慢性阻塞性肺部疾病患者使用長效型支氣管擴張吸入劑與心血管事件的相關風險評估

Risk for cardiovascular events associated with long-acting inhaled bronchodilator in patients with chronic obstructive pulmonary disease

趙曉鈡(Hsiao-Chung Chao)

指導教授 ： 蔡義弘

共同指導教授 ： 林佩津(Pei-chin Lin)

高雄醫學大學/藥學院/臨床藥學研究所/碩士(2012年)

摘要

研究背景
美國食品與藥物管理局(FDA)針對Spiriva HandiHaler (Tiotropium Bromide)發佈可能導致中風的訊息，共分析了29 個臨床研究初步發現病患使用Spivira Handihaler 治療一年相較於安慰劑組發生中風的風險較高(2 case per 1000)，但隨著UPLIFT臨床試驗公佈結果，FDA認為Tiotropium仍可使用在無禁忌症的COPD病患身上。
研究目的
分析慢性阻塞性肺部疾病患者，長期使用長效型支氣管擴張吸入劑後，其發生心血管事件的相關風險評估。
研究方法
本研究為回溯性研究，利用全民健康保險研究資料庫，以西元2005年百萬抽樣歸人檔，追蹤時間為西元1997年至2008年使用長效型支氣管擴張吸入劑的病患，且排除氣喘及未滿18歲的病患後分成三組。
研究結果
經篩選後共挑出596人次慢性阻塞性肺疾病患，其中長效型抗膽鹼支氣管擴張吸入劑佔196人次，長效乙型支氣管擴張吸入劑組佔318人次，合併使用組佔82人次，發現長效乙型支氣管擴張吸入劑相較於長效型抗膽鹼支氣管擴張吸入劑(aHR 1.88[0.84-2.41)或合併使用組(aHR 1.72[0.72-4.83])，皆沒有證據顯示會對心血管事件造成不良影響，長效型抗膽鹼支氣管擴張吸入劑甚至有保護效果的趨勢存在。
結論
從本研究眾多結果來看，長效型支氣管擴張吸入劑對於沒有任何
藥物禁忌症的慢性阻塞性肺疾病患，整體而言是安全的。

關鍵字

慢性阻塞性肺疾 ； 長效乙型支氣管擴張吸入劑 ； 長效抗膽鹼吸入劑 ； Spiriva HandiHaler ； 中風 ； 乙型作用劑

並列摘要

Background
The U.S. Food and Drug Administration (FDA) had post a messenger about the Spiriva HandiHaler (Tiotropium Bromide) that treat in patients with chronic obstructive pulmonary disease(COPD) may increase the risk of stroke. They analyses of twenty-nine trials and discovered patients who took the Spivira Handihaler treatment after one year, patients in the treatment group had higher risk of stroke (2 case per 1000) than patients in the placebo group. Until the results of UPLIFT trial, FDA's concluded that Spiriva HandiHaler could be use in COPD patients who had no contraindications.
Objective
Analysis of patients with chronic obstructive pulmonary disease who long-term use long-acting bronchodilator inhalation Agents, and assess the risk of cardiovascular events.
Methods
This study was a retrospective cohort study use the sampled Longitudinal Health Insurance Database 2005 (LHID2005). we choosed the patients with chronic obstructive pulmonary disease who had took long-acting bronchodilator first time from 1997 to 2008, and then divided into three groups. Besides, we exclude the patients with asthma and age less than eighyteen.
Results
Of a total frequency of 596 patients, including 196 long-acting anticholinergics bronchodilator inhaled users, 318 long-acting beta-2 agonists bronchodilator inhaled users and 82 combination group users. When we compare long-acting beta-2 agonists bronchodilator inhaled with long-acting anticholinergics bronchodilator inhaled(aHR 1.88[0.84-2.41) and combination groups(aHR 1.72[0.72-4.83]), the results shows that no relationship between the three groups in cardiovascular events.The long-acting anticholinergics bronchodilator inhaled even had protective effect trend.
Conclusions
Overall, we don't have evidence to proof that higher cardiovascular risk of long-acting inhaled bronchodilator. It's safe for our study in most instances.

並列關鍵字

COPD ； LABA ； Tiotropium ； Spiriva HandiHaler ； Stroke ； Beta-2 agonists

參考文獻

[1] U.S. Food and Drug Administration, Follow-Up to the October 2008 Updated Early Communication about an Ongoing Safety Review of Tiotropium (marketed as Spiriva HandiHaler).

http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm197429.htm

[2] 行政院衛生署. 慢性阻塞性肺疾治療藥物Tiotropium bromide藥物安全資訊.

http://www.doh.gov.tw/CHT2006/DM/DM2_p01.aspx?class_no=0&now_fod_list_no=&level_no=&doc_no=53108

[3] Tashkin DP, Celli B, Senn S, Burkhart D, Kesten S, Menjoge S, Decramer M; UPLIFT Study Investigators. A 4-year trial of tiotropium in chronic obstructive pulmonary disease. N Engl J Med. 2008 Oct 9;359(15):1543-54. Epub 2008 Oct 5.