What to do if a patient experiences dyspnea while taking Brilinta (ticagrelor)?

Management of Ticagrelor-Induced Dyspnea

Dyspnea associated with ticagrelor is usually mild and transient, and in most cases does not require discontinuation of therapy unless severe or persistent, as the benefits of continued therapy typically outweigh the risks.

Understanding Ticagrelor-Induced Dyspnea

• Dyspnea is a common side effect of ticagrelor, occurring in approximately 14-39% of patients, compared to only 7-9% with clopidogrel or placebo 1, 2
• Most instances of dyspnea are mild and/or last less than 24 hours, with onset typically within the first week of treatment (77% of cases) 2
• The mechanism is thought to be related to ticagrelor's ability to inhibit adenosine reuptake by erythrocytes, thereby increasing circulating adenosine levels 1
• Importantly, ticagrelor-induced dyspnea is not associated with any adverse changes in cardiac or pulmonary function 2
• Recent research suggests central apneas and chemoreflex sensitization may contribute to ticagrelor-related dyspnea 3

Assessment of Patients with Ticagrelor-Induced Dyspnea

• Evaluate severity of dyspnea using appropriate scales or physical signs of respiratory distress 4
• Assess vital signs including oxygen saturation, respiratory rate, heart rate, and blood pressure 5
• Rule out other potential causes of dyspnea such as heart failure, pulmonary edema, or respiratory infection 5
• Consider ECG and echocardiography if cardiac causes are suspected 5

Management Algorithm

For Mild to Moderate Dyspnea:

1. Reassurance and continued monitoring

   • Explain to the patient that dyspnea is a known side effect that is usually transient and not associated with cardiopulmonary damage 1, 2
   • Continue ticagrelor therapy as the benefits in reducing cardiovascular events outweigh the discomfort of mild dyspnea 1

2. Non-pharmacological interventions

   • Position the patient upright to optimize respiratory mechanics 6
   • Use of handheld fans directed at the face can help reduce the sensation of dyspnea 4, 6
   • Implement relaxation techniques and stress management 4

3. Symptomatic management if needed

   • Low-dose opioids may be considered for refractory dyspnea (e.g., morphine 2.5-10 mg PO every 2 hours PRN) 4, 6
   • For anxiety associated with dyspnea, benzodiazepines may be used cautiously (e.g., lorazepam 0.5-1 mg PO every 4 hours PRN) 4, 6

For Severe or Persistent Dyspnea:

1. Consider alternative P2Y12 inhibitors

   • Switch to clopidogrel or prasugrel if the dyspnea is intolerable or significantly impacts quality of life 1
   • Note that approximately 3% of patients discontinue ticagrelor due to dyspnea 2
   • In the TWILIGHT trial, dyspnea-related ticagrelor discontinuation occurred in 9.1% of patients at 15 months after PCI 7

2. Risk assessment before switching

   • Consider the increased risk of cardiovascular events with clopidogrel compared to ticagrelor 1
   • Prasugrel may be an alternative but is contraindicated in patients with prior stroke/TIA and not recommended in patients ≥75 years or <60 kg 1

Special Considerations

• Caffeine (an adenosine antagonist) does not appear to reduce ticagrelor-induced dyspnea, contrary to what might be expected based on the proposed adenosine-related mechanism 8
• Patients with risk factors including smoking, prior PCI, hypercholesterolemia, prior coronary artery bypass, peripheral artery disease, obesity, and older age are more likely to experience dyspnea with ticagrelor 7
• Asian patients appear to have a lower risk of dyspnea-related ticagrelor discontinuation 7
• Be aware that ticagrelor can also cause other side effects including asymptomatic bradycardia with ventricular pauses and modest increases in uric acid levels 1, 9

Common Pitfalls to Avoid

• Premature discontinuation of ticagrelor due to mild dyspnea, which could increase risk of cardiovascular events 1
• Failure to distinguish between ticagrelor-induced dyspnea and dyspnea from other causes such as heart failure or pulmonary conditions 5
• Overtreatment of mild dyspnea with excessive medications 4, 6
• Underappreciation of the impact of severe dyspnea on quality of life, which may necessitate switching to an alternative agent 7