Safety of PO Diltiazem in Patients with Reduced EF of 45-50%
Diltiazem should not be used in patients with reduced ejection fraction of 45-50% due to its negative inotropic effects and risk of worsening heart failure. 1
Rationale for Avoiding Diltiazem in Reduced EF
Guideline Recommendations
The 2016 ESC Guidelines for Heart Failure explicitly state that diltiazem and verapamil are not recommended to reduce blood pressure in patients with heart failure with reduced ejection fraction (HFrEF) because of their negative inotropic action and risk of worsening heart failure (Class III recommendation, Level C evidence) 1. This contraindication applies to patients with EF ≤50%.
For patients with HFrEF who develop systolic dysfunction (EF ≤50%), guidelines recommend:
- Discontinuing negative inotropic agents previously indicated, including diltiazem 1
- Implementing guideline-directed medical therapy for heart failure with reduced EF, including:
Definition of Reduced EF
According to the 2022 AHA/ACC/HFSA guidelines, patients with an EF of 41-49% are classified as having heart failure with mildly reduced ejection fraction (HFmrEF), while those with EF ≤40% have heart failure with reduced ejection fraction (HFrEF) 1. An EF of 45-50% falls into the mildly reduced category, where diltiazem should still be avoided.
Evidence on Diltiazem in Reduced EF
Recent Research
Recent studies examining diltiazem use in patients with reduced EF have shown concerning results:
A 2022 study found that patients with heart failure and reduced EF who received IV diltiazem for atrial fibrillation had a significantly higher incidence of worsening heart failure symptoms compared to those receiving metoprolol (33% vs. 15%, p=0.019) 3
A 2024 study reported that worsening heart failure occurred in 17% of patients with reduced EF (<50%) who received IV diltiazem for atrial fibrillation management, compared to only 4.8% in those with preserved EF (p=0.005) 4
A 2018 study found that IV diltiazem in patients with decreased EF was associated with a significantly higher frequency of acute kidney injury within 48 hours (10% vs 3.6% in normal EF, p=0.002) 5
Alternative Management Approaches
For patients with reduced EF (45-50%) who require rate control or antihypertensive therapy:
For rate control in atrial fibrillation:
- Beta-blockers are the preferred first-line agents
- Digoxin can be considered as an alternative
For hypertension management:
- ACE inhibitors or ARBs
- Beta-blockers
- Diuretics
- Hydralazine or amlodipine (if additional agents needed) 1
Special Considerations
While one older study from 1984 suggested potential hemodynamic benefits of diltiazem in severe heart failure 6, this is outweighed by more recent evidence and current guidelines that clearly recommend against its use.
The risk of worsening heart failure symptoms, increased oxygen requirements, and potential need for inotropic support make diltiazem an unsuitable choice for patients with EF in the 45-50% range.
Conclusion
Oral diltiazem should be avoided in patients with reduced ejection fraction of 45-50% due to its negative inotropic effects and the significant risk of worsening heart failure. Current guidelines and recent research consistently support this recommendation.