全髖關節置換術之後服用Statin類藥物可降低修正手術風險

作者：Nancy Fowler Larson  
出處：WebMD醫學新聞

　　May 13, 2010 — 根據發表於5月Journal of Bone and Joint Surgery, American Volume的一篇研究，初步全髖關節置換術(total hip arthroplasty，THA)之後服用statin類藥物，可大幅降低修正手術風險。
　　
　　THA(最常見的骨科手術)之後最常見的修正原因是，補綴部分鬆脫、感染、移位與骨折。Statin類藥物一般處方用於降低膽固醇值，不過，最近的臨床實驗研究指出，statin類藥物可能有抗發炎與抗氧化性質，可能和促進內皮功能有關，這些效果的證據越來越多。
　　
　　丹麥Aarhus大學醫院骨科與臨床流行病學科Theis Thillemann醫師等人寫道，在一些觀察型研究中，statin類藥物對於骨骼健康的可能效益，包括減少骨折風險、增加骨密度。再者，實驗研究提出statin類藥物對模擬骨科植入物鬆脫時的正面效果。
　　
　　研究目標是確認statin類藥物對初步THA後之修正風險的影響，研究者從丹麥臗關節置換登記中心獲得2,349名研究對象的資料，這個資料庫有所有公立和私人診所的病患資訊。在1996至2005年間，獲得一組進行初步臗關節置換術修正的研究對象資料，另外獲得2,349名接受全髖關節置換但無修正者的資料作為對照組。
　　
　　【領用處方12次之後 正面影響停止】
　　結果顯示，在THA之後，修正組有8.1% (n = 190人)、控制組有20.1% (n = 473人)領有至少一種statin藥物處方，Simvastatin佔所有處方的77%，其他則是atorvastatin、lovastatin、pravastatin、fluvastatin、cerivastatin和 rosuvastatin。
　　
　　有關statin類藥物對手術修正率之影響的研究發現如下：
　　* 進行THA的57,581人的10年失敗率為8.9% (95%信心區間[CI]為8.4% - 9.4%)。
　　* 相較於那些沒有statin藥物處方者，在statin藥物使用者中，10年時修正手術減少的校正相對風險(RR)是0.34 (95% CI，0.28 - 0.41)。
　　* 每多領一次statin藥物處方，則校正RR越低，但是領用超過12次statin藥物處方則又變高：3個月-1年領用1-4次處方者的RR為0.42 (95% CI，0.30 - 0.59)；1-2年領用5- 8次處方者為0.34(95% CI，0.23 - 0.51)；2-3年領用9-12次者為0.16 (95% CI，0.09 - 0.30)；3年以上領用超過12次者為0.36 (95% CI，0.26 - 0.50)。
　　
　　研究作者們寫道，手術修正風險減少是因為深部感染、置換物鬆脫、移位、置換物週邊骨折或其他因素而導致的修正風險降低，使用statin類藥物與因為疼痛或植入失敗造成的修正無關。術後使用statin類藥物與減少修正手術風險之間的機轉還不清楚。
　　
　　【研究限制】
　　研究者提出一些研究限制：
　　* 資料僅來自領用的處方，而非實際的藥物使用情況。
　　* 修正手術可能受到其他非必需因素影響，例如病患和醫師想要做修正、或者進行其他手術。
　　* 登記的資料可能不完整。
　　* Statin類藥物使用者可能比那些非使用者更在意自己的健康狀況，他們的生活型態和習慣如運動及減少飲酒等也可能對結果有所影響。
　　
　　【編輯評論：精確的分析】
　　溫哥華英屬哥倫比亞大學骨科主任、教授Bassam Masri醫師在編輯評論中表示，這個研究有精確的分析。Masri醫師也指出，研究作者們目前建議對那些進行髖關節置換術、但無其他原因須使用statin類藥物者開立處方，他表示，THA之後使用statin類藥物來降低修正手術風險的觀念，還需要進一步以其他研究重現並更加暸解機轉。
　　
　　Masri醫師表示，我同意這個結論，不過，此研究的資料相當令人信服，對其他醫學中心的研究者帶來刺激，特別是那些有豐富經驗者與大型登記中心，以強化這些研究發現。
　　
　　丹麥風濕病協會、Augustinus基金會、Korning基金會支持本研究，研究作者們與 Masri醫師皆宣告沒有相關財務關係。


Taking Statins After Primary Total Hip Arthroplasty May Substantially Lower Revision Risk

By Nancy Fowler Larson
Medscape Medical News

May 13, 2010 — Patients who take statins after primary total hip arthroplasty (THA) may greatly reduce the risk for revision surgery, according to a study published in the May issue of the Journal of Bone and Joint Surgery, American Volume.

The most common reasons for revision after THA — one of the most frequently performed orthopaedic surgical procedures — are aseptic loosening of prosthetic parts, infection, dislocation, and fracture. Statins are generally prescribed to lower cholesterol levels. However, recent experimental clinical studies have indicated that statins may also have anti-inflammatory and antioxidative properties and may be related to enhanced endothelial function. Evidence of these effects is growing.

"In some, but not all, observational studies, these potential beneficial effects of statins on bone health have been confirmed in terms of a decreased fracture risk and increased bone mineral density among statin users," write Theis Thillemann, MD, of the Departments of Orthopedics and Clinical Epidemiology at Aarhus University Hospital, Aarhus, Denmark, and colleagues. "Moreover, experimental studies have described positive effects of statins on conditions mimicking the course of aseptic loosening of orthopaedic implants."

The goal of the study was to examine the impact of statins on revision risks after primary THA. The investigators obtained data on 2349 subjects from the Danish Hip Arthroplasty Registry, in which all public and private clinics are required to enter information about each patient. Between 1996 and 2005, the primary subjects had a revision of a primary total hip replacement. A control group of 2349 other subjects underwent total hip replacement but no revision.

Positive Impact Stops After a Dozen Prescriptions

The results showed that 8.1% (n = 190) of the primary patients and 20.1% (n = 473) of the control group filled at least 1 statin prescription after the THA. Simvastatin accounted for 77% of the prescriptions, with atorvastatin, lovastatin, pravastatin, fluvastatin, cerivastatin, and rosuvastatin comprising the remainder.

Findings regarding the effect of statins on revision rates are as follows:

The underlying cohort of 57,581 THAs had a 10-year failure rate of 8.9% (95% confidence interval [CI], 8.4% - 9.4%).
In statin users, the reduced adjusted relative risk (RR) for revision at 10 years was 0.34 (95% CI, 0.28 - 0.41) vs those who did not fill a statin prescription.
The adjusted RR decreased in relationship to each additional statin prescription, except for patients who filled more than 12 statin prescriptions: 1 to 4 prescriptions in 3 months to 1 year of treatment produced an RR of 0.42 (95% CI, 0.30 - 0.59); 5 to 8 filled in 1 to 2 years of treatment, 0.34% (95% CI, 0.23 - 0.51); 9 to 12 filled in 2 to 3 years of treatment, 0.16% (95% CI, 0.09 - 0.30); and more than 12 filled in more than 3 years of treatment, 0.36 (95% CI, 0.26 - 0.50).
"The reduced revision risk was the result of a lower risk for revision due to deep infection, aseptic loosening of components, dislocation, periprosthetic fracture, and miscellaneous causes, whereas statin use was not associated with a risk of revision due to pain or implant failure," the study authors write. "The mechanism underlying the association between postoperative statin use and reduced revision risk is unclear."

Study Limitations

The researchers listed several limitations to the study:

Data were available only for prescriptions filled, not for actual medication use.
Numbers of revisions can be affected by factors other than need, including patient and surgeon willingness to undergo and perform further procedures.
The registry data may not be complete.
Statin users are reportedly more diligent about their health than nonusers, and their lifestyle habits such as exercising and limiting alcohol intake may have contributed to the results.
Editorial: "Rigorous Analysis"

In an accompanying editorial, Bassam Masri, MD, FRCSC, professor and head of the Department of Orthopaedics at the University of British Columbia, Vancouver, called the study a "rigorous analysis." Dr. Masri also noted that the study authors currently recommend against prescribing statins for patients undergoing hip replacement who do not require the drug for other reasons. He acknowledged the authors' belief that using statins to lower the risk for revision after THA should wait until the findings are replicated and the mechanisms are better understood.

"I would certainly agree with this conclusion," Dr. Masri said. "Nevertheless, the data in this study are very compelling and should stimulate researchers in other centers, particularly those with sophisticated and large-scale registries, to try to corroborate these findings."

The Danish Rheumatism Association, the Augustinus Foundation, and the Korning Foundation supported the study. The study authors and Dr. Masri have disclosed no relevant financial relationships.

J Bone Joint Surg Am. 2010;92:1063-1072.