Table 4.

Summary of risk factors, screening and investigations, and potential management options for the main cardiovascular toxicities associated with TKIs. ACE – Angiotensin-converting enzyme; ARB – Angiotensin receptor blocker; CAD – Coronary artery disease; DAPT – Dual anti-platelet therapy; LVEF – Left ventricular ejection fraction; LVSD – Left ventricular systolic dysfunction; MI – Myocardial infarction; NT-proBNP – N-terminal pro b-type natriuretic peptide; PVD – peripheral vascular disease.

Toxicity	Risk factors	Investigations / Screening	Management
Hypertension	Age (>65) Pre-existing hypertension Pre-existing vascular disease (stroke / MI / PVD) Diabetes Mellitus	Monitor weekly during first cycle 2- to 3- weekly thereafter Home blood pressure monitoring where possible	Control existing hypertension ACE inhibitor / ARB Dihydropyridine calcium channel blocker Beta blocker Diuretics Dose reduction / discontinuation of TKI with severe hypertension NOT verapamil or diltiazem
LV dysfunction	Pre-existing heart failure / LVSD Significant CAD Pre-existing hypertension Valvular heart disease Previous anthracycline exposure	Baseline imaging assessment Serial monitoring at 1 month and every 3 months on TKI Role for biomarker testing not yet defined (Troponin / NT-proBNP)	ACE inhibitor/ARB and beta blocker ± mineralocorticoid receptor antagonist in patients with heart failure Consider ACE inhibitor/beta blocker in asymptomatic LVSD Discontinuation of TKI with heart failure or significant reduction in LVEF
Myocardial infarction	Age (>65) Pre-existing CAD	Consider stress testing/coronary angiography in presence of potentially ischaemic symptoms at baseline	Anti-platelet primary prevention should be avoided Safest shortest duration of DAPT after percutaneous coronary intervention should be sought Discontinuation/interruption of TKI following MI
QT Prolongation	Age (>65) Electrolyte imbalance Hypothyroidism QT-prolonging drugs	Baseline ECG and electrolyte monitoring Serial monitoring	Withdraw QT-prolonging drugs Temporary withdrawal of TKI with QTc >500ms or increase of >60ms Discontinuation of TKI with Torades de Pointes