Can Entresto (sacubitril/valsartan) cause elevated hematocrit?

Can Entresto Cause Elevated Hematocrit?

No, Entresto (sacubitril/valsartan) does not cause elevated hematocrit; in fact, the valsartan component (an angiotensin receptor blocker) would theoretically cause a slight decrease in hematocrit through hemodilution, similar to other drugs in its class.

Mechanism and Expected Hematologic Effects

• Angiotensin receptor blockers like valsartan, which is a component of Entresto, typically cause mild hemodilution with a small decrease in hemoglobin and hematocrit, not an elevation 1
• This effect mirrors what is seen with related drug classes: thiazolidinediones cause decreases in hemoglobin ranging from 0.8 to 1.1 g/dL with hematocrit decreases of 2.3% to 3.6% due to increased plasma volume and hemodilution 1
• The mechanism involves increased plasma volume without changes in red blood cell production or turnover, resulting in a dilutional effect on hematocrit 1

Clinical Monitoring Recommendations

The American College of Cardiology recommends baseline assessment and regular monitoring of renal function and electrolytes (particularly potassium and magnesium) when initiating Entresto, but hematocrit elevation is not a recognized adverse effect requiring specific monitoring 2

• Primary monitoring should focus on:
  • Blood pressure (symptomatic hypotension is the most common cardiovascular side effect) 3, 4
  • Renal function (serum creatinine, eGFR) 2, 3
  • Serum potassium and magnesium levels 2
  • Signs of angioedema (particularly during the first weeks of therapy) 3

Important Clinical Pitfall

• If a patient on Entresto presents with elevated hematocrit, look for alternative causes rather than attributing it to the medication 5, 6
• Common alternative causes to investigate include:
  • Dehydration or volume depletion (especially if diuretic doses were recently increased)
  • Chronic hypoxemia from worsening heart failure
  • Sleep apnea
  • Chronic lung disease
  • Polycythemia vera or secondary erythrocytosis
  • Testosterone therapy or anabolic steroid use

Established Side Effect Profile

The documented adverse effects of Entresto that require monitoring are 5, 4:

• Symptomatic hypotension (most common cardiovascular side effect)
• Hyperkalemia (though less than with spironolactone)
• Potential for hypermagnesemia (particularly in patients with eGFR <30 mL/min/1.73m²) 2
• Angioedema (rare but serious, requires 36-hour washout from ACE inhibitors before initiation) 3
• Renal function deterioration in susceptible patients 2