点击显示 收起
新研究结果显示，当抗栓塞治疗与乙醯水杨酸（ASA）或是非类固醇抗发炎药物（NSAIDs）合并使用会增加肠胃道（GI）出血风险。
这项以群众为基础的、回溯性、案例控制研究发现，使用warfarin或是clopidogrel合并ASA或是NSAIDs类药物的病患，发生肠胃道出血的风险增加4~6倍。
牵涉到抗血小板药物及抗凝血药物的合并疗法与肠胃道出血的高风险有关，且其风险超过这两类药物单独使用；作者表示，医师应该注意这些风险，以评估病患的治疗风险与好处。
这项由魁北克蒙特娄麦奎尔大学健康中心的James Brophy医师与其同事进行的研究，线上发表于8月14日的加拿大医学会期刊上。
为了评估同时处方这些药物或是处方该药物合并其他药物，例如NSAIDs类药物，是否会增加肠胃道出血风险，研究者利用超过400项一般性执业纪录，包括英国一般性执业研究资料库，2000年至2005年的资料，找出4028位18岁以上第一次发生肠胃道出血的病患，这些受试者接着与资料库中的40,171位控制组病患进行比较。
为了加速病患其他疾病与生活型态的评估，所有病患必须有发生肠胃道出血前至少3年以上的病历纪录。
由于这样的研究目的，目前正在使用药物以第一次诊断肠胃道出血前90天有相关药物处方定义。
试验中的受试者，包括实验组与控制组的平均年龄为69岁，根据研究纪录，已知肠胃道出血危险因子，包括性别、酗酒、吸烟、使用acetaminophen、与肝脏衰竭，即使在多变项分析中仍然是重要的危险因子。
然而，他们发现合并使用ASA与其他药物，例如clopidogrel或是warfarin，发生肠胃道出血的风险比单独使用这些药物高。
举例来说，作者表示，仅使用ASA或是warfarin，发生肠胃道出血校正后风险分别为1.39与1.94；然而，当这两个药物同时处方时，肠胃道出血的校正后效应或是整体风险为6.48。
作者表示，处方任何一种NSAIDs类药物（不论是传统药物或是环氧化酶第二型选择性抑制剂）以及clopidogrel或warfarin都有类似的效应。
他们表示，其结果指出医师需要注意并衡量病患因为药物－药物交互作用的潜在风险，以及已知这些药物合并疗法所带来的好处。
在随后的主编评语中，多伦多Sunnybrook健康科学中心David Juurlink医师指出，对医师来说，潜在药物－药物交互作用的科学是个不曾间断且"令人气馁"的挑战。
Juurlink医师写道，部分来说，这是因为只有少数的控制性、以群众为基础的研究探讨药物交互作用；然而，研究者在这项研究中所采取的策略，提供了临床医师来自"现实世界"研究的数据，将门诊病患处方数据与临床预后结合。
他附带表示，这项研究提供临床医师与合并抗血小板药物及warfarin所增加风险的估计值，这同时提醒临床医师，如果我们选择处方合并使用这些药物，特别是长期使用，我们最好有这样治疗的理由，并适当地告知病患。
最后，Juurlink医师表示，麦奎尔的研究者们所采用"细心的"与"精致的"方法，提供我们对于了解这些药物交互作用非控制性观察研究所无法做到的贡献。
这项研究由加拿大健康研究机构与加拿大革新基金会资助，研究作者Joseph Delaney、Lucie Opatrny医师与James Brophy医师表示并没有与该研究相关的冲突；Samy Suissa博士表示他接受Sanofi-Aventis药厂Lantus与leflunomide药物的顾问费，但并未接受该文献中研究的药物clopidogrel的顾问费。
Combination Antithrombotic Therapy Linked to Greater Risk for GI Bleeds
By Caroline Cassels
Medscape Medical News
New research suggests there is a much higher increased risk for gastrointestinal (GI) bleeding when antithrombotic therapy is combined with acetylsalicylic acid (ASA) or nonsteroidal anti-inflammatory drugs (NSAIDs).
The population-based, retrospective, case-control study found a 4- to 6-fold increased risk for GI bleeds among patients who took warfarin or clopidogrel with ASA or NSAIDs.
"Drug combinations involving antiplatelets and anticoagulants are associated with a high risk of GI bleeding beyond that associated with each drug used alone. Physicians should be aware of these risks to better assess their patients' therapeutic risk/benefit profiles," the authors write.
Conducted by James Brophy, MD, PhD, and colleagues, from McGill University Health Centre, in Montreal, Quebec, the study is published online August 14 in the Canadian Medical Association Journal.
To assess whether coprescribing these drugs or prescribing them with other medications such as NSAIDs increases the risk of GI bleeding, investigators used records from more than 400 general practices included in the United Kingdom General Practice Research Database from 2000 to 2005. They identified 4028 patients over the age of 18 years presenting with their first-ever diagnosis of GI bleeding. These subjects were then matched with 40,171 controls from the same database.
To facilitate a full assessment of patient comorbidity and lifestyle information, all patients had to have medical records with at least 3 years of data recorded before their first GI bleed.
For the purposes of the study, current drug exposure was defined as a prescription in the 90 days before diagnosis of the first GI bleed.
The average age of study subjects — cases and controls — was 69 years. According to the study results, known risk factors for GI bleeding, including male sex, heavy alcohol use, smoking, acetaminophen use, and liver failure, were important predictors of risk even in the multivariate analysis.
However, they found the combined prescription of ASA with either clopidogrel or warfarin was associated with a greater risk for GI bleeding than with either drug alone.
For example, the authors note a prescription of ASA alone or warfarin alone was associated with an adjusted relative risk for GI bleeding of 1.39 and 1.94, respectively. However, when the 2 drugs were prescribed in combination, the adjusted effect, or total risk, for GI bleeding was 6.48.
The authors note that similar effects were seen among patients prescribed any NSAID (either a conventional one or a cyclooxygenase-2–selective inhibitor) with either clopidogrel or warfarin.
"Our results indicate that physicians need to be aware of and weight the potential risk for gastrointestinal bleeding due to drug-drug interactions with antithrombotic agents against the known therapeutic benefits of these drug combinations," they write.
In an accompanying editorial, David Juurlink, MD, PhD, from Sunnybrook Health Sciences Centre, in Toronto, Ontario, points out that that the science of potential drug interactions is an ongoing and "daunting" challenge for physicians.
In part, writes Dr. Juurlink, this is because there have been few controlled population-based studies that have explored drug interactions.
However, he notes, the approach taken by the investigators in the current study provides clinicians with data from a "real-world" study that links outpatient prescription data with clinical outcomes.
This research, he notes, provides clinicians with an estimate of the excess risk associated with combinations of antiplatelet agents and warfarin. It also "reminds clinicians that, if we opt to prescribe these drugs in combination, especially for an extended period, we had better have good reasons to do so and inform the patient appropriately."
Finally, writes Dr. Juurlink, the "thoughtful" and "sophisticated" approach taken by the McGill investigators "contributes to our understanding of these drug interactions in ways uncontrolled observations cannot."
This study was funded by the Canadian Institutes of Health Research and the Canadian Foundation for Innovation. Study authors Joseph Delaney, Lucie Opatrny, MD, and James Brophy, MD, PhD, report no conflict of interest related to the study. Samy Suissa, PhD, reports he has received consultancy fees from Sanofi-Aventis for Lantus and leflunomide but not for clopidogrel, which is studied in this paper.
Can Med Assoc J. 2007;177:347-351, 369-371.