Effects of telmisartan, irbesartan, valsartan, candesartan, and losartan on cancers in 15 trials enrolling 138 769 individuals
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BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARBs) reduce cardiovascular disease (CVD) events, but a recent meta-analysis of selected studies suggested that ARBs may increase cancer risks. OBJECTIVE: Candesartan, irbesartan, telmisartan, valsartan, and losartan were assessed for incident cancers in 15 large parallel long-term multicenter double-blind clinical trials of these agents involving 138,769 participants. PATIENTS AND METHODS: Individuals at high CVD risk were randomized to telmisartan (three trials, n=51,878), irbesartan (three trials, n=14,859), valsartan (four trials, n=44,264), candesartan (four trials, n=18,566), and losartan (one trial, n=9193) and followed for 23-60 months. Incident cancer cases were compared in patients randomized to ARBs versus controls. In five trials (n=42,403), the ARBs were compared to ACEi and in 11 trials (n=63,313) to controls without ACEi. In addition, in seven trials (n=47,020), the effect of ARBs with ACEi was compared to ACEi alone and in two trials ARBs with ACEi versus ARB alone (n=25,712). RESULTS: Overall, there was no excess of cancer incidence with ARB therapy compared to controls in the 15 trials [4549 (6.16%) cases of 73,808 allocated to ARB versus 3856 (6.31%) of 61 106 assigned to non-ARB controls; odds ratio (OR) 1.00, 95% confidence interval (CI) 0.95-1.04] overall or when individual ARBs were examined. ORs comparing combination therapy with ARB along with ACEi versus ACEi was 1.01 (95% CI 0.94-1.10), combination versus ARB alone 1.02 (95% CI 0.91-1.13), ARB alone versus ACEi alone 1.06 (95% CI 0.97-1.16) and ARB versus placebo/control without ACEi 0.97 (95% CI 0.91-1.04). There was no excess of lung, prostate or breast cancer, or overall cancer deaths associated with ARB treatment. CONCLUSION: There was no significant increase in the overall or site-specific cancer risk from ARBs compared to controls.