Keynote Message
Much progress has been accomplished over the last 30 years in the pharmacotherapy of human heart failure (HF). However, this is mainly limited to chronic HF with reduced ejection fraction (HFrEF). Evidence of benefit in HFrEF is of high level and based on multiple outcome trials (Level of evidence A), leading to strong grade of recommendations (Grade 1) in international guidelines. Angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) will soon be replaced by valsartan-sacubitril, a hybrid therapy comprising an ARB and a neprylisin inhibitor, which is shown to be more effective than ACEi (enalapril) in a recent landmark trial (PARADIGM-HF). Beta-blockers are the second pillar of therapy in HFrEF, and mineralocorticoid receptor antagonists (MRA) the third one, all based on high level of evidence for reducing CV mortality and HF admission. Ivabradine, a heart rate slowing agent, is grade II b level on the recent set of guidelines. However, despite being class IA guideline therapies, excessive perceived concern about safety hinders seriously optimal use in daily practice, depriving patients from such life saving therapy. Education, home monitoring and disease management programs are essential and help improve effective implementation and outcome.
Unfortunately, treatment of HF with preserved ejection fraction (HFpEF), which prevalence is ever rising as to become higher than that of HFrEF, is still empirical, relying only on better management of co-morbidities and risk factors, such as better control of hypertension and diabetes. All trials, with therapies effective in HFrEF, have been negative so far in HFpEF. One exception may be the MRA spironolactone, where some evidence suggests that it might be beneficial.
Another disappointing area is acute HF leading to hospital admission, the most common cause of admission in subjects more than 65 years of age and, together with cardiovascular death, source of the highest disability and socio-economic burden. None of the many trials is positive. Few medications add little to the decongesting effect of diuretic and nitrate vasodilator therapy. No therapy is associated with morbidity - mortality benefit. Therefore, the best treatment of acute HF is preventing it by the optimal use of chronic HF therapy.
Heart failure remains a very fertile area of investigation. Currently, many innovative compounds with various mechanisms of action are undergoing an extensive trial program.
Key References
1. Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, Falk V, González-Juanatey JR, Harjola VP, Jankowska EA, Jessup M, Linde C, Nihoyannopoulos P, Parissis JT, Pieske B, Riley JP, Rosano GM, Ruilope LM, Ruschitzka F, Rutten FH, van der Meer P; Authors/Task Force Members. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. European Heart Journal. 2016;37:2129–2200. doi: 10.1093/eurheartj/ehw128.
2. Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Colvin MM, Drazner MH, Filippatos GS, Fonarow GC, Givertz MM, Hollenberg SM, Lindenfeld J, Masoudi FA, McBride PE, Peterson PN, Stevenson LW, Westlake C. 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Journal of the American College of Cardiology. 2017, pii: S0735-1097(17)37087-0. doi: 10.1016/j.jacc.2017.04.025. [Epub ahead of print] PubMed PMID: 28461007.