Introduction Angiotensin Converting Enzyme Inhibitors (ACEI), Angiotensin Receptor Blockers (ARB), Calcium Channel Blocker (CCB) are used widely in the management of hypertension. Hypertension is a constituent of the diagnosis of metabolic syndrome, which is characterized by Obesity, Diabetes Mellitus, Insulin resistance and Dyslipidemia. We have previously demonstrated an association between metabolic syndrome and risk of hepatocellular cancer. There is conflicting data on the chemopreventative effects of ACEI, ARB and CCBs on solid organ cancers.
Aim To examine the association of ACEI, ARB and CCB use and risk of hepatocellular cancer using a primary care database.
Methods The THIN (The Health Improvement Network) database (UK) was interrogated to identify patients with a diagnosis of hepatocellular cancer and were matched with controls in a 1:2 fashion. Data on ACEI, ARB and CCB use was examined. Statin, Aspirin, Proton Pump Inhibitors (PPI) use were also additionally evaluated. A nested cohort analysis was performed and each case and corresponding control subject was followed longitudinally in the database to understand the temporal impact of ACEI, ARB and CCB use using time-dependent covariates.
Results 2998 patients (63% male, mean age 75 years) with hepatocellular cancer were age and gender-matched with 5996 controls. On univariate analysis, CCB use (Hazard ratio (HR) 0.89 (95% Confidence Intervals (CI) 0.82–0.97), p=0.005) was inversely associated with risk of hepatocellular cancer. ACEI (0.93 (0.86–1.01), p=0.085) and ARB (0.90 (0.796–1.027), p=0.12) did not demonstrate any association. CCB use was examined as a time-dependent covariate and duration of CCB use (1.60 (1.33–1.91), p<0.001) was associated its overall inverse association with hepatocellular cancer. This effect was not seen with ACEI (1.07 (0.95–1.20), p=0.25) or ARB (0.84 (0.64–1.105), p=0.211) use.
Statin use (0.74 (0.68–0.81), p<0.001) and aspirin use (0.88 (0.81–0.94), p<0.001 were inversely associated with hepatocellular cancer on univariate analysis. PPI use (2.02 (1.86–2.19), p<0.001) was also strongly associated with risk of hepatocellular cancer.
On multivariate analysis, CCB use was not associated with risk of hepatocellular cancer. Statin use (0.68 (0.62–0.74), p<0.001) demonstrated an inverse association whilst PPI use (1.92 (1.77–2.09), p<0.001) was associated with hepatocellular cancer risk. On modelling statin as a time-dependent covariate, longer duration of use (0.65 (0.46–0.81), p=0.001) was associated with its protective effect on hepatocellular cancer.
Conclusions ACEI, ARB and CCBs are not associated with risk of hepatocellular cancer. Longer duration of statin use has a potential protective effect against hepatocellular cancer. PPI use seems to be strongly associated with risk of hepatocellular cancer.
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