Optimizing CHF Therapy: The Role of Digoxin, Diuretics, and Aldosterone Antagonists Old Drugs for an Old Problem Jay Geoghagan, MD, FACC BHHI Primary Care Symposium February 28, 2014
None. Financial disclosures
Clinical Scenario J.R. is a 57 yo WM with an ischemic cardiomyopathy and EF 30%. He is six months out from an anterior MI with primary stenting performed. He has been hospitalized in the last year with symptomatic heart failure. Presently, he has mild DOE most every day. He has clear lungs and mild pedal edema. His Scr is 1.8 and K 4.4.
Clinical Scenario He is presently on an ACEI and betablocker at recommended doses and his BP is adequately controlled. He dislikes medications but hates hospitalizations even more. Which Guideline Directed Medical Therapies (GDMT) should be instituted to help further reduce his morbidity and mortality?
Clinical Scenario What is the heart failure stage and functional classification for this patient? Structural heart disease (EF 30%) with prior or current symptoms of heart failure (recently hospitalized). ACC Stage C Mild DOE with symptoms on most days. NYHA Class II
Clinical Scenario Why is this important? Therapies are driven by this classification. Digoxin, Diuretics, and Aldosterone Antagonists are used for symptomatic heart failure.
Stages, Phenotypes and Treatment of HF
So What Do We Do for J.R.? He has clinical signs of volume overload. He has been hospitalized within the last year for heart failure symptoms.
Pharmacologic Treatment for Stage C HFrEF
Pharmacological Treatment for Stage C HFrEF (cont.) Diuretics are recommended in patients with HFrEF who have evidence of fluid retention, unless contraindicated, to improve symptoms (COR I, LOE C). Loop diuretics given at a dose that results in euvolemia. At present, there is no evidence to favor one loop diuretic over another.
Pharmacological Treatment for Stage C HFrEF (cont.) Furosemide 20 to 40 mg once or twice daily. Maximum daily dose 600mg. Bumetanide 0.5 to 1.0 mg once or twice daily. Maximum daily dose 10mg. Torsemide 10 to 20 mg once daily. Maximum daily dose 200mg.
Pharmacological Treatment for Stage C HFrEF (cont.) In individual cases, one agent may work better than another. For severe cases, a thiazide type diuretic (e.g. metolazone) may be added for additional diuresis. All can cause prerenal azotemia and hypokalemia so appropriate monitoring should be employed.
So What Do We Do for J.R.? A loop diuretic is clearly appropriate. Careful discussion to avoid excess sodium. Avoidance of medications that interfere such as NSAIDS. Make sure there are not other medications responsible. Calcium channel blockers Glitazones Unfortunately, many of us stop here.
Can We Do More for Him? Are there other GDMT that should be employed?
Pharmacologic Treatment for Stage C HFrEF
Pharmacological Treatment for Stage C HFrEF (cont.) Aldosterone receptor antagonists are recommended in patients with NYHA class II-IV and who have LVEF of 35% or less to reduce morbidity and mortality. (COR 1, LOE A) Patients with NYHA class II should have a history of prior cardiovascular hospitalization or elevated plasma natriuretic peptide levels to be considered for aldosterone receptor antagonists. Creatinine should be 2.5 mg/dl or less in men or 2.0 mg/dl or less in women (or estimated glomerular filtration rate >30 ml/min/1.73m2) and potassium should be less than 5.0 meq/l.
Pharmacological Treatment for Stage C HFrEF (cont.) Spironolactone Start 12.5 to 25 mg once daily Maximum 25 mg once or twice daily Mean dose in clinical trials 26 mg/d Eplerenone Start 25 mg once daily Maximum 50 mg once daily Mean dose in clinical trials 42.6 mg/d
A Word About Nitrates/Hydralazine The combination of hydralazine and isosorbide dinitrate is recommended to reduce morbidity and mortality for patients self-described as African Americans with NYHA class III IV HFrEF receiving optimal therapy with ACE inhibitors and beta blockers, unless contraindicated (COR I, LOE A). A combination of hydralazine and isosorbide dinitrate can be useful to reduce morbidity or mortality in patients with current or prior symptomatic HFrEF who cannot be given an ACE inhibitor or ARB because of drug intolerance, hypotension, or renal insufficiency, unless contraindicated (COR IIa, LOE B).
Pharmacological Treatment for Stage C HFrEF (cont.) What is the magnitude of benefit for each therapy?
Medical Therapy for Stage C HFrEF: Magnitude of Benefit Demonstrated in RCTs GDMT RR Reduction in Mortality NNT for Mortality Reduction (Standardized to 36 mo) RR Reduction in HF Hospitalizations ACE inhibitor or ARB 17% 26 31% Beta blocker 34% 9 41% Aldosterone antagonist 30% 6 35% Hydralazine/nitrate 43% 7 33%
What Role for Digoxin? Digoxin can be beneficial in patients with HFrEF, unless contraindicated, to decrease hospitalizations for HF (COR IIa, LOE B). Added at low doses (0.125-0.25mg daily) to those already receiving GDMT. No mortality benefit. Narrow therapeutic range. High doses are not recommended.
So What Do We Do for J.R.? Add a diuretic and teach him about sodium and monitoring his weight. Once he is euvolemic, add an aldosterone antagonist with proper monitoring. Refer for ICD evaluation, but that s another talk.
Bottom Line! Diuretics treat volume overload. All patients with symptomatic heart failure should be considered for aldosterone antagonists. A combination of nitrates and hydralazine should be used if a patient can not take an ACEI or ARB. Digoxin is used for symptomatic patients who are on appropriate GDMT.
Questions?