Recommendations for the management of cardiovascular risk in patients with chronic myeloid leukemia on tyrosine kinase inhibitors: risk assessment, stratification, treatment and monitoring

Abstract

This manuscript summarizes the results of the consensus meeting composed of hematologists and cardiologists to establish recommendations for the prevention and follow-up of cardiovascular (CV) risk in patients with chronic myeloid leukemia (CML) treated with BCR-ABL tyrosine kinase inhibitors (TKIs) from the point of view of clinical practice and from the perspective of hematology consultation. In the first medical appointment, the CV risk factors should be identified to perform the baseline risk stratification, based on the Brazilian Guideline of Dyslipidemia and Atherosclerosis Prevention Update (risk levels: very high, high, intermediate and low). Once stratified, the treatment of the CV risk factors should be administered. If the patient presents risk factors, such as hypertension, diabetes, renal disease, smoking and hypercholesterolemia, the evaluation and initial treatment may be done by the hematologist, being an option the request for evaluation by a specialist. If the patient has a history of previous CV disease, we recommend referral to a specialist. As the CV risk score is dynamic and the control of risk factors can reduce the patient risk, this expert consensus recommends that the re-evaluation of the CV risk after the baseline should be performed at 3 months, 6 months and 12 months. After this period, it should be done annually and, for specific patients, at the clinician's discretion. The evaluation of the baseline CV risk and the safe administration of a TKI allow the patient to benefit from the maximum treatment, avoiding unwanted effects.

Keywords: Cardiovascular diseases; Leukemia, myeloid; Protein kinase inhibitors; Risk factors; Risk management.

Figure 1

Algorithm for cardiovascular risk stratification. Adapted from the online cardiovascular risk stratification tool developed by the Brazilian Society of Cardiology - Department of Atherosclerosis, Brazilian Society of Endocrinology and Metabology and the Brazilian Society of Diabetes. *Family history of a first-degree relative with premature CVD (<55 years for men and <65 years for women). †Smoking is defined as at least one cigarette in the last month. ‡Metabolic syndrome is defined according to the International Diabetes Federation. GSR: Global risk score, calculated depending on factors such as gender, age, systemic blood pressure, active treatment for hypertension, smoking, use of statins, total cholesterol and LDL-c. ABI: Ankle-Brachial Index; CAC: Coronary Artery Calcium; CT: computed tomography; CVD: cardiovascular disease; DM: diabetes mellitus; GFR: Glomerular Filtration Rate.

Figure 2

Flowchart for the treatment of hypertension. Adapted from the 7th Brazilian Arterial Hypertension Guideline. ACE: angiotensin-converting-enzyme; ARBs: angiotensin II receptor blockers; CCB: calcium channel blockers; CV: cardiovascular.

Figure 3

Treatment of diabetes mellitus type 2. Adapted from the Guidelines of the Brazilian Diabetes Society (2015–2016).

Figure 4

Targets and recommended treatment for the LDL-c control. Adapted from the online cardiovascular risk stratification tool developed by the Brazilian Society of Cardiology, Department of Atherosclerosis, Brazilian Society of Endocrinology and Metabology and the Brazilian Society of Diabetes. *Rosuvastatin and pravastatin are preferred treatments. Simvastatin and atorvastatin should be used with caution due to the possibility of drug interactions through the metabolism route. ^¥Expected % of reduction. ^†Target for LDL-c (mg/dL). ^‡Target for non-HDL-c (mg/dL).

Figure 5

CV risk monitoring during TKI treatment. BAI: brachial ankle index; CV: cardiovascular; PAOD: peripheral arterial occlusive disease.