Hypertensive Cardiotoxicity in Cancer Treatment—Systematic Analysis of Adjunct, Conventional Chemotherapy, and Novel Therapies—Epidemiology, Incidence, and Pathophysiology

Abstract

Cardiotoxicity is the umbrella term for cardiovascular side effects of cancer therapies. The most widely recognized phenotype is left ventricular dysfunction, but cardiotoxicity can manifest as arrhythmogenic, vascular, myocarditic and hypertensive toxicities. Hypertension has long been regarded as one of the most prevalent and modifiable cardiovascular risk factors in the general population, but its relevance during the cancer treatment journey may be underestimated. Hypertensive cardiotoxicity occurs de novo in a substantial proportion of treated cancer patients. The pathology is incompletely characterized—natriuresis and renin angiotensin system interactions play a role particularly in conventional treatments, but in novel therapies endothelial dysfunction and the interaction between the cancer and cardiac kinome are implicated. There exists a treatment paradox in that a significant hypertensive response not only mandates anti-hypertensive treatment, but in fact, in certain cancer treatment scenarios, hypertension is a predictor of cancer treatment efficacy and response. In this comprehensive review of over 80,000 patients, we explored the epidemiology, incidence, and mechanistic pathophysiology of hypertensive cardiotoxicity in adjunct, conventional chemotherapy, and novel cancer treatments. Conventional chemotherapy, adjunct treatments, and novel targeted therapies collectively caused new onset hypertension in 33–68% of treated patients. The incidence of hypertensive cardiotoxicity across twenty common novel therapies for any grade hypertension ranged from 4% (imatinib) to 68% (lenvatinib), and high grade 3 or 4 hypertension in < 1% (imatinib) to 42% (lenvatinib). The weighted average effect was all-grade hypertension in 24% and grade 3 or 4 hypertension in 8%.

Cancer Therapy-Related Cardiovascular Complications in Clinical Practice: Current Perspectives

“…HF affects 25% and 4% of patients treated with carfilzomib and bortezomib, respectively, and it most often occurs within the first weeks of chemotherapy [ 4 ]. Arterial hypertension is observed much less frequently in patients treated with PI: 6.5–12% of patients are affected [ 37 ]. An estimation of the initial CV risk, vigilance, and careful monitoring during treatment are important in the prevention of PI-related cardiotoxicity [ 38 ].…”

“…Additionally, taxanes can cause hypertension, although much less frequently than other chemotherapeutic agents. Hypertension was found in 0.8% of patients treated with paclitaxel and in 4% of those treated with cabazitaxel [ 37 ]. In rare cases, taxanes can also cause chest pain and acute coronary events (0.2–4% of paclitaxel-treated patients) due to vasoconstriction [ 40 ].…”

“…Arterial hypertension is one of the most common manifestations of TKI-associated cardiotoxicity, affecting the VEGF pathway in particular, and it usually occurs within the first few treatment cycles. The main cause for drug-induced hypertension is increased levels of endothelin-1, although activation of the renin–angiotensin–aldosterone system has also been reported as a cause [ 37 ]. The prevalence of arterial hypertension depends on the type of chemotherapy and is estimated to range from 4% (for imatinib) to 68% (for lenvatinib) [ 37 ].…”

“…The main cause for drug-induced hypertension is increased levels of endothelin-1, although activation of the renin–angiotensin–aldosterone system has also been reported as a cause [ 37 ]. The prevalence of arterial hypertension depends on the type of chemotherapy and is estimated to range from 4% (for imatinib) to 68% (for lenvatinib) [ 37 ]. The risk of CV complications is significantly higher in patients with stage II hypertension, type 2 diabetes mellitus, multiple CV risk factors, and documented pre-existing CV disease.…”

Hypertensive toxicity of thyrosine kinase inhibitors; Friend or Foe?

“…Approach to the patients with different grades of hypertensive cardio toxicity is presented in table 1. Several anti-cancer drugs other than VEGF inhibitors also may cause hypertensive cardio toxicity [4].…”