Outpatient Management of Heart Failure in the Elderly

1. Outpatient Management of Heart Failure in the Elderly Jocelyn D. Jones, PharmD, BCPS Associate Professor of Pharmacy Practice Florida A&M University College of Pharmacy and Pharmaceutical Sciences August 29, 2010

2. Objectives Discuss the prevalence of heart failure Review the classes and stages of heart failure Summarize differences between the young and the elderly Review the treatment options for the management of heart failure in the elderly

3. Prevalence 5.8 million people(US) Framingham Heart Study men 8 per 1000 (age 50 to 59 years) increasing to 66 per 1000 (ages 80 to 89 years) women (8 and 79 per 1000) 25% higher in African Americans 23 million worldwide >550,000 diagnosed each year More in women than men23 million worldwide >550,000 diagnosed each year More in women than men

4. Epidemiology 1,106,000 discharges 37.2 billion (2009) 80% of hospitalized are elderly HF related death 292,000 1 in 8 US deaths is HF related Heart failure discharges increased from 877,000 in 1996 (698,000 were 65 years of age or older) More healthcare costs are spent on the diagnosis and treatment of HF than on any other disease Despite improved pharmacotherapy for the management of ischemic heart disease, more patients survive to eventually develop HF and the rate of HF related death remains highHeart failure discharges increased from 877,000 in 1996 (698,000 were 65 years of age or older) More healthcare costs are spent on the diagnosis and treatment of HF than on any other disease Despite improved pharmacotherapy for the management of ischemic heart disease, more patients survive to eventually develop HF and the rate of HF related death remains high

5. NYHA Class I no limitations of activities of daily living (ADL) Class II Slight, mild limitations of ADL Comfortable at rest or with mild exertion Class III Marked limitations of ADL Comfortable only at rest Class IV Symptoms occur at rest Should be at complete rest Class IV- confined to bed or chair, any physical activity brings on discomfortClass IV- confined to bed or chair, any physical activity brings on discomfort

6. Stages of HF Stage A patients with coronary artery disease, hypertension, or diabetes mellitus Stage B patients who are asymptomatic but demonstrate LV hypertrophy (LVH) and/or impaired LV function Stage C patients with current or past symptoms of HF associated with underlying structural heart disease Stage D designates patients with truly refractory HF The HF writing committee previously developed a new approach to the classification of HF,2 one that emphasized both the development and progression of the disease. This classification system is intended to complement but in no way to replace the New York Heart Association (NYHA) functional classification, Stages A and B patients are best defined as those with risk factors that clearly predispose toward the development of HF. Stage A-who do not yet demonstrate impaired left ventricular (LV) function, hypertrophy, or geometric chamber distortion Stage C- bulk of pts with HFThe HF writing committee previously developed a new approach to the classification of HF,2 one that emphasized both the development and progression of the disease. This classification system is intended to complement but in no way to replace the New York Heart Association (NYHA) functional classification, Stages A and B patients are best defined as those with risk factors that clearly predispose toward the development of HF. Stage A-who do not yet demonstrate impaired left ventricular (LV) function, hypertrophy, or geometric chamber distortion Stage C- bulk of pts with HF

7. Independent Risk factors Male gender (risk ratio=1.4) Hypertension (risk ratio=2.5) Coronary artery disease (risk ratio= 4.0) Diabetes mellitus (risk ratio=1.6) Age (risk ratio=1.05)

8. Systolic versus diastolic Abnormal left ventricular ejection fraction (LVEF) <50% = systolic heart failure Normal LVEF = 50% = diastolic heart failure Diastolic HF increases with age (50%) LVSD- decrease in contractility of the left ventricle to provide adequate blood supply to the rest of the body. Diastolic left ventricular dysfunction is impaired relaxation of the left ventricle usually related to chronic hypertension or ischemic heart disease. Impaired or preserved systolic functionLVSD- decrease in contractility of the left ventricle to provide adequate blood supply to the rest of the body. Diastolic left ventricular dysfunction is impaired relaxation of the left ventricle usually related to chronic hypertension or ischemic heart disease. Impaired or preserved systolic function

9. Differences between the young and old Physiological alterations Weight loss, lower cholesterol, lower heart rate, reduced heart rate response to exercise, lower blood pressure Risk assessment and therapeutic goals different Presence of dementia Survival is no longer the primary goal Cachexia, low cholesterol are poor prognostic signs in heart failure and old age. Dementia- survival is no longer the primary goal. Assessment of the patient�s history may be less reliable and adherence to recommendations my be reduced. Involvement of Relatives and institutions becomes much more important.Cachexia, low cholesterol are poor prognostic signs in heart failure and old age. Dementia- survival is no longer the primary goal. Assessment of the patient�s history may be less reliable and adherence to recommendations my be reduced. Involvement of Relatives and institutions becomes much more important.

10. Differences between the young and old Co-morbidities and co-medication Highly prevalent in the elderly May limit therapeutic options Reduction of reserves and compensatory mechanisms Increase with age Reduced heart rate Less studied Preserved left ventricular ejection fraction (diastolic dysfunction) In pts >75, <10% have no additional co-morbidity. Co-morbidities directly and independently worsens prognosis. Increased risk of drug interactions and adverse effects as a result of polypharmacy. Makes use of most drugs used for HF treatment difficult Less studied- women, diastolic dysfunction In pts >75, <10% have no additional co-morbidity. Co-morbidities directly and independently worsens prognosis. Increased risk of drug interactions and adverse effects as a result of polypharmacy. Makes use of most drugs used for HF treatment difficult Less studied- women, diastolic dysfunction

11. Initial Assessment Class I Recommendations Thorough history and PE Assessment of ability to perform ADL Volume status, orthostatic blood pressure changes, measurement of weight and height, and calculation of body mass index Twelve-lead ECG and chest radiograph (posterior-anterior and lateral) ECHO History of alcohol or illicit drug use, chemotherapy drug use. BNP conc might increase with age, especially women, making it a less reliable diagnostic tool in older patients than in younger patients. BNP >400 pg/mL strongly suggest HF. History of alcohol or illicit drug use, chemotherapy drug use. BNP conc might increase with age, especially women, making it a less reliable diagnostic tool in older patients than in younger patients. BNP >400 pg/mL strongly suggest HF.

12. Class I Recommendations Obtain laboratory tests complete blood count urinalysis serum electrolytes (including calcium and magnesium) blood urea nitrogen serum creatinine fasting blood glucose (glycohemoglobin), lipid profile liver function tests thyroid-stimulating hormone

13. Treatment Recommendations FHx CM- Family history of cardiomyopathyFHx CM- Family history of cardiomyopathy

14. Diuretics ACC/AHA recommends with sodium restriction Rapid reduction of fluid overload No long term studies aldosterone antagonists Post hoc analysis have suggested unfavourable effects on prognosis Produce symptomatic benefits more rapidly than any other drug for HF. They can relieve pulmonary and peripheral edema within hours or days, whereas the clinical effects of digitalis, ACEIs, or beta blockers may require weeks or months to become apparent Diuretics may cause renin-angiotensin-aldosterone system activation, possibly leading to increased morbidity and mortality despite short-term symptomatic improvementProduce symptomatic benefits more rapidly than any other drug for HF. They can relieve pulmonary and peripheral edema within hours or days, whereas the clinical effects of digitalis, ACEIs, or beta blockers may require weeks or months to become apparent Diuretics may cause renin-angiotensin-aldosterone system activation, possibly leading to increased morbidity and mortality despite short-term symptomatic improvement

15. Important Points Interpatient and intrapatient variability of furosemide bioavailability in patients >65 years (mean 49%; range, 12%-112%) Low dose and high dose Increase dose until� Net urinary output increases to 0.5-1L/day Weight decreases 0.5-1kg/day Interpatient and intrapatient Based on these findings, intrapatient and interpatient variability in absorption might be considerable in the elderly patient population. Elderly patients are susceptible to orthostatic hypotension and worsening of renal function due to overdiuresis, close monitoring of individual response to treatment with diuretics is necessary in this patient population. Dosing A diuretic dose that is too low to provide an adequate clinical response might result in fluid retention, which may lead to diminished response to ACEI and decreased tolerability to Beta blocker therapy. High dose- volume contraction, increased risk of hypotension with the use of ACEI, B-blocker, and/or vasodilator, and/or risk for renal insufficiency with the use of an ACEI or an ARB Recommended to start low and increase dose until�. Interpatient and intrapatient Based on these findings, intrapatient and interpatient variability in absorption might be considerable in the elderly patient population. Elderly patients are susceptible to orthostatic hypotension and worsening of renal function due to overdiuresis, close monitoring of individual response to treatment with diuretics is necessary in this patient population. Dosing A diuretic dose that is too low to provide an adequate clinical response might result in fluid retention, which may lead to diminished response to ACEI and decreased tolerability to Beta blocker therapy. High dose- volume contraction, increased risk of hypotension with the use of ACEI, B-blocker, and/or vasodilator, and/or risk for renal insufficiency with the use of an ACEI or an ARB Recommended to start low and increase dose until�.

16. Loop vs Thiazide Diuretics Loop diuretics increase sodium excretion enhance free water clearance CrCL <10ml/min Torsemide- longer duration and superior action Thiazide diuretics increase fractional excretion of sodium decrease free water clearance CrCl<30ml/min Metolazone Loop diuretics Up to 25% of the filtered load Efficacy is maintained unless the renal function is severely impaired Thiazide diuretics By 5 to 10% of the filtered load Effectiveness is lost in patients with moderate renal dysfunction Metolazone is used in combination with loop diuretics for their synergistic effect. Used in pts who are resistant to increasing doses of loop diuretics. Loop diuretics Up to 25% of the filtered load Efficacy is maintained unless the renal function is severely impaired Thiazide diuretics By 5 to 10% of the filtered load Effectiveness is lost in patients with moderate renal dysfunction Metolazone is used in combination with loop diuretics for their synergistic effect. Used in pts who are resistant to increasing doses of loop diuretics.

17. Adverse effects Electrolyte imbalances hypokalemia hypomagnesemia digoxin increased with 2 non-potassium sparing diuretics ACEI or ARB alone or in combination with an aldosterone antagonist reduces risk hypotension and azotemia These imbalances should be treated aggressively to prevent arrhythmia. Very impt for patients receiving digoxin because hypokalemia and hypomagnesemia have been associated with an increased risk of digoxin induced arrhythmia. Can be corrected with potassium supplements or if severe, magnesium supplements ACEI or ARB Reduces risk of electrolyte depletion in pts receiving a loop diuretic If hypotension and azotemia are observed before the goals of treatment are reached, a decrease in dose should be considered.These imbalances should be treated aggressively to prevent arrhythmia. Very impt for patients receiving digoxin because hypokalemia and hypomagnesemia have been associated with an increased risk of digoxin induced arrhythmia. Can be corrected with potassium supplements or if severe, magnesium supplements ACEI or ARB Reduces risk of electrolyte depletion in pts receiving a loop diuretic If hypotension and azotemia are observed before the goals of treatment are reached, a decrease in dose should be considered.

18. Last Point on Diuretics Fluid retention resolves Maintain treatment to prevent volume overload Use minimal effective dose Frequent adjustments may be needed Close monitoring is mandatory Based on the patient�s fluid and hemodynamic status. Close monitoring- renal function and electrolytes Risks of dehydration and hypotension must always be considered since the clinical features may be nonspecific in these patientsBased on the patient�s fluid and hemodynamic status. Close monitoring- renal function and electrolytes Risks of dehydration and hypotension must always be considered since the clinical features may be nonspecific in these patients

19. Angiotensin Converting Enzyme Inhibitors (ACEI) First line therapy All pts with LV systolic dysfunction Long term with B-blocker Several large cohort studies in elderly Demonstrate benefit on hospitalization rate and survival Increasing age- independent predictor of ACEI non-use Preferred over ARBs and vasodilators Significantly reduces total mortality and morbidity in pts with HF Preferred- greater experience and evidenceSignificantly reduces total mortality and morbidity in pts with HF Preferred- greater experience and evidence

20. Angiotensin Converting Enzyme Inhibitors 34 double blind RCTs HF with LVEF<40% Significant reduction in total mortality OR 0.77; 95% CI, 0.67-0.88;p <0.001 Significant reduction in the combined end point of mortality and hospitalization OR 0.65;95% CI, 0.57-0.74; p<0.001 The ACC/AHA recommends the use of ACEI in pts with LVEF <40%, regardless of the presence of clinical symptoms of HFThe ACC/AHA recommends the use of ACEI in pts with LVEF <40%, regardless of the presence of clinical symptoms of HF

21. Important tips Start low, go slow Monitor renal function and serum potassium ? SCr 30-50% ? K+ to 5-5.5 mmol/L Prodrugs Watch fluid status Diuretic doses-IMPORTANT Abrupt withdrawal- NOT RECOMMENDED Should be initiated at a low dose, followed by a gradual up-titration if tolerated. Up to the target dose. If target dose cannot be tolerated, Beta blockers should be initiated without delay Monitor 1 to 2 weeks of treatment initiation and periodically thereafter, esp in pts with preexisting hypotension, hyponatremia, diabetes, or azotemia and those receiving potassium supplements. Prodrugs- most ACEI are prodrugs. Captopril and lisinopril, which are given as active drugs, might be preferred in pts with hepatic failure. Angiotensin converting enzyme inhibitors should not be prescribed without diuretics in patients with a current or recent history of fluid retention, because diuretics are needed to maintain sodium balance and prevent the development of peripheral and pulmonary edema Fluid retention can blunt the therapeutic effects of ACEI Fluid depletion can potentiate the adverse events associated with ACEI Pts should be given an appropriated dose of a diuretic before and during treatment with an ACEI to maintain fluid balance Abrupt withdrawal can lead to clinical deterioration. Avoid unless life threatening angioedema. Should be initiated at a low dose, followed by a gradual up-titration if tolerated. Up to the target dose. If target dose cannot be tolerated, Beta blockers should be initiated without delay Monitor 1 to 2 weeks of treatment initiation and periodically thereafter, esp in pts with preexisting hypotension, hyponatremia, diabetes, or azotemia and those receiving potassium supplements. Prodrugs- most ACEI are prodrugs. Captopril and lisinopril, which are given as active drugs, might be preferred in pts with hepatic failure. Angiotensin converting enzyme inhibitors should not be prescribed without diuretics in patients with a current or recent history of fluid retention, because diuretics are needed to maintain sodium balance and prevent the development of peripheral and pulmonary edema Fluid retention can blunt the therapeutic effects of ACEI Fluid depletion can potentiate the adverse events associated with ACEI Pts should be given an appropriated dose of a diuretic before and during treatment with an ACEI to maintain fluid balance Abrupt withdrawal can lead to clinical deterioration. Avoid unless life threatening angioedema.

22. ACEI-Adverse events Orthostatic hypotension Hypovolemia or hyponatremia Decrease dose of concurrent diuretics/ antihypertensives Decreased renal function ?SCr in 15 to 30% of pts with severe HF 5 to 15% of pts with mild to moderate HF Bilateral renal artery stenosis and concurrent NSAIDS Improvement with diuretic dose reduction Hyperkalemia Cough Angioedema Prevalence is ~50%. Reported more frequently in the first few days of treatment initiation of after an increase in dosage. The ACC/AHA recommends that if symptomatic hypotension occurs with administration of the first dose, a second dose might be tried with close monitoring. It may recur with repeated administration. The dosage of concurrent antihypertensive agents might need to be temporarily reduced and/or administration times staggered so that the peak effect does not coincide with that of the ACEI Glomerular filtration is critically dependent on angiotensin mediated efferent arteriolar vasoconstriction. ACEI may cause functional renal insufficiency by inhibiting angiotensin and leading to efferent arteriolar vasodilation Renal function may improve after reduction in the dose of the diuretic. If the dosage of the diuretic cannot be reduced because the patient has fluid retention, then the dose of ACEI may need to be reduced. Cough occurs in 5 to 10% of white patients and 50% Chinese patients Angioedema- <1% of pts Alternative treatment is an ARB (candesartan, valsartan). Angioedema has been reported to develop with ARB use after the occurrence of angioedema with ACE inhibition or independent of treatment with an ACEI. In the CHARM-Alternative study, angioedema with candesartan use was 7.7%Prevalence is ~50%. Reported more frequently in the first few days of treatment initiation of after an increase in dosage. The ACC/AHA recommends that if symptomatic hypotension occurs with administration of the first dose, a second dose might be tried with close monitoring. It may recur with repeated administration. The dosage of concurrent antihypertensive agents might need to be temporarily reduced and/or administration times staggered so that the peak effect does not coincide with that of the ACEI Glomerular filtration is critically dependent on angiotensin mediated efferent arteriolar vasoconstriction. ACEI may cause functional renal insufficiency by inhibiting angiotensin and leading to efferent arteriolar vasodilation Renal function may improve after reduction in the dose of the diuretic. If the dosage of the diuretic cannot be reduced because the patient has fluid retention, then the dose of ACEI may need to be reduced. Cough occurs in 5 to 10% of white patients and 50% Chinese patients Angioedema- <1% of pts Alternative treatment is an ARB (candesartan, valsartan). Angioedema has been reported to develop with ARB use after the occurrence of angioedema with ACE inhibition or independent of treatment with an ACEI. In the CHARM-Alternative study, angioedema with candesartan use was 7.7%

23. Angiotensin II Receptor Blockers

24. Val-HeFT 5010 pts with NYHA class II to IV HF (LVEF <40%) valsartan 160mg BID versus placebo 62.5 years (18-96) ACEI, B-blocker, and/or diuretic 27 months of follow up (19.7% vs 19.4%, valsartan vs placebo) Overall mortality was not significantly different between the 2 groups. However, the primary end point, a combination of mortality and morbidity (including cardiac arrest with resuscitation, hospitalization for HF, or receipt of IV inotropic or vasodilator therapy for >4 hours) was 13.2% lower with valsartan than with placebo (RR 0.87; 97.5% CI, 0.77-0.97). Overall mortality was not significantly different between the 2 groups. However, the primary end point, a combination of mortality and morbidity (including cardiac arrest with resuscitation, hospitalization for HF, or receipt of IV inotropic or vasodilator therapy for >4 hours) was 13.2% lower with valsartan than with placebo (RR 0.87; 97.5% CI, 0.77-0.97).

25. Val-HeFT Post hoc analysis Valsartan with an ACEI RR=0.57; 95% CI, 0.34-0.90 Valsartan without an ACEI RR=0.83; 95% CI, 0.72-0.95 Valsartan with ACEI and B-blocker RR=1.20; 95% CI, 0.99-1.45 Valsartan was associated with a favorable effect in pts who were receiving an ACEI and those who were notValsartan was associated with a favorable effect in pts who were receiving an ACEI and those who were not

26. CHARM-Alternative Trial R, DB 2028 pts Symptomatic HF and LVEF <40% not receiving an ACEI Mean age 66.5 years Candesartan 32mg once daily or placebo 33.7 mo f/u 33% candesartan vs. 40% placebo had CV disease related death or hospitalization Pts >75 years was 23.5%Pts >75 years was 23.5%

27. When to use an ARB? It is not recommended that an ARB be routinely added to the regimens of patients receiving current treatment with both an ACE inhibitor and a B-blocker Valsartan and candesartan serve as an alternative to those who cannot tolerate an ACEI Up titrate to target doses

28. ?eta Blockers ACC/AHA recommends beta blockers in addition to ACEI and a diuretic bisoprolol, SR metoprolol succinate, carvedilol 20,000 pts evaluated Initiate in elderly with reduced LVEF unless contraindicated Not without a diuretic� The effects of B-blockers have been evaluated in >20,000 pts with HF. These studies included elderly pts. Contraindications- bradycardia, decompensated HF, cardiogenic shock, sick sinus syndrome, second or third degree heart block In pts with current or recent fluid retention, beta blockers should not be prescribed without diuretics, because diuretics are needed to maintain sodium and fluid balance and prevent the exacerbation of fluid retention that can accompany the initiation of beta-blocker therapy The effects of B-blockers have been evaluated in >20,000 pts with HF. These studies included elderly pts. Contraindications- bradycardia, decompensated HF, cardiogenic shock, sick sinus syndrome, second or third degree heart block In pts with current or recent fluid retention, beta blockers should not be prescribed without diuretics, because diuretics are needed to maintain sodium and fluid balance and prevent the exacerbation of fluid retention that can accompany the initiation of beta-blocker therapy

29. Meta Analysis Dulin et al meta-analysis 5 clinical trials 12,729 pts (36.3% elderly) mortality in elderly (=65 years)vs. nonelderly (=65 years) elderly RR=0.76; nonelderly RR=0.66 no statistically significant difference

30. SENIORS Trial DB,PC 2128 elderly (age=70 years) h/o stable HF with LVEF <35% Nebivolol 1.25mg/day up to 10mg/day 12 mo f/u-14% reduction in all cause mortality or hospitalization for CV events Assessing the effects of nebivolol on morbidity and mortality Titrated by 2.5mg day every 1 to 2 weeks as toleratedAssessing the effects of nebivolol on morbidity and mortality Titrated by 2.5mg day every 1 to 2 weeks as tolerated

31. When to initiate a beta blocker� Not in an ICU No or minimal evidence of fluid overload or volume depletion No recent treatment with an intravenous positive inotropic agent.

32. More about Beta blockers Adverse Events fluid retention (5%) report excessive gains (>2kg/d) fatigue (23%) self limiting and resolves slowly increase or reduce doses difficult to differentiate bradycardia (9%)and hypotension (10%) esp carvedilol start low and titrate slow Fluid retention commonly (5%) occurs during initiation due to its negative inotropic effects. Diuretic dose may need to be increased Fatigue Treatment discontinuation is seldom warranted unless there is worsening renal function. In geriatric pts it is difficult to differentiate between fatigue caused by b-blocker use or due to a comorbidity (anemia or other medication) Bradycardia and hypotension may present as lightheadedness, dizziness, or blurred vision. Worrisome in geriatric pts who might be suspectible to falls, which may lead to additional adverse consequences If accompanied by signs of hypoperfusion (cold extremities, worsening of renal or hepatic function), decrease or d/c treatment Titrate at 1-2 week intervals Fluid retention commonly (5%) occurs during initiation due to its negative inotropic effects. Diuretic dose may need to be increased Fatigue Treatment discontinuation is seldom warranted unless there is worsening renal function. In geriatric pts it is difficult to differentiate between fatigue caused by b-blocker use or due to a comorbidity (anemia or other medication) Bradycardia and hypotension may present as lightheadedness, dizziness, or blurred vision. Worrisome in geriatric pts who might be suspectible to falls, which may lead to additional adverse consequences If accompanied by signs of hypoperfusion (cold extremities, worsening of renal or hepatic function), decrease or d/c treatment Titrate at 1-2 week intervals

33. Aldosterone antagonists ACC/AHA recommends as an addition to the HF regimen in pts with moderate to severe HF symptoms Careful monitoring of renal function and potassium concentrations SCr =2.5mg/dL in men or =2.0mg/dL in women K+ =5mEq/L NYHA class III and IV Monitoring- If monitoring of hyperkalemia or renal dysfunction is not feasible, the risks outweigh the benefits of treatment.NYHA class III and IV Monitoring- If monitoring of hyperkalemia or renal dysfunction is not feasible, the risks outweigh the benefits of treatment.

34. RALES 1663 patients NYHA class III and IV HF median age of 67 years Spironolactone 12.5mg once daily up to 25mg or placebo added to HF regimen of ACEI and/or diuretic RR reduction=30%; p<0.01 at 2 yrs

35. EPHESUS 3313 pts 64 years LVEF=40% and evidence of HF Eplerenone 25 to 50mg once daily significant reduction in mortality at 1 yr (from 13.6% to 11.8%; p=0.008) hyperkalemia-10.1% vs 4.6% (p=0.04) 3-14 days post myocardial infarction3-14 days post myocardial infarction

36. How to use aldosterone antagonists? Low dose aldosterone antagonist Assess renal function before treatment initiation Use low dose when combined with ACEI or ARB Avoid in CrCl<30ml/min K+ supplements K+ monitoring ACEI or ARB addition or dose increase >5.5mEq/L- reduce or d/c Should be used in elderly pts with moderate to severe HF Because elderly might be at risk for renal insufficiency, assess renal function before treatment initiation Spironolactone 12.5mg once daily or eplerenone 25mg once daily K+ supplements should be reduced or discontinued when aldosterone antagonist treatment is initiated K+ should be monitored 3 to 7 days after treatment initiation, monthly for the first 3 months, and every 3 months thereafter. ACEI and ARB Trigger a new cycle of monitoring If gynecomastia is a problem, consider eplerenoneShould be used in elderly pts with moderate to severe HF Because elderly might be at risk for renal insufficiency, assess renal function before treatment initiation Spironolactone 12.5mg once daily or eplerenone 25mg once daily K+ supplements should be reduced or discontinued when aldosterone antagonist treatment is initiated K+ should be monitored 3 to 7 days after treatment initiation, monthly for the first 3 months, and every 3 months thereafter. ACEI and ARB Trigger a new cycle of monitoring If gynecomastia is a problem, consider eplerenone

37. The last resort Digoxin Add to HF regimen in pts with LVSD with symptoms that persist therapy after optimization Digitalis Investigation Group 6800 pts HF symptoms and LVEF <45% Not associated with significant effect on mortality Reduced risk for hospitalization for worsening HF (RR=0.72; p<0.001) After optimization of treatment with an ACEI, a b-blocker, and/or a diuretic The only positive inotropic agent that does not increase mortality in pts with heart failure 27% enrolled were >70 years of ageAfter optimization of treatment with an ACEI, a b-blocker, and/or a diuretic The only positive inotropic agent that does not increase mortality in pts with heart failure 27% enrolled were >70 years of age

38. Caution in Elderly Initial dose 0.125mg daily or qod Loading dose not necessary 0.5-1.0 ng/mL Risk adjusted mortality increased >1.0 ng/mL Pulmonary congestion, diuretic use, impaired renal function, low body mass Monitor for adverse events Nausea, vomiting, visual disturbances, cardiac arrhythmia Sinus or AV block Drug-drug interactions The post hoc analysis of the DIG revealed that elderly pts and women are at risk of increased serum digoxin concentrations. It reduces the rate of hospitalization, but its toxicity must be considered In pts >70 years Loading dose- goal of treatment is long term reduction in the risk for hospitalization, not an acute reduction of symptoms Therapeutic digoxin concentration- Despite the conventional 0.8-2 ng/mL. >1.0ng/mL had a worse outcome compared with placebo and a smaller reduction in hospitalization due to heart failure. Adverse events may be associated with concurrent medications. Sinus or AV Block Elderly have a high risk of intrinsic risk. Digoxin use can worsen such a block. Therefore, unless the block has been addressed with a permanent pacemaker, digoxin should not be used. Drug-Drug Interactions Amiodarone, verapamil, and qunidine. Dose should be reduced if treatment with =1 of these drugs is initiated. The post hoc analysis of the DIG revealed that elderly pts and women are at risk of increased serum digoxin concentrations. It reduces the rate of hospitalization, but its toxicity must be considered In pts >70 years Loading dose- goal of treatment is long term reduction in the risk for hospitalization, not an acute reduction of symptoms Therapeutic digoxin concentration- Despite the conventional 0.8-2 ng/mL. >1.0ng/mL had a worse outcome compared with placebo and a smaller reduction in hospitalization due to heart failure. Adverse events may be associated with concurrent medications. Sinus or AV Block Elderly have a high risk of intrinsic risk. Digoxin use can worsen such a block. Therefore, unless the block has been addressed with a permanent pacemaker, digoxin should not be used. Drug-Drug Interactions Amiodarone, verapamil, and qunidine. Dose should be reduced if treatment with =1 of these drugs is initiated.

39. Vasodilators Add combination nitrates and hydralazine in pts whose symptoms persist despite treatment with an ACEI and B-blocker Intolerance to ACEI or ARB V-HeFT and A-HeFT Unknown proportion of pts >65 years Questionable benefit in elderly Hypotension and headache Because the elderly might have difficulties tolerating ACEI due to renal dysfunction, the guidelines recommend the use of nitrates and hydralazine as reasonable alternative Hypotension and headache limit their use in the elderly Because the elderly might have difficulties tolerating ACEI due to renal dysfunction, the guidelines recommend the use of nitrates and hydralazine as reasonable alternative Hypotension and headache limit their use in the elderly

40. Calcium Channel Blockers Not to be administered to patients with systolic HF May be administered to pts with diastolic HF and symptoms despite diuretics, beta blockers, ACEIs, and isosorbide dinitrate plus hydralazine

41. Summary Careful monitoring Adjustments for pharmacokinetic and pharmacodynamic changes Consideration of individual requirements and wishes Risks versus benefits Multidisciplinary approach needed Due to low adherence and low use of recommended drugs in the elderlyDue to low adherence and low use of recommended drugs in the elderly

42. References Aronow WS. Drug treatment of systolic and of diastolic heart failure in elderly persons. J Gerontol. 2005;159-1605. Cheng JWM, Nayar M. A review of heart failure management in the elderly populations. Am J of Geriatr Pharmacother. 2009;7:233-49. Leibundgut G, Pfisterer M, La Rocca PB. Drug treatment of chronic failure in the elderly. Drugs Aging. 2007;24(12):991-1006. Dulin BR, Haas SJ, Abraham WT, Krum H. Do elderly systolic heart failure patients benefit from beta blockers to the same extent as the non-elderly? Meta-analysis of >12,000 patients in large-scale clinical trials. Am J Cardiol. 2005;95:896-98. Ghio S, Magrini G, Serio A, et al, for the SENIORS investigators. Effects of nebivolol in elderly heart failure patients with or without systolic left ventricular dysfunction. Eur Heart J. 2006;27:562-68. Pitt B, Zannad F, Remme WJ, et al for the Randomized Aldactone Evaluation Study Investigators. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med. 1999;341:709-17.

43. References Pitt B, Remme W, Zannad F, et al, for the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study Investigators. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 2003;348:1309-21. Digitalis Investigation Group. The effect of digoxin on mortality and morbidity in patients with heart failure. N Engl J Med. 1997;336:525-33. Granger CB, McMurray JJ, Yusuf S, et al, for the CHARM Investigators and Committees. 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;362:772-76. Cohn JN, Tognoni G, for the Valsartan Heart Failure Trial Investigators. A randomized trial of angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med. 2001;345:1667-75.