老年患者开始降压治疗时髋部骨折风险高

明尼阿波利斯——美国骨矿研究学会(ASBMR)年会上报告的一项自身对照病例分析结果表明，老年患者开始服用降压药物后，短期内髋部骨折风险骤升。

多伦多大学的Debra Butt博士报告称，总体上，社区老年患者开始服用降压药物45天内，髋部骨折风险增加43%[发病率比(IRR)，1.41；95%置信区间(CI)，1.19~1.72]。在常用的5类抗高血压药物中，只有血管紧张素转换酶(ACE)抑制剂和β受体阻滞剂这2类药物可导致骨折风险显著增加。开始服用ACE抑制剂的患者早期骨折风险增加53%(IRR，1.53；95%CI，1.12~2.10)，而β受体阻滞剂使风险增加58%(IRR，1.58；95%CI，1.01~2.48)。


Debra Butt博士
 
这是首次报告上述相关性的基于人群的大规模研究。有关降压药物与骨折风险的相关性证据并不一致，大多数研究是对长期暴露进行评估，其机制被认为可能与骨量有关。另外，有研究显示老年患者开始服用降压药物后跌倒风险快速增加，认为可能与直立性低血压有关。最近一项分析报告还显示，校正混杂因素后，老年患者开始服用噻嗪类利尿药后最初3周内跌倒风险增加最为明显(IRR, 2.80) (Pharmacoepidemiol. Drug Saf. 2011;20:879-84)。

Butt博士利用安大略省6个卫生保健管理数据库资料，确认了301,591例新近接受治疗的≥66岁高血压患者，并分析他们在2000年4月1日~2009年3月31日期间发生髋部骨折的情况。风险期设定为初始接受抗高血压单药治疗的最初45天，治疗前以及治疗后450天观察期为对照期。分析排除了长期接受治疗的高血压患者以及可能已经使用了降压药物的糖尿病、心梗、心衰、心绞痛、心肌症和短暂性缺血发作等其他非高血压疾病患者。

基线时，仅有3%的患者在过去2年内曾发生需要住院治疗的跌倒事件，6%的患者有髋部骨折史，大部分(81%)患者为女性，中位年龄80.8岁。降压药物包括噻嗪类利尿药(23%)、ACE抑制剂(30%)、血管紧张素受体阻断剂(4%)、钙离子通道阻滞剂(17%)和β受体阻滞剂(26%)。观察期间确认了1,463例髋部骨折事件。

排除服用其他可能导致跌倒的药物以及能够导致跌倒的精神药物后，敏感性分析确认降压药物初始治疗与早期髋部骨折具有初步相关性，发病率比几乎相同，为1.42。研究者认为，基于上述结果，老年患者应慎重接受降压药物治疗。

但有与会者质疑，如何能在不了解绝对跌倒风险和髋部骨折风险的情况下，向患者解释用药风险和益处。还有人认为，该项研究提示存在相关风险，但在缺乏有关何时跌倒、发生骨折时患者站立还是坐着，以及血压下降程度等更多信息的情况下，很难转化为可行的临床指南。Butt博士解释称，为了制定临床指南，必须从证实相关性存在入手，目前这一领域的研究几乎还是空白，而这项研究仅是初步探索。

该项研究由安大略省政府资助，Butt博士报告无相关利益冲突。

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By: PATRICE WENDLING, Cardiology News Digital Network

MINNEAPOLIS – The risk of hip fracture among elderly patients spikes shortly after starting antihypertensive medications, judging from the findings of a large self-controlled, case series analysis.

Overall, elderly community-dwelling patients had a 43% increased risk of hip fracture within 45 days of initiating an antihypertensive therapy (incidence rate ratio, 1.41; 95% confidence interval, 1.19-1.72).

The risk was significantly higher only for two of the five classes of commonly used antihypertensive drugs: ACE inhibitors and beta-blockers.
 
The risk of early fracture rose by 53% for patients started on an ACE inhibitor (IRR, 1.53; 95% CI, 1.12-2.10) and by 58% for those on beta-blockers (IRR, 1.58; 95% CI, 1.01-2.48), Dr. Debra Butt reported at the annual meeting of the American Society of Bone and Mineral Research.

This is the first large population-based study to report such an association, and the evidence is conflicting regarding the association between antihypertensives and fracture risk. The majority of studies evaluate long exposure periods, where the underlying mechanism is thought to be related to bone mass.

On the other hand, there are studies of immediate increased risk of falls in the elderly started on antihypertensive drugs, where orthostatic hypotension is thought to be the underlying mechanism. One recently updated analysis reported that the effect on falls in the elderly was strongest in the first 3 weeks of a thiazide diuretic prescription (IRR, 2.80), after taking into account confounding factors (Pharmacoepidemiol. Drug Saf. 2011;20:879-84).

The current analysis used six health care administrative databases to identify 301,591 newly treated hypertensive patients at least 66 years of age living in Ontario and link them with hip fractures occurring from April 1, 2000, to March 31, 2009. The risk period was the first 45 days following initiation of monotherapy antihypertensive therapy, with control periods before and after treatment in a 450-day observation period.

The study excluded long-term care residents and patients with conditions other than hypertension for which an antihypertensive drug may have been prescribed such as diabetes, myocardial infarction, heart failure, angina, cardiomyopathy and transient ischemic attack.

At baseline, only 3% of patients had had a fall in the past year requiring hospital care and 6% had a history of past hip fracture. The majority of patients were female (81%) and the median age was 80.8 years.

Antihypertensive drugs included thiazide diuretics (23%), ACE inhibitors (30%), angiotensin receptor blockers (4%), calcium channel blockers (17%) and beta blockers (26%).

During the observation period, 1,463 hip fractures were identified, according to Dr. Butt of the department of family and community medicine, University of Toronto.

A sensitivity analysis that excluded use of other potential fall-causing drugs and psychotropic drugs that can trigger falls, confirmed the initial association between antihypertensive drug initiation and early hip fracture with a nearly identical incidence ratio of 1.42.

"Based on this finding, caution is advised when initiating antihypertensive drugs in the elderly," she said.

During a discussion of the study, however, concerns were raised about what to advise patients without knowing the absolute risk of falling and the risk of hip fracture while on antihypertensive medications vs. the benefits of treating hypertension.

One audience member said the study alerts clinicians to the risk but that it’s hard to draw any practical, clinical recommendations without more information such as when the falls occurred, whether the patient was standing or sitting down at the time of the fracture, or the magnitude of the hypertension decrease from baseline.

"In order to develop clinical recommendations, you have to start by demonstrating an association and that’s what our study does," Dr. Butt responded. "It’s a start, in an area where we have few studies that exist."

The government of Ontario funded the study. Dr. Butt reported no relevant conflicts of interest.