Aspirin did not significantly reduce the risk of vascular events nor significantly increase the risk of major bleeding. Major extracranial bleeding did occur less often in patients using low-dose aspirin (OR 0.32, P=0.009) compared with those who did not use aspirin. The analysis of aspirin and metastatic cancer comprised five randomized trials and a total of 17,285 study participants followed for an average of 6.5 years. The primary objective of each trial was prevention of vascular events. Overall, randomization to aspirin was associated with a 36% reduction in the hazard for cancer with metastasis (P=0.001), including a 46% reduction in the hazard for metastatic adenocarcinoma (P=0.0007). Aspirin reduced the risk of metastatic adenocarcinoma at diagnosis (HR 0.69, P=0.02) and during follow-up (HR 0.45, P=0.0009). The greatest benefit occurred in patients with colorectal cancer who did not have metastatic disease at diagnosis (OR 0.26, P=0.0008). A survival analysis showed that aspirin reduced cancer mortality only in patients with adenocarcinoma (HR 0.65, P=0.0002). The third article by Rothwell and co-authors described an analysis of 195 case-control and cohort studies of aspirin and cancer risk, which they compared with outcomes from six randomized trials. In the case-control studies, patients allocated to aspirin had a 38% lower risk of colorectal cancer (OR 0.62, P<0.0001) with minimal heterogeneity among the studies. Similarly consistent effects of aspirin emerged from analyses of esophageal, gastric, biliary, and breast cancer. Comparison with the randomized trials also demonstrated consistent effects. Estimated effects of aspirin in the cohort studies paralleled those of the case-control studies and were consistent with the randomized trials. An analysis limited to studies that stratified by cancer stage at diagnosis showed that regular aspirin use was associated with a 31% reduction in the risk of distant metastasis but not locoregional spread (OR 0.98). Eric Jacobs, PhD, a spokesperson for the American Cancer Society, characterized the analyses as "important new evidence that long-term daily aspirin, even at low doses, may lower the risk of developing cancer." Even so, the decision to initiate regular aspirin use should be individualized after a discussion between patient and physician, he said. "Because these results are new, it will take time for the broader scientific community to evaluate the data in the context of existing knowledge and to consider whether the clinical guidelines should be changed ... Clinical guidelines require a systematic analysis of for whom the benefits of aspirin use are likely to outweigh the risks." Primary source: Lancet Source reference: Rothwell PR, et al “Short-term effects of daily aspirin on cancer incidence, mortalilty, and nonvascular death: Analysis of the time course of risks and benefits in 51 randomized controlled trials” Lancet. 2012; DOI:10.1016/S01450-6736(11)61720-0. Additional source: Lancet Source reference: Rothwell PM, et al “Effect of daily aspirin on risk of cancer metastasis: A study of incident cancers during randomized controlled trials” Lancet 2012; DOI:10.1016/S0140-6736(12)60209-8. Additional source: Lancet Oncology Source reference: Rothwell PM, et al “Effects of regular aspirin on long-term cancer incidence and metastasis: A systematic comparison of evidence from observational studies versus randomized trials.” Lancet Oncol 2012; DOI:10.1016/S1470-2045(12)70112-2.