From the Guidelines
Beta-blockers should generally be continued or initiated in patients with severe heart failure with reduced ejection fraction (HFrEF) who are started on milrinone, but with careful consideration and monitoring. For patients already on beta-blockers, these should typically be continued at the current dose during milrinone therapy, though temporary dose reduction may be necessary if hemodynamic instability occurs 1. For beta-blocker naive patients, initiation should be delayed until the patient is hemodynamically stable and weaned off milrinone. When starting beta-blockers, begin with very low doses (e.g., carvedilol 3.125 mg twice daily, metoprolol succinate 12.5 mg daily, or bisoprolol 1.25 mg daily) and titrate slowly every 2-4 weeks as tolerated. Close monitoring of heart rate, blood pressure, and symptoms is essential during this process. The rationale for maintaining beta-blocker therapy is that these medications provide long-term mortality benefits in HFrEF, while milrinone offers short-term inotropic support. Beta-blockers and milrinone work through different mechanisms - beta-blockers reduce sympathetic stimulation while milrinone increases cardiac contractility through phosphodiesterase inhibition, bypassing beta-receptor signaling.
Key considerations for beta-blocker use in HFrEF patients on milrinone include:
- Initiating beta-blockers at low doses and titrating slowly to minimize adverse effects 1
- Monitoring patients closely for signs of hemodynamic instability or worsening heart failure symptoms
- Adjusting beta-blocker doses as needed to balance the benefits of long-term mortality reduction with the short-term risks of milrinone therapy
- Individualizing treatment based on patient-specific factors, such as comorbidities, renal function, and ability to follow up 1
By carefully managing beta-blocker therapy in patients with HFrEF who are started on milrinone, clinicians can optimize outcomes and reduce the risk of adverse events.
From the Research
Patient Management with HFrEF and Milrinone
- Patients with severe heart failure with reduced ejection fraction (HFrEF) who are started on milrinone infusion may still benefit from being placed on beta-blockers (BB) 2, 3.
- The use of beta-blockers in combination with milrinone has been shown to be well-tolerated, with no significant increase in adverse events or deterioration in clinical status 2, 3.
- Studies suggest that concomitant therapy with milrinone and a beta-blocker may allow for weaning off milrinone in some patients, and may also reduce mortality in certain cases 2, 3.
Treatment Strategies for HFrEF
- The management of HFrEF involves the use of diuretics to relieve symptoms, as well as disease-modifying drug and device therapies 4, 5.
- Unless there are specific contraindications, patients with HFrEF should be treated with a β-blocker and one of an angiotensin receptor-neprilysin inhibitor, angiotensin-converting enzyme inhibitor, or angiotensin receptor blocker as foundational therapy 5.
- Additional therapies, such as mineralocorticoid receptor antagonists, ivabradine, and hydralazine/isosorbide dinitrate, may also be beneficial in certain patients with HFrEF 5.
Optimization of HFrEF Prognosis-Modifying Drugs
- Recent expert consensus recommends the use of sacubitril/valsartan as first-line therapy for HFrEF, and emphasizes the importance of introducing four foundation HFrEF drugs (angiotensin receptor/neprilysin inhibitor, beta-adrenergic blocking agents, mineralocorticoid receptor antagonists, and sodium-glucose co-transporter 2 inhibitors) over a short-term period 6.
- The introduction of these drugs should be guided by a safety protocol, followed by a dose up-titration period 6.