[HEALTH]合併抗栓塞治療與腸胃道出血風險增加有關

作者：Caroline Cassels
出處：WebMD醫學新聞
　　August 21, 2007 — 新研究結果顯示，當抗栓塞治療與乙醯水楊酸（ASA）或是非類固醇抗發炎藥物（NSAIDs）合併使用會增加腸胃道（GI）出血風險。


這項以群眾為基礎的、回溯性、案例控制研究發現，使用warfarin或是clopidogrel合併ASA或是NSAIDs類藥物的病患，發生腸胃道出血的風險增加4~6倍。　　　　

牽涉到抗血小板藥物及抗凝血藥物的合併療法與腸胃道出血的高風險有關，且其風險超過這兩類藥物單獨使用；作者表示，醫師應該注意這些風險，以評估病患的治療風險與好處。　　　　

這項由魁北克蒙特婁麥奎爾大學健康中心的James Brophy醫師與其同事進行的研究，線上發表於8月14日的加拿大醫學會期刊上。　　　　

為了評估同時處方這些藥物或是處方該藥物合併其他藥物，例如NSAIDs類藥物，是否會增加腸胃道出血風險，研究者利用超過400項一般性執業紀錄，包括英國一般性執業研究資料庫，2000年至2005年的資料，找出4028位18歲以上第一次發生腸胃道出血的病患，這些受試者接著與資料庫中的40,171位控制組病患進行比較。　　　
　
為了加速病患其他疾病與生活型態的評估，所有病患必須有發生腸胃道出血前至少3年以上的病歷紀錄。　　　　
由於這樣的研究目的，目前正在使用藥物以第一次診斷腸胃道出血前90天有相關藥物處方定義。　　　　
試驗中的受試者，包括實驗組與控制組的平均年齡為69歲，根據研究紀錄，已知腸胃道出血危險因子，包括性別、酗酒、吸菸、使用acetaminophen、與肝臟衰竭，即使在多變項分析中仍然是重要的危險因子。　　　　
然而，他們發現合併使用ASA與其他藥物，例如clopidogrel或是warfarin，發生腸胃道出血的風險比單獨使用這些藥物高。　　　　

舉例來說，作者表示，僅使用ASA或是warfarin，發生腸胃道出血校正後風險分別為1.39與1.94；然而，當這兩個藥物同時處方時，腸胃道出血的校正後效應或是整體風險為6.48。　　　　
作者表示，處方任何一種NSAIDs類藥物（不論是傳統藥物或是環氧化酶第二型選擇性抑制劑）以及clopidogrel或warfarin都有類似的效應。　　　　

他們表示，其結果指出醫師需要注意並衡量病患因為藥物－藥物交互作用的潛在風險，以及已知這些藥物合併療法所帶來的好處。　　　　

在隨後的主編評語中，多倫多Sunnybrook健康科學中心David Juurlink醫師指出，對醫師來說，潛在藥物－藥物交互作用的科學是個不曾間斷且"令人氣餒"的挑戰Juurlink醫師寫道，部分來說，這是因為只有少數的控制性、以群眾為基礎的研究探討藥物交互作用；然而，研究者在這項研究中所採取的策略，提供了臨床醫師來自"現實世界"研究的數據，將門診病患處方數據與臨床預後結合。　　　　
他附帶表示，這項研究提供臨床醫師與合併抗血小板藥物及warfarin所增加風險的估計值，這同時提醒臨床醫師，如果我們選擇處方合併使用這些藥物，特別是長期使用，我們最好有這樣治療的理由，並適當地告知病患。　　　　
最後，Juurlink醫師表示，麥奎爾的研究者們所採用"細心的"與"精緻的"方法，提供我們對於了解這些藥物交互作用非控制性觀察研究所無法做到的貢獻。　　　　

這項研究由加拿大健康研究機構與加拿大革新基金會資助，研究作者Joseph Delaney、Lucie Opatrny醫師與James Brophy醫師表示並沒有與該研究相關的衝突；Samy Suissa博士表示他接受Sanofi-Aventis藥廠Lantus與leflunomide藥物的顧問費，但並未接受該文獻中研究的藥物clopidogrel的顧問費。

Combination Antithrombotic Therapy Linked to Greater Risk for GI Bleeds
By Caroline CasselsMedscape Medical News
August 21, 2007 — 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