[Hypercholesterolemia, from screening to treatment: Who, why and how to manage]. / Hypercholestérolémie, du dépistage au traitement : quelle prise en charge, pour qui et pour quel bénéfice.

Hypercholesterolemia refers to dyslipidemia with an increased circulating cholesterol levels. This is the most common dyslipidemia and is associated with an increased risk of developing atheromatous cardiovascular diseases. One of the major challenges in primary prevention is to define the threshold for therapeutic intervention that allow to obtain a significant clinical benefit without unnecessarily expose the patient to potential side effects of lipid-lowering treatments. It is also important to recall to screen patient for heterozygous familial hypercholesterolemia, a common genetic disease of lipid metabolism responsible for particularly severe and early coronary disease. In this article, the issues of hypercholesterolemia screening, the definition of therapeutic targets and expected benefits as well as the modalities of therapeutic management (by also addressing the problem of statin intolerance) will be addressed.

Bleeding complications and antithrombotic treatment in 264 pregnancies in antiphospholipid syndrome.

Purpose The purpose of this study was to evaluate the safety of antithrombotic treatments prescribed during pregnancy in patients with antiphospholipid syndrome (APS). Methods This international, multicenter study included two cohorts of patients: a retrospective French cohort and a prospective US cohort (PROMISSE study). Inclusion criteria were (1) APS (Sydney criteria), (2) live pregnancy at 12 weeks of gestation (WG) with (3) follow-up data until six weeks post-partum. According to APS standard of care, patients were treated with aspirin and/or low-molecular weight heparin (LMWH) at prophylactic (pure obstetric APS) or therapeutic doses (history of thrombosis). Major bleeding was defined as abnormal blood loss during the pregnancy and/or post-partum period requiring intervention for hemostasis or transfusion, or during the peripartum period greater than 500 mL and/or requiring surgery or transfusion. Other bleeding events were classified as minor. Results Two hundred and sixty-four pregnancies (87 prospectively collected) in 204 patients were included (46% with history of thrombosis, 23% with associated systemic lupus). During pregnancy, treatment included LMWH ( n = 253; 96%) or low-dose aspirin ( n = 223; 84%), and 215 (81%) patients received both therapies. The live birth rate was 89% and 82% in the retrospective and prospective cohorts, respectively. Adverse pregnancy outcomes occurred in 28% of the retrospective cohort and in 40% of the prospective cohort. No maternal death was observed in either cohort. A combined total of 45 hemorrhagic events (25%) occurred in the retrospective cohort, but major bleeding was reported in only six pregnancies (3%). Neither heparin nor aspirin alone nor combined therapy increased the risk of hemorrhage. We also did not observe an increased rate of bleeding in the case of a short interval between last LMWH (less than 24 hours) or aspirin (less than five days) doses and delivery. Only emergency Caesarean section was significantly associated with an increased risk of bleeding (odds ratio (OR) 5.03 (1.41-17.96); p=.016). In the prospective cohort, only one minor bleeding event was reported (vaginal bleeding). Conclusion Our findings support the safety of antithrombotic therapy with aspirin and/or LMWH during pregnancy in high-risk women with APS, and highlight the need for better treatments to improve pregnancy outcomes in APS. PROMISSE Study ClinicalTrials.gov identifier: NCT00198068.

Anticoagulation withdrawal in antiphospholipid syndrome: a retrospective matched-control study.

Background/Purpose Long-term anticoagulation is the standard treatment for thrombotic antiphospholipid syndrome (APS). However, in daily practice, the question of withdrawing anticoagulation may arise, without any evidence-based recommendations. This study aimed to assess outcomes in APS patients after anticoagulation withdrawal. Methods Thrombotic APS patients followed in our centre, whose anticoagulation was withdrawn after APS diagnosis, were retrospectively selected, and were match-controlled with patients under anticoagulation, based on sex, age, APS clinical phenotype and disease duration. Results Thirty cases with anticoagulation withdrawal were included. Median follow-up was 51 months (12-124). The risk of thrombotic relapse was higher in cases compared to controls (7.3% versus 1.5% patient-year ( p = 0.01); hazard ratio 4.8; 95% confidence interval (1.4-16.7)). Male gender, anti-ß2GP1 and triple positivity at inclusion were predictive factors for thrombotic relapse. Conversely, aspirin prescription was a protective factor against relapses. Persistence of LA, anti-ß2GP1 and triple positivity over time were associated with a higher risk of thrombosis and aPL disappearance with a lower risk. Conclusion In our study, anticoagulation withdrawal was associated with an increased risk of thrombotic relapse. Our findings emphasize the influence of anti-ß2GP1 and triple positivity persistence over time on the risk of relapse and the benefit of aspirin prescription when anticoagulation has been withdrawn.

Persistent triple antiphospholipid antibody positivity as a strong risk factor of first thrombosis, in a long-term follow-up study of patients without history of thrombosis or obstetrical morbidity.

Introduction The long-term risk of first thrombosis and benefit of prophylaxis in antiphospholipid antibody (aPL) carriers without history of thrombosis or obstetrical morbidity is poorly known. This study aimed to evaluate the long-term rate and risk factors associated with a first thrombosis in those patients. Patients and methods After a prior study ended in December 2005 and was already published, we extended the follow-up period of our cohort of aPL carriers. Results Ninety-eight of the 103 patients of the previous study were included. The annual first thrombosis rate was 2.3% per patient-year during a median of 13 years (6-17). None of the baseline characteristics was predictive of risk of first thrombosis, but persistent aPL over time were associated with an increased risk. The stronger association was found in triple aPL-positive carriers: OR 3.38 (95% CI: 1.24-9.22). Of note, conversely to our previous findings, no benefit of aspirin prophylaxis was observed. Conclusion The risk of first thrombosis in aPL carriers without history of thrombosis or obstetrical morbidity was significant, persisted linearly over time and was associated with persistent aPL. This risk was especially increased in triple aPL-positive carriers, in whom a close follow-up seems to be necessary. Nevertheless, the benefit of aspirin prophylaxis remained unclear.