Characteristics of patients with atrial fibrillation treated with direct oral anticoagulants and new insights into inappropriate dosing: results from the French National Prospective Registry: PAFF.

AIMS: Since the introduction of direct oral anticoagulant (DOAC) for atrial fibrillation (AF) therapy, inappropriate and/or underdosing of these drugs has been a major clinical challenge. We evaluated the characteristics of patients with AF treated with inappropriate and low-dose DOACs. METHODS AND RESULTS: Patients with AF treated with inappropriate and low-dose DOACs from October 2021 to December 2021 were evaluated from the French National Prospective Registry (PAFF). We evaluated 1890 patients with AF receiving DOACs (apixaban 55%, dabigatran 7%, and rivaroxaban 38%). Inappropriate dosing was noted in 18% of the population. Patients with appropriate dosing had less comorbidities: younger age (75 ± 10 vs. 82 ± 8 years old, P < 0.0001), reduced chronic renal failure (26 vs. 61%, P < 0.0001), and lower CHA2DS2VASc and HASBLED scores (3 ± 2 vs. 4 ± 3, P < 0.0001; 2 ±1 vs. 2 ± 2, P < 0.0001), respectively. In multivariate analysis, older age (P < 0.0001) and a higher CHA2DS2VASc score (P = 0.0056) were independently associated with inappropriate DOAC dosing. Among 472 patients (27%) treated with low-dose rivaroxaban or apixaban, 46% were inappropriately underdosed. Patients inappropriately underdosed were younger (82.3 ± 8.4 vs. 85.9 ± 5.9 years, P < 0.0001) with less chronic renal disease (47 vs. 98%, P < 0.0001). However, these patients had higher rates of prior haemorrhagic events (18 vs. 10%, P = 0.01), clopidogrel use (11 vs. 3%, P = 0.0002), and apixaban prescription (74 vs. 50%, P < 0.0001). CONCLUSION: Within this large registry, DOACs were associated with inappropriate dosing in 18% of cases. Independent predictors of inappropriate dosing were high CHA2DS2VASc scores and older age. Moreover, 46% of patients treated with low-dose DOACs were inappropriately underdosed and more frequently in patients treated with apixaban.

Very low levels of HDL cholesterol and atherosclerosis, a variable relationship--a review of LCAT deficiency.

A number of epidemiological and clinical studies have demonstrated that plasma high-density lipoprotein (HDL) level is a strong inverse predictor of cardiovascular events. HDL is believed to retard the formation of atherosclerotic lesions by removing excess cholesterol from cells and preventing endothelial dysfunction. Lecithin cholesterol acyltransferase (LCAT) plays a central role in the formation and maturation of HDL, and in the intravascular stage of reverse cholesterol transport: a major mechanism by which HDL modulates the development and progression of atherosclerosis. A defect in LCAT function would be expected to enhance atherosclerosis, by interfering with the reverse cholesterol transport step. As such, one would expect to find more atherosclerosis and cardiovascular events in LCAT-deficient patients. But this relationship is not always evident. In this review, we describe contradictory reports in the literature about cardiovascular risks in this patient population. We discuss the paradoxical finding of severe HDL deficiency and an absence of subclinical atherosclerosis in LCAT-deficient patients, which has been used to reject the hypothesis that HDL level is important in the protection against atherosclerosis. Furthermore, to illustrate this paradoxical finding, we present a case study of one patient, referred for evaluation of global cardiovascular risk in the presence of a low HDL cholesterol level, who was diagnosed with LCAT gene mutations.

Efficacy over time of a short overall atherosclerosis management programme on the reduction of cardiovascular risk in patients after an acute coronary syndrome.

INTRODUCTION: The prognostic significance of monitoring risk factors and adjusting treatments in patients after an acute coronary syndrome (ACS) is well documented. However, studies over the last few years show that secondary prevention objectives are rarely met. Prevention programmes are effective but their benefit is only partially maintained in long-term follow-up. AIM OF THE STUDY: To evaluate the efficacy of a global management programme for atherosclerosis (the CEPTA programme) on the long-term monitoring of cardiovascular risk factors, on adherence to treatment, and to compare the data of clinical events post-ACS with that contained in the scientific literature. PATIENTS AND METHODS: Six hundred and sixty consecutive patients were hospitalised three months after the occurrence of an ACS to evaluate residual risk factors, the atherosclerosis burden, and to undergo a treatment adjustment and a therapeutic and dietary education programme. We evaluated the impact of this long-term programme on the balance of risk factors, treatment maintenance and clinical events. At the end of an average follow-up of 20 months, 96.3% of patients were on antiaggregates, 86.0% were on beta-blockers or Verapamil, 62.4% were on angiotensin-converting enzyme inhibitors or angiotensin to receptor antagonists, 88.4% were on cholesterol-lowering medication and 75.5% were receiving a combination of beta-blocker antiaggregates and cholesterol-lowering drugs. Monitoring of LDL cholesterol and blood pressure was done in over 81 and 71% of patients, respectively. At 20 months of follow-up, total mortality was 3.6% and one cardiovascular event occurred in 12% of patients. In conclusion, this short programme following ACS is beneficial for the long-term management of cardiovascular risk factors and the sustainability of drug treatments.

Prevalence of metabolic syndrome after acute coronary syndrome and its prognostic significance.

Metabolic syndrome (MS) consists of a cluster of metabolic and hemodynamic disorders that promote the development of atherosclerosis and increase cardiovascular morbidity/mortality. We evaluated the prevalence and characteristics of MS after acute coronary syndrome (ACS) and the effect of intensive risk factor management on the morbidity/mortality associated with MS in a therapeutic cohort; 480 consecutive patients were summoned 3 months after an ACS for cardiovascular evaluation and management. Follow-up was carried out 16 months later. At 3 months after ACS, prevalence of MS was 20.8%, as assessed by criteria of the National Cholesterol Education Program Adult Treatment Panel III and 27.7% according to the definition of the International Diabetes Federation. The most common metabolic disorders were abdominal obesity, hypertriglyceridemia, and fasting hyperglycemia. Characteristics of the initial ACS showed no significant difference between the MS and non-MS groups. Atherosclerotic extent was greater in the MS group according to Adult Treatment Panel III. At follow-up, the MS and non-MS groups achieved optimal low-density lipoprotein cholesterol and blood pressure levels. During follow-up, there was an increase in total mortality in the MS group compared with the non-MS group (5.2% vs 1.4%, p <0.01) as assessed by International Diabetes Federation criteria; however, no difference in minor or major cardiovascular events was found between the 2 groups. In conclusion, MS was highly prevalent after an ACS, notably in young patients, and was not associated with a specific ACS presentation.