A focused review of gender differences in antithrombotic therapy

Background: The biological differences among male and female, based on distinctive expression of sex chromosomes, on varied gene-expression and on peculiar sexual hormones, lead to important differences in physiology and pathophysiology. Objective: The aim of this work was to briefly review the relationships among genderrelated differences and clinical implications in antithrombotic therapy, that could be related to sex-differences in platelet biology and coagulation reactions. Results: The major clinical setting in which antithrombotic drugs are involved for the treatment are atrial fibrillation, venous thromboembolisn, coronary artery disease and peripheral artery diseases. Considering that a consistent body of evidences suggests that, on one hand, human platelet activity may be influenced by sex and sex hormones and, on the other hand, estrogens are likely to play a crucial role on the transcriptional regulation of coagulation protein genes, the real impact of gender-related differences is still unclear. Moreover, women and men present different responses to antithrombotic drugs, reflecting genderspecific variances in pharmacokinetic profile, along with the physiological characteristics of each gender. Thus, the efficacy and adverse effects of antithrombotic drugs may vary according to gender. Conclusion: Several gender-related differences could be reported in haemostasis and thrombosis pathophysiological mechanisms. Moreover, several data documented relevant gender differences in antithrombotic management and clinical effectiveness. Further studies are still needed to completely elucidate these issues

Clinical features and management of venous thromboembolism in patients with Behçet’s syndrome : a single-center case–control study

Almost one third of patients with Beh\ue7et's syndrome (BS) display vascular involvement. However, data regarding the prevalence and management of venous thromboembolism (VTE) in BS are scanty. We assessed the differential characteristics between patients with and without VTE and the factors associated with VTE incidence. A case\u2013control study in a cohort of patients with BS was performed. 57 patients were included (56.1% women) with a mean follow-up of 10.56 (\ub1 10.7) years. Mean age at diagnosis of BS and diagnosis of the first VTE episode was 34.7 (\ub1 12.1) and 31.2 (\ub1 8.9) years, respectively. Erythema nodosum (OR 4.6, CI 95% 1.2\u201318.1) and fever (OR 8.2, CI 95% 1.6\u201342.1) were associated with a higher risk of VTE. 26 episodes of VTE were registered in 12/57 (21%) patients. 83.3% of patients were not diagnosed with BS when the first episode of VTE occurred and, among them, the episode of VTE led to the diagnosis of BS in 40% of cases. Half of patients had at least one VTE recurrence. The absence of immunosuppressive treatment was associated with a higher risk of developing a first episode of VTE (OR 20 CI 95% 19.2\u2013166.6). All patients were treated with anticoagulation and 75% were treated with immunosuppressants after the first VTE event. The diagnosis of VTE usually precedes that of BS, with a high frequency of VTE recurrence. Erythema nodosum and fever were associated with a higher risk of VTE, while the immunosuppressants showed a protective role for the development of VTE

Metabolic Syndrome in Heart Failure: Friend or Foe?

The interplay between metabolic syndrome (MetS) and heart failure (HF) is intricate. Population studies show that MetS confers an increased risk to develop HF and this effect is mediated by insulin resistance (IR). However, obesity, a key component in MetS and common partner of IR, is protective in patients with established HF, although IR confers an increased risk of dying by HF. Such phenomenon, known as "obesity paradox," accounts for the complexity of the HF-MetS relationship. Because IR impacts more on outcomes than MetS itself, the former may be considered the actual target for MetS in HF patients

Evaluation of the SAMe-TT2R2 score to predict the quality of anticoagulation control in patients with venous thromboembolism treated with vitamin K antagonists: Findings from the RIETE registry

Background: The time in therapeutic range (TTR) of patients with venous thromboembolism (VTE) treated with vitamin K antagonists (VKA) is usually below recommended, leading to higher frequency of vascular events, bleeding and mortality. The SAMe-TT2R2 prediction score discriminates those patients with high or low probability of obtaining poor INR control and its use is recommended in patients with atrial fibrillation. Its usefulness has been evaluated in patients with VTE, with conflicting results. Method: We included consecutive patients enrolled in Registro Informatizado Enfermedad TromboEmbolica (RIETE), a prospective multicenter VTE registry, treated with VKA for >90 days and a minimum of 3 INR determinations. We analyzed the relationship between the SAMe-TT2R2 score and TTR, determined by the Rosendaal method and by the percentage of INR determinations (after excluding the first month). A ROC curve was calculated considering a cut-off point of TTR ≥65% for good anticoagulation control. Results: 3893 patients were included and classified in high (1411 patients) or low (2482 patients) probability of obtaining poor INR control according to the total score obtained (0–1 points versus 2 points, respectively). TTR, calculated by direct method and Rosendaal method, was 51.2 (±23.4) and 55.4 (±25.9) in the high probability group; and 54.4 (±23.0) and 58.2 (±25.6) in the low probability group, respectively (p < 0.001 for both comparisons). The outcomes were similar between groups. The predictive capacity of the SAMe-TT2R2 score showed an area under the ROC curve of 0.54 (CI 95% 0.52–0.56) and 0.53 (CI 95% 0.51–0.55). Conclusions: In patients with VTE treated with VKA, the SAMe-TT2R2 score discriminated those patients with high probability of obtaining poor INR control, but with a low predictive capacity. Further studies are required to assess the usefulness of the score in clinical decision-making

Incidence of major adverse cardiovascular events among patients with provoked and unprovoked venous thromboembolism: Findings from the Registro Informatizado de Enfermedad Tromboemb\uf3lica Registry

Objective: Overlap exists between the risk factors for coronary artery disease and venous thromboembolism (VTE). However, a paucity of data is available on the incidence of major acute cardiovascular events (MACE) and major adverse limb events (MALE) among patients presenting with VTE. Moreover, it is unknown whether the rate of cardiovascular outcomes differs among patients with unprovoked vs provoked VTE. Methods: We analyzed the data from 2009 to 2017 in the Registro Informatizado de Enfermedad Tromboemb\uf3lica registry, an ongoing, multicenter, international registry of consecutive patients with a diagnosis of objectively confirmed VTE. The query was restricted it to patients with data entry for the arterial outcomes. The baseline prevalence of coronary artery disease risk factors was compared between patients with provoked (ie, immobility, cancer, surgery, travel &gt;6 hours, hormonal causes) and unprovoked VTE. After the initial VTE event, we followed up patients for the composite primary outcome of incident MACE (ie, stroke, myocardial infarction, unstable angina) and/or MALE (ie, major limb events). We used the \u3c72 test for baseline associations and a Cox proportional hazard for multivariate analysis. We used IBM SPSS, version 24 (IBM Corp, Armonk, NY) for statistical analysis. A P value of &lt;.05 was considered statistically significant. Results: We analyzed the data from 41,259 patients with VTE, of whom 22,633 (55.6%) had experienced a provoked VTE. During follow-up, the patients with provoked VTE were more likely to develop MACE or MALE than were patients with unprovoked VTE (hazard ratio [HR], 1.3; 95% confidence interval [CI], 1.1-1.5). The association of arterial events with recent immobility (HR, 1.4; 95% CI, 1.5-12.1) and cancer (HR, 1.7; 95% CI, 1.4-1.9) was strong. After adjusting for multiple conventional cardiovascular risk factors, provoked VTE, compared with unprovoked VTE, was significantly associated with an increased hazard for MACE (HR, 1.4; 95% CI, 1.1-1.7). Cancer remained a significant adjusted predictor for both MACE (HR, 1.7; 95% CI, 1.4-2.1) and MALE (HR, 2.1; 95% CI 1.01-4.6) in those with provoked VTE. Conclusions: Among patients with VTE, provoked cases, specifically those with cancer-associated VTE, have an increased risk of major arterial events