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Familial Hypercholesterolemia (‘FH’) is the most prevalent genetic cause of premature atherosclerotic cardiovascular disease (ASCVD). FH has an estimated prevalence of 1:300 in the general population in the Netherlands. FH is characterized by lifelong elevation of LDL cholesterol, resulting in a profoundly increased risk of coronary heart disease (CHD) and premature death. Early identification of FH and intensive LDL cholesterol management are essential to minimize the lifetime cumulative cholesterol burden and associated risks. FH is inherited. Typically, parents with one pathogenic mutation have a 50% chance of passing down the condition to each child. Therefore, it is essential to screen first degree relatives (children, parents, brothers & sisters) of an individual diagnosed with FH, to detect other family members who may have inherited FH. LEEFH network In the Netherlands we have long track record with FH index identification, cascade screening of first degree relatives and associated research activities. Stichting LEEFH support healthcare professionals pro-actively to pursue cascade screening, aiming to identify FH-patients as early as possible. LEEFH works in a voluntary network with 39 hospitals (LEEFH centres) to optimize FH care and cascade screening. Over the years, an active database has been built up with approximately 7,000 family pedigrees and more than 37,000 FH positive tested patients. Annually, we detect ~ 300 FH+ indexes (new FH families) and 500 FH+ family members by cascade screening. A unique example of early prevention. The Research LEEFH supports research activities in the field of FH detection and treatment with its acquired knowledge, database and network. Recent examples of this include FH identification via central laboratory data, electronic health records and general practitioners. We also participate in research projects with other genetic disorders in order to further improve cascade screening through knowledge sharing (for example in the consortium ‘eCG Family Clinic’ (e-Cardiovascular Genetics Family Clinic). The Orgin The LEEFH network is a voluntary partnership since 2013. 39 hospitals are now affiliated. Each hospital (LEEFH center) has a number of healthcare professionals with a great deal of knowledge and affinity with FH. The LEEFH network aims to prevent (unnecessary) cardiovascular diseases by a) detecting FH family members through cascade screening and b) creating more awareness about FH. We do a lot of knowledge sharing about FH, both among ourselves and also through regional meetings with families and general practitioners. We have signed network agreements with ‘who’ does ‘what’ and ‘when’ in the cascade screening . The aim is to inform and support each family in the right way in the cascade screening. The DNA diagnostics are carried out by the Amsterdam UMC. Application forms and test packages are available via Stichting LEEFH.

Digoxin is the oldest, market-authorized drug for heart failure (HF), and very cheap. A large trial with digoxin, the DIG trial, executed in the early nineties revealed a highly significant reduction in HF hospitalizations, but no effect on mortality. A post-hoc analysis of the DIG trial suggests that low serum concentrations of digoxin may not only improve HF hospitalizations but also mortality in chronic HF patients. To validate these findings, a prospective, randomized, placebo-controlled trial is required to redefine the role of digoxin in modern HF treatment. The Focus The primary objective of this study is to investigate whether low-level digoxin (targeting serum concentrations of 0.5-0.9 ng/mL), compared to a placebo, reduces (repeated) HF hospitalizations, (repeated) urgent HF hospital visits, and cardiovascular mortality when added to standard guideline-recommended therapies in chronic HF patients with reduced or mid-range ejection fractions (LVEF ≤50%). The Research This proposed trial is a national, multicenter, randomized, double-blind, placebo-controlled clinical trial involving 982 chronic HF patients aged ≥18 years, classified as NYHA II to ambulatory IV, LVEF ≤50%, and specific serum NT-proBNP concentrations based on rhythm and recent HF hospitalization status. Patients must also be on guideline-recommended therapies. The study population includes at least one-third with atrial fibrillation (AF) and one-third women to represent the real-life HF population. Patients were randomized to receive either a low-level digoxin or a placebo in a double-blinded manner. Digoxin Teva will be administered orally, starting at doses of 0.2mg or 0.1mg (based on age, renal function, and concomitant medication). No loading dose is given to the placebo group. After 4 weeks of evaluating medication (digoxin or placebo), concentrations will be measured. Dose adjustments will be made if needed to reach the target serum digoxin concentration range of 0.5-0.9ng/mL. The outcomes in reducing adverse cardiovascular events in patients with chronic heart failure of low-dose digoxin will be compared to the outcomes of the placebo. The origin This study was funded as part of the Dutch Heart Foundation's collaboration with the ZonMw GGG program on Good Use of Medicines (Goed Gebruik Geneesmiddelen) for better treatment of heart failure and atrial fibrillation, which was one of the 5 priority's that the Dutch Heart Foundation set in 2014. The DECISION study involves 38 hospitals and is led by cardiologists from UMC Groningen and the WCN.