Publications

Hormone-replacement therapy (HRT) has been used for more than 40 years to reduce perimenopausal symptoms. Estrogens may protect brain structures and functional systems affected by Alzheimer's disease, which suggests that maintaining high levels of hormones with HRT can protect against Alzheimer's disease. Moreover, high premenopausal estrogen concentrations are thought to be protective against stroke and, consequently, in the past, HRT was considered to be a potential protective agent against stroke. However, large clinical trials have failed to demonstrate a benefit from HRT on either cognitive performance or risk of dementia. In addition, although HRT has been associated with a reduction in the risk of heart disease in observational studies, results regarding stroke have been less clear. Recently, evidence has shown that HRT does not reduce but actually increases vascular risk. Here, the data from the most important studies are examined, concluding that HRT has no beneficial effect on dementia or stroke risk reduction in postmenopausal women.

Purpose: To investigate outcomes in patients with non-valvular atrial fibrillation (AF) who discontinue oral anticoagulant (OAC) therapy within 12 months compared with those who persist on OAC therapy after 12 months. Methods: In the ongoing, international GARFIELD Registry, a total of 12,458 prospective newly diagnosed AF patients were enrolled at 739 sites in 30 countries between March 2010 and January 2013. Results are reported at 1-year follow-up. Event rates over a period of 12 months in patients on OAC therapy were analysed for patients who discontinued therapy and those who persisted. Results: Of the 7350 patients prescribed an OAC after AF diagnosis, 1729 discontinued therapy within 12 months (23.5%). Risk scores were similar between groups. Patients treated with OAC/antiplatelet combination at baseline were more likely to discontinue therapy than those on OAC alone. Event rates for stroke/systemic embolism (SE), major bleeding, and all-cause death were significantly higher in patients who discontinued OAC therapy. Conclusion: Markedly higher rates of death along with increased stroke/SE and serious bleeding were observed in patients who discontinued OAC therapy within 12 months.

The long-term risk for major bleeding in patients receiving extended (beyond the initial 3 to 6 months) anticoagulant therapy for a first unprovoked venous thromboembolism (VTE) is uncertain.To determine the incidence of major bleeding during extended anticoagulation of up to 5 years among patients with a first unprovoked VTE, overall, and in clinically important subgroups.MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from inception to 23 July 2021.Randomized controlled trials (RCTs) and prospective cohort studies reporting major bleeding among patients with a first unprovoked VTE who were to receive oral anticoagulation for a minimum of 6 additional months after completing at least 3 months of initial anticoagulant treatment.Two reviewers independently abstracted data and assessed study quality. Unpublished data required for analyses were obtained from authors of included studies.Among the 14 RCTs and 13 cohort studies included in the analysis, 9982 patients received a vitamin K antagonist (VKA) and 7220 received a direct oral anticoagulant (DOAC). The incidence of major bleeding per 100 person-years was 1.74 events (95% CI, 1.34 to 2.20 events) with VKAs and 1.12 events (CI, 0.72 to 1.62 events) with DOACs. The 5-year cumulative incidence of major bleeding with VKAs was 6.3% (CI, 3.6% to 10.0%). Among patients receiving either a VKA or a DOAC, the incidence of major bleeding was statistically significantly higher among those who were older than 65 years or had creatinine clearance less than 50 mL/min, a history of bleeding, concomitant use of antiplatelet therapy, or a hemoglobin level less than 100 g/L. The case-fatality rate of major bleeding was 8.3% (CI, 5.1% to 12.2%) with VKAs and 9.7% (CI, 3.2% to 19.2%) with DOACs.Data were insufficient to estimate incidence of major bleeding beyond 1 year of extended anticoagulation with DOACs.In patients with a first unprovoked VTE, the long-term risks and consequences of anticoagulant-related major bleeding are considerable. This information will help inform patient prognosis and guide decision making about treatment duration for unprovoked VTE.Canadian Institutes of Health Research. (PROSPERO: CRD42019128597).

Clinical guidelines advise similar anticoagulant treatment for symptomatic and incidental cancer-associated venous thromboembolism (VTE). We investigated clinical features and outcomes of cancer patients with incidental or symptomatic VTE randomized in the Caravaggio study.We performed a predefined sub-analysis of the Caravaggio study in order to investigate the clinical features and outcomes of incidental and symptomatic VTE in patients with cancer. The relative efficacy and safety of apixaban and dalteparin in patients with incidental and symptomatic VTE was also assessed.The Caravaggio study compared apixaban to dalteparin for the 6-month treatment of cancer-associated VTE. The primary efficacy and safety outcomes were recurrent VTE and major bleeding.Two hundred thirty patients (20%) had incidental and 925 (80%) symptomatic VTE. Pulmonary embolism with or without deep vein thrombosis as index event, colorectal cancer, Eastern Cooperative Oncology Group (ECOG) score of 0, and locally advanced or metastatic cancer were more frequent in patients with incidental VTE. Deep vein thrombosis as index event, hematological cancer, and ECOG score of 2 were more frequent in patients with symptomatic VTE. Ten patients (4.3%) with incidental and 68 (7.4%) with symptomatic VTE had recurrent VTE (hazard ratio [HR] 0.57, 95% confidence interval [CI] 0.29-1.10). Major bleeding occurred in 12 (5.2%) patients with incidental VTE and in 33 (3.6%) patients with symptomatic VTE (HR 1.43, 95% CI 0.74-2.77). When comparing apixaban to dalteparin in patients with symptomatic and incidental VTE, the HR for recurrence was 0.73 (95% CI 0.45-1.19) and 0.41 (95% CI 0.11-1.56), respectively, and the HR for major bleeding 0.93 (95% CI 0.47-1.83) and 0.96 (95% CI 0.31-2.96), respectively.Compared to cancer patients with symptomatic VTE, those with incidental VTE have different clinical features at presentation, with a numerically lower incidence of recurrent VTE and a numerically higher incidence of major bleeding.

In a meta-analysis of results from 21 randomized trials comparing antiplatelet therapy with placebo in 18,270 patients with prior stroke or transient ischemic attack, antiplatelet therapy was associated with a 28% relative odds reduction in nonfatal strokes and a 16% reduction in fatal strokes, while another trial for secondary prevention with atorvastastin 80 mg showed a 16% risk reduction in time to first occurrence of stroke (adjusted hazard ratio: 0·84, 95% CI: 0·71–0·99). However, few studies have examined the sex differences regarding the efficacy of these treatments. Specifically, recent studies have reported higher rates of perioperative complications during endarterectomy in women. Nonetheless, to date, the data on the effects of carotid artery stenting in women, coming from diverse studies and meta-analyses, have been limited owing to the small number of female patients examined. Owing to this, the evidence of the benefit for women is unclear. Peculiar pathophysiological aspects of stroke, the higher stroke risk in some specific periods in life (e.g., pregnancy, puerperium and older age) and worse documented stroke outcome in women suggest that sex does matter in stroke management. Thus, future randomized controlled trials need to be sex-balanced, in order to better understand the efficacy of appropriate secondary stroke prevention therapy in women.