Beta-Blocker and Losartan for Heart Failure with Reduced Ejection Fraction
For patients with HFrEF, use an ACE inhibitor (not losartan) as first-line therapy along with one of the three evidence-based beta-blockers (bisoprolol, carvedilol, or metoprolol succinate), and reserve ARBs like losartan only for patients who cannot tolerate ACE inhibitors. 1
Primary Recommendation: ACE Inhibitors Over ARBs
ACE inhibitors are the preferred renin-angiotensin system blocker for all patients with symptomatic HFrEF, as they have Class I, Level A evidence for reducing mortality and HF hospitalization. 1
Losartan (an ARB) should only be used when ACE inhibitors are not tolerated (typically due to cough or angioedema), as ARBs are considered second-line therapy with less robust mortality data compared to ACE inhibitors. 1
The 2016 ESC guidelines explicitly state that "it is unclear whether ARBs are as effective as ACE inhibitors for mortality reduction." 1
Beta-Blocker Selection and Dosing
Only three beta-blockers have proven mortality benefit in HFrEF:
- Bisoprolol
- Carvedilol (target: 25 mg twice daily)
- Metoprolol succinate (sustained-release; target: 200 mg once daily) 1, 2
These are NOT interchangeable with other beta-blockers - using non-evidence-based beta-blockers is not recommended. 2
Initiation Strategy
Start both medications in stable patients:
Begin ACE inhibitor first in patients not already on therapy, with careful monitoring of blood pressure and renal function. 1
Initiate beta-blocker therapy once the patient is stable, volume-optimized, and off intravenous diuretics/inotropes. 1
Start beta-blockers at low doses and titrate gradually to target or maximally tolerated doses, as higher doses are associated with better clinical outcomes. 2, 3, 4
Aim for at least 50% of target dose when full target dose cannot be achieved. 2
Critical Pitfalls to Avoid
Do not combine an ARB with both an ACE inhibitor and mineralocorticoid receptor antagonist (MRA) - this triple combination increases risk of renal dysfunction and hyperkalemia and is explicitly not recommended (Class III). 1
Never abruptly discontinue beta-blockers - this can lead to clinical deterioration. 2
Do not use metoprolol tartrate (short-acting) - only metoprolol succinate (sustained-release) has proven mortality benefit. 1, 2
Avoid calcium channel blockers with negative inotropic effects (diltiazem, verapamil) in HFrEF, as they increase risk of HF worsening and hospitalization. 1
Monitoring Requirements
Check blood pressure, renal function (creatinine), and electrolytes (potassium) 1-2 weeks after each dose increment. 1
Recheck at 3 months, then at 6-month intervals. 1
Monitor for signs of fluid retention requiring diuretic adjustment. 1
When Losartan Is Appropriate
Use losartan (or another ARB) only in these specific scenarios:
ACE inhibitor intolerance due to cough or angioedema. 1
As an alternative when ACE inhibitors cause unacceptable side effects. 1
If using an ARB, it should still be combined with a beta-blocker to achieve dual neurohormonal blockade. 1
Additional Foundation Therapies
Once ACE inhibitor (or ARB if intolerant) and beta-blocker are established:
Add a mineralocorticoid receptor antagonist (spironolactone or eplerenone) for patients who remain symptomatic despite ACE inhibitor and beta-blocker therapy. 1
Consider SGLT2 inhibitors as part of contemporary quadruple therapy for HFrEF. 3
Use loop diuretics for symptom relief in patients with fluid retention, but these do not reduce mortality. 1