The mechanism for the possible increase in new cancer occurrences associated with ARBs is uncertain, according the authors. Although experimental studies using cancer cell lines and mouse models have implicated the renin-angiotensin system in the regulation of cell proliferation, tumor growth, angiogenesis, and metastasis, and evidence shows that both angiotensin II type-1 blockade with ARB and direct stimulation of angiotensin II type-2 are capable of stimulating tumor angiogenesis in vivo, the authors wrote, “the relevance of these observations in human malignancy is largely unknown.”
Although the findings of this study are limited by the fact that the pooled results come from trials not designed to explore cancer outcomes as the primary end point and by the lack of individual patient level cancer data, “meta-analysis 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 wrote, noting that the findings “warrant further investigation.”
My Take
Dealing With Drug Safety Questions
The meta-analysis linking angiotensin receptor blockers with an increased risk of incident cancer raises crucial drug safety questions.
While the meta-analysis has its strengths—particularly its size, the thoroughness of the literature search, and the application of appropriate filters to exclude potentially unreliable data—there are also important weaknesses, including the study's post hoc nature and the fact that the trials were not designed to explore cancer outcomes,” leading the investigators to be “appropriately cautious” in their interpretation of the data.
Until regulators review the possible association between ARB use and cancer and report their findings, “we should use ARBs, particularly telmisartan, with greater caution. ARBs can be reserved for patients with intolerance to ACE inhibitors.” Using ARBs more selectively will also save money, “since nearly all ARBs are proprietary while ACE inhibitors are generic.”
STEVEN E. NISSEN, M.D., is chair of the department of cardiovascular medicine at the Cleveland Clinic. His remarks were made in an accompanying commentary (Lancet Oncol. 2010 [doi:10.1016/S1470-2045(10)70142-X]). He has received research support for clinical trials from Pfizer, Astra Zeneca, Novartis, Novo Nordisk Roche, Daiichi-Sankyo, Takeda, Sanofi-Aventis, Resverlogix, and Eli Lilly. He consults for many pharmaceutical companies, but requires them to donate all honoraria or consulting fees directly to charity.
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