Can nivolumab (Opdivo) and ipilimumab (Yervoy) cause tachycardia?

Nivolumab and Ipilimumab Can Cause Tachycardia

Yes, nivolumab (Opdivo) and ipilimumab (Yervoy) can cause tachycardia as part of their cardiovascular immune-related adverse events (irAEs). While tachycardia specifically may not be the most commonly reported cardiovascular toxicity, it can occur as a manifestation of myocarditis, pericarditis, or other cardiac irAEs associated with these immune checkpoint inhibitors.

Cardiovascular Toxicities of Immune Checkpoint Inhibitors

Incidence and Risk

• Cardiovascular complications of immune checkpoint inhibitors (ICPis) are rare but potentially life-threatening
• Occur in <0.1% of patients receiving these therapies based on pharmaceutical safety databases 1
• Risk increases with combination therapy: ipilimumab plus nivolumab has higher rates of cardiovascular complications (0.28%) compared to nivolumab alone (0.06%) 1
• Mortality is high, with death frequently secondary to refractory arrhythmia or cardiogenic shock 1

Types of Cardiovascular Toxicities

Cardiac irAEs can manifest in various forms:

1. Arrhythmias including tachycardia:

   • Both supraventricular tachycardias (more benign) and ventricular tachycardias (potentially fatal) have been reported 1
   • Can lead to sudden death in severe cases

2. Myocarditis:

   • Immune-mediated myocarditis may result in heart failure or arrhythmias including tachycardia
   • Can be fulminant, progressive, and life-threatening 1
   • Pathology shows lymphocytic infiltration in the myocardium and myocardial conduction system 1

3. Other cardiac toxicities:

   • Cardiomyopathy
   • Heart failure
   • Conduction abnormalities including heart block
   • Pericarditis and pericardial effusions
   • Acute coronary syndrome (rare) 1

Risk Factors for Cardiac Toxicity

Recent research has identified several risk factors for cardiac toxicity with immune checkpoint inhibitors:

• Female gender (3.34 times higher risk)
• African American race (3.39 times higher risk)
• Tobacco use (4.21 times higher risk) 2

Clinical Presentation

Patients with cardiac toxicity may present with:

• Arrhythmias including tachycardia
• Palpitations
• Chest pain
• Signs and symptoms of heart failure (shortness of breath, peripheral edema, pleural effusion, fatigue)
• Severe cases can present with cardiogenic shock or sudden death
• Patients can also present with nonspecific symptoms like fatigue, malaise, myalgia, and/or weakness 1

Timing of Onset

Cardiovascular irAEs typically occur early in treatment:

• Can develop as soon as 2 weeks and as late as 32 weeks after initiation of treatment
• Median onset is around 10 weeks after initiation of therapy 1
• Recent data suggests that 80% of adverse events occur within three months for both nivolumab-ipilimumab and nivolumab-relatlimab combinations 3

Comparison Between Regimens

When comparing nivolumab plus ipilimumab versus other combinations:

• Nivolumab plus ipilimumab is linked with a broader range of immune-related toxicities
• Recent data shows nivolumab plus relatlimab has higher cardiac-specific risks, including myocarditis and troponin elevation 3

Management of Cardiac Toxicities

For grade 2-3 cardiac toxicities:

• Continue immune checkpoint inhibitor therapy
• Manage according to American College of Cardiology/American Heart Association guidelines
• Consider cardiology consultation 1

For grade 4 cardiac toxicities:

• Permanently discontinue immune checkpoint inhibitor therapy
• Admit patient and manage with guidance from cardiology
• Seek respiratory and hemodynamic support as needed 1

For suspected myocarditis or severe cardiac toxicity:

• High-dose corticosteroids should be initiated rapidly
• Escalation to other immunosuppressive drugs (infliximab, mycophenolate mofetil, anti-thymocyte globulin) may be necessary if symptoms don't respond to steroids 1

Monitoring Recommendations

Given the potentially fatal nature of cardiac toxicities:

• Patients receiving combination therapy (nivolumab plus ipilimumab) should have increased cardiac monitoring due to higher risk
• Early detection through cardiac biomarkers and ECG monitoring may help identify asymptomatic cases
• Patients with risk factors (female gender, African American race, tobacco use) may benefit from early referral to a cardio-oncologist 2

Conclusion

While tachycardia itself is not specifically listed as the most common cardiac adverse event, it is a recognized manifestation of the broader spectrum of cardiovascular toxicities associated with nivolumab and ipilimumab. The combination therapy carries a higher risk of cardiovascular complications compared to monotherapy. Healthcare providers should maintain vigilance for cardiac symptoms, particularly in high-risk patients, and be prepared to intervene promptly with appropriate immunosuppressive therapy when cardiac toxicity is suspected.