98,377 patients with VTE were included: 616 with active brain cancer, 16,807 with active nonbrain cancer, and 80,954 without active cancer. At 3 months follow-up, ICH occurred in 2.8%, 0.3%, and 0.2% of the patients, respectively, and was fatal in 1.3%, 0.2%, and 0.1%, respectively. Both rates of major bleeding (3.7% vs 3.2% vs 1.5%, respectively) and recurrent VTE (3.9% vs 3.4% vs 1.1%, respectively) were higher in patients with brain or nonbrain cancer than in patients without cancer. Glioblastomas were associated with a numerically higher risk of ICH, fatal ICH, and recurrent VTE than other brain tumors.
In patients with VTE, active brain cancer was associated with a higher risk of ICH or fatal ICH than nonbrain or no active cancer. Further studies are needed to assess the value of different treatment approaches in patients with brain cancer and VTE.
•Treatment of venous thromboembolism in patients with brain cancer is challenging.•This was a multicenter study of patients with brain cancer, nonbrain cancer, or no cancer.•Patients with brain cancer had a 13-fold higher risk of intracranial hemorrhage than patients without cancer.•In patients with brain cancer, rates of intracranial hemorrhage and fatal bleeding increase over time after venous thromboembolism.
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