Sacubitril/Valsartan vs Lisinopril in Dilated Cardiomyopathy
Sacubitril/valsartan is superior to lisinopril (or any ACE inhibitor) for patients with dilated cardiomyopathy and HFrEF, reducing cardiovascular death or heart failure hospitalization by 20% compared to ACE inhibitors. 1, 2
Evidence for Superiority
The PARADIGM-HF trial definitively established that sacubitril/valsartan reduces the composite endpoint of cardiovascular death or HF hospitalization by 20% (HR 0.80; 95% CI 0.73-0.87, p<0.0001) compared to enalapril, with benefits seen in both cardiovascular death (HR 0.80; 95% CI 0.71-0.89) and heart failure hospitalization (HR 0.79; 95% CI 0.71-0.89) individually. 2 All-cause mortality was also significantly reduced (HR 0.84; 95% CI 0.76-0.93, p=0.0009). 2
Current Guideline Recommendations
The 2022 ACC/AHA/HFSA guidelines recommend sacubitril/valsartan over ACE inhibitors for symptomatic HFrEF patients, with evidence supporting both:
- Replacement strategy: Switching from ACE inhibitors in patients already on optimal medical therapy 1
- De novo initiation: Starting sacubitril/valsartan directly without prior ACE inhibitor exposure, which simplifies management and is supported by recent trial data 1, 3
For patients with dilated cardiomyopathy specifically, sacubitril/valsartan demonstrates superior cardiac remodeling effects, with studies showing increased left ventricular ejection fraction and decreased left ventricular volumes. 3 In real-world DCM patients, 57.7% achieved reverse remodeling within 24 months, with 46% improving LVEF above 35%. 4
Practical Implementation Algorithm
Starting sacubitril/valsartan:
If ACE inhibitor-naive: Start sacubitril/valsartan 24/26 mg twice daily 3, 5
If on low/medium-dose ACE inhibitor: Start sacubitril/valsartan 24/26 mg twice daily 3, 5
If on high-dose ACE inhibitor: Start sacubitril/valsartan 49/51 mg twice daily 3, 5
Mandatory washout: Wait 36 hours after stopping ACE inhibitor before initiating sacubitril/valsartan to avoid angioedema 3
Titration schedule: Double the dose every 2-4 weeks as tolerated to reach target dose of 97/103 mg twice daily 3, 5
Special Considerations for DCM Patients
Predictors of favorable response in DCM patients include:
High-risk patients requiring lower starting dose (24/26 mg twice daily):
- Severe renal impairment (eGFR <30 mL/min/1.73 m²) 3, 5
- Moderate hepatic impairment (Child-Pugh B) 3
- Age ≥75 years 3, 5
- Systolic BP <100 mmHg (though not an absolute contraindication) 3
Critical Warnings
Discontinuing sacubitril/valsartan leads to clinical deterioration: Patients who stopped sacubitril/valsartan after ≥5 months and switched back to ACE inhibitors showed significant worsening of NYHA class, LVEF, and end-diastolic volume (p=0.001 for all parameters) despite being compliant with optimal conventional therapy. 6 This underscores that once started, sacubitril/valsartan should be continued unless contraindicated.
Absolute contraindications:
- History of angioedema with prior ACE inhibitor or ARB 3, 5
- Concomitant ACE inhibitor use 3, 5
- Pregnancy or lactation 3
Monitoring Requirements
- Blood pressure, renal function (serum creatinine, eGFR), and serum potassium at baseline and regularly during titration 3
- Particular vigilance when combined with mineralocorticoid receptor antagonists (which should be continued as cornerstone therapy) 3
- Caution when potassium >5.0 mEq/L 1, 3
Managing Common Barriers
Asymptomatic hypotension: Not a reason to avoid initiation or titration; sacubitril/valsartan maintains efficacy even with systolic BP <110 mmHg 3
Symptomatic hypotension: Reduce diuretic dose first in non-congested patients, or temporarily reduce sacubitril/valsartan dose then re-titrate (40% of patients requiring temporary dose reduction were successfully restored to target doses) 3
Mild creatinine elevation (<0.5 mg/dL increase): Acceptable and does not require dose adjustment 3