Switching to Losartan in Patients on Isosorbide
Losartan can be safely initiated and used concurrently with isosorbide dinitrate without contraindication, as both medications are part of guideline-directed medical therapy for heart failure with reduced ejection fraction (HFrEF) and are commonly used together. 1
No Drug Interaction or Contraindication
There is no pharmacologic contraindication to using losartan and isosorbide together. The 2022 AHA/ACC/HFSA guidelines explicitly list both ARBs (including losartan) and isosorbide dinitrate/hydralazine as separate, complementary therapies for HFrEF that can be used simultaneously. 1
Both medications work through different mechanisms: losartan blocks angiotensin II at AT-1 receptors, while isosorbide dinitrate is a nitrate vasodilator. These complementary pathways do not create problematic interactions. 2
Initiation Protocol for Losartan
Start losartan at 25-50 mg once daily and titrate to a target dose of 50-150 mg once daily (maximum 150 mg daily). 1
Begin with the lower starting dose (25 mg) if the patient has:
- Hypotension or borderline blood pressure
- Volume depletion
- Renal insufficiency
- Advanced age 1
Uptitrate every 1-2 weeks as tolerated, aiming for the target dose of 150 mg daily for maximum mortality benefit. The HEAAL study demonstrated that 150 mg losartan daily prevents one primary cardiovascular event for every 31 patients treated over 4 years compared to 50 mg daily. 3
Monitoring Requirements
Check renal function and serum potassium within 1-2 weeks of initiating losartan and periodically thereafter. 1
Monitor blood pressure at each dose escalation to avoid hypotension, particularly since the patient is already on a vasodilator (isosorbide). 4
Be especially vigilant in patients with:
- Pre-existing hypotension or hyponatremia
- Diabetes mellitus
- Baseline renal dysfunction (azotemia)
- Concurrent potassium supplementation 1
Continue Isosorbide Dinitrate
Maintain the patient's current isosorbide regimen unchanged when adding losartan. 1
The standard dosing for isosorbide dinitrate in HFrEF is 20-30 mg three times daily, with a target of 40 mg three times daily (120 mg total daily). 1, 4
The combination of hydralazine and isosorbide dinitrate provides a 43% relative risk reduction in mortality with an NNT of 25 over 10 months—one of the most potent mortality benefits in HFrEF. 1
Critical Safety Consideration
Ensure the patient is not taking phosphodiesterase-5 inhibitors (sildenafil, tadalafil, vardenafil), as these are absolutely contraindicated with nitrates due to risk of profound, life-threatening hypotension. 4
Clinical Context
Losartan has a favorable drug interaction profile with minimal CYP450-mediated interactions and no clinically significant interactions with common cardiovascular medications. 2
The combination of an ARB (losartan) with isosorbide dinitrate/hydralazine is particularly beneficial in patients who cannot tolerate ACE inhibitors or ARNIs, or in self-identified Black patients with HFrEF where this combination has specific mortality benefit. 1
Do not discontinue isosorbide when initiating losartan—both medications provide independent, additive mortality benefits in HFrEF. 1