Yes, both ARNI and SGLT2 inhibitors are indicated and should be initiated in this asymptomatic HFrEF patient despite the blood pressure of 90/60 mmHg.
In asymptomatic HFrEF patients with low blood pressure already on a beta-blocker, SGLT2 inhibitors should be started first, followed by low-dose ARNI, as these medications provide mortality benefit regardless of blood pressure and SGLT2 inhibitors have minimal effect on BP. 1
Rationale for Treatment Despite Low BP
The 2025 ESC Heart Failure Association consensus specifically addresses this clinical scenario. Asymptomatic low BP (90/60 mmHg) should not be a barrier to guideline-directed medical therapy (GDMT) initiation 1. The key distinction is that this patient lacks symptoms of hypoperfusion—no dizziness, fatigue, or signs of organ hypoperfusion. Low BP readings alone do not indicate poor tolerance to heart failure medications 1.
Sequencing Strategy for This Patient
Step 1: Initiate SGLT2 Inhibitor Immediately
- Start dapagliflozin 10 mg daily or empagliflozin 10 mg daily
- SGLT2 inhibitors have the least effect on blood pressure among all HFrEF medications 1
- Benefits emerge within weeks, with 17% relative risk reduction in mortality 2
- These agents may actually increase BP in some low BP patients by improving cardiac output 1
Step 2: Add Low-Dose ARNI
After SGLT2i is tolerated (typically 1-2 weeks):
- Start sacubitril/valsartan at very low dose: 24/26 mg twice daily (not the standard starting dose) 1
- If heart rate >70 bpm, this can be initiated alongside or after beta-blocker optimization
- Up-titrate weekly by small increments (to 49/51 mg twice daily, then 97/103 mg twice daily) 1
- Target dose: 97/103 mg twice daily, but accept highest tolerated dose
Step 3: Consider MRA Addition
- Add spironolactone 12.5-25 mg daily if eGFR >25-30 mL/min and potassium <5.0 mEq/L
- MRAs also have minimal BP-lowering effect 1
Critical Implementation Points
Monitor closely but do not delay initiation:
- Up-titrate one drug at a time with 1-2 week intervals 1
- BP may actually improve with therapy as cardiac output increases 1
- Assess for volume status—reduce diuretics if patient is euvolemic, as overdiuresis contributes to low BP 1
Red flags requiring therapy modification (not present in this patient):
- Systolic BP <80 mmHg 1
- Symptomatic hypotension with dizziness, presyncope, or fatigue
- Signs of hypoperfusion (cool extremities, altered mental status, oliguria)
Common Pitfalls to Avoid
Do not withhold life-saving therapy based on asymptomatic low BP alone 1. The mortality benefit of these medications far outweighs theoretical BP concerns in stable patients.
Do not assume low BP is medication-related if patient is stable on current therapy 1. First evaluate for:
- Overdiuresis (most common reversible cause)
- Non-HF medications (alpha-blockers for BPH, calcium channel blockers, antidepressants)
- Valvular disease or ischemia
Avoid selective beta-blocker up-titration before adding ARNI/SGLT2i in low BP patients. The algorithm prioritizes SGLT2i and MRA first due to neutral BP effects 1.
Do not use standard ARNI starting dose (49/51 mg twice daily) in low BP patients—begin at 24/26 mg twice daily 1.
Non-Pharmacological Adjuncts
While initiating medications:
- Space out medication timing to reduce synergistic hypotensive effects 1
- Encourage exercise/physical training (improves orthostatic tolerance and BP) 1
- Consider compression stockings if orthostatic symptoms develop
- Educate patient that transient dizziness is acceptable and does not require therapy cessation 1
Expected Outcomes
The combination of ARNI + beta-blocker + MRA + SGLT2i provides:
- 15.63% improvement in LVEF compared to placebo 3
- Superior to traditional ACEi + beta-blocker + MRA by 3.83-5.83% in LVEF improvement 3
- Number needed to treat: 27 patients for 36 months to prevent one death with ARNI; 22 patients for 18 months with SGLT2i 2
The mortality and morbidity benefits of completing quadruple therapy vastly outweigh the risks of asymptomatic low blood pressure in this stable patient.