Major bleedings other than gastrointestinal (GI) and intracranial (ICH) and mortality rates associated with antiplatelet drugs in real-world clinical practice are unknown. The objective was to ...estimate major bleeding risk and mortality among new users of antiplatelet drugs in real-world clinical practice. A population-based prospective cohort using the French national health data system (SNIIRAM), identified 69,911 adults living within five well-defined geographical areas, who were new users of antiplatelet drugs in 2013-2015 and who had not received any antithrombotics in 2012. Among them, 63,600 started a monotherapy and 6,311 a dual regimen. Clinical data for all adults referred for bleeding was collected from all emergency departments within these areas, and medically validated. Databases were linked using common key variables. The main outcome measure was time to major bleeding (GI, ICH and other bleedings). Secondary outcomes were death, and event-free survival (EFS). Hazard ratios (HR) were derived from adjusted Cox proportional hazard models. We used Inverse Propensity of Treatment Weighting as a stratified sensitivity analysis according to the antiplatelet monotherapy indication: primary prevention without cardiovascular (CV) risk factors, with CV risk factors, and secondary prevention. We observed 250 (0.36%) major haemorrhages, 81 ICH, 106 GI and 63 other types of bleeding. Incidences were twice as high in dual therapy as in monotherapy. Compared to low-dose aspirin (less than or equal to 100 mg daily), high-dose (> 100 up to 325 mg daily) was associated with an increased risk of ICH (HR = 1.80, 95%CI 1.10 to 2.95). EFS was improved by high-dose compared to low-dose aspirin (1.41, 1.04 to 1.90 and 1.32, 1.03 to 1.68) and clopidogrel (1.30, 0.73 to 2.3 and 1.7, 1.24 to 2.34) respectively in primary prevention with and without CV risk factors. The incidence of major bleeding and mortality was low. In monotherapy, low-dose aspirin was the safest therapeutic option whatever the indication.
Influence of Omeprazole on the Antiplatelet Action of Clopidogrel Associated With Aspirin: The Randomized, Double-Blind OCLA (Omeprazole CLopidogrel Aspirin) Study Martine Gilard, Bertrand Arnaud, ...Jean-Christophe Cornily, Grégoire Le Gal, Karine Lacut, Geneviève Le Calvez, Jacques Mansourati, Dominique Mottier, Jean-François Abgrall, Jacques Boschat In a previous observational study, we found the effect of clopidogrel as tested by vasodilator-stimulated phosphoprotein (VASP) phosphorylation to be diminished in patients receiving proton pump inhibitor treatment. In this double-blind placebo-controlled trial, 124 consecutive patients were randomized to receive either associated omeprazole (20 mg/day) or placebo for 7 days. The clopidogrel effect was tested on Day 1 and Day 7 in both groups by measuring platelet phosphorylated VASP. Our main end point was to compare platelet activation in the 2 groups. Omeprazole significantly decreased the antiplatelet effect of clopidogrel as assessed by a VASP phosphorylation test (p < 0.0001).
We aimed to identify risk factors for recurrent venous thromboembolism (VTE) after unprovoked pulmonary embolism.Analyses were based on the double-blind randomised PADIS-PE trial, which included 371 ...patients with a first unprovoked pulmonary embolism initially treated during 6 months who were randomised to receive an additional 18 months of warfarin or placebo and followed up for 2 years after study treatment discontinuation. All patients had ventilation/perfusion lung scan at inclusion (
at 6 months of anticoagulation).During a median follow-up of 41 months, recurrent VTE occurred in 67 out of 371 patients (6.8 events per 100 person-years). In main multivariate analysis, the hazard ratio for recurrence was 3.65 (95% CI 1.33-9.99) for age 50-65 years, 4.70 (95% CI 1.78-12.40) for age >65 years, 2.06 (95% CI 1.14-3.72) for patients with pulmonary vascular obstruction index (PVOI) ≥5% at 6 months and 2.38 (95% CI 1.15-4.89) for patients with antiphospholipid antibodies. When considering that PVOI at 6 months would not be available in practice, PVOI ≥40% at pulmonary embolism diagnosis (present in 40% of patients) was also associated with a 2-fold increased risk of recurrence.After a first unprovoked pulmonary embolism, age, PVOI at pulmonary embolism diagnosis or after 6 months of anticoagulation and antiphospholipid antibodies were found to be independent predictors for recurrence.
To summarize and compare the effectiveness of pharmacological thromboprophylaxis to pneumatic compression devices (PCD) for the prevention of venous thromboembolism in patients with acute ...intracerebral hemorrhage.
MEDLINE, PUBMED, EMBASE, and CENTRAL were systematically searched to identify randomized and non-randomized studies that compared each intervention directly to each other or against a common control (hydration, anti-platelet agents, stockings) in adults with acute spontaneous intracerebral hemorrhage. Two investigators independently screened the studies, extracted data, and appraised risk of bias. Studies with a high risk of bias were excluded from our final analysis. The primary outcome was the occurrence of venous thromboembolism (proximal deep vein thrombosis or pulmonary embolism) in the first 30 days.
8,739 articles were screened; four articles, all randomized control trials, met eligibility criteria. Bayesian network meta-analysis was performed to calculate risk estimates using both fixed and random effects analyses. 607 patients were included in the network analysis. PCD were associated with a significant decrease in venous thromboembolism compared to control (OR: 0.43, 95% Credible Limits CrI: 0.23-0.80). We did not find evidence of statistically significant differences between pharmacological thromboprophylaxis and control (OR: 0.93, 95% CrI: 0.19-4.37) or between PCD and pharmacological thromboprophylaxis (OR: 0.47, 95% CrI: 0.09-2.54).
PCDs are superior to control interventions, but meaningful comparisons with pharmacotherapy are not possible due to a lack of data. This requires further exploration via large pragmatic clinical trials.
PROSPERO: CRD42018090960.
The optimal duration of anticoagulation after a first episode of unprovoked deep-vein thrombosis is uncertain. We aimed to assess the benefits and risks of an additional 18 months of treatment with ...warfarin
placebo, after an initial 6 months of anticoagulation for a first unprovoked proximal deep-vein thrombosis. We conducted a multicenter, randomized, double-blind, controlled trial comparing an additional 18 months of warfarin with placebo in patients with a unprovoked proximal deep-vein thrombosis initially treated for 6 months (treatment period: 18 months; follow up after treatment period: 24 months). The primary outcome was the composite of recurrent venous thromboembolism or major bleeding at 18 months. Secondary outcomes were the composite at 42 months, as well as each component of the composite, and death unrelated to pulmonary embolism or major bleeding, at 18 and 42 months. All outcomes were centrally adjudicated. A total of 104 patients, enrolled between July 2007 and October 2013 were analyzed on an intention-to-treat basis; no patient was lost to follow-up. During the 18-month treatment period, the primary outcome occurred in none of the 50 patients in the warfarin group and in 16 out of 54 patients (cumulative risk, 29.6%) in the placebo group (hazard ratio, 0.03; 95% confidence interval: 0.01 to 0.09;
<0.001). During the entire 42-month study period, the composite outcome occurred in 14 patients (cumulative risk, 36.8%) in the warfarin group and 17 patients (cumulative risk, 31.5%) in the placebo group (hazard ratio, 0.72; 95% confidence interval: 0.35-1.46). In conclusion, after a first unprovoked proximal deep-vein thrombosis initially treated for 6 months, an additional 18 months of warfarin therapy reduced the composite of recurrent venous thrombosis and major bleeding compared to placebo. However, this benefit was not maintained after stopping anticoagulation.
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Cancer and factor V Leiden mutation are both risk factors for venous thromboembolism (VTE). Cancer critically increases the thrombotic risk whereas Factor V Leiden is the most common pro-thrombotic ...mutation. The impact of the factor V Leiden on the risk of VTE in cancer patients remains uncertain.
To assess the impact of factor V Leiden mutation in cancer-associated thrombosis.
The EDITH hospital-based case-control study enrolled 182 patients with cancer and VTE as well as 182 control patients with cancer, matched for gender, age and cancer location, between 2000 and 2012, in the University Hospital of Brest. All cases and controls were genotyped for the factor V Leiden mutation and interviewed with a standardized questionnaire.
Twenty one of 182 (11.5%) patients with cancer-associated thrombosis carried the factor V Leiden mutation and 4 of 182 (2.2%) controls with cancer but no venous thrombosis. In multivariate analysis including cancer stage and family history of VTE, cancer patients with factor V Leiden mutation had a seven-fold increased risk of venous thromboembolism (adjusted odds ratio OR, 7.04; 95% CI, 2.01-24.63).
The pro-thrombotic Factor V Leiden mutation was found to be an independent additional risk factor for venous thromboembolism in cancer patients and might therefore be considered in the individual thrombotic risk assessment.
Interstitial lung disease (ILD) encompasses various parenchymal lung disorders, which has the potential to increase the risk of venous thromboembolism (VTE). To evaluate, in patients with ILD and ...VTE, the risk of recurrent VTE during follow-up after stopping anticoagulation. This was a cohort of patients with a first VTE recruited between 1997 and 2015. The primary outcome was adjudicated fatal or nonfatal recurrent VTE after stopping anticoagulation. Main secondary outcomes were major or clinically relevant non-major bleeding under anticoagulation. Among 4314 patients with VTE, 50 had ILD diagnosed before VTE. Of these, anticoagulation was stopped in 30 patients after a median duration of 180 days and continued indefinitely in 20 patients. During a median follow-up of 27.8 months after anticoagulation discontinuation, recurrent VTE occurred in 15 on 30 patients (annual incidence of 19.2 events per 100-person-years 95%CI 12.0–29.3, case-fatality rate of 6.7% 95%CI 1.21–29.8). The risk of recurrence was threefold higher when VTE was unprovoked and case-fatality rate of recurrence was increased by 3 when VTE index was PE. During the anticoagulant period, (median duration of 8.6 months), 6 patients had a major or clinically relevant bleeding (annual incidence of 7.3 events per 100-person-years 95%CI 3.4–15.1, case-fatality rate of 16.7% 95%CI 3.0–56.4). In patients with ILD, the risk of recurrent VTE after stopping anticoagulation and the risk of bleeding under anticoagulation were very high. Our results suggest that anticoagulation should not be prolonged beyond 3–6 months of anticoagulation in most of cases.
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