手術前投予Fluvastatin可能改善血管手術後的心臟預後
作者：Laurie Barclay, MD
出處：WebMD醫學新聞
September 16, 2009 — 根據一項於9月3日發表於新英格蘭醫學期刊的雙盲、安慰劑控制組控制研究結果，術前投予fluvastatin可能改善血管手術後的心臟預後。
荷蘭鹿特丹Erasmus醫學中心的Olaf Schouten博士與其來自荷蘭心臟超音波，以壓力型超音波心臟風險評估研究團隊（DECREASE III）的同事們寫到，不良心臟事件在血管手術後是很常見的，我們假設手術前投予fluvastatin將可以改善心臟預後。
過去接受過statin治療的病患，在接受血管手術前，被隨機分派接受每天一次80 mg緩釋型的fluvastatin或安慰劑，加上一個乙型阻斷劑。在隨機分派與手術進行前，量測病患的血脂肪、介白素-6與C反應蛋白濃度。
試驗主要的預後是手術後30天內心肌缺血，以心臟超音波短暫異常、肌動蛋白T釋放，或兩者皆有定義。次級預後終點為綜合心臟血管原因的死亡、與非致命性心肌梗塞。
在心臟手術前平均37天，250位病患被隨機分派接受fluvastatin治療、而247位病患接受安慰劑。在fluvastatin組，非安慰劑組，整體膽固醇濃度、低密度脂蛋白濃度、介白素-6與C反應蛋白濃度都顯著降低。
手術後心肌缺血的主要試驗終點發生在27位（10.8%）使用fluvastatin的病患身上，安慰劑組則是47位（19.0%）（風險比值[HR]為0.55；95%信賴區間[CI]為0.34-0.88；P=0.01）。次級試驗終點合併心因性死亡、或是心肌梗塞，在fluvastatin組有12位病患（4.8%）、安慰劑組則是25位病患（10.1%）（HR為0.47；95% CI為0.24-0.94；P=0.03）。
研究作者們寫到，以fluvastatin治療並不會顯著增加不良事件率。接受血管手術的病患們，手術前投予fluvastatin治療與術後心臟預後改善有關。
這項研究的一個限制是缺乏心臟血管原因死亡或是非致命性心肌梗塞綜合預後的統計力量。
研究作者們的結論是，最近來自美國心臟學會與心臟醫學會（ACC-AHA）的治療指引，以及週邊血管疾病處理指引跨大西洋學會內共識都指出，對於接受血管手術病患而言，使用statin是適當的，不論他們是否有其他臨床危險因子。這些指引是根據回溯性研究結果；目前這項前瞻性研究確認了這些建議。
諾華藥廠、荷蘭健康研究與發展組織、Erasmus醫學中心、Stichting Lijfen Leven與荷蘭心臟醫學會贊助這項研究。試驗作者中有三位表示接受Medtronic、Cardialysis、Boston Scientific、 Bristol-Myers Squibb Medical Imaging、St. Jude Medical、GE Healthcare、Edwards Life Science、Novartis以及/或是與Merck公司有資金上的往來。
Perioperative Fluvastatin May Improve Cardiac Outcomes After Vascular Surgery
By Laurie Barclay, MD
Medscape Medical News
September 16, 2009 — Perioperative treatment with fluvastatin may improve cardiac outcomes after vascular surgery, according to the results of a double-blind, placebo-controlled trial reported in the September 3 issue of the New England Journal of Medicine.
"Adverse cardiac events are common after vascular surgery," write Olaf Schouten, MD, PhD, from Erasmus Medical Center, Rotterdam, the Netherlands, and colleagues from the Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography Study Group (DECREASE III). "We hypothesized that perioperative statin therapy would improve postoperative outcomes."
Patients who had not previously been treated with a statin were randomly assigned to receive either 80 mg of extended-release fluvastatin or placebo once daily, in addition to a beta-blocker, before undergoing vascular surgery. At the time of randomization and before surgery, patients had measurements of lipid, interleukin-6, and C-reactive protein levels.
The main outcome of the study was myocardial ischemia occurring within 30 days after surgery, which was defined as transient electrocardiographic abnormalities, release of troponin T, or both. The secondary outcome measure was a composite of death from cardiovascular causes and nonfatal myocardial infarction.
At a median of 37 days before vascular surgery, 250 patients were randomly assigned to fluvastatin treatment and 247 patients to placebo. In the fluvastatin group, but not in the placebo group, total cholesterol, low-density lipoprotein cholesterol, interleukin-6, and C-reactive protein levels were significantly decreased.
The primary endpoint of postoperative myocardial ischemia occurred in 27 patients (10.8%) in the fluvastatin group vs 47 (19.0%) in the placebo group (hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.34 - 0.88; P = .01). The secondary composite outcome of death from cardiovascular causes or myocardial infarction occurred in 12 patients (4.8%) in the fluvastatin group and 25 patients (10.1%) in the placebo group (HR, 0.47; 95% CI, 0.24 - 0.94; P = .03).
"Fluvastatin therapy was not associated with a significant increase in the rate of adverse events," the study authors write. "In patients undergoing vascular surgery, perioperative fluvastatin therapy was associated with an improvement in postoperative cardiac outcome."
A limitation of the study was that the trial lacked statistical power for the composite outcome of risk for death from cardiovascular causes or nonfatal myocardial infarction.
"Recent guidelines from the American College of Cardiology and the American Heart Association (ACC–AHA) and the TransAtlantic Inter-Society Consensus on the management of peripheral arterial disease indicate that statin use is appropriate in patients undergoing vascular surgery, regardless of whether they have other clinical risk factors," the study authors conclude. "These guidelines are based on retrospective studies; the results of the current prospective trial confirm these recommendations."
Novartis, the Netherlands Organization for Health Research and Development, Erasmus Medical Center, Stichting Lijfen Leven, and the Netherlands Heart Foundation supported this study. Three of the study authors have disclosed various financial relationships with Medtronic, Cardialysis, Boston Scientific, Bristol-Myers Squibb Medical Imaging, St. Jude Medical, GE Healthcare, Edwards Life Science, Novartis, and/or Merck.
N Engl J Med. 2009;361:980-989.
