Is Anakinra (interleukin-1 receptor antagonist) effective for treating cardiogenic shock?

Anakinra for Cardiogenic Shock

Anakinra is not recommended for routine treatment of cardiogenic shock, as major cardiovascular guidelines do not include it in the management algorithm for this condition. The established treatment approach prioritizes immediate revascularization, hemodynamic support with inotropes and vasopressors, and mechanical circulatory support when needed 1.

Current Guideline-Based Management of Cardiogenic Shock

The 2022 AHA/ACC/HFSA guidelines and 2018 ESC guidelines establish a clear treatment hierarchy for cardiogenic shock that does not include anakinra 1:

First-Line Interventions

• Immediate revascularization is paramount for ischemic cardiogenic shock, with PCI indicated within 2 hours if coronary anatomy is suitable 1
• Intravenous inotropic support (dobutamine 2-20 μg/kg/min) to increase cardiac output when signs of organ hypoperfusion persist despite volume replacement 1, 2
• Vasopressor therapy with norepinephrine as the preferred agent when mean arterial pressure requires pharmacologic support 1, 3
• Invasive hemodynamic monitoring with arterial line and consideration of pulmonary artery catheterization 1, 2

Second-Line Interventions

• Short-term mechanical circulatory support may be considered in refractory cardiogenic shock based on patient age, comorbidities, and neurological function 1, 3
• Multidisciplinary shock team approach, which has been associated with improved 30-day mortality (HR 0.61; 95% CI 0.41-0.93) 1, 2

Limited Evidence for Anakinra in Cardiac Conditions

While anakinra has shown promise in specific inflammatory cardiac conditions, the evidence does not support its use in typical cardiogenic shock:

Where Anakinra Has Evidence

• Fulminant myocarditis: Case reports demonstrate dramatic improvement in cardiac function within 24-72 hours when myocarditis causes cardiogenic shock, with successful weaning from mechanical support 4, 5
• Post-MI remodeling: A small pilot study (n=10) showed anakinra reduced left ventricular end-systolic volume index by a median of 5.2 ml/m² compared to placebo, but this was for preventing remodeling, not treating acute shock 6
• MIS-C with cardiovascular shock: Pediatric guidelines give anakinra high consensus for children with COVID-19 hyperinflammation and shock, particularly before mechanical ventilation 1, 7

Critical Distinction

These conditions represent inflammatory/immune-mediated cardiac dysfunction, not the typical cardiogenic shock from acute MI, decompensated heart failure, or mechanical complications that comprise the majority of cardiogenic shock cases 1.

Why Anakinra Is Not Standard Therapy

The major cardiovascular society guidelines (AHA/ACC 2022, ESC 2018, ESC 2016) make no mention of anakinra or IL-1 blockade in their cardiogenic shock management algorithms 1. This absence is notable because:

• Cardiogenic shock requires immediate hemodynamic stabilization with proven therapies (inotropes, vasopressors, revascularization) that work within minutes to hours 2, 3
• The inflammatory component of typical cardiogenic shock is secondary to tissue hypoperfusion, not the primary driver 1
• No randomized controlled trials have evaluated anakinra specifically for cardiogenic shock outside of inflammatory/immune-mediated etiologies 4, 5, 6

When to Consider Anakinra (Off-Guideline)

Based on case reports and small studies, anakinra might be considered only in highly selected scenarios:

• Fulminant myocarditis with cardiogenic shock refractory to standard support, where inflammatory pathophysiology is the primary driver 4, 5
• Dosing: 100 mg/day subcutaneously or higher doses (>4 mg/kg/day IV) for severe cases 1, 4, 5
• Monitoring: Watch for liver function test abnormalities 1, 7
• Timing: May be most beneficial before invasive mechanical ventilation 1

Common Pitfalls

• Do not delay proven therapies (revascularization, inotropes, mechanical support) to trial anakinra in typical cardiogenic shock 1, 2
• Do not use anakinra as first-line therapy for cardiogenic shock—it has no guideline support and lacks evidence in this population 1
• Recognize that case reports of success in fulminant myocarditis do not translate to efficacy in ischemic or other forms of cardiogenic shock 4, 5
• Avoid assuming all cardiogenic shock has an inflammatory component amenable to IL-1 blockade—most cases result from pump failure requiring mechanical/hemodynamic support 1