Rethinking cardiovascular risk stratification in TKI-treated chronic myeloid leukemia

Tyrosine kinase inhibitors (TKIs) targeting BCR::ABL1 have transformed chronic myeloid leukemia (CML) into a chronic condition with near-normal life expectancy, but peripheral artery disease (PAD) has emerged as a major source of morbidity, particularly with nilotinib and ponatinib. Current cardiovascular management relies on general population risk scores and ankle-brachial index (ABI) measurement, tools not designed to capture TKI-specific vascular biology or detect subclinical arterial damage.

We appraise cardiovascular risk stratification tools and vascular imaging modalities in the context of TKI-treated CML, and propose an integrated algorithm combining dual risk scoring, ABI, and targeted femoral duplex ultrasound (DUS).

Vascular outcome reporting in TKI trials is hampered by terminological inconsistency: Major Adverse Limb Events (MALE), the standard limb-specific endpoint in contemporary cardiovascular trials, has never been adopted in any TKI/CML publication. Existing risk scores (SCORE2, HFA-ICOS) neither capture TKI-accelerated atherosclerosis nor discriminate limb-specific risk. ABI detects only established stenosis and is further limited by TKI-induced medial arterial calcification. The femoral artery is both the earliest site of subclinical atherosclerosis and the preferential anatomical target of TKI-induced vascular damage; thus, femoral plaque detection may serve as a risk reclassification instrument. Because vascular risk differs by line of therapy and imaging resources are finite, screening should be targeted to patients in whom the result would change agent selection and preventive strategies.

Integrating femoral DUS into cardiovascular risk stratification shifts the objective from diagnosing established disease to preventing it. Whether this translates into fewer events remains to be demonstrated.