Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.
J Intern Med. 2013 Oct;274(4):342-50. doi: 10.1111/joim.12087. Epub 2013 Jun 3.
The aim of this study was to investigate the occurrence of heart failure in patients treated with bisphosphonates.
In this nationwide retrospective cohort study from Denmark, all users of bisphosphonates and raloxifene between 1996 and 2006 (n = 102 342) were included in the 'exposed' group and three age- and gender-matched subjects (n = 307.026) from the general population comprised the control group. The risk of heart failure was estimated by Cox proportional hazard analyses.
The mean follow-up times were 2.8, 5.5 and 4.9 years for alendronate-, etidronate- and raloxifene-treated patients, respectively. The absolute risk of heart failure was 4.4% in the exposed group and 3.7% in the control group (P < 0.01). The relative risk (RR) of heart failure was significantly increased in users of bisphophonates: crude RR 1.71 [95% confidence interval (CI) 1.63-1.79]; adjusted hazard ratio (HR) 1.41 (95% CI 1.34-1.48). By comparison, raloxifene, which is used for the same indication but has a different mechanism of action, was not associated with an increased risk of heart failure: adjusted HR 1.07 (95% CI 0.76-1.50). When the two most commonly used bisphosphonates, alendronate and etidronate, were analysed separately, significant trends in the risk of heart failure were observed across refill compliance strata. The risk of heart failure increased significantly with increasing refill compliance for etidronate (P for trend < 0.01), whereas it decreased for alendronate (P for trend < 0.01).
Bisphosphonate users were at increased risk of heart failure compared to age- and gender-matched control subjects. However, users of alendronate showed a dose-dependent reduction in this risk, suggesting that alendronate may reduce the risk of heart failure.
本研究旨在探讨接受双膦酸盐治疗的患者心力衰竭的发生情况。
本项来自丹麦的全国性回顾性队列研究纳入了 1996 年至 2006 年间所有使用双膦酸盐和雷洛昔芬的患者（n=102342）作为“暴露”组，每个暴露组患者匹配 3 名年龄和性别相匹配的来自普通人群的受试者（n=307026）作为对照组。采用 Cox 比例风险分析估计心力衰竭风险。
阿仑膦酸盐、依替膦酸盐和雷洛昔芬治疗患者的中位随访时间分别为 2.8、5.5 和 4.9 年。暴露组心力衰竭的绝对风险为 4.4%，对照组为 3.7%（P<0.01）。双膦酸盐使用者心力衰竭的相对风险（RR）显著增加：未校正 RR 1.71（95%置信区间[CI] 1.63-1.79）；校正后的危险比（HR）为 1.41（95%CI 1.34-1.48）。相比之下，用于相同适应证但作用机制不同的雷洛昔芬与心力衰竭风险增加无关：校正后的 HR 为 1.07（95%CI 0.76-1.50）。当分别分析两种最常用的双膦酸盐（阿仑膦酸盐和依替膦酸盐）时，在不同的 refill compliance 分层中观察到心力衰竭风险呈显著的趋势。依替膦酸盐 refill compliance 越高，心力衰竭风险显著增加（趋势 P<0.01），而阿仑膦酸盐则降低（趋势 P<0.01）。
与年龄和性别匹配的对照组相比，双膦酸盐使用者心力衰竭的风险增加。然而，阿仑膦酸盐使用者的这种风险呈剂量依赖性降低，表明阿仑膦酸盐可能降低心力衰竭的风险。
