Heart failure

Study casts shadow over long term safety of ACE inhibitors

Angiotensin converting enzyme inhibitors (ACEIs) are associated with an increased risk of lung cancer, according to an observational study that compared the blood pressure lowering drugs with angiotensin receptor blockers.

While the risk for individuals was ‘modest’ the small relative effects seen in their study “could translate into large absolute numbers of patients at risk,” wrote the authors led by Professor Laurent Azoulay at McGill University in Canada in their study published in the BMJ.

The study analysed UK primary care records of nearly one million patients with no previous history of cancer treated with an antihypertensive between 1995 and 2015.

After a follow up of 6.4 years the researchers identified 7,952 cases of lung cancer – a rate of 1.3 per 1000 person years.

Once confounders such as smoking status, age and weight were taken into account the use of ACEIs was associated with an overall 14% increased risk of lung cancer compared with ARBs at a rate of 1.6 v 1.2 cases per 1000 person years.

The risk increased with longer durations of use, with a HR of 1.22 (95% CI 1.06 to 1.40) after five years of use, peaking after more than 10 years of use to a hazard ratio of 1.31 (95% CI 1.08 to 1.59).

The study authors say the association between ACEIs and lung cancer is biologically plausible as the drug class metabolises bradykinin.

“Bradykinin receptors have been located on various cancerous tissues including lung cancer and bradykinin may directly stimulate growth of lung cancer,” they wrote.

In a linked editorial, Associate Professor Deirdre Cronin Fenton from the Department of Clinical Epidemiology at Aarhus University in Denmark, said 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.”

She said the findings also highlighted that concerns about the long term risk of lung cancer “should be balanced against gains in life expectancy associated with use of ACEIs”.

“Further studies with long term follow-up are now needed to enhance the scientific evidence on the long term safety of these drugs,” she added.

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