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Medical Treatment of Chronic Heart Failure in the Elderly

Medical Treatment of Chronic Heart Failure in the Elderly. 24 th January, 2008 Intensive Care Unit United Christian Hospital. Drug Treatment of Chronic Heart Failure in the Elderly. THERAPY IN PRACTICE Drugs Aging 2007; 24 (12): 991-1006

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Medical Treatment of Chronic Heart Failure in the Elderly

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  1. Medical Treatment of Chronic HeartFailure in the Elderly 24th January, 2008 Intensive Care Unit United Christian Hospital

  2. Drug Treatment of Chronic HeartFailure in the Elderly THERAPY IN PRACTICE Drugs Aging 2007; 24 (12): 991-1006 Gregor Leibundgut, Matthias Pfisterer and Hans-Peter Brunner-La Rocca Cardiology, University Hospital Basel, Basel, Switzerland

  3. Congestive Heart Failure Congestive heart failure is a growing public health problem worldwide, particularly in the elderly population, in whom it has a substantial impact on quality of life and survival. Heart failure is the most common cause of hospitalisation over the age of 65 years. Approximately 80% of patients hospitalised with heart failure are aged >65 years.* *Masoudi FA, Havranek EP, Krumholz HM. The burden of chronic congestive heart failure in older persons: magnitude and implications for policy and research. Heart Fail Rev 2002; 7: 9-16

  4. Prevalence and Incidence of Heart Failure in the Elderly The prevalence of heart failure is continuously increasing because of the aging of the population. The prevalence of heart failure in the overall population in the US was 2.3% in 2003,* but increases from 2% to 3% at age 65 years to approximately 8% in persons aged 75–86 years.# * Thom T, Haase N, Rosamond W, et al. Heart disease and stroke statistics: 2006 update. A report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 2006; 113: e85-151 # Kupari M, Lindroos M, Iivanainen AM, et al. Congestive heart failure in old age: prevalence, mechanisms and 4-year prognosis in the Helsinki Ageing Study. J Intern Med 1997; 241: 387-94

  5. Prevalence and Incidence of Heart Failure in the Elderly The incidence of heart failure approaches 1% in the population after age 65 years and the annual rate of new or recurrent heart failure events increases from 2.2% at age 65–74 years to 7.3% at age >=85 years.* * Thom T, Haase N, Rosamond W, et al. Heart disease and stroke statistics: 2006 update. A report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 2006; 113: e85-151

  6. Congestive Heart Failure Congestive heart failure (CHF) is a clinical syndrome that results from the inability of the heart to generate cardiac output sufficient to meet the demands of the body. Symptoms of heart failure may be caused by poor tissue perfusion (e.g. fatigue, poor exercise tolerance, reduced mental capacity), by the congestion of the vascular beds (e.g. dyspnoea, chest rales, pleural effusion, pulmonary oedema, distended neck veins, congested liver, peripheral oedema).

  7. Congestive Heart Failure The functional capacity and quality of life of affected individuals are often substantially reduced. This is particularly true in elderly patients since the window between demand and capacity narrows significantly with aging even in healthy patients.* *Puggaard L. Age-related decline in maximal oxygen capacity: consequences for performance of everyday activities. J Am Geriatr Soc 2005; 53: 546-7

  8. Difficulty in Congestive Heart Failure Diagnosis Heart failure-related symptoms in the elderly are often nonspecific and may be obscured by the presence of multiple co-morbidities,* for example, the presence of cognitive impairment may limit the ability of elderly patients to appropriately report symptoms. *Morgan S, Smith H, Simpson I, et al. Prevalence and clinical characteristics of left ventricular dysfunction among elderly patients in general practice setting: cross sectional survey. BMJ 1999; 318: 368-72

  9. Difficulty in Congestive Heart Failure Diagnosis Heart failure symptoms are often attributed to aging rather than recognised as disease related. In addition, confirmation of the diagnosis of heart failure is often thought to be not worthwhile in (very) elderly patients. In daily practice, elderly patients very often do not undergo the appropriate diagnostic work-up.* *Muntwyler J, Abetel G, Gruner C, et al. One-year mortality among unselected outpatients with heart failure. Eur Heart J 2002; 23: 1861-6

  10. Challenges of Heart Failure Treatment in the Elderly Physiology changes with age and polypharmacy complicates therapy. The aim of therapy may change in the presence of co-morbidities such as cancer or dementia. Drug interactions and adverse effects are frequent in heart failure in general, but increase significantly with age. Most clinical trials have excluded the elderly population. In particular, patients aged >=75 years have been barely represented in large trials. * *Heiat A, Gross CP, Krumholz HM. Representation of the elderly, women, and minorities in heart failure clinical trials. Arch Intern Med 2002; 162: 1682-8

  11. Focuses The differences between elderly and younger patients with heart failure Summarises the evidence available for treatment in elderly patients with heart failure Attempts to provide an approach to drug therapy in daily practice in elderly patients with heart failure

  12. Why Are Elderly Patients Different? Weight loss is more often a problem than a therapeutic goal in the elderly. in which cachexia is a poor prognostic sign in heat failure.* Low cholesterol is an unfavourable prognostic sign in both heart failure and old age # and there is no evidence that lipid-lowering agents in elderly patients with heart failure is beneficial. * Ponikowski P, Piepoli M, Chua TP, et al. The impact of cachexia on cardiorespiratory reflex control in chronic heart failure. Eur Heart J 1999; 20: 1667-75 # Pekkanen J, Nissinen A, Vartiainen E, et al. Changes in serum cholesterol level and mortality: a 30-year follow-up. The Finnish cohorts of the Seven Countries Study. Am J Epidemiol 1994; 139: 155-65

  13. Why Are Elderly Patients Different? The prevalence of dementia also increases with age. Pharmacological treatment, particularly those improving prognosis, may be less appropriate in the demented patient. Co-morbidities are highly prevalent in elderly patients with heart failure. In patients aged >=75 years, <10% have no additional co-morbidity.* This influences prognosis significantly *Brunner-La Rocca HP, Buser PT, Schindler R, et al. Management of elderly patients with congestive heart failure: design of the Trial of Intensified versus standard Medical therapy in Elderly patients with Congestive Heart Failure (TIME-CHF). Am Heart J 2006; 151: 949-55

  14. Why Are Elderly Patients Different? Polypharmacy is highly prevalent in the elderly population with heart failure and this has implications for treatment* and increases possibility of drug interaction. Adverse drug reactions occur more frequently among elderly patients, especially in those with polypharmacy, and show a good correlation with increasing age.# *McGann PE. Comorbidity in heart failure in the elderly. Clin Geriatr Med 2000; 16: 631-48 *Lien CT, Gillespie ND, Struthers AD, et al. Heart failure in frail elderly patients: diagnostic difficulties, co-morbidities, polypharmacy and treatment dilemmas. Eur J Heart Fail 2002; 4: 91-8 #Burgess CL, Holman CD, Satti AG. Adverse drug reactions in older Australians, 1981–2002. Med J Aust 2005; 182: 267-70

  15. Why Are Elderly Patients Different? Compensatory mechanisms are reduced with age. Heart rate may be reduced as a result of sick sinus syndrome or a higher degree atrioventricular block, and blunting of baroreceptor function as well as orthostatic dysregulation of blood pressure are often observed. This makes use of most drugs used for heart failure treatment, particularly [beta]-adrenoceptor antagonists, often difficult. This should not be used as an excuse for inappropriate medical therapy of heart failure in elderly patients.

  16. Why Are Elderly Patients Different? The pharmacokinetics and pharmacodynamics of drugs may change in older age. The most important factor in this regard is the progressive decline in renal function with age. Reduced renal function is an independent risk factor for worsening heart failure.* *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: 759-66

  17. Cockcroft-Gault equation: Modification of Diet in Renal Disease equation:

  18. Why Are Elderly Patients Different? There is high proportion of elderly patients with preserved left-ventricular ejection fraction (LVEF) heart failure [diastolic heart failure].* Diastolic heart failure is associated with older age, female sex and no history of myocardial infarction. Appropriate therapy for diastolic heart failure is largely unknown. *Owan TE, Hodge DO, Herges RM, et al. Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med 2006; 355: 251-9 *Bursi F, Weston SA, Redfield MM, et al. Systolic and diastolic heart failure in the community. JAMA 2006; 296: 2209-16

  19. Table I. Differences between elderly and younger patients (adapted from Bulpitt) From:   Leibundgut: Drugs Aging, Volume 24(12).2007.991-1006

  20. Where Are We? Both US and European guidelines provide chronic heart failure treatment recommendations that are not substantially influenced by age. The American College of Cardiology guidelines recommend that “evidence-based therapy for heart failure be used in the elderly patient, with individualised consideration of the elderly patient’s altered ability to metabolise or tolerate standard medications (Level of Evidence C)”.

  21. Medications in institutionalised patients with heart failure aged >65 years (mean 87 ± 8 years) according to advance directive level.

  22. Table II. Evidence level for chronic heart failure therapy relative to age From:   Leibundgut: Drugs Aging, Volume 24(12).2007.991-1006

  23. Evidence? Most of the evidence is indirect and randomised controlled trials have mostly been conducted in patient populations on average 10 years (or even more) younger than patients with heart failure seen in the community.* *Fonarow GC, Yancy CW, Heywood JT. Adherence to heart failure quality-of-care indicators in US hospitals: analysis of the ADHERE Registry. Arch Intern Med 2005; 165: 1469-77

  24. Therapy in Heart Failure with Reduced Left-Ventricular Systolic Function

  25. Diuretics

  26. Diuretics Diuretics, particularly loop diuretics, are well established for rapid reduction of the symptoms of fluid overload, but there are no randomised controlled trials assessing their prognostic effect in heart failure. Indirect evidence from post hoc analyses of large trials has even suggested unfavourable effects of diuretic use on prognosis.# #Ahmed A, Husain A, Love TE, et al. Heart failure, chronic diuretic use, and increase in mortality and hospitalization: an observational study using propensity score methods. Eur Heart J 2006; 27: 1431-9

  27. Diuretics Diuretics may cause renin-angiotensin-aldosterone system (RAAS) activation, possibly leading to increased morbidity and mortality despite short-term symptomatic improvements. Elderly patients frequently require higher doses of diuretics because of a reduced GFR, but they may also be more susceptible to deterioration of renal function as a response to diuretic therapy.

  28. Diuretics Because of risk of dehydration and hypotension with uncertain effect on prognosis, diuretics should be used at the minimal effective dose.

  29. ACE Inhibitors

  30. ACE Inhibitors ACE inhibitors are first-line therapy for patients with heart failure. ACE inhibitors have been shown to significantly reduce total mortality and morbidity in patients with heart failure, with a class effect assumed.* *Garg R, Yusuf S. Overview of randomized trials of angiotensin-converting enzyme inhibitors on mortality and morbidity in patients with heart failure: Collaborative Group on ACE Inhibitor Trials. JAMA 1995; 273: 1450-6 *Flather MD, Yusuf S, Kober L, et al. Long-term ACE-inhibitor therapy in patients with heart failure or left-ventricular dysfunction: a systematic overview of data from individual patients. ACE-Inhibitor Myocardial Infarction Collaborative Group. Lancet 2000; 355: 1575-81

  31. ACE Inhibitors Benefits were seen irrespective of age.# Relatively few (8.4%) patients aged >=75 years were included in the original studies of the meta-analysis. The benefit might have been smaller in this age group compared with younger patients (i.e. hazard ratio for combined endpoint 0.89 vs 0.67–0.77 in other age groups). #Flather MD, Yusuf S, Kober L, et al. Long-term ACE-inhibitor therapy in patients with heart failure or left-ventricular dysfunction: a systematic overview of data from individual patients. ACE-Inhibitor Myocardial Infarction Collaborative Group. Lancet 2000; 355: 1575-81

  32. ACE Inhibitors There are no studies available reporting outcomes with ACE inhibitors compared with placebo in sufficiently large elderly patient populations and it is very unlikely that such studies will ever be performed. Thus, there is no direct proof for an improved outcome with ACE inhibitors in patients with heart failure aged >=75 years.

  33. ACE Inhibitors Indirect evidence uniformly suggests an improved outcome. Several large cohort studies in elderly patients indicated a large benefit not only on hospitalisation rate but also on survival.* Sin DD, McAlister FA. The effects of beta-blockers on morbidity and mortality in a population-based cohort of 11,942 elderly patients with heart failure. Am J Med 2002; 113: 650-6 Havranek EP, Abrams F, Stevens E, et al. Determinants of mortality in elderly patients with heart failure: the role of angiotensin-converting enzyme inhibitors. Arch Intern Med 1998; 158: 2024-8 Pulignano G, Del Sindaco D, Tavazzi L, et al. Clinical features and outcomes of elderly outpatients with heart failure followed up in hospital cardiology units: data from a large nationwide cardiology database (IN-CHF Registry). Am Heart J 2002; 143: 45-55

  34. ACE Inhibitors * Most ACE inhibitors are cleared by the kidney and starting and target doses need to modified in line with renal function. Alternatively, fosinopril, which undergoes dual elimination, may be used. * The risks of hypotension, renal failure and hyperkalaemia increase with age. Reduced starting doses and careful up-titration are crucial to increase tolerability. * Serum potassium and creatinine levels must be regularly monitored. An increase in serum creatinine of 30–50% after initiation and an increase in serum potassium to 5–5.5 mmol/L is acceptable. * Most ACE inhibitors are prodrugs. Captopril and lisinopril, which are given as active drugs, might be preferred in patients with hepatic failure.

  35. Angiotensin Receptor Blockers

  36. Angiotensin Receptor Blockers Angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]) are the alternative for patients who cannot tolerate ACE inhibitors. Compared with ACE inhibitors, ARBs have been better studied in elderly patients. The ELITE (Evaluation of Losartan in the Elderly)-II trial included only patients with heart failure aged >60 years (mean 71 years) and in other studies, the proportion of patients aged >75 years was larger than in the ACE inhibitor trials.

  37. Angiotensin Receptor Blockers Studies suggest that ARBs are probably equivalent to ACE inhibitors. Granger CB, McMurray JJ, Yusuf S, et al. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARM-Alternative trial. Lancet 2003; 362: 772-6 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: 1414-21 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: 1582-7 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: 1893-906

  38. [beta]-Adrenoceptor Antagonists

  39. [beta]-Adrenoceptor Antagonists Dose-dependent benefit not only for ACE inhibitor therapy but also for [beta]-adrenoceptor blockade in patients aged >=65 years. Subgroup analyses of some large randomised trials suggested that [beta]-adrenoceptor antagonists are effective irrespective of age. CIBIS (Cardiac Insufficiency Bisoprolol Study)-II trial MERIT-HF (Metoprolol Succinate Controlled-Release/Extended-Release Randomized Intervention Trial in Heart Failure) trial

  40. [beta]-Adrenoceptor Antagonists SENIORS (Study of the Effects of Nebivolol Intervention on Outcomes and Rehospitalization in Seniors with Heart Failure), which investigated the effects of nebivolol in patients aged >70 years only. Nebivolol reduced the combined endpoint of all-cause mortality and cardiovascular hospitalisation significantly by 14% in truly elderly patients (mean age 76 years). All-cause mortality alone was not significantly reduced. The trend was towards less benefit in the older subgroup. The hazard ratio was 0.79 in patients younger than the median age of 75.2 years compared with 0.92 in patients aged >75.2 years, although this difference was not statistically significant.

  41. [beta]-Adrenoceptor Antagonists Therapeutic strategy ‘start low – go slow’ is crucial to [beta]-adrenoceptor antagonist treatment, particularly in elderly patients. [beta]-Adrenoceptor antagonists should be started at the lowest available dose and up-titrated at intervals of no less than 1 week (usually 2 weeks). At the same time, it is important to note that [beta]-adrenoceptor antagonist therapy should be initiated and up-titrated in all patients without absolute contraindications irrespective of age.

  42. Table III. Some properties of the four [beta]-adrenoceptor antagonists that may be used in heart failure From:   Leibundgut: Drugs Aging, Volume 24(12).2007.991-1006

  43. Aldosterone Receptor Antagonists

  44. Aldosterone Receptor Antagonists The aldosterone receptor antagonist spironolactone improved outcome by 30% in patients who remained symptomatic during daily life activities (New York Heart Association [NYHA] >= grade III) despite standard therapy in the RALES (Randomized Aldactone Evaluation Study) trial. The result was independent of age and was statistically significant in the prespecified subgroup of patients aged >67 years.

  45. Aldosterone Receptor Antagonists More selective aldosterone receptor antagonist eplerenone was investigated in patients with CHF 3–14 days after a myocardial infarction in the EPHESUS (Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study) trial. 15% relative risk reduction in all-cause mortality and a 13% relative risk reduction in death from cardiac causes or hospitalisation due to cardiovascular events. But the study was conducted in the era that beta-blockers not widely used.

  46. Aldosterone Receptor Antagonists EPHESUS trial subgroup analysis did not show a statistically significant difference between patients aged younger and older than 65 years But again a trend to lower efficacy in elderly patients was seen.

  47. Digoxin

  48. Digoxin • Digoxin is the only positive inotropic agent that does not increase mortality in patients with heart failure. It reduces the rate of hospitalisation.* *DIG. The effect of digoxin on mortality and morbidity in patients with heart failure: the Digitalis Investigation Group. N Engl J Med 1997; 336: 525-33 • But its toxicity must be considered, especially in the elderly.

  49. Digoxin A recent post hoc analysis of the DIG (Digitalis Intervention Group) trial revealed that Elderly patients and women are at particular risk for increased serum digoxin concentration (SDC) Other predictors of increased SDC were pulmonary congestion, use of diuretics and, as expected, impaired renal function, lower body mass index and digoxin dosage. Patients with an SDC of >=1 ng/mL had a worse outcome compared with placebo. Ahmed A, Rich MW, Love TE, et al. Digoxin and reduction in mortality and hospitalization in heart failure: a comprehensive post hoc analysis of the DIG trial. Eur Heart J 2006; 27: 178-86

  50. Digoxin A low dose of digoxin (0.0625-0.125 mg/day) may still be given to symptomatic patients and measurement of SDC is important. Digoxin currently has a class IIa recommendation in both European and American guidelines for patients in sinus rhythm with reduced left-ventricular systolic function who remain symptomatic while receiving standard medical therapy.

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