Angiotensin-receptor blockers (ARBs) are a class of drugs approved for the treatment of several common conditions, such as hypertension and heart failure. Recently, regulatory agencies have started to identify possibly carcinogenic nitrosamines and azido compounds in a multitude of formulations of several ARBs, resulting in progressive recalls.
In a recent study, researchers have found that the risk of cancer with ARBs (and specifically lung cancer) increases with increasing cumulative exposure to these drugs. The study findings were published in the journal Plos One on March 02, 2022.

Cumulative exposure is a fundamental factor in the epidemiology of chronic disease, especially in cancer epidemiology. Unfortunately, the relationship between cumulative exposure to ARBs and the risk of cancer is not known. Therefore, Dr Ilke Sipahi performed a meta-regression analyses to provide additional insight into the ARB-cancer link by examining whether there is a relationship between the degree of cumulative exposure to ARBs and the risk of cancer in randomized trials.
In this new meta-analysis, Dr Ilke Sipahi includes 15 randomized controlled trials. The two co-primary outcomes were the relationship between cumulative exposure to ARBs and risk of all cancers combined and the relationship between cumulative exposure and risk of lung cancer. In this analysis, the researchers randomly assigned 74,021 patients to an ARB group resulting in a total cumulative exposure of 172,389 person-years of exposure to daily high dose (or equivalent), and 61,197 patients to the control group.
Key findings of the study:
Upon analysis, the researcher found a highly significant correlation between the degree of cumulative exposure to ARBs and risk for all cancers combined (slope = 0.07; P < .001) and also lung cancer (slope = 0.16; P = .003).
In trials where the cumulative exposure was greater than 3 years of exposure to a daily high dose, he noted a statistically significant increase in risk for all cancers combined (risk ratio [RR], 1.11).
He found no statistically significant increase in the risk of lung cancers in trials where the cumulative exposure was greater than 2.5 years (I2 = 0%, RR 1.21).
In trials with lower cumulative exposure to ARBs, he observed no increased risk either for all cancers combined or lung cancer.
The authors concluded, "This analysis shows that risk of cancer and specifically lung cancer increase with increasing cumulative exposure to ARBs. Detailed and impartial analysis of the vast amount of patient-level data of randomized trials that the regulatory agencies already have, including examination of cumulative exposure—risk relationship, can confirm the current findings. Because of the ongoing widespread use of ARBs globally, their potential of excess cancer risk with long-term use has profound implications for patients and prescribing clinicians."
For further information:
DOI: https://doi.org/10.1371/journal.pone.0263461