Medication Categories for Cardiomyopathy and Congestive Heart Failure
Core Pharmacological Categories for Heart Failure with Reduced Ejection Fraction (HFrEF)
The four foundational medication classes for HFrEF now include ACE inhibitors/ARBs/ARNi, beta-blockers, mineralocorticoid receptor antagonists, and SGLT2 inhibitors, all of which should be initiated and optimized to improve survival and reduce morbidity. 1
1. Renin-Angiotensin-Aldosterone System (RAAS) Inhibitors
ACE Inhibitors: First-line therapy for all patients with significantly reduced left ventricular ejection fraction unless contraindicated 1. Examples include enalapril, lisinopril, and captopril. These agents improve survival, reduce hospitalizations, and attenuate ventricular remodeling 2.
Angiotensin II Receptor Blockers (ARBs): Alternative for patients who cannot tolerate ACE inhibitors due to cough or angioedema 1. Examples include valsartan, losartan, and candesartan. Valsartan specifically demonstrated efficacy in heart failure trials 3.
Angiotensin Receptor-Neprilysin Inhibitors (ARNi): Sacubitril/valsartan represents a newer option with Class 2a recommendation for HFmrEF and Class 2b for HFpEF 1.
Aldosterone Antagonists/Mineralocorticoid Receptor Antagonists (MRAs): Spironolactone or eplerenone should be added for patients with functional class III-IV heart failure who have adequate renal function (creatinine ≤2.5 mg/dL in men or ≤2.0 mg/dL in women) and normal potassium (<5.0 mEq/L) 1, 4, 5. These agents reduce sudden death risk in severe symptomatic heart failure 2.
2. Beta-Adrenergic Antagonists (Beta-Blockers)
Recommended for all stable patients with HFrEF, starting with very low doses (bisoprolol 1.25 mg, carvedilol 3.125 mg twice daily, or metoprolol succinate 12.5-25 mg once daily) and doubling every 1-2 weeks if tolerated 5.
Particularly beneficial for patients with dilated cardiomyopathy and high-risk patients after acute myocardial infarction 1.
In restrictive cardiomyopathy, beta-blockers decrease heart rate to increase diastolic filling period, allowing better ventricular filling 4.
Evidence shows attenuation of ventricular remodeling, improvement in ventricular function, and enhanced survival when added to ACE inhibitors 2.
3. Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors
Now included as the fourth foundational medication class for HFrEF with Class 1 recommendation 1.
Class 2a recommendation for HFmrEF and HFpEF, representing a significant advance in treatment options 1.
Examples include dapagliflozin and empagliflozin.
4. Diuretics
Loop Diuretics: Essential for managing fluid overload and congestion 1, 5. Examples include furosemide (20-40 mg), bumetanide (0.5-1.0 mg), and torsemide (10-20 mg once daily) 4.
Primarily provide symptom relief without proven mortality reduction 5.
Critical caveat in restrictive cardiomyopathy: Must use judiciously with low initial doses to avoid excessive preload reduction, as the ventricle is critically dependent on adequate filling pressures; excessive diuresis can precipitate severe hypotension and low cardiac output 4.
Thiazide Diuretics: Can be combined with loop diuretics in diuretic-resistant patients 6.
Aldosterone Inhibitors: Listed separately above as they provide prognostic benefit beyond diuresis 1.
5. Cardiac Glycosides
Digoxin: Indicated for patients with heart failure due to systolic dysfunction not adequately responsive to ACE inhibitors and diuretics 1. Also used for rate control in atrial fibrillation with rapid ventricular rates 1.
Relatively low dosages recommended (serum concentrations ≤1.0 ng/dL) 2.
Improves hemodynamics and symptomatology by increasing inotropy, though prognostic effects remain unproven 7.
6. Vasodilators
Hydralazine and Isosorbide Dinitrate Combination: Recommended for patients who cannot take ACE inhibitors 1. Can be added for patients not responding adequately to ACE inhibitors 1.
Nitrates: Nitroglycerin (topical, oral, or sublingual) for symptom management 1. Useful in diastolic dysfunction to reduce filling pressures 1.
Oral Vasodilators: Other agents beyond those specified above, most commonly nitrates and hydralazine 1.
7. Intravenous Agents for Acute/Refractory Heart Failure
IV Inotropic Agents: Dobutamine (2-5 µg/kg/min low dose preferred) or milrinone (50 µg/kg loading dose, then 0.375-0.75 µg/kg/min) for temporary improvement in cardiac output and renal blood flow 1.
IV Natriuretic Peptides: Nesiritide for acute decompensation 1.
IV Vasodilators: For acute management of severe symptoms 1.
8. Calcium Channel Blockers
Generally contraindicated in systolic heart failure in the absence of coexistent angina or hypertension (Class III recommendation) 1.
Verapamil: May be used in restrictive cardiomyopathy and hypertrophic cardiomyopathy to decrease heart rate and increase diastolic filling period 4. Can improve diastolic dysfunction by augmenting ventricular relaxation 1.
Nifedipine: Particularly contraindicated due to potent vasodilating properties, especially with outflow obstruction 1.
9. Antiarrhythmic Agents
Amiodarone: Preferred antiarrhythmic in heart failure as it does not depress left ventricular function 1, 6. May improve survival in patients with nonischemic cardiomyopathy 1.
Other antiarrhythmics generally contraindicated in heart failure; specific indications should be noted if used 1.
Caution: Avoid combination therapy with disopyramide and amiodarone, or quinidine and verapamil due to proarrhythmia concerns 1.
10. Anticoagulants
Warfarin: Indicated for patients with atrial fibrillation or previous history of systemic or pulmonary embolism 1. Consider in patients with very low ejection fraction or intracardiac thrombi even in sinus rhythm 1.
Heparin: For acute management or bridging therapy 1.
11. Antiplatelet Agents
Aspirin: Commonly prescribed, particularly in ischemic cardiomyopathy 1.
Non-aspirin Antiplatelet Agents: Clopidogrel or other P2Y12 inhibitors 1.
12. If Inhibitors
- Ivabradine: Reduces heart rate in patients with stable NYHA class II-IV heart failure, LVEF ≤35%, and resting heart rate ≥70 bpm on optimized therapy including beta-blockers 8. Demonstrated reduction in hospitalization for worsening heart failure (hazard ratio 0.82) 8.
13. Lipid-Lowering Agents
Statins (HMG Co-A Reductase Inhibitors): Important for risk factor modification, particularly in ischemic cardiomyopathy 1, 2.
Other agents include fibrates, nicotinic acid, and resin drugs 1.
14. Supportive Medications
Electrolytes: Potassium and magnesium supplementation as needed 1.
Oxygen Therapy: For chronic use in hypoxemic patients 1.
Morphine Sulfate: May be administered orally or intravenously for pain or pulmonary edema 1.
Specific Considerations by Cardiomyopathy Type
Diastolic Dysfunction/HFpEF
Diuretics and nitrates: Primary agents to reduce elevated filling pressures without significantly reducing cardiac output 1.
Beta-blockers: May improve diastolic filling by reducing heart rate 1.
ACE inhibitors: Frequently used though evidence is limited; may improve cardiac relaxation and distensibility 1, 4.
Calcium channel blockers and beta-blockers: Class II recommendation for potential direct improvement of diastolic dysfunction 1.
Positive inotropic agents: Class III (contraindicated) in absence of systolic dysfunction 1.
Hypertrophic Cardiomyopathy
Avoid: Nifedipine, nitroglycerin, ACE inhibitors, digitalis in presence of resting or provokable outflow obstruction 1.
Phosphodiesterase inhibitors: Use with caution due to mild afterload reducing effect 1.
End-Stage/Dilated Phase Cardiomyopathy
- Transition to standard HFrEF therapy: ACE inhibitors, angiotensin-II receptor blockers, diuretics, digitalis, beta-blockers, or spironolactone when systolic dysfunction develops 1.
Critical Monitoring Requirements
Measure serum electrolytes, urea, and creatinine during titration of all heart failure medications 4.
Monitor potassium and renal function every 5-7 days after treatment initiation until stable, then every 3-6 months 4.
Regular evaluation of volume status, blood pressure, and renal function essential 4.