Angiotensin receptor blocker (ARB) and cancer risk

A meta-analysis has been undertaken with respect to cancer risk associated with angiotensin receptor blockers (ARBs) (1)

• patients randomly assigned to receive ARBs had a significantly increased risk of new cancer occurrence compared with patients in control groups (7.2%vs 6.0%, risk ratio [RR] 1.08, 95% CI 1.01-1.15; p=0.016)
  • when analysis was limited to trials where cancer was a prespecified endpoint, the RR was 1.11 (95% CI 1.04-1.18, p=0.001)
  • no statistically significant difference in cancer deaths was observed (1.8%vs 1.6%, RR 1.07, 0.97-1.18; p=0.183)
  • meta-analysis included data relating to telmisartan, losartan and candesartan
• the increased risk of new cancer occurrence is modest but significant
  • the clinical significance of this potential excess cancer risk is unknown
  • the finding of a 1.2% increase in absolute risk of cancer over an average of 4 years
    • this finding needs to be considered in the context of an estimated 41% lifetime cancer risk for an individual (2)
  • the variation in the magnitude of effect with different durations of exposure is unknown
  • it is unknown whether the other ARBs (valsartan, irbesartan, olmesartan, and eprosartan) not included in the meta-analysis are associated with an increased risk of new cancer occurrence
  • in this analysis, the increased cancer occurrence did not result in a significant excess in cancer deaths, although oncogenesis, tumour growth, and treatment failure followed by death is typically a slow process
  • study has important limitations
    • the study pooled the results of a group of trials that were not designed to explore cancer outcomes as the primary outcome measure
    • adjudication of cancer diagnoses was not uniform among the included studies
    • however, when analysis was limited to the three trials where cancer was a prespecified endpoint and cancer data were collected rigorously, there was a significant increase in risk of cancer with ARBs
    • meta-analyses are generally considered less convincing than a large prospective trial designed to assess the outcome of interest
      • however, meta-analyses can be useful in providing insights into issues of safety and rare adverse events that might provide the hypothesis for a prospective trial
  • the authors concluded that ".... this meta-analysis shows that ARBs are associated with a modestly increased risk of new cancer occurrence. Among the solid organ cancers examined, only the risk of lung cancer was significantly increased. Given limited data, it is not possible to draw conclusions about the exact risk of cancer associated with each particular ARB..." (1)

Reference:

• 1) Simon DI et al. Angiotensin-receptor blockade and risk of cancer: meta-analysis of randomised controlled trials. Lancet Oncol. 2010 Jul;11(7):627-36. Epub 2010 Jun 11.
• 2) NC Institute, Surveillance Epidemiology and End Results (SEER) Cancer Statistics Review 1975–2006 http://seer.cancer.gov/csr/1975_2006/results_merged/topic_lifetime_risk.pdf