By Lilian Anekwe
A leading epidemiology expert has called for an ‘urgent’ safety review after a meta-analysis published in Lancet Oncology found patients on angiotensin receptor blockers have a ‘modestly increased’ risk of cancer.
An analysis of data from randomised controlled trials – which included new cancer diagnoses in five trials of 60,000 patients, common solid organ tumours in five trials of 68,000 patients and cancer deaths in eight trials of 93,000 patients, found no statistically significant difference in cancer deaths.
But patients randomly assigned to receive ARBs had a 1.2% higher absolute risk of new cancer occurrence compared with patients receiving controls.
When the analysis was limited to trials where cancer was a prespecified endpoint, the relative risk of cancer was 11% higher in patients on ARBs that in controls.
Only the incidence of new lung cancers was significantly higher in patients on ARBs, at 0.9%, than in those assigned to receive control at 0.7%, a 25% increased relative risk.
Dr Ilke Sipahi, a researcher in cardiovascular medicine at the University Hospitals Case Medical Center in Cleveland, made cautious conclusions but wrote in Lancet Oncology that the findings ‘warrant further investigation’.
‘The increased risk of new cancer occurrence is modest but significant. However, the clinical significance of this potential excess cancer risk is unknown.
‘The finding of a 1.2% increase in absolute risk of cancer needs to be interpreted in view of the estimate 41% lifetime cancer risk.’
In an accompanying editorial Dr Steven Nissen, chair of cardiovascular medicine at the Cleveland Clinic, USA, and a world-renowned epidemiologist, described the results of the meta-analysis as ‘disturbing and provocative’.
‘Regulators must review the possible association between ARB use and cancer, and promptly report their findings. In the interim, we should use ARBs, particularly telmisartan, with greater caution.
‘These drugs are often overprescribed, as a result of aggressive marketing and in the absence of evidence that they are better than ACE inhibitors.
‘ARBs can be reserved for patients with intolerance to ACE inhibitors. More selective use of ARBs will also save money for healthcare systems, since nearly all ARBs are proprietary and ACE inhibitors are generic.’
Telmisartan was given to 86% of patients in the trials. A statement from Boehringer Ingelheim, the manufacturer of telmisartan, said the post-hoc nature of the meta-analysis, and the fact that it analysed trials that were not designed to explore cancer outcomes, weakened the evidence.
‘[The] meta-analysis… is mainly based on the combination arm of telmisartan and ramipril, an angiotensin converting enzyme ACE inhibitor, and not on the trial arms of each compound separately.
‘Peer-reviewed meta-analyses of aggregate published data like Sipahi et al. have their appropriate place in scientific research. However, these analyses have well-recognised limitations, such as combining study summaries rather than analyzing individual patient data.’
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