ACE inhibitors associated with higher lung cancer risk compared to ARBs in observational study
An editorial cautioned clinicians and patients to balance these observed findings against the potential benefits of antihypertensive drugs while more research is done.
Angiotensin-converting enzyme (ACE) inhibitors were associated with a 14% increased risk of lung cancer compared to angiotensin-receptor blockers (ARBs), an observational study found, with the risk rising to 31% among people using ACE inhibitors for more than a decade.
Researchers analyzed primary care records in the U.K. for 992,061 adult patients who started taking a new antihypertensive drug between 1995 and 2015. Patients were followed for an average of 6.4 years, during which time 7,952 cases of lung cancer were found (1.3 per 1,000 person-years). Results were published by The BMJ on Oct. 24.
After adjustment for age, sex, body mass index, smoking status, alcohol-related disorders, and history of lung diseases, use of ACE inhibitors was associated with an overall 14% increased risk of lung cancer compared with ARBs (1.6 vs. 1.2 cases per 1,000 person-years). Associations were evident after five years of use (hazard ratio, 1.22; 95% CI, 1.06 to 1.40) and were stronger in patients who used ACE inhibitors for more than 10 years (31% increased risk).
An association between ACE inhibitors and lung cancer is biologically plausible, the authors noted, since ACE inhibitors metabolize bradykinin, causing an accumulation of it in the lungs, and bradykinin receptors have been located on various cancerous tissues, including lung cancer.
“Although the magnitudes of the observed estimates are modest, these small relative effects could translate into large absolute numbers of patients at risk for lung cancer, so these findings need to be replicated in other settings,” the authors wrote.
An editorial concluded, “Although a 14% relative increase in lung cancer incidence might not translate to a large absolute risk, the findings are important given the considerable use of [ACE inhibitors] worldwide. Nonetheless, in an individual patient, concerns about the long term risk of lung cancer should be balanced against gains in life expectancy associated with use of [ACE inhibitors].”