Can Aldactone (Spironolactone) Be Used in a Patient with LVEF 45%?
Yes, spironolactone may be considered for a patient with LVEF 45%, particularly if they have symptomatic heart failure, elevated natriuretic peptides, or recent heart failure hospitalization, though the evidence is stronger for lower ejection fractions and this represents a Class 2b recommendation.
Understanding the Ejection Fraction Context
Your patient with LVEF 45% falls into the heart failure with mildly reduced ejection fraction (HFmrEF) category, defined as LVEF 41-49% 1. This is a distinct phenotype from HFrEF (≤40%) where spironolactone has Class I evidence, and from HFpEF (≥50%) where evidence is weaker 1.
Guideline Recommendations for LVEF 45%
The 2022 ACC/AHA/HFSA guidelines give spironolactone a Class 2b recommendation (Level of Evidence B-R) for HFmrEF, meaning it "may be considered" to reduce heart failure hospitalizations and cardiovascular mortality 1. This is a weaker recommendation than the Class I indication for HFrEF 2.
The strength of benefit appears greatest at the lower end of the HFmrEF spectrum (LVEF 41-45%) rather than at 45-49% 1, 3. Since your patient is at LVEF 45%, they sit at the threshold where evidence becomes less robust.
Evidence Supporting Use at LVEF 45%
Post-hoc Analysis Data
TOPCAT post-hoc analysis examined 520 patients with LVEF 44-49% and showed spironolactone reduced the composite endpoint of cardiovascular death, heart failure hospitalization, or resuscitated sudden death, driven mainly by cardiovascular mortality reduction 1, 3.
However, this benefit was predominantly seen in patients enrolled in North and South America, not in Russia/Georgia where medication adherence was questionable 1, 3.
TOPCAT subgroup analysis specifically for patients with LVEF 45-57% (lower range) suggested potential benefit, though the primary trial for HFpEF (LVEF ≥45%) failed to meet its primary endpoint 1.
Real-World Registry Data
- A Japanese registry study of 457 HFmrEF patients showed spironolactone use at discharge was associated with a 37% reduction in the composite of all-cause death or HF rehospitalization (adjusted HR 0.63,95% CI 0.44-0.90) 4.
Clinical Decision Algorithm for LVEF 45%
Step 1: Assess Symptom Status
- If symptomatic (NYHA Class II-IV): Stronger consideration for spironolactone 3
- If asymptomatic: Weaker rationale for initiation
Step 2: Check Biomarker Status
- Elevated BNP/NT-proBNP or recent HF hospitalization: Increases appropriateness 3
- Normal biomarkers and no recent events: Consider alternative therapies first
Step 3: Verify Safety Parameters
Before prescribing, confirm 1, 5, 3:
- Serum potassium <5.0 mEq/L
- **Serum creatinine <2.5 mg/dL** (or eGFR >30 mL/min/1.73m²)
- Not on other potassium-sparing diuretics
Step 4: Consider Therapy Hierarchy
SGLT2 inhibitors have stronger evidence (Class 2a) in HFmrEF compared to spironolactone (Class 2b) 3. If your patient is not already on an SGLT2 inhibitor, prioritize that first 3.
Step 5: Optimize Foundational Therapies
Ensure patient is already on 1:
- ACE inhibitor, ARB, or ARNI
- Evidence-based beta-blocker (carvedilol, metoprolol succinate, or bisoprolol)
Dosing Strategy for LVEF 45%
Start with 12.5-25 mg daily and titrate to a maximum of 25-50 mg daily based on tolerance 5, 3. The target dose from landmark trials is spironolactone ≥25 mg daily 1.
Mandatory Monitoring Protocol
Critical monitoring schedule to prevent life-threatening hyperkalemia 5, 6:
- Within 3 days of initiation: Check potassium and creatinine
- At 1 week: Recheck potassium and creatinine
- Monthly for 3 months: Continue monitoring
- Every 3 months thereafter: During stable therapy
Hyperkalemia Management Algorithm 5
- Potassium 5.0-5.5 mEq/L: Continue current dose with close monitoring
- Potassium >5.5 mEq/L: Halve the spironolactone dose and recheck within 3 days
- Potassium >6.0 mEq/L: Stop spironolactone immediately
Common Pitfalls and Caveats
Hyperkalemia Risk
Hyperkalemia risk increases dramatically when combined with ACE inhibitors/ARBs, which is the typical clinical scenario 5, 6. Do not combine spironolactone with other potassium-sparing diuretics (amiloride, triamterene) 5.
Gynecomastia
Gynecomastia occurs in approximately 10% of men on spironolactone 5. Consider switching to eplerenone if this occurs, though eplerenone has less robust data in HFmrEF.
Regional Variation in Evidence
The TOPCAT trial showed marked regional variation, with benefit only in the Americas cohort 1, 3. This raises questions about generalizability and medication adherence.
Special Consideration: Poorly Controlled Hypertension
If your patient has poorly controlled hypertension in addition to LVEF 45%, spironolactone becomes more attractive as it provides additional blood pressure reduction and has established efficacy for resistant hypertension 1, 6.
Comparison to HFrEF and HFpEF
- For HFrEF (LVEF ≤40%): Spironolactone is Class I with proven 30% mortality reduction 5, 2
- For your patient (LVEF 45%): Class 2b recommendation with weaker evidence 1
- For HFpEF (LVEF ≥50%): Not routinely recommended; TOPCAT showed no significant reduction in primary endpoint 1, 5
Bottom Line for LVEF 45%
Spironolactone is reasonable to consider if your patient is symptomatic, has elevated natriuretic peptides or recent HF hospitalization, meets safety criteria (K+ <5.0, Cr <2.5), and is already on optimal doses of ACE inhibitor/ARB and beta-blocker 1, 3. However, prioritize SGLT2 inhibitors first if not already prescribed, as they have stronger evidence in this population 3. Close monitoring for hyperkalemia is mandatory 5, 6.