How Can BTK Inhibitors for CLL Impact Your Heart Health?

CLL specialists often talk about how the first-generation BTK inhibitor ibrutinib (Imbruvica, Janssen Biotech) has worse heart-related side effects like atrial fibrillation than next-generation BTK inhibitors zanubrutinib (Brukinsa, BeiGene), acalabrutinib (Calquence, AstraZeneca) and pirtobrutinib (Jaypirca, Eli Lilly).  

Researchers conducted a study to examine the heart-related side effects of BTK inhibitors more in-depth. Learn how BTK inhibitors may impact heart health in people with chronic lymphocytic leukemia (CLL) and ways to manage these side effects. 

What are the Heart-Related Side Effects of BTK Inhibitors? 

Some of the potential side effects of BTK inhibitors are irregular heartbeats called arrhythmias. One of the types of arrhythmias is called atrial fibrillation, as it affects the upper chambers of the heart. 

In atrial fibrillation, the nodes of the heart that send electrical pulses to set its pace are irregular and too fast. This can cause blood to pool in the heart’s chamber, allowing blood clots to form. These blood clots can travel to areas like the brain, potentially causing a stroke. 

(Image source: Shutterstock)

Treatments for atrial fibrillation help regulate the heart’s pace to reduce the risk of stroke or death. If properly treated, atrial fibrillation is not usually life-threatening. 

If you experience symptoms of atrial fibrillation like irregular and fast heartbeat, lightheadedness, extreme fatigue, shortness of breath, or chest pain, contact your doctor, who can help you meet with a heart specialist called a cardiologist. They will conduct tests like an electrocardiogram (ECG) to monitor heart arrhythmias and create a treatment plan to manage the condition. 

How Many CLL Patients Developed Heart Arrhythmias on BTK Inhibitors? 

Researchers evaluated electrocardiogram (ECG) results of 98 CLL patients who had been taking a BTK inhibitor for an average of 34 months. 61.2% of the patients were taking ibrutinib. The other 38.8% were taking a next-generation BTK inhibitor (zanubrutinib, acalabrutinib, or pirtobrutinib). 36% of the patients taking a next-generation BTK inhibitor had previously taken ibrutinib and then switched.  27.6% of patients had experienced a prior heart arrhythmia before starting a BTK inhibitor. At the time of testing, up to 20% of patients were already taking heart medication like beta-blockers or calcium channel blockers to manage an arrhythmia. 

At the time of the ECG test: 

•  72.4% of CLL patients had a heart arrhythmia
  • 16.3% of these were new cases of atrial fibrillation. Patients had a greater chance of developing atrial fibrillation if they took ibrutinib instead of next-generation BTK inhibitors.
  • 14.3% were ventricular tachycardia (the heart’s lower chambers beat quickly in a coordinated way, preventing the heart from pumping enough blood to the body’s tissues).
  • 31.6% were SVTs (supraventricular tachycardia, an irregularly fast heartbeat caused by altered electrical signaling in the heart. It is usually harmless and doesn’t last long. If SVTs continue to occur, they can develop into atrial fibrillation).  

After the new diagnosis, CLL patients who took heart arrhythmia treatments saw an improvement in the condition. 

Why Do BTK Inhibitors Cause Heart Issues? 

In the case of ibrutinib, researchers believe it causes heart arrhythmias because of off-target effects. This means that instead of only inhibiting the BTK molecule to limit CLL progression, it also impacts other molecules in the body, like C-terminal Src kinase (CSK), which helps regulate your heartbeat. 

Other reasons why BTK inhibitors may impact heart health are thought to be related to increasing inflammation, thickening of heart valves, and damage to the heart wall’s muscles. 

It’s important to note that the risk of developing heart arrhythmias increases with age. They are especially common for people over the age of 60. It is possible you may have had an arrhythmia before starting a BTK inhibitor. 

If you develop a heart arrhythmia during treatment with a BTK inhibitor, your CLL specialist may recommend reducing the dose. They may also suggest adding a heart arrhythmia medication or choosing a different CLL treatment altogether.  

Summary

A study showed that for CLL patients who had taken BTK inhibitors for an average of 34 months, 72.4% of them had irregular heartbeats (called arrhythmias) when evaluated by an electrocardiogram (ECG) test. The specific types of arrhythmias included atrial fibrillation, ventricular tachycardia, and supraventricular tachycardia. Patients who took ibrutinib over next-generation BTK inhibitors were more likely to develop atrial fibrillation. Medicines that treat arrhythmias help manage patients' heart conditions. Please talk to your CLL specialist if you have any concerns regarding heart health while taking a BTK inhibitor. 

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Sources: 

• Atrial fibrillation burden and clinical outcomes following BTK inhibitor initiation
• Atrial Fibrillation Treatment
• About Atrial Fibrillation
• Ibrutinib-Mediated Atrial Fibrillation Attributable to Inhibition of C-Terminal Src Kinase
• Src-family Protein Tyrosine Kinases: A promising target for treating Cardiovascular Diseases  
• Supraventricular tachycardia
• Mechanisms of Arrhythmias and Conduction Disorders in Older Adults