Angiotensin converting enzyme inhibitors (ACEIs) are associated with a higher risk of lung cancer than angiotensin receptor blockers (ARBs), especially if used for more than five years, a study in The BMJ has found.1
Although the risk to individual patients is modest, the absolute numbers of patients at risk for lung cancer is potentially large because ACEIs are widely prescribed, said the researchers.
Evidence suggests that ACEIs increase the risk of lung cancer through the build-up of bradykinin and substance P in the lung. These chemicals have been found on lung cancer tissue, and bradykinin may directly stimulate the growth of lung cancer; however, previous observational studies examining this association are limited and have reported inconsistent results.
To better understand this possible association a team of researchers, led by Laurent Azoulay at McGill University in Canada, analysed UK primary care records of nearly a million patients who started taking a new antihypertensive drug from 1995 to 2015.
Patients were aged at least 18 with no previous cancer and were followed up for an average of 6.4 years, during which time 7952 cases of lung cancer were identified (a rate of 1.3 cases per 1000 person years).
After considering potentially confounding factors including age, sex, weight, smoking status, alcohol related disorders, and history of lung diseases, the use of ACEIs was associated with an overall 14% higher risk of lung cancer than ARBs (1.6 v 1.2 cases per 1000 person years; hazard ratio 1.14 (95% confidence interval 1.01 to 1.29)).
Associations were evident after five years of use and increased with longer use, particularly in patients who used ACEIs for more than 10 years (31% increased risk; hazard ratio 1.31 (1.08 to 1.59)).
Because of the potential impact on many people the findings “should be replicated in other settings, particularly among patients exposed for longer durations,” said the researchers.
In a linked editorial,2 Deirdre Cronin Fenton, from the Department of Clinical Epidemiology at Aarhus University in Denmark, said that, although a 14% relative increase in lung cancer incidence may not translate to a large absolute risk, “the findings are important given the considerable use of ACEIs 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 ACEIs,” she wrote. “Further studies with long term follow-up are now needed to enhance the scientific evidence on the long term safety of these drugs.”