Safety of direct oral anticoagulants in patients with hereditary hemorrhagic telangiectasia.

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is a rare vascular dysplasia resulting in visceral arteriovenous malformations and smaller mucocutaneous telangiectasia. Most patients experience recurrent nosebleeds and become anemic without iron supplementation. However, thousands may require anticoagulation for conditions such as venous thromboembolism and/or atrial fibrillation. Over decades, tolerance data has been published for almost 200 HHT-affected users of warfarin and heparins, but there are no published data for the newer direct oral anticoagulants (DOACs) in HHT. METHODS: To provide such data, a retrospective audit was conducted across the eight HHT centres of the European Reference Network for Rare Multisystemic Vascular Diseases (VASCERN), in Denmark, France, Germany, Italy, the Netherlands and the UK. RESULTS: Although HHT Centres had not specifically recommended the use of DOACs, 32 treatment episodes had been initiated by other clinicians in 28 patients reviewed at the Centres, at median age 65 years (range 30-84). Indications were for atrial fibrillation (16 treatment episodes) and venous thromboembolism (16 episodes). The 32 treatment episodes used Apixaban (n = 15), Rivaroxaban (n = 14), and Dabigatran (n = 3). HHT nosebleeds increased in severity in 24/32 treatment episodes (75%), leading to treatment discontinuation in 11 (34.4%). Treatment discontinuation was required for 4/15 (26.7%) Apixaban episodes and 7/14 (50%) Rivaroxaban episodes. By a 4 point scale of increasing severity, there was a trend for Rivaroxaban to be associated with a greater bleeding risk both including and excluding patients who had used more than one agent (age-adjusted coefficients 0.61 (95% confidence intervals 0.11, 1.20) and 0.74 (95% confidence intervals 0.12, 1.36) respectively. Associations were maintained after adjustment for gender and treatment indication. Extreme hemorrhagic responses, worse than anything experienced previously, with individual nosebleeds lasting hours requiring hospital admissions, blood transfusions and in all cases treatment discontinuation, occurred in 5/14 (35.7%) Rivaroxaban episodes compared to 3/15 (20%) Apixaban episodes and published rates of ~ 5% for warfarin and heparin. CONCLUSIONS: Currently, conventional heparin and warfarin remain first choice anticoagulants in HHT. If newer anticoagulants are considered, although study numbers are small, at this stage Apixaban appears to be associated with lesser bleeding risk than Rivaroxaban.

Diet and myocardial infarction: a nested case-control study in a cohort of elderly subjects in a Mediterranean area of southern Italy.

BACKGROUND AND AIM: We evaluated the incidence of myocardial infarction (MI) in a population of Southern Italy and the relationship of dietary macronutrients with incident MI. METHODS AND RESULTS: The ONCONUT cohort included 5632 subjects followed-up, over 50 years, recruited in 1992. At baseline, they completed a validated semi-quantitative food frequency questionnaire and gave details of their medical history. After 5years they were traced by their family physician, who found 108 incident MI. Ninety-seven of them and 194 controls, sampled from the noncases at baseline and paired for diabetes to the cases, entered this nested case-control study. MI rate per 1000 person-years was 9.6 in males and 3.7 in females. In non-diabetics, saturated fat were associated with MI directly (odds ratio (OR): tertile 2 vs. 1 = 2.32, tertile 3 vs. 1 = 2.82; chi-square for trend, p = 0.03) and polyunsaturated fats inversely (OR: tertile 2 vs. 1 = 0.80, tertile 3 vs. 1 = 0.37; chi-square for trend, p = 0.05), while in diabetics, starchy carbohydrates (OR: tertile 2 vs. 1 = 1.51, tertile 3 vs. 1 = 6.73; chi-square for trend, p = 0.01) and glycaemic index (OR: tertile 2 vs. 1 = 2.74, tertile 3 vs. 1 = 5.34; chi-square for trend, p = 0.01) were associated directly with MI. CONCLUSIONS: MI incidence in this population was lower than that found in northern countries. In non-diabetics, saturated fats were associated directly and polyunsaturated fat inversely with MI; in diabetics, starchy carbohydrates and high-glycaemic-index foods were associated directly with MI.