Outcome Improvement of Patients with Heart Failure and Reduced Ejection Fraction: Has it Ended in the New Millennium?

This editorial refers to ‘Use of evidence-based therapy and survival in heart failure in Sweden 2003–2012’, by T. Thorvaldsen, published in this issue on pages 503–511. Survival of patients with heart failure (HF) seems to have improved over the last decades,1-3 specifically in patients with reduced ejection fraction (EF) as several trials have consistently demonstrated that medical treatment with angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), mineralocorticoid antagonists (MRAs), and beta-adrenergic blockers (BBs) improves the survival rate of patients with this clinical condition.4 Further, in selected patients with severe HF and reduced EF, the placement of implantable cardioverter defibrillators (ICD) with or without cardiac resynchronization therapy (CRT) is recommended as these device therapies can improve patient survival.4 This evidence has been widely incorporated into current guidelines that provide health professionals with recommendations for optimal medical care.4 In this context, the evaluation of changes in outcome profiles of patients in clinical practice was generally conducted using administrative databases which have the advantage of considering ‘real world evidence’ but with the limitation of having scarce clinical data, the most important of which is the possibility of distinguishing between patients with reduced or preserved EF.1, 3, 5 Thorvaldsen et al.6 analysed the large Swedish registry on patients with HF with the aim of assessing the use of contemporary evidence-based pharmacological and non-pharmacological treatments in patients with reduced EF (<30%) and the related survival between 2003 and 2012. The main messages of this effort can be summarized as follows: (i) the use of recommended drug treatments (ACE inhibitors, ARBs, and BBs) increased just slightly, being already elevated at the beginning of the observation period (2003); (ii) device therapies (CRT, ICD) increased significantly over this time period but with rates that in absolute terms remained really poor, showing a clear gap between guideline recommendations and actual use in clinical practice; (iii) as a consequence, short- and long-term survival rates did not significantly change from 2003 to 2012. We can conclude that, in a very educated population of cardiologists and general practitioners such as that of Sweden, all the possible improvements in the pharmacological therapy of patients with HF and reduced EF had already been implemented in the 1990s and nothing relevantly new has happened in the new century in terms of drug prescriptions. This observation reflects the paucity, in the last 15 years, of new evidence in terms of life-saving pharmacological treatments. The only exception has been ivabradine,7 but has been indicated only for reducing HF hospitalizations in selected patients in sinus rhythm and high heart rate, and the extension of MRA use to less severe patients, such as those in New York Heart Association (NYHA) class II.8 However, the recommendations regarding this new evidence were not incorporated in the guidelines until 2012,4 that is after the period of observation of the Thorvaldsen study.6 If the substantial similarity in drug treatment between 2003 and 2012 is understandable in the absence of new relevant evidence, it is difficult to explain why the guideline recommendations regarding devices were not substantially implemented in a context in which health professionals dealing with HF are generally very expert and appropriately updated from a cultural point of view, specifically in a country, such as Sweden, which is without apparent great restrictions in the use of medical resources. A different situation has been described for patients with acute myocardial infarction whose survival improved in Sweden over a similar time span with the implementation of updated therapeutic strategies, showing even a better survival profile when compared with that of UK.9 Unfortunately, Thorvaldsen et al.6 did not provide information regarding the specific indications or contraindications to the use of ICD and/or CRT but, even considering that advanced age and co-morbidities could be reasonable obstacles to device implantation, the gap between guideline recommendations and current practice needs to be narrowed. In this sense, training of health professionals, including general practitioners and nurses, who frequently manage the outpatient clinics in Sweden, should be focused not only on pharmacological treatments but also on the favourable evidence obtained with device therapy in severe patients with HF and reduced EF. Two other observations deserve a comment. First, the number of patients followed by nurse-led HF clinics significantly increased over time (from 32% in 2003–2005 to 53% in 2009–2012). The substantial similarity in survival rates observed in these different time periods suggests that this management approach did not result in a clear mortality benefit. However, it could be very interesting to see if this approach can have a favourable association with a reduction in HF hospitalizations, which is the major determinant of the burden of HF, including costs for healthcare systems both in the past and at present.5, 10-12 Second, if adherence to current guideline recommendations for drug treatment by Swedish physicians dealing with HF seems to be appropriate, there is an exception: treatment with statins. The prescription of these drugs increased significantly from 2003 to 2012 (from 41% to 54%) despite the clear evidence of no favorable effects in terms of reduction in either mortality or hospitalizations for HF demonstrated by two specific large scale randomized clinical trials, the CORONA13 and GISSI-HF14 trials. Owing to the fact that patients with HF are usually treated with a large number of drugs related to HF but also have frequent co-morbidities, adherence to drug treatment remains a relevant issue. For this reason, a careful consideration not only of the necessary prescriptions but also of those that can be avoided should be put into practice in the everyday activity of professionals managing patients with HF. In conclusion, the study by Thorvaldsen et al.6 underlines the fact that, in the Swedish context in which evidence-based medicine was and remains the rule, no further improvement in survival has been achieved in the last 10 years, in the absence of new life-saving treatments. It could be interesting to see how the implementation of the most recent evidence regarding (i) the broader indications of MRAs for mild symptomatic HF patients, (ii) ivabradine in selected patients, and (iii) the introduction in routine care of valsartan/sacubitril, recently demonstrated to be superior to enalapril,15 could have an impact on the survival profile of patients with HF and reduced EF. The lack of improvement in survival was also likely the result of the slow introduction into clinical practice of device therapy, which merits specific educational programmes and training not only for cardiologists but also for general practitioners and nurses who frequently have the responsibility to manage these patients. Finally, the study reinforces the concept that we need observational research after the results of clinical trials become available to understand how the messages from controlled research incorporated in the guidelines can be translated into the real world practice, the obstacles and the gaps in applying them, and the impact of these recommendations on the history of non-selected patients with HF in daily practice. Outside of the submitted work A.P.M. is member of Steering Committees of study supported by Bayer, Novartis and Cardiorentis. Conflict of interest: none declared.