© 2007 European Society of Cardiology
Filling the gap between guidelines and clinical practice in heart failure treatment — Still a far cry from reality
Sticares Cardiovascular Research Institute Rhoon, P.O. Box 882, 3160 AB Rhoon, The Netherlands Tel.: +31 10 485 51 77; fax: +31 10 485 48 33. E-mail address: w.j.remme{at}sticares.org
Heart failure (HF) treatment has progressed considerably over the last two decades. Whereas before that time only a symptomatic approach was possible, subsequent large controlled studies with angiotensin converting enzyme (ACE) inhibitors, beta-blockers, aldosterone inhibitors and angiotensin receptor blockers (ARBs) (in that order) have clearly demonstrated the potential of these neurohormonal antagonists to improve survival and clinical wellbeing of HF patients and to retard HF progression [1-9]. Moreover, when administered at an earlier, asymptomatic stage, some of these agents may prevent or delay the occurrence of symptomatic HF [10]. These beneficial effects are apparent with mono-therapy, but increase significantly in size when different types of agents are combined. Of importance, each of the neurohormonal antagonists mentioned above has a positive effect on aspects of cardiac remodelling, which is pivotal to the occurrence and progression of heart failure. This helps to explain why these agents beneficially affect the clinical syndrome (although anti-remodelling properties do not necessarily always translate into long-term clinical benefit).
Guidelines on the treatment of HF are invariably and by necessity based on the results from controlled clinical trials and subsequent editions reflect the available knowledge at the time of publication. Thus, the 1997 European Society of Cardiology (ESC) therapy guidelines indicated that ACE inhibitors were mandatory treatment for all stages of HF, including asymptomatic LV dysfunction, and recommended beta-blockers for mild-moderate HF [11]. The 2001 version broadened beta-blocker use to all stages of symptomatic HF and post-infarct LV dysfunction; added aldosterone antagonists in advanced HF and angiotensin receptor antagonists in case of intolerability to ACE inhibitors [12]. The 2005 update indicated that angiotensin receptor blockers should be added to ACE inhibitors in mild-moderate heart failure [13]. All along, it was stressed that in the absence of fluid retention ACE inhibitors, and not diuretics, should preferably be first-line therapy.
Importantly, each guideline also stipulated the optimal dose of each drug used for HF therapy, based on the target dosages used in the studies in which the specific drug in question was shown to be effective.
Guidelines are, correctly, considered to reflect (inter)national consensus on how best to treat a patient, based on expert opinion and reliable study data. Consequently, they should have an important impact on the management of HF patients in daily clinical care.
Since the ESC provided firm recommendations for ACE inhibitors and beta-blockers in the 1997 guidelines and for aldosterone antagonists and angiotensin receptor antagonists (in case of intolerance to ACE inhibitors) in the 2001 guidelines, there has been ample time to adapt daily practice. Therefore, one might expect that heart failure patients in Europe will have been treated in accordance with ESC guideline directives for years, particularly as in many countries the ESC guidelines have been translated or incorporated into local guidelines.
Unfortunately, this is not the case. In general, the uptake of the guidelines into clinical practice has been slow and the number of patients receiving recommended therapies is far from optimal.
Thus, in the IMPROVEMENT study which was performed in general practice in 1999-2000 the use of ACE inhibitors and beta-blocking drugs was 60% and 34%, respectively [14]; in the EuroHeart Failure Survey (cardiologist and internist practices, 2000-2001) 62% and 37% [15], and in the MAHLER study (cardiologists, 2001-2002) 69% and 53%, respectively [16]. ARBs were prescribed in 5%, 4.5% and 18%, respectively, in these three surveys.
Although comparisons between these studies are not really possible (different health care providers, different patient populations in terms of cardiac function, hospitalised versus out-patient treatment), by and large the percentages of patients on mandatory HF treatment (as suggested by the guidelines) between 1999 and 2002 appear insufficient. Has this changed in more recent years?
In this issue of the European Journal of Heart Failure, De Groote and co-workers ask whether the gap between clinical practice and guidelines in HF treatment is being filled [17]. In 2005, they performed a survey, the IMPACT-RECO study, amongst 519 French private cardiologists who entered 1917 patients with NYHA class II-IV HF and a left ventricular ejection fraction < 40% in the survey (one third had been hospitalised for worsening heart failure in the preceding 6 months). Mean age was 70 years and 74% were male. 71% received ACE inhibitors, 21% ARBs, 65% beta-blockers and 35% spironolactone. A combination of an ACE inhibitor or ARB and a beta-blocker was prescribed in 61%. The authors concluded that their survey showed an increase in prescription rates of recommended HF therapy, particularly of beta-blockers.
This is undoubtedly true when compared to a similar albeit smaller survey amongst the same population of French cardiologists performed in 1999, at least as far as beta-blockers are concerned [18]. Only 14% of patients were prescribed beta-blockers after inclusion, while 54% received ACE inhibitors. In 1999, guidelines did not suggest an ARB for patients with intolerance to ACE inhibition, but instead the combination hydralazine-nitrates, so in this case the comparison needs to be restricted to ACE inhibitors only.
A major caveat when comparing these two studies, is the fact that two of the three major beta-blocker trials in mild/ moderate heart failure were only reported in 1999 [5,6]. Hence, it may not be surprising that beta-blocker use was low in 1999.
How then does IMPACT-RECO compare to later studies? To answer this question, the studies used by the authors in Figure 2 of their article are not particularly useful, with the exception of the French Survey [18] mentioned above, due to different patient populations (LV dysfunction was not required in the CNCF [19], different types of physicians [20], or small sample size [21].
By contrast, the MAHLER study [16] is comparable to IMPACT-RECO, as only cardiologists (from 6 European countries, including France) participated and only symptomatic out-patients with objective evidence of LV dysfunction were included. The study was performed in 2001-2002 and was further comparable to the IMPACT-RECO study in terms of age, sex and severity of heart failure. In MAHLER, 87% of patients received an ACE inhibitor or ARB, 53% a beta-blocker and 28% an aldosterone antagonist. Thus, in the 4 years between both studies no difference in ACE inhibitor/ARB use (approximately 90% of patients in both studies), only a modest increase in beta-blocker uptake, and even less so in spironolactone, were found.
Can we say then, as suggested by de Groote et al., that the gap between guidelines and clinical practice is being filled?
Certainly not! Although there has been an improvement in medication use by French private cardiologists, the situation is still not optimal. It is unlikely that a better score can be reached in the use of RAS inhibitors (91% of the patients in IMPACT-RECO were on either an ACE inhibitor or an ARB); however, the number of patients on beta-blockade should further increase. Older age, an important determinant of beta-blocker use in the IMPACT-RECO study, need not be a major concern. Elderly heart failure patients tolerate beta-blockers well [22]. Furthermore, there is a misconception that bronchospasm often occurs with beta-blockade in heart failure, although this may depend on the type of beta-blocker used [23].
Also, the use of aldosterone antagonists is still too low in IMPACT-RECO (34.5% in NYHA class III/IV patients). One can hardly argue that this reflects a major improvement in heart failure therapy!
Finally, and possibly the major concern with regard to uptake of guideline recommendations into clinical practice, there was considerable under-treatment in terms of dosages used. This is a frequent observation in heart failure surveys and IMPACT-RECO is not different. The fact that over time there is no sign of improvement in this regard (particularly with beta-blockade) is worrying. Arguably there is no point in putting as many patients as possible on mandated therapy if dose levels remain too low to know with a reasonable certainty that they are effective.
The clinician's concern about adverse effects and the often lengthy time needed for up-titration are the major obstacles in reaching target doses in stable heart failure patients, rather than real intolerance to a drug. Most likely, it is perceived as safer to stay at the lower dose level and not to venture to those levels which may (incorrectly) be perceived as dangerous. However, with exceptions, adverse effects can be overcome in different ways during careful up-titration. It is questionable, though, whether this is understood by all clinicians.
In the end, it is all a question of education.
Doctors need to understand the importance of prescribing the medication shown to be beneficial in large and diverse populations of heart failure patients at the required dosages, and to understand the realistic adverse effects they may encounter in this process and how to cope with these effects. Guidelines have been written for this purpose. Although a doctor may decide not to act according to guideline recommendations in an individual patient, the gap between these guidelines and clinical practice, such as it exists today, will have to be closed eventually.
It may take a while, though, if ever...
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