As heart failure (HF) emerges as one of the key problems of modern cardiology, numerous articles are being published that report novel and intriguing results. The next step is to select findings with irrefutable clinical impact, based on large, randomised, clinical trials and to further implement them into clinical practice. Therefore, in order to help physicians treating HF patients, it is crucial to develop guidelines that are evidence-based and provide compelling information on how to select the optimal strategy for HF management.
Cardiology societies in Europe and the US have already addressed
such a need by issuing regular updates of the Guidelines for Heart Failure
Diagnosis and Treatment. The most recent update of the European Society of
Cardiology (ESC) guidelines was published in 2005, and the task force is now
finalising the new, comprehensive version, which will be presented at this
year’s ESC meeting in Munich. In this article, only selected aspects of
pharmacological therapy will be briefly discussed.
Guidelines on Pharmacological Treatments
Recent ESC guidelines clearly state that four classes of drugs
that target neuroendocrine activation, i.e. angiotensin-converting enzyme
inhibitors (ACEi), angiotensin-receptor blockers (ARBs), beta-blockers and
aldosterone antagonists reduce mortality and morbidity in HF.
In general, patients should receive a combination of ACEI and beta-blockers, whose doses need to be up-titrated to either those levels recommended by the guidelines, or to the maximal level tolerated. This approach results in a reduction in mortality and morbidity and improvement in clinical status. Intolerance is rare, provided that patients are carefully followed and comprises for ACEI – cough, symptomatic hypotension, and renal dys function, and for beta-blockers – hypotension, bradycardia and worsening of HF.
ARBs are recommended in symptomatic patients intolerant to ACEI,
and can be considered in combination with ACEI and beta-blockers in patients
who remain symptomatic to reduce cardiovascular mortality, hospital admissions
and improve symptoms. Use of such triple combinations may cause hypotension and
renal dysfunction and requires careful monitoring of blood chemistry.
The guidelines recommend aldosterone antagonists in patients remaining in advanced HF (NYHA III-IV) in addition to ACEI, beta-blocker and diuretics, but whether they exert favourable effects in mild HF needs to be established.
Renal dysfunction, hyperkalaemia and antiandrogenic effects for
spironolactone (mainly gynaecomastia) are the main causes of intolerance.
Monitoring of renal function and electrolytes is recommended once they are
introduced into therapy.
Diuretics are essential when fluid overload is present. However,
there are no controlled, randomised trials investigat ing whether diuretics
affect patient outcome. Results of recently published studies raised concerns
that high doses of diuretics may be related to impaired outcome. Digoxin is
also commonly used in HF patients with concomitant atrial fibrillation and may
reduce HF hospitalisations and improve symptoms.
The guidelines did not make any recommendation as to whether statins should be used in HF – when they were published, no data from randomised clinical trials existed. Only recently, the results of the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA) has demonstrated that rosuvastatin does not reduce the primary composite outcome of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke or the number of deaths from any cause in older patients with systolic HF, although it reduces the number of cardiovascular hospitalisations.
There was no concern regarding the safety of rosuvastatin in HF.
Translating these slightly surprising results into clinical practice, it seems
acceptable to continue with statin prescription for patients with ischaemic HF
and left ventricular systolic dysfunction, until future studies shed more
Other Treatment Options
Other pharmacological treatments are recommended in specific situations, i.e., in those with HF and angina nitrates and amlodipine, which can safely relieve angina symptoms; for atrial fibrillation, amiodarone is the drug of choice and other antiarrhythmics should be avoided; as these patients are at the highest risk of thromboembolism, they should be considered for anticoagulation. Cardioverterdefibrillators and cardiac resynchronisation pacemakers are also recommended in selected HF patients.
Practising physicians ask whether adherence to the guidelines
translates into better outcomes in real life. In the MAHLER sur vey (Medical
Management of Chronic Heart Failure in Europe and its Related Costs) the impact
of implementation of ESC treatment guidelines on disease outcome was evaluated.
This survey, which comprised a population of 1410 HF patients, showed that
proper adherence to guidelines is a strong predictor of less HFrelated and all
cardiovascular hospitalisations in practice. A similar study from Germany
concluded that adherence to ESC guidelines was a strong predictor of better
survival and the benefit was irrespective of sex, age and left ventricle
Gap Between HF Guidelines and Clinical Practice
Despite the benefit of adherence to guidelines and European endorsement of them, all reported registries show clinical practice continues to lag behind recommendations. The Euro-Heart Failure Survey II was performed between October 2004 and August 2005 in 133 European centres to characterise patients hospitalised with acute HF.
On admission, of those already diagnosed with HF, 63% were receiving ACEi, 38% aldosterone antagonist, but only 46% betablockers and 10% ARB. On discharge, 72% were treated with ACEi, 10% with ARB, 59% with beta-blockers and 54% with aldosterone antagonist. Patients were followed for up to one year and the rate of use of lifesaving therapies in HF was fairly constant (at the end of year: 70%, 15%, 70%, 40% for AECi, ARB, beta-blockers and aldosterone-antagonist, respectively: data not published).
However, the study was performed in experienced hospital
centres, and therefore may overestimate the real use of lifesaving therapies in
non-specialist environments, in which most HF patients are treated.
Particularly, it may be the case for combined therapy – though it is estimated,
that less than half of HF patients are treated with an optimal combination of
ACEi and beta-blockers. Also, as the current use of ACEi and ARB is already
fairly high in Europe, the rate of beta-blocker use is still unacceptably low.
Arguments Against Guidelines Persist
Many physicians are still reluctant to start beta-blockers in HF patients. Even specialists are using too-low dosages of life-saving medications, as in everyday clinical practice for an elderly, vulnerable patient with many co-morbidities, uptitration of beta-blockers or ACEi may even be dangerous.
Other arguments against the application of high doses and combination
of life-saving therapies may be that the guidelines never address all the
individual aspects such as relative contra-indication, poor tolerance,
coexisting co-morbidities, other medications used by a patient, etc., that may impact
therapy. However, many studies refute this, as applying a thorough clinical check-up
over long-term follow-up together with a rule “start low, go slow” usually
minimises side-effects and risks of intolerance and successfully up-titrate a