Hypertension in cancer patients treated with anti-angiogenic based therapy: a population-based cohort study

Objective: Data from randomized clinical trials showed that new-onset hypertension is a common side effect of anti-angiogenic drugs. We compared the cumulative incidence of new-onset hypertension in cancer patients treated with either anti-angiogenic based therapy (AAG) or other chemotherapy only, and in patients who did not received antineoplastic agents (untreated). Design and method: Retrospective population-based cohort study based on the healthcare utilization databases of Lombardy Region (Italy). We identified the cohort of patients aged 40 years or older with a new diagnosis of cancer between 2009 and 2017. We excluded patients with antihypertensive treatment in the five years before cancer diagnosis. We 1:1:1 matched each patient who started a therapy with AAG (index case) with one patient treated with other chemotherapy only and with one untreated patient by date of cancer diagnosis, tumoral site and date of start of antineoplastic therapy. We followed-up each of the three matched patients from the date of start of AAG of the index case until the first date between onset of antihypertensive treatment with at least 3 prescriptions (the outcome of interest), death, migration or 2 years after the start of follow-up. We estimated the incidence cumulative function by considering death as competing event and we fitted a Fine and Grey regression model, adjusted for age, sex and Cancer Multimorbidity Score, in order to estimate the association between treatment and new-onset hypertension. Results: The final cohort included 3,333 1:1:1 matched patients (median age 62 years; 43.6% males). The cumulative incidence of new-onset hypertension was higher among patients treated with AAG, as compared to others. The cumulative incidence rapidly increased 1 year (26.3%) after starting therapy with AAG. The adjusted hazard ratios were 3.73 (95% CI 3.34 to 4.15) and 4.00 (3.56 to 4.48), when compared to patients treated with other chemotherapy and with those untreated, respectively. Moreover, patients treated with AAG also showed a significant increased risk of major cardiovascular events compared to others. Conclusions: Cancer patients treated with AAG showed a markedly higher risk of new-onset hypertension. The risk rapidly increased 1 year after the start of therapy.