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More work should be dedicated to the science of implementing evidence-based medicine

The Philip Poole Wilson lecture, which will be presented at the Inaugural Session of Heart Failure 2017, will be delivered by Professor Faiez Zannad (Department of Cardiovascular Disease, and the Clinical Investigation Centre at the Academic Hospital in Nancy, France). 

Heart Failure

Entitled “Mineralocorticoid receptor antagonists: Navigating the landscape, from trials to clinical practice and to reverse translational science”, the lecture looked at how mineralocorticoid receptor antagonists (MRAs) can be better employed in clinical practice.

Speaking to Heart Failure 2017 Congress News, Prof. Zannad said that the European Society of Cardiology Eurobservational registries have consistently shown that class IA evidence-based lifesaving therapy is not being properly used.

“Successful application goes beyond simply drafting guidelines and measuring the width of the gap between guidelines and clinical practice. Misunderstanding and excessive concern about renin angiotensin system [RAS] inhibitors and MRA-related worsening renal function and hyperkalaemia are important barriers to the adoption of evidence-based practice.”

He added that insufficient promotion of the drugs by pharmaceutical companies acts in synergy with the lack of education about their application to hinder the use of MRAs in clinical practice.

“I believe we should encourage better education and implementation of the guidelines, possibly through appropriate disease management and/or telemedicine programmes. We are also working on home self-monitoring of congestion, renal function, and serum potassium to improve outcomes through enabling better use of RAS inhibitors and MRAs. The recent advent of new potassium binders might also help, although only if these are subjected to outcome trials with the objective that the preventive use of such agents may improve outcomes through the optimisation of MRA therapy.”

Prof. Zannad expressed disappointment at the failure to adopt trial results, despite the highest level of evidence, and strong recommendations in international guidelines.

“The most important development in my career in the management of heart failure has been the strong improvement in heart failure outcomes, with a three-fold decrease in all-cause death and a dramatic decrease in the rate of sudden death observed in trials for ACE [angiotensin converting enzymes] inhibitors, beta-blockers, MRAs, and more recently sacubutril-valsartan in heart failure with reduced ejection fraction [HFrEF]. But clearly, evidence generation is not enough. More work should be dedicated to the science of implementing evidence-based medicine.”

He cited the American Heart Association initiative Get With The Guidelines, which has not yet been replicated in Europe, as an example of how to put clinical trial results into practice, and added: “When I was on the board of the Heart Failure Association of the European Society of Cardiology, I encouraged the design and promotion of a European initiative (Aim High), which proactively promoted guideline and evidence implementation at the individual patient and physician levels.”

Prof. Zannad, who will receive a lifetime achievement award at the session, has had a long and distinguished career in heart failure. He highlighted his work with Professor Bertram Pitt (University of Michigan), which provided the evidence to establish MRAs as a Class IA therapy in HFrEF, as one of his greatest achievements. He also helped to design and conduct the landmark CIBIS beta-blocker trial.

He said: “Another achievement, which is much less visible and which left me very disappointed, was establishing the largest French heart failure disease management programme in my region of Lorraine. This cost-effectively decreased HF admissions and all-cause death. Unfortunately, an ill-guided decision by the Lorraine health authorities led to it being discontinued.”

Prof. Zannad pointed out that the history of MRAs reflected a typical reverse translational track, and said it was a nice example of how clinical science can inform basic science.

“Aldosterone and MRAs were discovered almost 40 years ago, long before the focus on renin angiotensin system antagonists. But it is only since the remarkable positive findings of the RALES trial, which was initiated simply on conceptual speculations, that interest in the basic science of mineralocorticoids has revived. Since then there have been many breakthroughs.”

He concluded: “We are still at the beginning of the MRA revolution. More advances will become possible with newer and better tolerated—possibly non-steroidal—MRAs, some of which are under development or entering early clinical trials.”

Inaugural Session
Saturday 29 April 17:40–19:00; room HUGO