高度曝露史他汀類藥物治療降低新發生失智風險性之研究

許多研究指出，史他汀類藥物使用者罹患新發生失智（NOD）的風險較低。但是，其他研究顯示相反的結果。在這項研究中，我們調查了史他汀類藥物的使用者與新發性失智(NOD)之間的關係。這是一項縱向性(longitudinal cohort study)研究，使用了台灣健康保險資料庫的數據。納入了2002年1月至2013年12月患有新發生失智(NOD)和非新發生失智(non-NOD)的患者。我們估算了危險比（HRs）的新發生失智(NOD)與史他汀類藥物的使用相關，而非使用史他汀類藥物受試者則作為參考組。在研究期間，有100,610名高脂血症患者中有19,522例新發生失智的病例。在調整病患的性別，年齡，合併症和同時用藥之後，史他汀類藥物使用者新發生失智的風險明顯低於非使用者（風險比0.95，95％信賴區間 0.94–0.96； P值＜0.001）。依累計定義的每日劑量(cumulative defined daily doses)介於28至365、366至730，以及大於730來比較非使用者新發生失智的調整後風險比，分別是1.53（95％信賴區間，1.45-1.62），0.63（95％信賴區間，0.57-0.71）和0.34（95％信賴區間，0.30–0.38）。我們認為史他汀類藥物的使用與減少新發生失智的風險有關。史他汀類藥物暴露劑量高對新發生失智的保護作用越好。這項研究還強調，高劑量的史他汀類藥物具有降低新發生失智的劑量效應。

Several studies have shown that statin users have a lower risk of new-onset dementia (NOD) compared nonusers. However, other studies have shown opposite results. In this study, we investigated the association between the use of statins and the development of NOD.This was a longitudinal cohort study using data from claim forms submitted to the Taiwanese Bureau of National Health Insurance. The study included patients with NOD and non-NOD subjects from January 2002 to December 2013. We estimated the hazard ratios(HRs) of NOD associated with statin use, whereas nonuser subjects were used as a reference group.A total of 19,522 NOD cases were identified in 100,610 hyperlipidemic patients during the study period. The risk of NOD, after adjusting for sex, age, comorbidities, and concurrent medication, was lower among statin users than nonusers (HR 0.95, 95% CI[confidence interval] 0.94–0.96; P<.001). The adjusted HRs for NOD were 1.53 (95% CI, 1.45–1.62), 0.63 (95% CI, 0.57–0.71), and 0.34 (95% CI, 0.30–0.38) when the cumulative defined daily doses ranged from 28 to 365, 366 to 730, and more than 730 relative to nonusers, respectively.We concluded that statin use is associated with a decreasedNODrisk. The protective effect of statins forNODseemedto be related to high exposure to statins. This study also highlights that high exposure to statins has a dose-response effect on lowering NOD risk.Abbreviations: ACEI = angiotensin converting enzyme inhibitor, ARB = angiotensin receptor blocker, CCB = calcium channel blocker, cDDD = cumulative defined daily dose, CHD = coronary heart disease, CI = confidence interval, CVA = cerebrovascular attack, CVD = cardiovascular disease, DDD = defined daily dose, DHP = dihydropyridine, DM = diabetes mellitus HR = hazard ratio, ICD-9 = International Classification of Diseases, Ninth Revision, NOD = new-onset dementia.