Diagnosis, monitoring and management of HTN in anticancer therapies

According to the National Cancer Institute (NCI), hypertension (HTN) is one of the most common adverse effects (AEs) in anticancer therapies.1 Anticancer drug associated with HTN includes vascular endothelial growth factor inhibitors (VEGFis) and other adjunctive therapies (e.g., glucocorticoids, erythropoietin).1 Before starting anticancer therapy, it is essential to evaluate the presence of underlying cardiovascular disease (CVD) and risk factors in patients, with the ideal blood pressure (BP) control established ahead of the beginning of potentially cardiotoxic anticancer drugs.1 In the ASN Kidney Week 2022, Dr. Agnes S. Kim from the UConn Health Calhoun Cardiology Center, the United States, shared her view on HTN in cancer patients.1 

Nearly all clinical trials have determined that VEGFis resulted in greater BP, including 30%-80% of patients developing HTN and nearing all with an absolute elevation in BP.1 New onset or deteriorating HTN usually occurs within the first few weeks of the therapy, although it can happen within the first 24 hours.1 The VEGFi therapy contributes to HTN in a dose-dependent manner, which is reversible after the termination of VEGFi.1 Acute rise in BP is a problem for patients who are previously unconditioned to the chronic effects of HTN, with the potential acute end-organ complications of HTN being myocardial ischemia, left ventricular (LV) systolic dysfunction, heart failure (HF), stroke, cerebral hemorrhage, posterior reversible encephalopathy syndrome (PRES), and renal failure.1 

Other factors contributing to HTN in cancer patients include carotid baroreceptor dysfunction, paraneoplastic syndrome, abdominal radiotherapy, radical nephrectomy, white coat and masked HTN, other psychological (e.g., pain, anxiety) and social (e.g., diet, weight gain) factors.1 

It is generally recommended by experts that bevacizumab and other VEGFis can be initiated safely in patients with a BP of <160/100mmHg in the office, or <150/95mmHg at home.1 Patients on VEGFis are highly advised to maintain a BP of <140/90mmHg to prevent end-organ damage, also avoiding the need for anticancer therapy dose reduction or disruption.1 The commencement of anticancer therapy should not be delayed for rigorous BP control, but rather established simultaneously.1 As an acute increase in BP is most common soon after VEGFi initiation, regular BP monitoring is recommended once the therapy starts.1 Experts also recommend weekly BP monitoring during the first cycle, and subsequently every 2-3 weeks, along with monitoring the signs and symptoms of HTN complications.1 Evidence showed that in patients with renal cell carcinoma (RCC), there was a rapid increase in BP within the first few weeks of the first cycle of sunitinib therapy in both initially normotensive and hypertensive patients.1 Dose reduction or withholding of VEGFis is rare and only be considered if the patient has a very high BP that is associated with acute, HTN-mediated organ damage, or if BP remains severely uncontrolled at >160/100mmHg even with multiple BP medications, or when the decision is made upon cautious multidisciplinary discussion and a personalized risk-benefit evaluation.1 

The European Society of Cardiology (ESC) recommends that anti-HTN therapy starts from a BP level of >140/90mmHg, and should be reviewed in patients with a rapid BP elevation (i.e., diastolic BP increase >20mmHg) following cancer treatment initiation.1 Relatively flexible BP targets should be set for palliative patients with end-stage cancer since long-term CVD avoidance may not be a priority.1 It has been shown that antihypertensive therapy did not impair the efficacy of VEGFi therapy and was prescribed according to comorbidities.1 The first-line antihypertensive therapy includes dihydropyridine calcium channel blockers (CCBs) (i.e., amlodipine) and angiotensin-converting enzyme inhibitors (ACEis) or angiotensin receptor blockers (ARBs), with most patients acquire the combination therapy.1 Yet, non-dihydropyridine CCBs (i.e., verapamil, and diltiazem) are the exception, as they inhibit cytochrome P450 CYP3A, which metabolizes certain VEGFis like sunitinib and sorafenib, resulting in elevated drug levels.1 

BP monitoring is also an important post-cancer therapy, due to the risk of rebound HTN and watershed ischemia.1 Post-cancer therapy patients are deemed to have American College of Cardiology/American Heart Association (ACC/AHA) stage A HF (i.e., no evidence of structural heart disease or symptoms of HF, but at the risk of developing HF), and thus having a goal BP of <130/80mmHg.1 

In summary, novel anticancer therapies can have potent HTN effects and cause an acute rise in BP that may potentially lead to end-organ damage; therefore, appropriate screening for HTN, regular home blood pressure monitoring (HBPM), and early diagnosis are essential.1 Treatment of BP is important to minimize anticancer therapy interruptions, with an overarching goal of minimizing CV events while maximizing the benefits of cancer treatment.1 It is also significant to have a personalized risk-benefit evaluation for decision-making.1 

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