Hypertension and renal disease prevention before cancer therapy

Risk stratification and screening for hypertension and renal dysfunction

Assessment for preexisting cardiovascular disease and cardiovascular risk factors should be made in all patients prior to starting VEGFI therapy ( Table 11.1 ). This should be performed by the oncology team in the first instanceand should include a detailed history, physical examination, and focused investigations to screen for risk factors and preexisting end-organ damage. It is important to identify any history of preexisting hypertension or established cardiovascular disease, including ischemic heart disease, cerebrovascular disease, peripheral arterial disease, retinal disease, and heart failure. Additional cardiovascular risk factors, including smoking and family history of premature cardiovascular disease, should be identified. Renal function should be assessed at baseline via serum creatinine and estimated glomerular filtration rate (GFR) measurement. Preexisting proteinuria should also be assessed, at a minimum by use of urinary dispstick, and preferably by laboratory measurement of protein-to-creatine ratio. Where possible, ambulatory BP monitoring should be used to identify preexisting hypertension and office BP should always be measured prior to commencing therapy. ^, Lipid profile andfasting plasma glucose should be measured in all patients. A baseline electrocardiogram and echocardiogram should be obtained.

The over-arching aim of these assessments is not to exclude patients from treatment with a VEGFI, but to provide a systematic means of identifying and addressing modifiable risk factors to reduce the risk of developing acute cardiovascular complications during and after treatment. By addressing these issues proactively, it is intended that patients should be able to receive the optimal cancer therapy, at the optimal dose, and for the optimal time to allow maximum anticancer effects to be achieved without interruption or cessation because of concerns about cardiovascular toxicity. It is very important to note that the treatment of VEGFI-associated hypertension does not impair the VEGFI anticancer effect.

Given that almost every patient commenced on VEGFI therapy will have a treatment-associated rise in blood pressure (outlined in detail in Chapter 20 ), ^, it is important to identify those at greatest risk. It is clear that there would be clinical value in a risk prediction tool for VEGFI-associated hypertension and end-organ effects from hypertension. This could be used to facilitate more intensive BP monitoring and early intervention, particularly in those most vulnerable. However, the currently available data are insufficient to inform such a tool and the use of circulating and urinary biomarkers to identify such patients is limited at present. In the absence of validated risk-stratification tools, clinical assessment should focus on conventional cardiovascular risk factors.

In patients proposed to receive other treatments with cardiotoxicity potential similar attention should be paid to the assessment and treatment of blood pressures. Whereas the primary cardiotoxic effect of many of these drugs is on the myocardium, the consequences of myocardial toxicity are further potentiated by coexisting hypertension.

Correcting modifiable risk factors

It is accepted that strict control of cardiovascular risk factors to minimize the risk of the development of toxicity is an important part of the treatment of patients. Adequate BP control should be accomplished before starting treatment, and intensive monitoring of BP and up-titration of antihypertensive therapy may be required to minimize any delay in starting cancer treatment. Lifestyle modifications should be instituted, including reduced alcohol consumption, smoking cessation and, where possible, physical exercise. Management of diabetes should also be optimized, with input from diabetologists where appropriate.

The risks of delaying anticancer therapy for optimization of the cardiovascular status always need to be balanced with the hazards of incomplete control or suboptimal management of cardiovascular disease and risks.

Diagnosis and monitoring of hypertension before treatment

The criteria for the diagnosis of hypertension vary across international guidelines and this variation is primarily a reflection of a differing interpretation of data from the Systolic Blood Pressure Intervention Trial (SPRINT) trial. SPRINT demonstrated that cardiovascular outcomes in patients at high risk were improved by intensive blood pressure reduction. This trial was conducted in a noncancer population and extrapolation of the results to those with cancer and particularly those to be treated with VEGFI requires careful consideration. Patients with cancer may be at greater risk of iatrogenic hypotension, particularly in the context of intercurrent infection or hemorrhage. Additionally, the balance of competing cardiovascular and oncologic risk needs careful assessment. The Cardiovascular Toxicities Panel, Convened by the Angiogenesis Task Force of the National Cancer Institute Investigational Drug Steering Committee recommended a goal of blood pressure less than 140/90 mm Hg for patients on VEGFI therapy and a goal of less than 130/80 mm Hg for those with diabetes and/or chronic kidney disease. More recent American College of Cardiology/American Heart Association guidelines recommend more stringent BP control, with antihypertensive therapy being commenced in patients with blood pressure greater than 130/80 mm Hg and with high cardiovascular risk, defined as individuals with existing cardiovascular disease, a calculated 10-year cardiovascular risk of more than 10%, or those who have other risk factors (e.g., kidney disease or diabetes). Conversely, current European Society of Cardiology guidelines and its position paper on cardiovascular toxicity of anticancer therapy recommend treatment initiation at blood pressures above 140/90 mm Hg. ^, Taking these variations in recommendations and the increased risk of the rapid and potentially severe rise in BP seen with almost all patients receiving VEGFI therapy into consideration, we recommend a target BP of below 130/80 mm Hg prior to starting treatment. However, the start of anticancer treatment should not be delayed in order to achieve strict blood pressure control, and we agree with the National Cancer Institute Investigational Drug Steering Committee’s recommendation that blood pressure should be below 140/90 mm Hg before initiating VEGFI therapy as an absolute minimum. Decisions on antihypertensive therapy, BP control, and timing of initiation of VEGFI therapy should be made following input from both oncology and cardiovascular specialists to ensure timely optimal cardiovascular status is achieved prior to commencing VEGFI therapy.

For those patients with preexisting hypertension already receiving antihypertensive treatment, it is important to ensure adherence to therapy, the optimal choice of agent, and the dosing regimen. It may be necessary to change to an alternative agent, up-titrate the current dosing regimen or to add an additional agent. In most cases the choice of antihypertensive drug(s) should follow clinical guidelines for the general, noncancer, population, but particular preference for the use of ACEi/ARB (angiogensin-converting enzyme inhibitor/angiotensin receptor blocker) in patients with hypertension scheduled to receive drugs with a known cardiotoxic profile, particularly anthracyclines and/or trastuzumab. Non-dihydropyridine calcium channel blockers should be avoided in patients due to be treated with VEGFI. Other pertinent aspects for the choice of antihypertensive therapy in patients with cancer are outlined elsewhere (see Chapter 20 , Table 20.2 ). Referral to a hypertension specialist or cardiovascular-oncologist may be appropriate if there is any difficulty with achieving target blood pressure.