AJT: More data links ARBs to cancer

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To add to the controversial data surrounding the ARB/cancer debate, a study published online Sept. 19 in the American Journal of Transplantation has found that ARB/ACE inhibitor treatment in kidney transplant recipients may be associated with a significant increase in the rate of respiratory tumors in smokers.

In 2010, Ilke Sipahi, MD, of the University Hospitals Case Medical Center in Cleveland, and colleagues conducted a meta-analysis and reported that ARBs could increase the rates of new cancers by 8 to 11 percent. While these data have been debated, in the current study, Gerhard Opelz, PhD, and Bernd Döhler, PhD, of the University of Heidelberg in Heidelberg, Germany, set out to evaluate whether cancer risk was a factor in kidney transplant patients who were treated with ACE inhibitors and ARBs at one-year. Opelz and Döhler enrolled 9,079 kidney transplant patients who received ACE inhibitors or ARBs during the Collaborative Transplant Study (CTS).

The mean duration of follow-up was 4.9 years and 89,616 patient-years were analyzed during post-transplant years two through eight. During follow-up, Opelz and Döhler reported 872 nonskin cancers that were diagnosed. These cancers were most frequently associated with the urinary tract, digestive organs, lymphoid and hematopoietic tissues, respiratory organs and male genital organs. Skin cancers were reported in 866 patients.

Of the 107 malignant tumors diagnosed in the respiratory and intrathoracic organs, 91 cases were localized in the lungs; nine in the larynx; two in the pleura; two in the nasal cavities and one in the thymus heart and mediastinum; and two in the thoracic organs.

Incidences of any type of nonskin tumors during years two through eight were higher in patients treated with ACE inhibitors/ARBs when compared with patients who did not receive these treatments, 8.5 percent vs. 6.4 percent, respectively. During a Cox regression analysis, ACE inhibitor/ARB treatment was associated with a significant increase in the incidence of nonskin malignancies only in the subgroup of patients who had a history of smoking.

Additionally, the researchers noted a significant increase of respiratory/intrathoracic tumors in patients who received ACE inhibitors/ARBs at one year. The cumulative incidence to year eight of these tumors was higher in patients receiving ACE inhibitors/ARBs at year-one post-transplant.

The cumulative risk for the years two through eight of malignant tumors in respiratory/intrathoracic organs was higher among the 5,190 patients with a history of smoking compared with those patients who did not have a history of smoking, 2.34 percent vs. 0.39 percent.

“This analysis of more than 24,000 kidney transplant patients shows only a small and nonsignificant overall increase in the rate of nonskin malignancies in patients receiving ACEi/ARB therapy versus untreated individuals,” Opelz and Döhler wrote. “However, a marked (nearly 50 percent) and statistically significant increase in the risk of respiratory/intrathoracic malignancies was observed in ACEi/ARB-treated patients.”

Importantly, the researchers found that there was 2.5-fold increase in the risk of respiratory/intrathoracic tumors in smokers who received ACE inhibitors or ARBs compared with nonsmokers.

These findings were comparable to those of Sipahi et al, who conducted a meta-analysis of non-transplant patients and found an increase in respiratory/intrathoracic tumors in patients administered ACE inhibitors or ARBs.

The authors noted that the lack of distinction between treatment with ACE inhibitor or ARB therapy was a limitation of the study.