Despite valsartan’s widespread use, few studies have explored its potential carcinogenicity. We evaluated the association between valsartan and cancer.
We conducted a retrospective cohort study using data from 2002 to 2015 gathered from the National Health Insurance database. Patients with hypertension aged ≥ 30 who used valsartan or other angiotensin II receptor blockers (ARBs) were included. Eligible patients were those with no prior history of the use of any ARBs, diagnosis of cancer, or organ transplantation in the 4 years predating their first use of the drugs of interest. The primary and secondary outcomes included the occurrence of all cancers and site-specific solid cancers, respectively. After applying propensity score (PS) matching, Cox regression was used to calculate the hazard ratios (HRs) and 95 % confidence intervals (CIs).
A total of 1,550,734 individuals were identified as new users of valsartan or other ARBs. Of the 153,047 valsartan users, 16,047 were diagnosed with cancer. No increased risk of overall cancer was observed in valsartan users as compared to other ARB users (aHR = 1.00; 95 % CI, 0.98–1.02). Valsartan was, however, associated with a slightly elevated risk of liver (aHR = 1.09; 95 % CI, 1.01–1.16) and kidney cancer (aHR = 1.11; 95 % CI, 1.02–1.22).
Compared with other ARBs, valsartan did not increase the risk of overall cancer. A slightly increased risk for some solid cancers was associated with valsartan use, though the absolute rate difference was small.
- • Valsartan did not increase the risk of cancer compared with other ARBs.
- • Valsartan increased the risk of some cancers, but the absolute rate difference was small.
- • No increased risk of cancer was found with increasing duration or cumulative dose.
Angiotensin II receptor blockers (ARBs) are widely used to treat hypertension, heart failure, and diabetic nephropathy . For decades, the risk of cancer associated with ARBs has remained ambiguous. In in vitro and in vivo studies that have examined the role of renin-angiotensin system, the blockage of angiotensin receptors has been shown to have beneficial effects on tumor growth, vascularization, and metastasis . Although a number of previous studies have concluded that ARBs are not associated with a higher risk of cancer , several studies have reported a positive association between the two . This discrepancy may have been caused by different compositions of ARB ingredients in each study. Considering the tremendous molecular variation and broad physiochemical differences in ARBs , it is necessary to evaluate comparative cancer risk between ARBs.
Despite the advent of a new generation of ARBs, valsartan remains among the most commonly used drugs and still retains a clinically important position. While widely used, there is limited evidence as to its comparative carcinogenicity. Most studies have not considered the potential differences in the risk between ARBs, or have focused on telmisartan . One landmark study involving a meta-analysis revealed an increased risk of a new cancer diagnosis associated with the use of ARBs (risk ratio [RR] = 1.08; 95 % confidence interval [CI], 1.01–1.15); however, most patients included in the study were telmisartan users . A subsequent meta-analysis and cohort study suggested that cancer risk was no higher with telmisartan than with other ARBs . A meta-analysis conducted by the ARB Trialists Collaboration revealed no increased risk of cancer associated with the use of any of the tested ARBs (telmisartan, irbesartan, valsartan, candesartan, and losartan) . These findings, however, were obtained from randomized controlled trials that included a restricted population, with a follow-up at 23–60 months.
We therefore examined cancer risk associated with specific ARBs, in this paper focusing on valsartan using the Korean nationwide database. Thirteen years of population-based data was used to investigate the long-term safety of valsartan.