IN CONTROL II

In the past decade, there has been significant progress in understanding sex- and gender-based differences in cardiovascular diseases (CVD). However, this knowledge remains scattered across medical literature, highlighting the need for a centralized platform accessible to healthcare professionals, scientists, policymakers, and patients. The IMPRESS consortium aims to establish a knowledge platform focused on gathering, summarizing, and prioritizing existing knowledge related to sex- and gender-specific aspects of CVD. This initiative seeks to promote the implementation of existing knowledge into clinical practice, identify knowledge gaps, and inform policymakers about areas requiring additional attention. In substantial portions of women with symptoms of myocardial ischemia, obstructive disease in the epicardial coronary arteries is absent. Currently, such women undergo multiple diagnostic tests, which do not always result in a conclusive diagnosis. IMPRESS seeks to reduce missed and delayed diagnoses of heart diseases in women, improving cardiovascular care outcomes nationwide. The knowledge platform will serve as a national resource, fostering collaboration and supporting the adoption of sex- and gender-sensitive practices in cardiovascular medicine. The Research IMPRESS consolidates existing knowledge, fosters research, and implements findings into practice wherever possible (for example by creating a Decision Support Tool for primary care and for cardiologists). Within the IMPRESS consortium, the following studies are being conducted: Delphi study: delayed or missed diagnosis of heart disease Silent heart attacks: causes, symptoms, and risk factors of silent myocardial infarctions UMCU-IMPRESS pilot study: undetected coronary microvascular disease (CMD) Peripheral-Flow: LASCA technique in CMD Dutch registry of coronary function tests   The origin In the past decade, the understanding of sex- and gender differences in CVD has considerably improved. However, relevant evidence is scattered throughout the medical literature. There is a need to make this information easily accessible to health care professionals, scientists, policy makers and patients. Implementation of existing knowledge in clinical practice will then be promoted, knowledge gaps identified, and policy makers informed on the areas that need additional attention. This is also of high importance to the Dutch Heart Foundation, which therefore funded the IMPRESS consortium; a collaboration between several DCVA partners; the Nederlandse Vereniging voor Cardiologie (NVVC), WCN, Netherlands Heart Institute (NLHI), ZonMw and the Dutch Heart Foundation, supported by the DCVA.  

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.