Table 3.

ESC-SCORE risk categories and monitoring during treatment with ponatinib (adapted from [52, 53])

Low to moderate risk
− ESC-SCORE <5%
− Many middle-aged subjects belong in this category; strongly influenced by obesity, total cholesterol and triglycerides, familiar history of coronary disease.	Use of ponatinib possible Risk factor modification and lifestyle changes based on guidelines; consider statin therapy (e.g., atorvastatin) to keep (fasting) LDL-C <115 mg/dL (<3 mmol/L)a
Monitoring: − History-taking and clinical examination, lab tests including diabetes and serum lipid profile (every 3 months in year 1, then every 6–12 months) −BP monitoring (every 3 months in year 1, then semiannually); self-monitoring with documentation as appropriate (20–30% incidence of hypertension during ponatinib treatment) − ECG (semiannually); ABI, stress ECG/alternative stress test (annually)

High-risk
Subjects with any of the following: − ESC-SCORE between 5% and <10% − Markedly elevated single risk factors, such as cholesterol >310 mg/dL (8 mmol/L) or severe hypertension (≥180/110 mm Hg) − Moderate CKD (GFR 30–59 mL/min)	Use of ponatinib possible; alternative TKIs should be considered (benefit-risk assessment) Prospective dose reduction; Risk factor modification and lifestyle changes based on guidelines; consider statin therapy (e.g., atorvastatin) to keep (fasting) LDL-C <100 mg/dL (<2.6 mmol/L)
Intensified monitoring: As indicated for low-/moderate-risk group, plus: − Regular blood pressure self-monitoring (documentation), − History-taking and clinical examination, lab tests including diabetes and lipid profile (quarterly) − ABI (semiannually)

Very high-risk
Subjects with any of the following: − ESC-SCORE ≥10% − Documented CVD (previous AMI, ACS, coronary revascularization, stroke, TIA or PAD) − DM with target organ damage, for example, proteinuria or with a major risk factor (smoking, hypertension, high cholesterol) − Severe CKD (GFR <30 mL/min)	Ponatinib should be used only if strictly indicated; use of alternative TKI when possible Prospective dose reduction; risk factor modification and lifestyle changes; more aggressive treatment of dyslipidemia with target (fasting) LDL <70 mg/dL (<1.8 mmol/L)
Intensified monitoring: as indicated for high-risk group

^aHaving considered the very low risk introduced by statin therapy, the panel felt that low- to medium-risk patients treated with ponatinib should probably merit earlier or more vigorous statin control of LDL-cholesterol. ABI, ankle-brachial index; ACS, acute coronary syndrome; AMI, acute myocardial infarction; BP, blood pressure; CKD, chronic kidney disease; DM, diabetes mellitus; ECG, electrocardiogram; ESC, European Society of Cardiology; GFR, glomerular filtration rate; PAD, peripheral artery disease; TIA, transient ischemic attack; SCORE, systematic coronary risk evaluation.