Montreal—Could use of certain blood-pressure drugs raise the risk developing lung cancer?

A report in The BMJ suggests that might be the case with angiotensin-converting enzyme (ACE) inhibitor drugs to lower blood pressure, compared with angiotensin- receptor blockers (ARBs).

While the risk is fairly low overall, it is especially elevated among patients using ACE inhibitors for more than 5 years, according to a study team led by Canadian researchers from the Lady Davis Institute at Jewish General Hospital and McGill University.

Because ACE inhibitors are so widely prescribed, small relative effects could translate into large absolute numbers of patients at risk for lung cancer, study authors emphasize.

ACE inhibitors, which are effective in treating hypertension, can lead to buildup of protein-like chemicals, bradykinin and substance P, in the lung, according to background information in the article, which adds that the chemicals are sometimes present in lung-cancer tissue and that bradykinin may directly stimulate the growth of lung cancer.

Previous observational studies examining the association are limited and report inconsistent results, however, according to the researchers. To determine the association with increased lung cancer risk, the study team conducted a population- based cohort study using the UK Clinical Practice Research Datalink.

The focus was on 992,061 patients newly treated with antihypertensive drugs between January 1, 1995, and December. 31, 2015. Patients were followed until the end of 2016. Researchers were looking for incident lung cancer associated with the time varying use of ACE inhibitors, compared with use of ARBs, overall, by cumulative duration of use, and by time since initiation.

Over a mean of 6.4 years, 7,952 incident lung-cancer events occurred (crude incidence 1.3 ([95% CI 1.2- 1.3]) per 1,000 person years).

Results indicate that, overall, use of ACE inhibitors was associated with an increased risk of lung cancer (incidence rate 1.6 vs. 1.2 per 1,000 person years; hazard ratio 1.14, 95% CI 1.01-1.29), compared with use of ARBs.

“Hazard ratios gradually increased with longer durations of use, with an association evident after five years of use (hazard ratio 1.22, 1.06-1.40) and peaking after more than 10 years of use (1.31, 1.08-1.59). Similar findings were observed with time since initiation,” researchers write.
“In this population based cohort study, the use of ACEIs was associated with an increased risk of lung cancer,” study authors conclude. “The association was particularly elevated among people using ACEIs for more than five years. Additional studies, with long term follow-up, are needed to investigate the effects of these drugs on incidence of lung cancer.”

In a related editorial, commentators from Aarhus University in Denmark point out that 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 ACEIs worldwide.”

In an individual patient, the editorialists note, concerns about the long-term risk of lung cancer “should be balanced against gains in life expectancy associated with use of ACEIs.”

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