Treatment with angiotensin-converting enzyme inhibitors (ACE-I) does not increase the risk of cancer diagnosis in the medium term (up to around 5 years), according to a meta-analysis of randomised controlled trials.

It is postulated that the renin-angiotensin system is important in tumour growth and metastasis, and a meta-analysis of clinical trial data published last year found a small but statistically significant apparent increase in cancer risk associated with angiotensin receptor blocker (ARB) treatment.* As a result, the authors of this report aimed to determine whether any there was any association between ACE-I treatment and cancer risk in clinical trials. They carried out a literature search for randomised controlled trials of ACE-I therapy in humans that enrolled at least 100 participants, lasted at least 12 months, and reported cancer outcomes. Major exclusion criteria included ARB treatment in at least one study arm, and trials where an ACE-I was used in all arms. Primary outcomes were the risk ratios (RR) of cancer occurrence and cancer death, with gastrointestinal cancer as a secondary outcome as one trial suggested specifically an increase in such cancers.

The initial search yielded 3,979 possibly relevant reports, of which 3,880 were excluded on the basis of title and abstract to leave 99 that were assessed in full. Of these, 14 trials (n=61,774) reported cancer data: 10 reporting new cancer occurrence, 7 cancer death, and 5 GI cancers (n=23,291). Study follow-up ranged from 2.6 to 5.3 years (3.0 to 5.3 for larger trials, n<1,000). In the trials, patients assigned to ACE-I treatment did not have a significantly increased of any cancer occurrence (RR 1.01;  95% CI 0.95 to 1.07, p = 0.78), or of cancer death (RR 1.00, 95% CI 0.88 to 1.13, p = 0.95). There was also no significant association with GI cancer (RR 1.09, 95% CI 0.88 to 1.35, p = 0.43). Subgroup analyses found no differences in trials where the control was placebo, where the occurrence was 5.5% in both ACE-I and placebo arms (RR 1.00, 95% CI 0.88 to 1.12, p = 0.95).

The authors conclude that in the clinical trials of ACE-I, these drugs were not associated with an increased risk of cancer. They caution on the limitations of their analysis, notably the relatively short duration of follow-up that cannot rule out an effect with longer exposures, and the fact that the trials were not designed to explore cancer outcomes. 

*[Editor’s note: An FDA safety review initiated following publication of the meta-analysis concluded that treatment with ARBs for high blood pressure does not increase the risk of cancer].