The interaction test did not 3-Deazaneplanocin A hydrochloride showed significant differences in the cardiac risk between high dose and low dose subgroups. Apparently, even low-dose bevacizumab is associated with the increased risk of ischemic heart disease. The data suggests that the so called low dose of bevacizumab may be already reaching the saturation level to induce cardiac ischemia. Our study has the following limitations. First, the ability to detect ischemic heart disease may vary among institutions in which these trials were performed, and may cause bias of the reported incidence rates. A higher risk of adverse events was Adaptaquin observed in patients with colorectal cancer – probably the statistical difference found on RR was related only to the sample size. Because in all groups of patients treated with bevacizumab the risk of ischemic heart disease was about 1%. As the number of patients included in this analysis was limited, the contribution of bevacizumab to ischemic heart disease in colorectal cancer patients remain poorly defined. There are two hypotheses to explain this result: firstly, the fact that trials being as divergent in their results as in their designs could influence the data and consequently introduce bias. The second explanation is a possible interaction of bevacizumab. Second, the incidences of ischemic heart disease showed significant heterogeneity among the included studies. This may reflect differences in sample sizes, tumor type, concomitant chemotherapies, and many other factors among these studies. Despite these differences, the RRs reported by all of these studies showed remarkable nonheterogeneity. In addition, calculation using the randomeffects model for incidence estimation may be able to minimize the problem. Third, the present study has the typical limitations of the meta-analytical methodology. Our findings and interpretations were limited by the quality and quantity of data that is available. An analysis of individual patient data would be more powerful to confirm our findings. The search covered a range of relevant sources. However, it was restricted only to English publications. Another concern is the possible existence of some unpublished studies, which could lead to potential publication bias, although we found no indication of such bias by using statistical methods designed to detect it. And we thought it was essential to evaluate the risk of cardiac events related to the combination of bevacizumab with different chemotherapy regimens. Our results indicated that bevacizumab was not found to significantly increase the risk of cardiac ischemia in 5-FU regimens patients in comparison with controls.