Is preventive medicine responsible for the increasing prevalence of heart failure?

Abstract

Studies done in the USA1US Department of Human and Health Services Detailed diagnoses and procedures, national hospital discharge survey. National Center for Health Statistics, Washington DC1990Google Scholar and Scotland2McMurray J McDonagh T Morrison CE Dragie HJ Trends in hospitalization for heart failure in Scotland 1980–1990.Eur Heart J. 1993; 14: 1158-1162Crossref PubMed Scopus (309) Google Scholar have shown that there has been a progressive and dramatic increase in the prevalence of heart failure as a hospital diagnosis during the past 30–40 years. This increase shows no sign of abating and is partially attributable to heightened interest in heart failure causing increased diagnosis and reporting. There also seems to be sufficient evidence to suggest that there is a true increase in the disorder. The reasons are multifactorial, but two of the major factors appear to be the general ageing of the population in developed countries and increased survival after myocardial infarction.Risk factors responsible for the development and progression of atherosclerotic coronary artery disease are well known. The factors that predispose patients with coronary disease to the development of heart failure are not clear, but recurrent infarction is a major factor. Hoffman and colleagues3Hoffman RM Psaty BM Kronmal RA Modifiable risk factors for incident heart failure in the coronary artery surgery study.Arch Intern Med. 1994; 154: 417-423Crossref PubMed Scopus (42) Google Scholar studied all patients with documented coronary artery disease eligible for the multicentre, randomised, controlled Coronary Artery Surgery Study to find out which modifiable cardiovascular risk factors predispose to heart failure. At the 12-year follow-up, the cumulative incidence of heart failure was 20·6%. Cigarette smoking, high body-mass index, myocardial infarction during follow-up, older age, female sex, and baseline left-ventricle dysfunction were risk factors for the development of heart failure. Other factors have also been implicated such as: myocardial wall stress, uncorrected myocardial ischaemia, persistent coronary artery occlusion, and neurohormonal (particularly renin-angiotensin and sympathetic) overactivity. The Framingham study4Kannel WB Epidemiology and prevention of cardiac failure: Framingham Study insights.Eur Heart J. 1987; 8: 23-26Crossref PubMed Google Scholar also identified the following independent risk factors for the development of heart failure: low vital capacity, rapid heart rate, diabetes, cardiac enlargement, high body-mass index (in women), high serum cholesterol (in men aged <65 years), cigarette smoking, proteinuria, and high haematocrit. These risk factors were in addition to hypertension, evidence of left-ventricle hypertrophy on electrocardiogram (ECG), and coronary disease. The findings of this study would suggest that conventional strategies for secondary prevention of coronary artery disease may work as primary preventive measures of heart failure. There is evidence showing this effect in a number of settings.Antihypertensive trialsIn the Framingham study4Kannel WB Epidemiology and prevention of cardiac failure: Framingham Study insights.Eur Heart J. 1987; 8: 23-26Crossref PubMed Google Scholar hypertension was reported as a precursor to nearly 90% of cases of heart failure, whereas coronary disease was seen in only 50%. Some 485 men and women developed first evidence of coronary heart failure during follow-up. The annual incidence increased from three per 1000 people at age 35–64 years to ten per 1000 people at age 65–94 years with a predominance of cases seen in men. Hypertension has not been identified as such a common precursor in more recent studies, possibly because of improved antihypertensive care in the community.5Parameshwar J Poole Wilson PA Sutton GC Heart failure in a district general hospital.J R Coll Physicians Lond. 1992; 26: 139-142PubMed Google Scholar This would be evidence in practice that the development of heart failure can be prevented by treating its precursors. The true prevalence of hypertension-related heart failure is, however, probably still underestimated because of the common practice of attributing heart failure to coronary disease and giving less attention to the antecedent causes of the coronary disease. There is evidence that treating hypertension, particularly systolic hypertension in the elderly, can reduce the development of heart failure. In the Systolic Hypertension in the Elderly Program (SHEP),6SHEP Cooperative Research GroupPrevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension.in: Final results of the systolic hypertension in the elderly program. JAMA. 265. 1991: 3255-3264Google Scholar for example, 4736 patients older than 60 years with systolic blood pressure of 160–219 mm Hg and diastolic blood pressure of less than 90 mm Hg were randomly allocated a regimen of chlorthalidone 12·5–25 mg (followed when necessary by atenolol 25–50 mg) or placebo. During an average follow-up of 4·5 years, new cases of heart failure were significantly reduced by 54%. There were also significantly fewer strokes, along with non-significant trends of less myocardial infarctions and a lower total mortality.Hypolipidaemic trialsIn the developed world, dyslipidaemias are a common and powerful risk factor for the development of coronary disease, and are therefore likely to be important in causing ischaemic heart failure. In the double-blind 4S trial,7Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. 344. 1994: 1383-1389Google Scholar 4444 patients with angina pectoris or previons myocardial infarction and serum cholesterol of 5·5–8·0 mmol/L, who were on a lipid-lowering diet, were randomly allocated simvastatin or placebo. Median follow-up was 5·4 years. 256 (12%) patients in the placebo group died, compared with 182 (8%) in the simvastatin group, with a relative risk of death in the simvastatin group of 0·70 (95% CI 0·58–0·85, p=0·0003). There were 189 coronary deaths in the placebo group and 111 in the simvastatin group (relative risk 0·58 [0·46–0·73]). Other benefits of treatment included a 37% reduction (p<0·00001) in the risk of undergoing procedures for myocardial revascularisation. In a subsequent post-hoc analysis, which was separately reported,8Kjekshus J Pedersen TR Olsson AG Faergeman O Pyorala K The effects of simvastatin on the incidence of heart failure in patients with coronary heart disease.J Cardiac Failure. 1997; 3: 249-254Summary Full Text PDF PubMed Scopus (338) Google Scholar new cases of heart failure developed in 9% of the 4S patients at a rate of about 2% per year. Simvastatin significantly reduced the risk of developing heart failure, (figure 1) and simultaneously reduced the mortality of patients who did develop heart failure, with a 19% risk reduction in those who developed heart failure compared with a 28% reduction in mortality in those who did not (figure 2). Although this analysis was not a prespecified secondary analysis, it does suggest that lipidreducing therapy in patients with chronic ischaemic heart disease both reduces the risk of heart failure and heartfailure-related mortality once it has developed. Simvastatin presumably acts by preventing recurrent infarctions, although ancillary non-hypolipidaemic actions of the statins, such as the improvement of endothelial function and effects on platelets, may play a part.Figure 2Mortality rates in patients on simvastatin or placeboShow full captionBased on whether the patient developed heart failure during follow-up (two columns on the left) or not (two columns on the right). Adapted with permission from 8Kjekshus J Pedersen TR Olsson AG Faergeman O Pyorala K The effects of simvastatin on the incidence of heart failure in patients with coronary heart disease.J Cardiac Failure. 1997; 3: 249-254Summary Full Text PDF PubMed Scopus (338) Google Scholar.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Neurohormonal inhibitionIn patients with large infarcts associated with a low ejection fraction or transient heart failure, the use of inhibitors of angiotensin-converting enzyme (ACE) reduces mortality, hospital admission for heart failure, and the new development of heart failure.9Pfeffer MA Braunwald E Moye LA et al.Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction.in: Results of the survival and ventricular enlargement trial (SAVE). N Engl J Med. 327. 1992: 669-677Google Scholar, 10ISIS-4 Collaborative GroupISIS-4: a randomised factorial trial assessing early oral captopril, oral mononitrate, and intravenous magnesium sulphate in 58 050 patients with suspected acute myocardial infarction.Lancet. 1995; 345: 669-685Crossref PubMed Scopus (1922) Google Scholar, 11The Acute Infarction Ramipril Efficacy (AIRE) Study InvestigatorsEffect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure.Lancet. 1993; 342: 821-828Summary PubMed Scopus (2340) Google Scholar, 12Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Micardio (GISSI-3)Effects of lisinopril and transdermal glyceryl trinitrate singly and together on 6-week mortality and ventricular function after acute myocardial infarction.Lancet. 1994; 343: 1115-1122PubMed Google Scholar, 13Kober L Torp-Pedersen C Carlsen JE et al.A clinical trial of the angiotensin-converting-enzyme inhibitor trandolapril in patients with left ventricular dysfunction after myocardial infarction.N Engl J Med. 1995; 333: 1670-1676Crossref PubMed Scopus (1635) Google Scholar The latter effect is thought to be due to the beneficial effects on left-ventricle remodelling. ACE inhibitors also seem to prevent the development of new heart failure and hospital admissions for deteriorating heart failure in symptom-free dysfunction of the left ventricle14The SOLVD InvestigatorsEffect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions.N Engl J Med. 1992; 327: 685-691Crossref PubMed Scopus (3492) Google Scholar, 15Pitt B Use of converting enzyme inhibitors in patients with asymptomatic left ventricular dysfunction.J Am Coll Cardiol. 1993; 22: 158A-161ASummary Full Text PDF PubMed Scopus (26) Google Scholar and mild heart failure.16Kleber FX Niemoller L Doering W Impact of converting enzyme inhibition on progression of chronic heart failure: results of the Munich Mild Heart Failure Trial.Br Heart J. 1992; 67: 289-296Crossref PubMed Scopus (119) Google Scholar However, evidence of this association is not as clear as evidence for non-ischaemic heart failure. In the studies of Left Ventricular Dysfunction (SOLVD) Prevention Trial,14The SOLVD InvestigatorsEffect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions.N Engl J Med. 1992; 327: 685-691Crossref PubMed Scopus (3492) Google Scholar 4228 patients with a left-ventricular ejection fraction of 35% or less who were not receiving drug therapy for heart failure were assessed. Patients randomly assigned enalapril 2·5–20 mg daily showed a 37% reduction in the development of heart failure and a 36% reduction in hospital admission for heart failure (p=0·001).There is also evidence that some β-blockers can reduce mortality of episodes of worsening heart failure in selected patients with chronic heart failure.17Packer M Bristow MR Cohn JN et al.The effect of carvedilol on morbidity and mortality in patients with chronic heart failure.N Engl J Med. 1996; 334: 1349-1355Crossref PubMed Scopus (4176) Google Scholar, 18MacMahon S Sharpe N Doughty R et al.Randomised, placebo-controlled trial of carvedilol in patients with congestive heart failure due to ischaemic heart disease.Lancet. 1997; 349: 375-380Summary Full Text Full Text PDF PubMed Scopus (711) Google Scholar In a secondary analysis of The Cardiac Arrhythmia Suppression Trial (CAST),19Kennedy HL Brooks MM Barker AH et al.Beta-blocker therapy in the Cardiac Arrhythmia Suppression Trial (CAST).Am J Cardiol. 1994; 74: 674-680Summary Full Text PDF PubMed Scopus (180) Google Scholar in patients with a history of congestive heart failure, β-blocker therapy was independently associated with longer time to occurrence of new or worsened congestive heart failure (p=0·015).Other therapies for acute myocardial infarctionThrombolysis to restore perfusion of jeopardized myocardium can partially preserve ventricular function. In patients with a large area of the myocardium at risk if thrombolysis is instituted early after the onset of symptoms, ischaemic heart failure can be prevented.20Hugenholtz PG Simoons ML Can thrombolysis prevent ischemic heart failure?.Cardiology. 1988; 75: 90-102Crossref PubMed Scopus (2) Google Scholar, 21Fibrinolytic Therapy Trialists' (FTT) Collaborative GroupIndications for fibrinolytic therapy in suspected acute myocardial infarction: collaborative overview of early mortality and major morbidity results from all randomised trials of more than 1000 patients.Lancet. 1994; 343: 311-322Summary PubMed Scopus (2807) Google Scholar Similar benefits are likely for aspirin, which also reduces mortality. Also, patients suitable for angioplasty, direct angioplasty would prevent heart failure by protecting the myocardium at risk.Other strategies to prevent heart failurePotential precipitating factors that led to cardiac decompensation and subsequent hospital admission for heart failure were examined by Ghali and colleagues22Ghali JK Kadakia S Cooper R Ferlinz J Precipitating factors leading to decompensation of heart failure.in: Traits among urban blacks. Arch Intern Med. 148. 1988: 2013-2016Google Scholar in 101 patients from a large public hospital. Potential precipitating factors for decompensating heart failure were identified in 93% of patients. Among these factors were: lack of adherence to the prescribed medicines (64%), non-compliance with diet (22%), cardiac arrhythmias (29%), and social, emotional, or environmental factors (26%). These factors showed that rehabilitation and education of patients could prevent the development of cardiac decompensation and heart failure.Why is the prevalence of heart failure increasing?Against the background of successful preventive strategies why is heart failure increasing? The answer may be that the uptake of the trial treatments in routine practice in the community may be slow and inadequate. There is evidence, for example, that the prescription of ACE inhibitors for patients with heart failure remained below 50% for several years after the evidence for their beneficial effects were shown. It may be that the true burden of heart failure in the community lies with the elderly, and that evidence from trials, and hence treatments, are relevant to a much younger population. These treatments may not be effective or practicable in the very elderly. Lastly, these treatments might delay rather than prevent heart failure. With patients surviving myocardial infarction for longer, there are simply more patients who survive to develop heart failure at an older age. Definitive evidence for this statement is difficult to obtain, but all successful heart-failure trials have led to more patients with heart failure in the active-treatment group than in the placebo group because of increased survival in the active-treatment group. On a population level, increased survival translates to more, not less, heart-failure consultations and a greater health-care burden. Although we must pursue all lines of attack to prevent heart failure from developing in high-risk groups, we must also appreciate that successes in reducing mortality in patients with established heart failure and increasing survival after large myocardial infarctions will mean more patients survive and more patients have, or are at risk of, heart failure. We cannot assume that the current epidemic of heart failure shows any signs of abating.Andrew J S Coats is supported by Viscount Royston Trust and the British Heart Foundation. Studies done in the USA1US Department of Human and Health Services Detailed diagnoses and procedures, national hospital discharge survey. National Center for Health Statistics, Washington DC1990Google Scholar and Scotland2McMurray J McDonagh T Morrison CE Dragie HJ Trends in hospitalization for heart failure in Scotland 1980–1990.Eur Heart J. 1993; 14: 1158-1162Crossref PubMed Scopus (309) Google Scholar have shown that there has been a progressive and dramatic increase in the prevalence of heart failure as a hospital diagnosis during the past 30–40 years. This increase shows no sign of abating and is partially attributable to heightened interest in heart failure causing increased diagnosis and reporting. There also seems to be sufficient evidence to suggest that there is a true increase in the disorder. The reasons are multifactorial, but two of the major factors appear to be the general ageing of the population in developed countries and increased survival after myocardial infarction. Risk factors responsible for the development and progression of atherosclerotic coronary artery disease are well known. The factors that predispose patients with coronary disease to the development of heart failure are not clear, but recurrent infarction is a major factor. Hoffman and colleagues3Hoffman RM Psaty BM Kronmal RA Modifiable risk factors for incident heart failure in the coronary artery surgery study.Arch Intern Med. 1994; 154: 417-423Crossref PubMed Scopus (42) Google Scholar studied all patients with documented coronary artery disease eligible for the multicentre, randomised, controlled Coronary Artery Surgery Study to find out which modifiable cardiovascular risk factors predispose to heart failure. At the 12-year follow-up, the cumulative incidence of heart failure was 20·6%. Cigarette smoking, high body-mass index, myocardial infarction during follow-up, older age, female sex, and baseline left-ventricle dysfunction were risk factors for the development of heart failure. Other factors have also been implicated such as: myocardial wall stress, uncorrected myocardial ischaemia, persistent coronary artery occlusion, and neurohormonal (particularly renin-angiotensin and sympathetic) overactivity. The Framingham study4Kannel WB Epidemiology and prevention of cardiac failure: Framingham Study insights.Eur Heart J. 1987; 8: 23-26Crossref PubMed Google Scholar also identified the following independent risk factors for the development of heart failure: low vital capacity, rapid heart rate, diabetes, cardiac enlargement, high body-mass index (in women), high serum cholesterol (in men aged <65 years), cigarette smoking, proteinuria, and high haematocrit. These risk factors were in addition to hypertension, evidence of left-ventricle hypertrophy on electrocardiogram (ECG), and coronary disease. The findings of this study would suggest that conventional strategies for secondary prevention of coronary artery disease may work as primary preventive measures of heart failure. There is evidence showing this effect in a number of settings. Antihypertensive trialsIn the Framingham study4Kannel WB Epidemiology and prevention of cardiac failure: Framingham Study insights.Eur Heart J. 1987; 8: 23-26Crossref PubMed Google Scholar hypertension was reported as a precursor to nearly 90% of cases of heart failure, whereas coronary disease was seen in only 50%. Some 485 men and women developed first evidence of coronary heart failure during follow-up. The annual incidence increased from three per 1000 people at age 35–64 years to ten per 1000 people at age 65–94 years with a predominance of cases seen in men. Hypertension has not been identified as such a common precursor in more recent studies, possibly because of improved antihypertensive care in the community.5Parameshwar J Poole Wilson PA Sutton GC Heart failure in a district general hospital.J R Coll Physicians Lond. 1992; 26: 139-142PubMed Google Scholar This would be evidence in practice that the development of heart failure can be prevented by treating its precursors. The true prevalence of hypertension-related heart failure is, however, probably still underestimated because of the common practice of attributing heart failure to coronary disease and giving less attention to the antecedent causes of the coronary disease. There is evidence that treating hypertension, particularly systolic hypertension in the elderly, can reduce the development of heart failure. In the Systolic Hypertension in the Elderly Program (SHEP),6SHEP Cooperative Research GroupPrevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension.in: Final results of the systolic hypertension in the elderly program. JAMA. 265. 1991: 3255-3264Google Scholar for example, 4736 patients older than 60 years with systolic blood pressure of 160–219 mm Hg and diastolic blood pressure of less than 90 mm Hg were randomly allocated a regimen of chlorthalidone 12·5–25 mg (followed when necessary by atenolol 25–50 mg) or placebo. During an average follow-up of 4·5 years, new cases of heart failure were significantly reduced by 54%. There were also significantly fewer strokes, along with non-significant trends of less myocardial infarctions and a lower total mortality. In the Framingham study4Kannel WB Epidemiology and prevention of cardiac failure: Framingham Study insights.Eur Heart J. 1987; 8: 23-26Crossref PubMed Google Scholar hypertension was reported as a precursor to nearly 90% of cases of heart failure, whereas coronary disease was seen in only 50%. Some 485 men and women developed first evidence of coronary heart failure during follow-up. The annual incidence increased from three per 1000 people at age 35–64 years to ten per 1000 people at age 65–94 years with a predominance of cases seen in men. Hypertension has not been identified as such a common precursor in more recent studies, possibly because of improved antihypertensive care in the community.5Parameshwar J Poole Wilson PA Sutton GC Heart failure in a district general hospital.J R Coll Physicians Lond. 1992; 26: 139-142PubMed Google Scholar This would be evidence in practice that the development of heart failure can be prevented by treating its precursors. The true prevalence of hypertension-related heart failure is, however, probably still underestimated because of the common practice of attributing heart failure to coronary disease and giving less attention to the antecedent causes of the coronary disease. There is evidence that treating hypertension, particularly systolic hypertension in the elderly, can reduce the development of heart failure. In the Systolic Hypertension in the Elderly Program (SHEP),6SHEP Cooperative Research GroupPrevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension.in: Final results of the systolic hypertension in the elderly program. JAMA. 265. 1991: 3255-3264Google Scholar for example, 4736 patients older than 60 years with systolic blood pressure of 160–219 mm Hg and diastolic blood pressure of less than 90 mm Hg were randomly allocated a regimen of chlorthalidone 12·5–25 mg (followed when necessary by atenolol 25–50 mg) or placebo. During an average follow-up of 4·5 years, new cases of heart failure were significantly reduced by 54%. There were also significantly fewer strokes, along with non-significant trends of less myocardial infarctions and a lower total mortality. Hypolipidaemic trialsIn the developed world, dyslipidaemias are a common and powerful risk factor for the development of coronary disease, and are therefore likely to be important in causing ischaemic heart failure. In the double-blind 4S trial,7Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. 344. 1994: 1383-1389Google Scholar 4444 patients with angina pectoris or previons myocardial infarction and serum cholesterol of 5·5–8·0 mmol/L, who were on a lipid-lowering diet, were randomly allocated simvastatin or placebo. Median follow-up was 5·4 years. 256 (12%) patients in the placebo group died, compared with 182 (8%) in the simvastatin group, with a relative risk of death in the simvastatin group of 0·70 (95% CI 0·58–0·85, p=0·0003). There were 189 coronary deaths in the placebo group and 111 in the simvastatin group (relative risk 0·58 [0·46–0·73]). Other benefits of treatment included a 37% reduction (p<0·00001) in the risk of undergoing procedures for myocardial revascularisation. In a subsequent post-hoc analysis, which was separately reported,8Kjekshus J Pedersen TR Olsson AG Faergeman O Pyorala K The effects of simvastatin on the incidence of heart failure in patients with coronary heart disease.J Cardiac Failure. 1997; 3: 249-254Summary Full Text PDF PubMed Scopus (338) Google Scholar new cases of heart failure developed in 9% of the 4S patients at a rate of about 2% per year. Simvastatin significantly reduced the risk of developing heart failure, (figure 1) and simultaneously reduced the mortality of patients who did develop heart failure, with a 19% risk reduction in those who developed heart failure compared with a 28% reduction in mortality in those who did not (figure 2). Although this analysis was not a prespecified secondary analysis, it does suggest that lipidreducing therapy in patients with chronic ischaemic heart disease both reduces the risk of heart failure and heartfailure-related mortality once it has developed. Simvastatin presumably acts by preventing recurrent infarctions, although ancillary non-hypolipidaemic actions of the statins, such as the improvement of endothelial function and effects on platelets, may play a part. In the developed world, dyslipidaemias are a common and powerful risk factor for the development of coronary disease, and are therefore likely to be important in causing ischaemic heart failure. In the double-blind 4S trial,7Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. 344. 1994: 1383-1389Google Scholar 4444 patients with angina pectoris or previons myocardial infarction and serum cholesterol of 5·5–8·0 mmol/L, who were on a lipid-lowering diet, were randomly allocated simvastatin or placebo. Median follow-up was 5·4 years. 256 (12%) patients in the placebo group died, compared with 182 (8%) in the simvastatin group, with a relative risk of death in the simvastatin group of 0·70 (95% CI 0·58–0·85, p=0·0003). There were 189 coronary deaths in the placebo group and 111 in the simvastatin group (relative risk 0·58 [0·46–0·73]). Other benefits of treatment included a 37% reduction (p<0·00001) in the risk of undergoing procedures for myocardial revascularisation. In a subsequent post-hoc analysis, which was separately reported,8Kjekshus J Pedersen TR Olsson AG Faergeman O Pyorala K The effects of simvastatin on the incidence of heart failure in patients with coronary heart disease.J Cardiac Failure. 1997; 3: 249-254Summary Full Text PDF PubMed Scopus (338) Google Scholar new cases of heart failure developed in 9% of the 4S patients at a rate of about 2% per year. Simvastatin significantly reduced the risk of developing heart failure, (figure 1) and simultaneously reduced the mortality of patients who did develop heart failure, with a 19% risk reduction in those who developed heart failure compared with a 28% reduction in mortality in those who did not (figure 2). Although this analysis was not a prespecified secondary analysis, it does suggest that lipidreducing therapy in patients with chronic ischaemic heart disease both reduces the risk of heart failure and heartfailure-related mortality once it has developed. Simvastatin presumably acts by preventing recurrent infarctions, although ancillary non-hypolipidaemic actions of the statins, such as the improvement of endothelial function and effects on platelets, may play a part. Neurohormonal inhibitionIn patients with large infarcts associated with a low ejection fraction or transient heart failure, the use of inhibitors of angiotensin-converting enzyme (ACE) reduces mortality, hospital admission for heart failure, and the new development of heart failure.9Pfeffer MA Braunwald E Moye LA et al.Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction.in: Results of the survival and ventricular enlargement trial (SAVE). N Engl J Med. 327. 1992: 669-677Google Scholar, 10ISIS-4 Collaborative GroupISIS-4: a randomised factorial trial assessing early oral captopril, oral mononitrate, and intravenous magnesium sulphate in 58 050 patients with suspected acute myocardial infarction.Lancet. 1995; 345: 669-685Crossref PubMed Scopus (1922) Google Scholar, 11The Acute Infarction Ramipril Efficacy (AIRE) Study InvestigatorsEffect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure.Lancet. 1993; 342: 821-828Summary PubMed Scopus (2340) Google Scholar, 12Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Micardio (GISSI-3)Effects of lisinopril and transdermal glyceryl trinitrate singly and together on 6-week mortality and ventricular function after acute myocardial infarction.Lancet. 1994; 343: 1115-1122PubMed Google Scholar, 13Kober L Torp-Pedersen C Carlsen JE et al.A clinical trial of the angiotensin-converting-enzyme inhibitor trandolapril in patients with left ventricular dysfunction after myocardial infarction.N Engl J Med. 1995; 333: 1670-1676Crossref PubMed Scopus (1635) Google Scholar The latter effect is thought to be due to the beneficial effects on left-ventricle remodelling. ACE inhibitors also seem to prevent the development of new heart failure and hospital admissions for deteriorating heart failure in symptom-free dysfunction of the left ventricle14The SOLVD InvestigatorsEffect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions.N Engl J Med. 1992; 327: 685-691Crossref PubMed Scopus (3492) Google Scholar, 15Pitt B Use of converting enzyme inhibitors in patients with asymptomatic left ventricular dysfunction.J Am Coll Cardiol. 1993; 22: 158A-161ASummary Full Text PDF PubMed Scopus (26) Google Scholar and mild heart failure.16Kleber FX Niemoller L Doering W Impact of converting enzyme inhibition on progression of chronic heart failure: results of the Munich Mild Heart Failure Trial.Br Heart J. 1992; 67: 289-296Crossref PubMed Scopus (119) Google Scholar However, evidence of this association is not as clear as evidence for non-ischaemic heart failure. In the studies of Left Ventricular Dysfunction (SOLVD) Prevention Trial,14The SOLVD InvestigatorsEffect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions.N Engl J Med. 1992; 327: 685-691Crossref PubMed Scopus (3492) Google Scholar 4228 patients with a left-ventricular ejection fraction of 35% or less who were not receiving drug therapy for heart failure were assessed. Patients randomly assigned enalapril 2·5–20 mg daily showed a 37% reduction in the development of heart failure and a 36% reduction in hospital admission for heart failure (p=0·001).There is also evidence that some β-blockers can reduce mortality of episodes of worsening heart failure in selected patients with chronic heart failure.17Packer M Bristow MR Cohn JN et al.The effect of carvedilol on morbidity and mortality in patients with chronic heart failure.N Engl J Med. 1996; 334: 1349-1355Crossref PubMed Scopus (4176) Google Scholar, 18MacMahon S Sharpe N Doughty R et al.Randomised, placebo-controlled trial of carvedilol in patients with congestive heart failure due to ischaemic heart disease.Lancet. 1997; 349: 375-380Summary Full Text Full Text PDF PubMed Scopus (711) Google Scholar In a secondary analysis of The Cardiac Arrhythmia Suppression Trial (CAST),19Kennedy HL Brooks MM Barker AH et al.Beta-blocker therapy in the Cardiac Arrhythmia Suppression Trial (CAST).Am J Cardiol. 1994; 74: 674-680Summary Full Text PDF PubMed Scopus (180) Google Scholar in patients with a history of congestive heart failure, β-blocker therapy was independently associated with longer time to occurrence of new or worsened congestive heart failure (p=0·015). In patients with large infarcts associated with a low ejection fraction or transient heart failure, the use of inhibitors of angiotensin-converting enzyme (ACE) reduces mortality, hospital admission for heart failure, and the new development of heart failure.9Pfeffer MA Braunwald E Moye LA et al.Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction.in: Results of the survival and ventricular enlargement trial (SAVE). N Engl J Med. 327. 1992: 669-677Google Scholar, 10ISIS-4 Collaborative GroupISIS-4: a randomised factorial trial assessing early oral captopril, oral mononitrate, and intravenous magnesium sulphate in 58 050 patients with suspected acute myocardial infarction.Lancet. 1995; 345: 669-685Crossref PubMed Scopus (1922) Google Scholar, 11The Acute Infarction Ramipril Efficacy (AIRE) Study InvestigatorsEffect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure.Lancet. 1993; 342: 821-828Summary PubMed Scopus (2340) Google Scholar, 12Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Micardio (GISSI-3)Effects of lisinopril and transdermal glyceryl trinitrate singly and together on 6-week mortality and ventricular function after acute myocardial infarction.Lancet. 1994; 343: 1115-1122PubMed Google Scholar, 13Kober L Torp-Pedersen C Carlsen JE et al.A clinical trial of the angiotensin-converting-enzyme inhibitor trandolapril in patients with left ventricular dysfunction after myocardial infarction.N Engl J Med. 1995; 333: 1670-1676Crossref PubMed Scopus (1635) Google Scholar The latter effect is thought to be due to the beneficial effects on left-ventricle remodelling. ACE inhibitors also seem to prevent the development of new heart failure and hospital admissions for deteriorating heart failure in symptom-free dysfunction of the left ventricle14The SOLVD InvestigatorsEffect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions.N Engl J Med. 1992; 327: 685-691Crossref PubMed Scopus (3492) Google Scholar, 15Pitt B Use of converting enzyme inhibitors in patients with asymptomatic left ventricular dysfunction.J Am Coll Cardiol. 1993; 22: 158A-161ASummary Full Text PDF PubMed Scopus (26) Google Scholar and mild heart failure.16Kleber FX Niemoller L Doering W Impact of converting enzyme inhibition on progression of chronic heart failure: results of the Munich Mild Heart Failure Trial.Br Heart J. 1992; 67: 289-296Crossref PubMed Scopus (119) Google Scholar However, evidence of this association is not as clear as evidence for non-ischaemic heart failure. In the studies of Left Ventricular Dysfunction (SOLVD) Prevention Trial,14The SOLVD InvestigatorsEffect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions.N Engl J Med. 1992; 327: 685-691Crossref PubMed Scopus (3492) Google Scholar 4228 patients with a left-ventricular ejection fraction of 35% or less who were not receiving drug therapy for heart failure were assessed. Patients randomly assigned enalapril 2·5–20 mg daily showed a 37% reduction in the development of heart failure and a 36% reduction in hospital admission for heart failure (p=0·001). There is also evidence that some β-blockers can reduce mortality of episodes of worsening heart failure in selected patients with chronic heart failure.17Packer M Bristow MR Cohn JN et al.The effect of carvedilol on morbidity and mortality in patients with chronic heart failure.N Engl J Med. 1996; 334: 1349-1355Crossref PubMed Scopus (4176) Google Scholar, 18MacMahon S Sharpe N Doughty R et al.Randomised, placebo-controlled trial of carvedilol in patients with congestive heart failure due to ischaemic heart disease.Lancet. 1997; 349: 375-380Summary Full Text Full Text PDF PubMed Scopus (711) Google Scholar In a secondary analysis of The Cardiac Arrhythmia Suppression Trial (CAST),19Kennedy HL Brooks MM Barker AH et al.Beta-blocker therapy in the Cardiac Arrhythmia Suppression Trial (CAST).Am J Cardiol. 1994; 74: 674-680Summary Full Text PDF PubMed Scopus (180) Google Scholar in patients with a history of congestive heart failure, β-blocker therapy was independently associated with longer time to occurrence of new or worsened congestive heart failure (p=0·015). Other therapies for acute myocardial infarctionThrombolysis to restore perfusion of jeopardized myocardium can partially preserve ventricular function. In patients with a large area of the myocardium at risk if thrombolysis is instituted early after the onset of symptoms, ischaemic heart failure can be prevented.20Hugenholtz PG Simoons ML Can thrombolysis prevent ischemic heart failure?.Cardiology. 1988; 75: 90-102Crossref PubMed Scopus (2) Google Scholar, 21Fibrinolytic Therapy Trialists' (FTT) Collaborative GroupIndications for fibrinolytic therapy in suspected acute myocardial infarction: collaborative overview of early mortality and major morbidity results from all randomised trials of more than 1000 patients.Lancet. 1994; 343: 311-322Summary PubMed Scopus (2807) Google Scholar Similar benefits are likely for aspirin, which also reduces mortality. Also, patients suitable for angioplasty, direct angioplasty would prevent heart failure by protecting the myocardium at risk. Thrombolysis to restore perfusion of jeopardized myocardium can partially preserve ventricular function. In patients with a large area of the myocardium at risk if thrombolysis is instituted early after the onset of symptoms, ischaemic heart failure can be prevented.20Hugenholtz PG Simoons ML Can thrombolysis prevent ischemic heart failure?.Cardiology. 1988; 75: 90-102Crossref PubMed Scopus (2) Google Scholar, 21Fibrinolytic Therapy Trialists' (FTT) Collaborative GroupIndications for fibrinolytic therapy in suspected acute myocardial infarction: collaborative overview of early mortality and major morbidity results from all randomised trials of more than 1000 patients.Lancet. 1994; 343: 311-322Summary PubMed Scopus (2807) Google Scholar Similar benefits are likely for aspirin, which also reduces mortality. Also, patients suitable for angioplasty, direct angioplasty would prevent heart failure by protecting the myocardium at risk. Other strategies to prevent heart failurePotential precipitating factors that led to cardiac decompensation and subsequent hospital admission for heart failure were examined by Ghali and colleagues22Ghali JK Kadakia S Cooper R Ferlinz J Precipitating factors leading to decompensation of heart failure.in: Traits among urban blacks. Arch Intern Med. 148. 1988: 2013-2016Google Scholar in 101 patients from a large public hospital. Potential precipitating factors for decompensating heart failure were identified in 93% of patients. Among these factors were: lack of adherence to the prescribed medicines (64%), non-compliance with diet (22%), cardiac arrhythmias (29%), and social, emotional, or environmental factors (26%). These factors showed that rehabilitation and education of patients could prevent the development of cardiac decompensation and heart failure. Potential precipitating factors that led to cardiac decompensation and subsequent hospital admission for heart failure were examined by Ghali and colleagues22Ghali JK Kadakia S Cooper R Ferlinz J Precipitating factors leading to decompensation of heart failure.in: Traits among urban blacks. Arch Intern Med. 148. 1988: 2013-2016Google Scholar in 101 patients from a large public hospital. Potential precipitating factors for decompensating heart failure were identified in 93% of patients. Among these factors were: lack of adherence to the prescribed medicines (64%), non-compliance with diet (22%), cardiac arrhythmias (29%), and social, emotional, or environmental factors (26%). These factors showed that rehabilitation and education of patients could prevent the development of cardiac decompensation and heart failure. Why is the prevalence of heart failure increasing?Against the background of successful preventive strategies why is heart failure increasing? The answer may be that the uptake of the trial treatments in routine practice in the community may be slow and inadequate. There is evidence, for example, that the prescription of ACE inhibitors for patients with heart failure remained below 50% for several years after the evidence for their beneficial effects were shown. It may be that the true burden of heart failure in the community lies with the elderly, and that evidence from trials, and hence treatments, are relevant to a much younger population. These treatments may not be effective or practicable in the very elderly. Lastly, these treatments might delay rather than prevent heart failure. With patients surviving myocardial infarction for longer, there are simply more patients who survive to develop heart failure at an older age. Definitive evidence for this statement is difficult to obtain, but all successful heart-failure trials have led to more patients with heart failure in the active-treatment group than in the placebo group because of increased survival in the active-treatment group. On a population level, increased survival translates to more, not less, heart-failure consultations and a greater health-care burden. Although we must pursue all lines of attack to prevent heart failure from developing in high-risk groups, we must also appreciate that successes in reducing mortality in patients with established heart failure and increasing survival after large myocardial infarctions will mean more patients survive and more patients have, or are at risk of, heart failure. We cannot assume that the current epidemic of heart failure shows any signs of abating.Andrew J S Coats is supported by Viscount Royston Trust and the British Heart Foundation. Against the background of successful preventive strategies why is heart failure increasing? The answer may be that the uptake of the trial treatments in routine practice in the community may be slow and inadequate. There is evidence, for example, that the prescription of ACE inhibitors for patients with heart failure remained below 50% for several years after the evidence for their beneficial effects were shown. It may be that the true burden of heart failure in the community lies with the elderly, and that evidence from trials, and hence treatments, are relevant to a much younger population. These treatments may not be effective or practicable in the very elderly. Lastly, these treatments might delay rather than prevent heart failure. With patients surviving myocardial infarction for longer, there are simply more patients who survive to develop heart failure at an older age. Definitive evidence for this statement is difficult to obtain, but all successful heart-failure trials have led to more patients with heart failure in the active-treatment group than in the placebo group because of increased survival in the active-treatment group. On a population level, increased survival translates to more, not less, heart-failure consultations and a greater health-care burden. Although we must pursue all lines of attack to prevent heart failure from developing in high-risk groups, we must also appreciate that successes in reducing mortality in patients with established heart failure and increasing survival after large myocardial infarctions will mean more patients survive and more patients have, or are at risk of, heart failure. We cannot assume that the current epidemic of heart failure shows any signs of abating. Andrew J S Coats is supported by Viscount Royston Trust and the British Heart Foundation.