Cardiovascular Risks and Drug Interactions Shape BTK Inhibitor Selection in Clinical Practice

In this interview with Pharmacy Times at Oncology Pharmacists Connect in Austin, TX, Kim Nguyen, PharmD, discusses findings from her abstract, Evaluating Clinical Safety of BTK Inhibitors: Cardiovascular Events and Drug-Drug Interactions. Nguyen highlights important differences in cardiovascular toxicity profiles among BTK inhibitors, emphasizing the need to consider patient-specific cardiovascular risk factors when selecting therapy and noting that acalabrutinib may be preferred for some patients at higher risk of atrial fibrillation or hypertension. She also discusses how real-world evidence complements clinical trial data by providing insights into treatment outcomes among patients with more complex comorbidities and medication regimens.

Pharmacy Times: Your analysis found notable differences in cardiovascular toxicity among BTK inhibitors, particularly regarding atrial fibrillation and hypertension. How do these findings influence your approach to selecting a BTK inhibitor for patients with preexisting cardiovascular comorbidities?

Kim Nguyen, PharmD: These findings reinforce the importance of individualized, patient-centered care when selecting a BTK inhibitor for patients with preexisting cardiovascular disease. I carefully review each patient's medical history, cardiovascular risk factors, and current medications before making a treatment recommendation.

I also focus on prevention and early monitoring of cardiovascular adverse events, involve patients and their families in treatment decisions, and adjust therapy as needed based on the patient's overall risk profile. For patients who are at higher risk for atrial fibrillation or hypertension, I would be more likely to select acalabrutinib over ibrutinib because of its more favorable cardiovascular toxicity profile.

Pharmacy Times: You observed that hypertension rates with acalabrutinib appeared higher in real-world studies than in randomized clinical trials. What do you think this discrepancy tells us about managing BTK inhibitors in everyday clinical practice, and how should pharmacists interpret these data when counseling patients?

Nguyen: I think the key message is that real-world evidence complements clinical trial data. It reminds us that the patients we treat every day may experience toxicities differently than those enrolled in clinical trials, which is why individualized care, proactive monitoring, and patient education are so important.

As pharmacists, it is important to recognize that randomized clinical trials are conducted under controlled conditions and often include highly selected patient populations with relatively short follow-up periods. As a result, the patients enrolled in these trials may not fully reflect those we see in routine clinical practice, who often have multiple comorbidities and complex medication regimens.

This highlights the importance of taking an individualized approach to patient care. When interpreting these data, pharmacists should consider both clinical trial evidence and real-world experience to make informed treatment decisions and tailor therapy to each patient's needs. Ongoing monitoring is essential, and therapy adjustments may be required to ensure treatment remains both safe and effective.

When counseling patients, it is equally important to set appropriate expectations and educate them about potential adverse effects, how to monitor their blood pressure and cardiovascular health, and when to seek medical attention. Empowering patients to actively participate in their care can help identify potential issues early and improve overall treatment outcomes.

Pharmacy Times: Given the prevalence of CYP3A4-mediated drug interactions with BTK inhibitors, what are some of the most common interaction challenges you encounter in practice, and what strategies can pharmacists use to proactively identify and manage them?

Nguyen: One of the most common interaction challenges I encounter in practice is obtaining complete medication and medical histories. Patients do not always disclose over-the-counter products, herbal supplements, or medications prescribed by other health care providers.

For example, herbal products such as St. John's wort, as well as medications prescribed by other specialists, can significantly affect CYP3A4 metabolism. These interactions may alter BTK inhibitor exposure and potentially impact both safety and efficacy.

Another common challenge involves patients receiving anticoagulants or antiplatelet agents. Managing these therapies alongside BTK inhibitors can increase bleeding risk and often requires close coordination among multiple health care professionals, including hematologists, cardiologists, surgeons, pharmacists, nurses, patients, and caregivers. Different prescribers may also have varying approaches to monitoring, laboratory testing, imaging, and decisions regarding when to hold, resume, or adjust BTK inhibitor therapy before and after procedures.

As pharmacists, I believe our role is to proactively identify and manage these risks through comprehensive medication histories, medication reconciliation, and thorough patient counseling. It is important to educate patients before procedures, follow up with them afterward, and ensure clear communication among all members of the health care team.

Equally important is empowering patients and caregivers to actively participate in their care by understanding potential drug interactions, knowing which symptoms to monitor for, and recognizing when to seek medical attention. Taking this collaborative, patient-centered approach helps ensure that BTK inhibitor therapy remains both safe and effective.

Pharmacy Times: As newer agents such as pirtobrutinib continue to enter clinical practice, what additional real-world evidence would you most like to see to better understand their long-term cardiovascular safety profiles compared with earlier-generation BTK inhibitors?

Nguyen: Pirtobrutinib is one of the newer BTK inhibitors entering clinical practice, and I would like to see more real-world evidence with longer follow-up to better characterize its safety profile.

In particular, I am interested in cardiovascular outcomes such as bleeding, heart failure, atrial fibrillation, and hypertension, especially in broader patient populations with multiple comorbidities. It is also important to better understand the safety of pirtobrutinib in patients with preexisting cardiovascular disease and in those taking concomitant medications that may involve CYP3A4-mediated drug interactions.

In addition, more standardized definitions of cardiovascular adverse events, along with larger cohort studies, would improve the quality and comparability of the available evidence.

Finally, comparative real-world studies evaluating pirtobrutinib alongside covalent BTK inhibitors would be particularly valuable. These data could help guide treatment selection and improve our understanding of long-term cardiovascular risk in clinical practice.

You can view the full abstract here.