refuted by the new evidence."An editorial accompanying the ARB Trialists' report called it a "happy end of the angiotensin-receptor antagonists cancer story" [6]. In it, Dr Giuseppe Mancia (University of Milano-Bicocca, Monza, Italy) writes, "We can thus safely conclude that current evidence by no means indicates any risk of cancer associated with use of angiotensin-receptor antagonists, which patients can continue to take for their documented antihypertensive efficacy, cardiovascular protection, and good tolerability profile."But in an email to heartwire , the lead author of the meta-analysis that sparked the debate said, "There are major methodological problems with both of these studies." Pasternak et al looked at data that are "unreliable to study the cancer risk with ARBs," said Sipahi, given an abundance of potentially confounding differences between the ARB and non-ARB groups.And the analysis from the ARB Trialists Collaboration "mixes data from trials with the highest exposure to ARBs for the longest durations, which show an excess in cancers, with several low-exposure trials using lower drug doses, with shorter follow-ups or low compliance rates, that do not show such excess. Dilution of the data in this manner makes the excess cancer risk disappear," he said. "When it comes to cancer, the degree of exposure is of utmost importance, whether it is radiation or chemicals."Incident Cancer Risk Flat, Cancer Mortality Down Pasternak et al roped together several government databases in Denmark to identify new users of either ARBs (n=107 466) or ACE inhibitors (n=209 692) who had no history of cancer and were aged at least 35 from 1998 through 2006 and compared them for the primary end point of incident cancer overall, as well as by subtype of malignancy, and for overall cancer mortality.Over mean follow-ups of 2.9 years for ARBs and 2.1 years for ACE inhibitors, the adjusted relative risk (RR) for incident cancer was 0.99 (95% CI 0.951.03) for the former vs the latter. Covariates included age, sex, socioeconomic status, degree of urbanization, use of other antihypertensive drugs, comorbidities, and hospitalizations during the previous three years; "we did not have data on smoking."A history of prior ARB use was not significantly associated with cancer risk compared with past use of ACE inhibitors. The cancer mortality RR for ARBs was significant at 0.77 (95% CI 0.720.82).In subgroup analyses, there was no significant association between ARB use and cancers of the mouth/pharynx, gastrointestinal tract, lungs, bone and joints, skin, breast, female genital organs, urinary tract, nervous system, endocrine glands, mesothelial tissue, hematopoietic tissue, or lymph nodes compared with ACE-inhibitor use. On the other hand, the adjusted RR for male genital cancers was 1.15 (95% CI 1.021.28).Expanding on his criticisms of the analysis, Sipahi specified what he sees as potential confounding factors, including that ARB recipients were "younger, richer, and had fewer comorbidities, including history of heart attack, heart failure, [chronic obstructive pulmonary disease], and diabetes. So ARB patients were overall healthier. This actually led to a significantly lower risk of cancer in patients taking ARBs, which became nonsignificant only after correcting for some confounders. However, there are [also] unrecorded confounders (eg, data on