摘要：研究背景：鈣離子拮抗劑為一廣泛使用的降血壓藥物，然而近期有研究指出使用鈣離子拮抗劑可能會 增加乳癌的風險，且此風險於長期使用鈣離子拮抗劑的婦女更甚。由於高血壓通常需長期服藥治療， 因此進一步了解及評估鈣離子拮抗劑的使用與乳癌的風險實為臨床治療上一重要課題。研究目的：比較1)使用鈣離子拮抗劑或其他降血壓藥物在55歲以上女性高血壓患者發生乳癌的風 險，2)使用不同種類鈣離子拮抗劑(dihydropyridine versus non-dihydropyridine)與乳癌發生的風險，以 及3)不同鈣離子拮抗劑或其他降血壓藥物治療期間(< 5年，5-9年，2 10年)發生乳癌的風險。研究方法：本實驗為回溯性世代研究，以1996至2013年台灣全民健康保險研究資料庫為資料來源。 本實驗評估對象為55歲以上初次使用降血壓藥物的女性高血壓患者，並排除在開始服用降血壓藥物 之前曾罹患癌症之病人。乳癌發生率將以卜瓦松迴歸模型進行估計。我們將利用傾向分數配對來校 正潛在的干擾因子，更將進一步利用Cox比例風險回歸模型來比較鈣離子拮抗劑或其他降血壓藥物 的使用者由第一次降血壓藥物處方日期後180天至第一次發生乳癌之時間。預期結果：本實驗結果將進一步釐清鈣離子拮抗劑與乳癌發生風險的關聯性，並將有助於臨床醫師選 擇及評估更年期後婦女降血壓的藥物治療。
Abstract: Background: Calcium channel blockers (CCBs) are one of the most commonly prescribed antihypertensive medications in Taiwan. However, there are rising concerns about the potential link between CCB use and elevated risk of breast cancer, especially among long-term CCB users. Given the widespread use of CCBs, a careful examination on the association between CCB use and breast cancer risk is warranted. The goal of this study is to evaluate the association between calcium channel blocker use and risk of breast cancer among women aged 55 years or older in Taiwan using the National Health Insurance Research Database (NHIRD).Objectives: 1) To compare the incidence of breast cancer between patients who initiated CCBs and other non-CCB antihypertensive treatments, 2) to compare the risk of breast cancer between different types of CCBs (dihydropyridine versus non-dihydropyridine) among CCB users, and 3) to compare the incidence of breast cancer between CCB users and other non-CCB antihypertensive users by treatment durations (< 5 years, 5-9 years, and > 10 years).Method: This will be a retrospective cohort study with a new antihypertensive user design. The 1996-2013 NHIRD will serve as the data source. We will first include women with at least one inpatient or two outpatient diagnoses of hypertension (ICD-9-CM: 401.xx) in the initial sample. The date of the first antihypertensive prescription on or after January 1st, 1997 will serve as the index date. Patients will be considered as new antihypertensive users if they did not use any antihypertensive medications during 12 months before the index date (i.e., the pre-index period). Patients will be excluded if they were less than 55 years old on the index date or had a diagnosis of cancer (ICD-9-CM: 140.xx-239.xx) during the pre-index period. Breast cancer risk will be compared between patients receiving CCBs and other first-line antihypertensives (i.e., diuretics, angiotensin-converting-enzyme inhibitors [ACEIs]/angiotensin II receptor blockers [ARBs]) by both the intent-to-treat and as-treated approaches. We will start to follow patients at 180 days after the index date to account for the induction of cancer, and follow-up will end until at first diagnosis of breast cancer (ICD-9-CM: 174.xx) or administrative censoring. Poisson regressions will be used to calculate the incidence rate of breast cancer. Propensity score matching will be applied to adjust for confounding, and Cox proportional hazards models will be used to generate the adjusted hazard ratios of breast cancer.Anticipated Results: Findings from this study will improve our understanding on the effect of CCBs on breast cancer, especially for long-term (> 10 years) CCB use. By using the NHIRD, our results will have better generalizability for Asian populations than previous studies, and our findings will be highly applicable to the daily clinical practice in Taiwan. Given that hypertension often requires long-term treatment, findings from this study will not only help to resolve the issue of CCB safety, but also help physicians to better select antihypertensive treatments for women aged 55 year or older. Results from this study will be turned into publications in peer-review journals and international conferences.
calcium channel blockers
National Health Insurance Research Database