Calcium channel blockers are associated with lower gastric cancer risk: A territory‐wide study with propensity score analysis

Prior studies showed that calcium channel blockers (CCBs) could modify cancer risk, but data on gastric cancer (GC) are limited. We aimed to investigate whether CCBs could modify GC risk in Helicobacter pylori‐eradicated patients. H pylori‐infected patients with hypertension who are aged ≥50 and had received clarithromycin‐based triple therapy between 2003 and 2016 were identified from a territory‐wide healthcare database. Patients with eradication failure, GC diagnosed within 6 months after HP eradication, and gastric ulcer were excluded. Time‐fixed Cox model with one‐to‐one propensity score matching was used to calculate hazard ratio (HR) of GC with CCBs. Sensitivity analysis using time‐dependent multivariable Cox model in which CCB use was treated as time‐varying covariate was also performed to address immortal time bias. 17 622 (29.6%) H pylori‐eradicated patients with hypertension were included. During a median follow‐up of 8.6 years, 105 (0.6%) developed GC. After PS matching, CCBs were associated with a lower GC risk (HR: 0.56; 95% CI: 0.32‐0.97). Time‐dependent analysis showed consistent result (aHR: 0.50; 95% CI: 0.33‐0.75). A longer duration of CCB use was associated with even lower GC risk (adjusted HR [aHR]: 0.69; 95% CI: 0.61‐0.79 for every 1‐year increase in use). Long‐acting CCBs (aHR: 0.47; 95% CI: 0.29‐0.76) and dihydropyridines (aHR: 0.49; 95% CI: 0.32‐0.73) conferred greater benefit than short‐acting ones (aHR: 0.60; 95% CI: 0.36‐1.03) and nondihydropyridines (aHR: 0.76; 95% CI: 0.24‐2.48). The aHR was 0.57 (95% CI: 0.34‐0.97) for noncardia and 0.59 (95% CI: 0.27‐1.31) for cardia cancer. Use of CCBs was associated with lower risk of GC development in H pylori‐eradicated patients, in a duration‐ and dose‐response manner. What's new? Even though Helicobacter pylori infection is the most important risk factor of gastric cancer, eradication of H. pylori only reduces gastric cancer development by about half. However, there is still a paucity of studies on pharmacological agents that could modulate the risk of gastric cancer development. In this large retrospective cohort study, the use of calcium channel blockers was associated with a lower gastric cancer risk among H. pylori‐eradicated patients in a duration‐ and dose‐response manner. Calcium channel blockers could be considered as the preferred anti‐hypertensive therapy in patients with hypertension who are also at risk of gastric cancer.