Table 4.
Summary Take-Home Points and Selected Common Issues That Remain to Be Addressed With BTK Inhibitor Therapies
| Key take home points |
| BTK inhibitors dramatically improve survival outcomes in CLL and other malignancy populations |
| BTK inhibitors are associated with a >4-fold increase in AF and other arrhythmiasa when compared with patients not exposed to BTK inhibitor therapy, with some unique cardiotoxic mechanisms |
| New or worsened hypertension is common with BTK inhibitor use (ibrutinib, acalabrutinib, zanubrutinib) |
| Other cardiovascular events (eg, heart failure, ventricular arrhythmias) are increased with BTK inhibitor use |
| Although less than ibrutinib, newer BTK inhibitors still appear to link with increased cardiotoxic risk |
| Early hypertension and older age appear to disproportionately increase the risk of AF and other cardiotoxic events with BTK inhibitor therapy among CLL patients |
| Cardiovascular events (eg, AF, ventricular arrhythmias) influence long-term cardiovascular and overall survival after BTK inhibitor treatment |
| Caution should be used when interpreting clinical trial data for BTK inhibitor cardiotoxic risk assessment, because many trials do not systematically quantify or ascertain subclinical CVD events |
| Evidence gaps and future research directions |
| Specific predictive factors of long-term cardiotoxic risk with BTK inhibitor therapies in CLL and other hematologic malignancy populations |
| Mechanisms underlying increased cardiotoxic risk, beyond selectivity (given emerging data suggesting residual cardiac risk with selective BTK inhibitors) |
| Comparison of cardiac toxicities profiles of newer BTK inhibitors (eg, acalabrutinib vs zanubrutinib) |
| True burden of arrhythmia(s) or hypertension using systematic ECG or blood pressure monitoring with BTK inhibitor treatment |
| True incidence, predictive factors, and preventative strategies for potentially fatal ventricular arrhythmias |
| Role of subclinical remodeling (eg, fibrosis) and early hypertension in major cardiotoxic event susceptibility |
| Optimal strategy for preventing (and/or controlling) hypertension and other cardiovascular events with BTK inhibitor therapy; and for BTK inhibitor rechallenge |
| Personalized cardioprotection strategies/plan (eg, integrating biologic, genetic, and imaging markers) |
Note: Shared decision-making with patients should be considered where appropriate.
CLL = chronic lymphocytic leukemia; CVD = cardiovascular disease; ECG = electrocardiogram; other abbreviations as in Table 3.