REVIEW OF THE NEW ESC GUIDELINES FOR THE

European Heart Journal Supplements (2005) 7 (Supplement J), J15–J20 doi:10.1093/eurheartj/sui058

Aldo P. Maggioni* ANMCO Research Centre, Via La Marmora 34, 50121 Firenze, Italy

KEYWORDS Treatment guidelines; Pharmacological management; Heart failure

Chronic heart failure (CHF) is associated with a high burden of mortality and morbidity and is the leading principal hospital diagnosis among older adults. As a result of the complexities associated with this condition and the occurrence of asymptomatic disease and comorbidities, heart failure patients are often misdiagnosed or underprescribed effective medications. The European Society of Cardiology (ESC) guidelines for the diagnosis and treatment of CHF, were developed to provide clinicians with practical, evidence-based guidance on the optimal management of patients with this condition. The guidelines have recently been updated to incorporate diagnostic, safety, and efficacy data from large-scale clinical trials that were not available for the development of earlier guidance documents. This article discusses five pharmacological strategies for the management of CHF (angiotensin-converting enzyme-inhibitors, beta-blockers, diuretics, aldosterone antagonists, and angiotensin-II type-1 receptor blockers) in the context of the 2005 ESC CHF guidelines. Data from recent largescale, randomized, placebo-controlled trials are discussed and the updated guidelines are compared with recommendations from the earlier 2001 guidance document.

Introduction Chronic heart failure (CHF) is associated with a high burden of mortality and morbidity, reduced quality-oflife, and increasing healthcare costs.1–4 It is recognized as the leading principal hospital diagnosis among older adults5 and is associated with a poorer 5-year survival rate than some of the most common malignancies (bowel, ovarian, prostate, bladder, and breast cancers).4 In the US Framingham study, 5-year CHF-related mortality approached 50%,2 whereas a study in the Scottish population indicated that 75% of patients admitted to hospital with a diagnosis of CHF died within 5 years.4 As CHF is largely a disease of old age, occurring in approximately 10% of elderly adults,2,3 it is becoming increasingly prevalent with the gradual ageing of the global population.1 Estimates suggest that as many as 30 million adults living within the 47 member states represented by the European Society of Cardiology (ESC)— with an estimated total population of approximately

* Corresponding author. Tel: þ39 0 55 500 1703; cfax: þ39 0 55 583400. E-mail address: [email protected]

1000 million—may be affected by CHF,6 whereas nearly 1 million new cases are diagnosed worldwide each year.6 Such large patient populations present a substantial economic burden to healthcare providers. A UK study undertaken in 1994 indicated that CHF imposed diagnostic and management costs on the National Health Service of approximately £360 million (E533 million) in that year, representing a financial burden similar to those of asthma and stroke combined.2 CHF is a complex condition that can result from a number of disease processes and is frequently associated with asymptomatic disease, atypical symptoms, and the presence of comorbid conditions.2,7–11 These factors present a considerable challenge to physicians in terms of accurate diagnosis and management, and contribute to the misdiagnosis of patients and the underprescription of evidence-based treatments.9,12 Evidence-based medicine represents the most effective means of ensuring that patients receive high-quality care and appropriate pharmacological management, and the development of international treatment guidelines, when appropriately implemented, provides the ideal vehicle for the widespread dissemination of such

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Review of the new ESC guidelines for the pharmacological management of chronic heart failure

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The ESC 2001 guidelines for the management of CHF The 2001 ESC guidelines recommended that all patients with severe CHF [New York Heart Association (NYHA) class IV] should receive pharmacological treatment with an angiotensin-converting enzyme-inhibitor (ACE-I), a beta-adrenergic antagonist, and spironolactone, together with a diuretic for symptomatic relief of fluid overload.8 In patients with NYHA class I–III CHF, the guidelines advised the administration of an ACE-I and a beta-blocker together with a diuretic, if the patient showed signs of fluid retention. Patients intolerant to ACE-I should be considered for alternative therapy with an ARB, whereas those intolerant to beta-blockers should be administered concurrent ARB and ACE-I therapy.8 Thus, the guidelines strongly advised the prescription of ACE-I as a first-line therapy (Class of recommendation I, level of evidence A ) in conjunction with diuretics and beta-blockers for all patients with symptomatic CHF and left ventricular systolic dysfunction (LVSD). However, the recommendations remained cautious regarding the efficacy of ARBs in CHF. Physicians were advised that the safety of adding ARBs to a combined ACE-I/beta-blocker treatment regimen required further investigation and that the efficacy of ARBs in reducing mortality, in comparison with ACE-I, was unknown.8 The following sections present recommendations from the 2005 guidelines for the use of five key pharmacological therapies in the management of CHF: ACE-I,

diuretics, beta-blockers, aldosterone antagonists, and ARBs (Figure 1 ). The recommendations are discussed in relation to earlier guidance from the 2001 guidelines.

The 2005 ESC guidelines: revised recommendations for pharmacological management of CHF Angiotensin-converting enzyme-inhibitors Numerous clinical trials have shown that ACE-I confer considerable, sustained survival benefits in patients with CHF and LVSD16 and are associated with reductions in all-cause mortality, disease progression, and hospitalizations in most CHF patient populations.17–19 As a result, ACE-I were recommended in the 2001 guidelines as a first-line therapy to improve survival in CHF patients with LVSD (NYHA II–IV) and as an agent whose continued use should be considered in patients who are or become asymptomatic (NYHA class I).8 Few new data have become available concerning ACE-I since the development of the 2001 guidelines, the major publications of note since that time including a metaanalysis evaluating the benefits of ACE-I according to gender, race, and diabetic status18 and an ESC expert consensus document concerning ACE-I in cardiovascular (CV) disease.19 Thus, the indication for these agents has undergone no changes in the 2005 guidance document. ACE-I are recommended as a first-line therapy in symptomatic and asymptomatic patients with reduced left ventricular (LV) systolic function (EF , 40–45%) to reduce hospitalizations and improve survival, symptoms, and functional capacity (Class of recommendation I, level of evidence A ).15 They are also recommended as the initial therapy in patients without fluid retention, in conjunction with diuretics in patients with fluid retention (Class of recommendation I, level of evidence B ) and to improve survival/reduce hospitalizations in patients with transient symptoms of CHF or transient CHF symptoms following acute myocardial infarction (AMI) (Class of recommendation I, level of evidence A ) (Figure 1 ).15 In patients with diastolic heart failure (HF), ACE-I may have short- and long-term benefits through their antihypertensive effects, whereas in elderly CHF patients, they are effective and well-tolerated.15

Diuretics Because of their efficacy in controlling the symptoms of congestion, diuretics are widely accepted as a beneficial therapeutic strategy in CHF management and remain a major element in the treatment of this condition.20 In the 2001 guidelines, diuretics were recommended as first-line treatments that are essential for the symptomatic relief of fluid overload.8 Few additional data have become available concerning the efficacy of diuretics in CHF since the development of the 2001 guidance document and the indication for this drug class remains largely unchanged in the revised guidelines (Figure 1 ).15


data to practising physicians. The ESC guidelines for the diagnosis and treatment of CHF, compiled in 1995 and 1997, respectively, and combined and updated in 2001, were developed to provide physicians and other healthcare professionals with practical, evidence-based guidance on the optimal diagnosis and management of CHF patients.8,13,14 These guidelines have recently undergone further revisions to incorporate data from ESC Task Force reports and to reflect the findings of recent large-scale clinical trials.15 The updated 2005 guidelines incorporate diagnostic, safety, and efficacy data that were not available for the development of earlier guidance documents. They also pay particular attention to the management of CHF patients with preserved left ventricular ejection fraction (PLVEF), a patient subgroup that remains poorly characterized in terms of epidemiology and optimal treatments and for whom limited data are available on which to base treatment recommendations.7,11,15 This article will discuss pharmacological strategies for the optimum management of CHF in the context of the revised 2005 guidelines and will compare their updated guidance with recommendations from the 2001 guidelines. Particular attention will be paid to angiotensin-II type-1 receptor blockers (ARBs), which are given stronger recommendations in the revised guidance document owing to the publication in recent years of supportive safety and efficacy data.

A.P. Maggioni

ESC guidelines for the management of CHF

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Diuretics are essential for symptomatic treatment of fluid overload and may result in rapid improvement in dyspnoea and increased exercise tolerance (Class of recommendation I, level of evidence A ).15 They should always be administered in combination with ACE-I and beta-blockers, if tolerated (Class of recommendation I, level of evidence C ); potassium-sparing diuretics should only be prescribed if hypokalaemia persists despite ACE inhibition, or in severe HF despite combined ACE inhibition and low-dose spironolactone (Class of recommendation I, level of evidence C ).15 In patients with diastolic HF, diuretics may be necessary during episodes of fluid overload but should be used with caution; in elderly CHF patients, they may be less effective and associated with reduced renal function.15 Diuretics were introduced in CHF management before the introduction of large-scale clinical trials and no controlled, randomized trials have assessed their effects on symptoms or survival. Consequently, uncertainty remains concerning their precise therapeutic efficacy as long-term treatments, within polytherapeutic strategies and in the management of systolic vs. diastolic HF.21 However, a meta-analysis performed since the development of the 2001 guidelines has indicated that, compared

with control groups, diuretics are associated with a reduced risk of worsening HF, improved exercise tolerance and a trend towards reduced mortality;20 these findings have been incorporated into the revised guidance document.15

Beta-blockers It is well-established that beta-blockers are associated with considerable benefits in CV disease;22 however, physicians’ perceptions that beta-blockers are contraindicated in CHF and concerns over adverse effects during titration have resulted in a general reluctance to prescribe beta-blockers in CHF, particularly to elderly patients.22–24 Substantial evidence is now available to support the efficacy of beta-blockers in CHF, including elderly subjects (Figure 1 ).23 In their meta-analysis, Lechat et al. 24 concluded that the addition of a beta-blocker to conventional treatments in CHF was associated with reductions in the risks of morbidity/mortality (37%) and hospitalization for CHF (41%), together with haemodynamic and symptomatic improvements,25 and data from subsequent clinical trials support these findings.26–28 On the basis of such


Figure 1 Pharmacological therapy of symptomatic chronic heart failure due to systolic left ventricular dysfunction. (Reproduced from Swedberg et al. 15 by permission of Oxford University Press.)

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Aldosterone antagonists Spironolactone was the only aldosterone antagonist to be recommended for optimal patient management in the 2001 guidelines. In addition to ACE-I and diuretics, this agent was recommended to improve survival and reduce morbidity in patients with advanced HF (NYHA class III–IV). However, physicians were advised that the onset of gynaecomastia might require the cessation of spironolactone therapy.8 Since the publication of the 2001 guidelines, safety and efficacy data have been published concerning the use of eplerenone for the management of LV hypertrophy (4-E LV hypertrophy study)30 and AMI complicated by LVSD and HF [EPHESUS study (Eplerenone Post-acute Myocardial Infarction Heart Failure Efficacy and Survival Study)].31 In the 4-E study, co-administration of eplerenone and enalapril in patients with essential hypertension and LV hypertrophy was associated with significant reductions in LV mass and provided additive benefits in terms of blood pressure reduction and albuminuria.30 Data from EPHESUS revealed that, compared with optimal medical therapy alone, eplerenone treatment reduced the relative risks of hospitalization for HF [relative risk reduction (RRR), 15%; P ¼ 0.03], sudden death (RRR, 11%; P ¼ 0.03) and death from any cause or any hospitalization (RRR, 8%; P ¼ 0.02). Eplerenone treatment was associated with an increased risk of serious hyperkalaemia (5.5% vs. 3.9% with optimal

medical therapy; P ¼ 0.002) but no deaths attributable to hyperkalaemia.31 The revised guidelines reflect these study data and recommend the use of aldosterone antagonists in the management of advanced HF (NYHA III–IV). Aldosterone antagonists are recommended to improve morbidity and mortality in patients with advanced HF (in addition to ACE-I, beta-blockers, and diuretics) and in post-MI patients with HF and LVSD (in addition to ACE-I and beta-blockers) (Figure 1 ). Clinicians are also warned that patients receiving these agents should be monitored carefully to minimize the risk of severe hyperkalaemia.15 There is currently no evidence to suggest whether aldosterone antagonists are effective in patients with NYHA class I–II HF. As a result, extending the guidelines concerning the use of these agents in less symptomatic clinical situations remains a challenge.

Angiotensin-II type-1 receptor blockers Perhaps, the greatest amendments to the updated guidelines concern the use of ARBs in CHF management following the publication of data from the VALIANT (VALsartan In Acute Myocardial iNfarcTion)32 trial and, in particular, the CHARM (Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity) trial programme.33 In the 2001 guidelines, ARBs were given a cautious recommendation as a symptomatic treatment that might be considered in ACE-intolerant patients or, in combination with ACE-I, in patients with worsening HF.8 The guidelines advised that ARBs are associated with fewer side effects than ACE-I but that superiority over ACE-I had not been shown and that negative interactions with double (ARB þACE-I) or triple (ARB þ ACE-I þ betablocker) therapy regimens may occur.8 These recommendations were based largely on findings from the ELITE (Evaluation of Losartan In The Elderly) and ELITE II (Losartan Heart Failure Survival Study) studies, which provided only limited efficacy and safety data concerning ARBs.8,34,35 Early data from Val-HeFT36 suggested a beneficial effect of adding an ARB to an ACE-I plus betablocker-based regimen in terms of a combined morbidity and mortality endpoint but demonstrated no favourable effect in terms of all-cause mortality. The more recent publication of findings from VALIANT and CHARM provides greater support for the efficacy of ARBs in post-MI/LVSD and CHF, respectively, and has enabled a re-evaluation of their role in patient management.32,33,37–41 Data from VALIANT suggested that VALSARTAN is as effective as captopril in patients at high risk for CV events post-MI.32 In CHARM, candesartan was associated with a 9% reduction in all-cause mortality (P ¼ 0.055; covariate adjusted hazard ratio 0.90; P ¼ 0.032) due to 12% fewer CV deaths overall (CHARM-Overall).33 Candesartan also conferred a 12% reduction in all-cause mortality in patients with low EF (CHARM Low LVEF)41 and significant reductions in CV death and hospital admissions for CHF in ACE-intolerant patients with LVSD (CHARM-Alternative; rate of CV death/hospitalization: candesartan, 33%;


data, the 2001 guidelines recommended the use of bisoprolol, metoprolol controlled release/extended release (CR/XL), or carvedilol for the treatment of patients with stable, mild, moderate, or severe HF (NYHA II–IV) and in patients with LVSD with or without symptomatic HF following AMI.8 Although the varying pharmacological profiles, and in some cases efficacy of the beta-blockers were acknowledged at the time of development of the 2001 guidelines, a class effect had not been established.8 To address this issue, the COMET (Carvedilol Or Metoprolol European Trial) trial investigators randomized more than 5000 CHF patients to metoprolol or carvedilol and showed a 17% greater reduction in total mortality with carvedilol, suggesting the presence of agent-specific effects.29 The COMET data indicated that dosage and choice of betablocker may impact considerably on patient outcomes.22 On the basis of such findings, the revised 2005 guidelines state more strongly the beneficial effects of betablockers on outcomes in CHF—counselling that even low-dose beta-blocker therapy is superior to treatment without a beta-blocker—and advise of the differences in clinical effects between agents, recommending only the administration of bisoprolol, carvedilol, metoprolol CR/ XL, or nebivolol (Class of recommendation I, level of evidence A ).15 The revised guidelines also emphasize the benefits of beta-blockers in LVSD, recommending these agents as the only drug class that significantly improves LVEF. The additive benefits of a combined ACE-I and beta-blocker-based regimen are also emphasized.15

A.P. Maggioni

ESC guidelines for the management of CHF

Management of the elderly and patients with HF and preserved LVEF In the management of elderly CHF patients, the 2005 guidelines remain cautious because of a lack of trial data and concerns over comorbidities and altered pharmacokinetic and pharmacodynamic properties of CV drugs in these patients. Healthcare practitioners are advised that ACE-I, ARBs, and beta-blockers are effective and well-tolerated in elderly patients if administered with caution and monitored with care.15 Owing to a lack of strong supportive data, no firm conclusions are drawn regarding optimum therapies for patients with PLVEF in the new guidelines. As in the 2001 guidelines, physicians are advised to prescribe beta-blockade to lower heart rate and increase the diastolic period, and verapamil-type calcium antagonists, ACE-I and diuretics are also recommended.8,15 In addition, it is suggested, based on data from CHARMPreserved,39 that high-dose ARB therapy may be introduced to reduce requirements for hospitalization.15

Summary The ESC 2001 guidelines for the diagnosis and treatment of CHF provided clear recommendations concerning the optimal use of pharmacological agents in CHF management, based on clinical trial evidence available at the time of development. The 2005 revision of the guidelines has sought to refine, improve, and update these diagnostic and treatment recommendations to enable clinicians to achieve more effective control of symptoms, improvements in quality-of-life and reductions in the rates of mortality and hospitalization. It is to be hoped that widespread dissemination of the 2005 guidelines and their implementation in routine clinical practice will help to address the high burden of CHF and improve prognosis and quality-of-life for affected patients.

Acknowledgements This work was supported by an unrestricted educational grant from Takeda Pharmaceutical Company Limited. Content from the 2001 and 2005 ESC CHF guidelines8,15 is cited with permission granted by the ESC.

Conflict of interest: A.P.M. has received honoraria for presentations.

References 1. McMurray J, McDonagh T, Morrison CE et al. Trends in hospitalization for heart failure in Scotland 1980–1990. Eur Heart J 1993;14: 1158–1162. 2. Dargie HJ, McMurray JJ. Diagnosis and management of heart failure. BMJ 1994;308:321–328. 3. Gibbs LM, Addington-Hall J, Gibbs JS. Dying from heart failure: lessons from palliative care. Many patients would benefit from palliative care at the end of their lives. BMJ 1998;317:961–962. 4. Stewart S, MacIntyre K, Hole DJ et al. More ‘malignant’ than cancer? Five-year survival following a first admission for heart failure. Eur J Heart Fail 2001;3:315–322. 5. Croft JB, Giles WH, Pollard RA et al. Heart failure survival among older adults in the United States: a poor prognosis for an emerging epidemic in the Medicare population. Arch Int Med 1999; 159:505–510. 6. McMurray JJV, Stewart S. The burden of heart failure. Eur Heart J 2002;4(Suppl.):D50–D58. 7. Mosterd A, Hoes AW, de Bruyne MC et al. Prevalence of heart failure and left ventricular dysfunction in the general population: The Rotterdam Study. Eur Heart J 1999;20:447–455. 8. Remme WJ, Swedberg K, The Task Force for the diagnosis and treatment of chronic heart failure of the European Society of Cardiology. Guidelines for the diagnosis and treatment of chronic heart failure. Eur Heart J 2001;22:1527–1560. 9. Davis RC, Hobbs FD, Kenkre JE et al. Prevalence of left ventricular systolic dysfunction and heart failure in high risk patients: community based epidemiological study. BMJ 2002;325:1156. 10. Cleland JG, Swedberg K, Follath F et al. The EuroHeart Failure survey programme—a survey on the quality of care among patients with heart failure in Europe. Part 1: patient characteristics and diagnosis. Eur Heart J 2003;24:442–463. 11. Hogg K, Swedberg K, McMurray J. Heart failure with preserved left ventricular systolic function; epidemiology, clinical characteristics, and prognosis. J Am Coll Cardiol 2004;43:317–327.


placebo, 40%).38 Subgroup analysis in Val-HeFT supported these findings, showing a 44% reduction in the relative risk of morbidity/mortality with valsartan in ACE-intolerant CHF patients (rate of morbidity/mortality: valsartan, 24.9%; placebo, 42.5%).42 Addressing concerns over the safety of triple therapy, the CHARM data revealed that candesartan reduced the risk of CV death and hospitalization for CHF in low EF patients already receiving ACE-I and/or beta-blocker therapy (CHARM-Added).37 Also of note was the occurrence of favourable trends with candesartan in patients with preserved LVEF (CHARM-Preserved), in whom fewer CV outcomes (hospitalizations for HF, new-onset diabetes, non-fatal MI, non-fatal stroke) and hospital admissions were observed with candesartan in addition to optimal medical treatment.39 Thus, evidence from large-scale clinical trials suggests that ARBs represent a good alternative to ACE-I to reduce mortality and morbidity in ACE-intolerant CHF patients. In addition, ARBs confer incremental clinical benefits, with an acceptable safety profile, when added to conventional medical treatment that includes ACE-I. Recommendations for the use of ARBs in the updated guidelines reflect these findings (Figure 1 ).15 ARBs are recommended as an alternative to ACE-I to improve morbidity and mortality in symptomatic ACE-intolerant patients (Class of recommendation I, level of evidence B ). Physicians are advised that ARBs show similar efficacy to ACE-I in reducing mortality and morbidity in CHF and AMI/LVSD patients.15 Citing data from Val-HeFT, CHARMAdded, and VALIANT, the guidelines recommend the use of ARBs—in addition to ACE-I therapy—to reduce morbidity and mortality in patients who remain symptomatic and advise that no evidence has been found to suggest deleterious effects from the co-administration of ARBs with ACE-I and/or beta-blockers.15

J19

J20

29.

30.

31.

32.

33.

34.

35.

36.

37.

38.

39.

40.

41.

42.

strategies for left ventricular dysfunction Pilot study. Circulation 2000;101:378–384. Poole-Wilson PA, Swedberg K, Cleland JG et al. Comparison of carvedilol and metoprolol on clinical outcomes in patients with chronic heart failure in the carvedilol or metoprolol European Trial (COMET): randomised controlled trial. Lancet 2003;362:7–13. Pitt B, Reichek N, Willenbrock R et al. Effects of eplerenone, enalapril, and eplerenone/enalapril in patients with essential hypertension and left ventricular hypertrophy: the 4E-left ventricular hypertrophy study. Circulation 2003;108:1831–1838. Pitt B, Remme W, Zannad F et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 2003;348:1309–1321. Pfeffer MA, McMurray JJ, Velazquez EJ et al. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med 2003; 349: 1893–1906. Pfeffer MA, Swedberg K, Granger CB et al. Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme. Lancet 2003;362:759–766. Pitt B, Segal R, Martinez FA et al. Randomised trial of losartan versus captopril in patients over 65 with heart failure (Evaluation of Losartan in the Elderly Study, ELITE). Lancet 1997;349:747–752. Pitt B, Poole-Wilson PA, Segal R et al. Effect of losartan compared with captopril on mortality in patients with symptomatic heart failure: randomised trial—the Losartan Heart Failure Survival Study ELITE II. Lancet 2000;355:1582–1587. Cohn JN, Tognoni G, Glazer RD et al. Rationale and design of the Valsartan Heart Failure Trial: a large multinational trial to assess the effects of valsartan, an angiotensin-receptor blocker, on morbidity and mortality in chronic congestive heart failure. J Card Fail 1999;5:155–160. McMurray JJ, Ostergren J, Swedberg K et al. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors: the CHARM-Added trial. Lancet 2003;362:767–771. Granger CB, McMurray JJ, Yusuf S et al. Effects of candesartan in patients with chronic heart failure and reduced leftventricular systolic function intolerant to angiotensin-convertingenzyme inhibitors: the CHARM-Alternative trial. Lancet 2003; 362:772–776. Yusuf S, Pfeffer MA, Swedberg K et al. Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved Trial. Lancet 2003;362: 777–781. Solomon SD, Wang D, Finn P et al. Effect of candesartan on causespecific mortality in heart failure patients: the Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity (CHARM) program. Circulation 2004;110:2180–2183. Young JB, Dunlap ME, Pfeffer MA et al. Mortality and morbidity reduction with Candesartan in patients with chronic heart failure and left ventricular systolic dysfunction: results of the CHARM low-left ventricular ejection fraction trials. Circulation 2004;110:2618–2626. Maggioni AP, Anand I, Gottlieb SO et al. Effects of valsartan on morbidity and mortality in patients with heart failure not receiving angiotensin-converting enzyme inhibitors. J Am Coll Cardiol 2002; 40:1414–1421.


12. Komajda M, Follath F, Swedberg K et al. The EuroHeart Failure Survey programme—a survey on the quality of care among patients with heart failure in Europe. Part 2: treatment. Eur Heart J 2003; 24:464–474. 13. The Task Force on Heart Failure of the European Society of Cardiology. Guidelines for the diagnosis of heart failure. Eur Heart J 1995;16:741–751. 14. The Task Force of the Working Group on Heart Failure of the European Society of Cardiology. The treatment of heart failure. Eur Heart J 1997;18:736–753. 15. Swedberg K, The Task Force for the Diagnosis and Treatment of Chronic Heart Failure of the European Society of Cardiology. Guidelines for the diagnosis and treatment of chronic heart failure. Eur Heart J 2005;26:1115–1140. 16. Swedberg K, Kjekshus J, Snapinn S. Long-term survival in severe heart failure in patients treated with enalapril. Ten year follow-up of CONSENSUS I. Eur Heart J 1999;20:136–139. 17. Garg R, Yusuf S. Overview of randomized trials of angiotensinconverting enzyme inhibitors on mortality and morbidity in patients with heart failure. Collaborative Group on ACE Inhibitor Trials. JAMA 1995;273:1450–1456. 18. Shekelle PG, Rich MW, Morton SC et al. Efficacy of angiotensinconverting enzyme inhibitors and beta-blockers in the management of left ventricular systolic dysfunction according to race, gender, and diabetic status: a meta-analysis of major clinical trials. J Am Coll Cardiol 2003;41:1529–1538. 19. Lopez-Sendon J, Swedberg K, McMurray J et al. Expert consensus document on angiotensin converting enzyme inhibitors in cardiovascular disease. The Task Force on ACE-inhibitors of the European Society of Cardiology. Eur Heart J 2004;25:1454–1470. 20. Faris R, Flather M, Purcell H et al. Current evidence supporting the role of diuretics in heart failure: a meta analysis of randomised controlled trials. Int J Cardiol 2002;82:149–158. 21. Gupta S, Neyses L. Diuretic usage in heart failure: a continuing conundrum in 2005. Eur Heart J 2005;26:644–649. 22. Lopez-Sendon J, Swedberg K, McMurray J et al. Expert consensus document on beta-adrenergic receptor blockers. Eur Heart J 2004;25:1341–1362. 23. Bandyopadhyay S, O’Mahony MS. Beta-blockers in left ventricular systolic dysfunction—from evidence to practice. Age Ageing 2002;31:23–28. 24. Maggioni AP, Sinagra G, Opasich C et al. Treatment of chronic heart failure with beta adrenergic blockade beyond controlled clinical trials: the BRING-UP experience. Heart 2003;89:299–305. 25. Lechat P, Packer M, Chalon S et al. Clinical effects of betaadrenergic blockade in chronic heart failure: a meta-analysis of double-blind, placebo-controlled, randomized trials. Circulation 1998;98:1184–1191. 26. CIBIS II Investigators and Committees. The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): A randomised trial. Lancet 1999; 353:9–13. 27. MERIT-HF Study Group. Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet 1999;353:2001–2007. 28. The RESOLVD Investigators. Effects of metoprolol CR in patients with ischemic and dilated cardiomyopathy: the randomized evaluation of

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REVIEW OF THE NEW ESC GUIDELINES FOR THE

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