高血壓病患長期使用鈣離子阻斷劑與癌症風險相關性初探：全人口研究

研究背景鈣離子阻斷劑是用於降低血壓的其中一類藥品。鈣離子阻斷劑包括：Amlodipine, Benidipine, Felodipine, Lacidipine, Lercanidipine,Nicardipine, Nifedipine, Nisoldipine, Nitrendipine, Diltiazem,Verapamil。許多研究探討高血壓治療藥品和癌症之間的關聯，但尚未有明確定論。高血壓為慢性疾病，多數病患須長期用藥控制血壓，因此長期的用藥安全應持續進行，本研究將評估台灣高血壓病患使用鈣離子阻斷劑相較未使用者的癌症發病率是否有差異。研究方法本研究為回溯性世代研究，使用台灣全民健康保險資料庫的數據。使用鈣離子阻斷劑大於180 天且服藥順從性良好的高血壓病患，作為暴露組，未使用鈣離子阻斷劑的高血壓病患作為非暴露組，比較兩族群癌症的發病率。高血壓患者按國際疾病分類第9 版（ICD-9-CM 401.xx-405.xx）選擇。鈣離子阻斷劑根據藥品解剖學、治療學及化學分類系統編碼（Anatomical Therapeutic Chemical code, ATC CODE）C08CAxx，C08DAxx 和C08DBxx 作為篩選。研究追蹤至癌症發生或2010 年12 月31 日止。以Cox 迴歸分析（Cox proportional hazardmodel）計算風險比（Hazard Ratios, HR）。研究結果原本有232,286 名高血壓個案，經排除條件後，留下228,461 名高血壓個案。長期使用鈣離子阻斷劑有17,149 名個案，其中男性佔56.32%（9,659 位），未使用者有11,312 名，男性佔57.48%（6,502位），長期使用者平均年齡為61.4（±12.4）歲，未使用者平均年齡為58.0（±13.8）歲。利用Kaplan-Meier curve 分析暴露組與非暴露組發生癌症之關係，使用Log rank test 顯示兩組具有統計上顯著差異，以Cox 迴歸分析診斷癌症的風險暴露組是非暴露組的0.843 倍，95%信賴區間0.804-0.884，p 值<0.05。結論本研究是對於有無長期使用鈣離子阻斷劑是否增加罹患癌症的風險之初步研究。研究主要發現，是否長期使用鈣離子阻斷劑與未來罹患癌症之人數分布，有顯著差異；這結果指出，長期使用鈣離子阻斷劑，可能降低罹癌的風險。

關鍵字

高血壓；鈣離子阻斷劑；癌症

並列摘要

Background Calcium channel blockers are drugs used to lower blood pressure. Examples of calcium channel blockers include: Amlodipine, Benidipine, Felodipine, Lacidipine, Lercanidipine, Nicardipine, Nifedipine, Nisoldipine, Nitrendipine, Diltiazem, Verapamil.Numerous studies have examined the association of antihypertensive medication use and incident cancer; some, but not all, studies have reported no association. This paper studies, evaluation the cancer morbidity in hypertension patient used calcium channel blocker. The research focuses on the hypertension patient long term use calcium channel blockers to compare non-use diagnosis cancer rate. Methods Data were obtained from the Taiwan National Health Insurance research database. Hypertensive patients who used calcium channel blockers for more than 180 days, as an exposed group. Hypertensive patients who did not use calcium channel blockers as a non-exposed group. Incidences of any type of cancer between exposed group and non-exposed group were compared. Hypertension patients were selected by International Classification of Disease, Ninth Revision, Clinical Modification diagnostic criteria (ICD-9 code 401.xx-405.xx). Calcium channel blockers identification was according to the Anatomical Therapeutic Chemical classifications C08CAxx, C08DAxx, and C08DBxx. Results A total of 28,461 patients with diagnosed hypertension were identified from a cohort database of 1 million individuals from January 1, 1996, to December 31, 2010.Among them, 17,149 (60.25%) had received calcium channel blockers for hypertension. The end point was the development of any type of cancer before the end of 2010. The log-rank test showed that the occurrence rate of newly diagnosed cancers in the subjects receiving calcium channel blockers was significantly lower than those receiving treatment without calcium channel blockers. Conclusions In conclusion, long-term use of calcium channel blockers is associated with a lower incidence of cancer occurrence, thereby suggesting that calcium channel blockers may prevent cancer development.