系統識別號 U0026-0107201014474300
論文名稱(中文) 選擇性第二型環氧酶抑制劑與傳統非類固醇抗發炎劑於栓塞性中風老年患者之藥物流行病學研究
論文名稱(英文) Pharmacoepidemiologic Research for Ischemic Stroke in Elderly Patients Who Taking Cyclo-oxygenase-2 inhibitors or Conventional Non-steroidal Anti-inflammatory Drugs
校院名稱 成功大學
系所名稱(中) 藥學生物科技研究所
系所名稱(英) Institute of Biopharmaceutical Sciences
學年度 98
學期 2
出版年 99
研究生(中文) 鄭靜蘭
研究生(英文) Ching-Lan Cheng
學號 tb893101
學位類別 博士
語文別 英文
論文頁數 92頁
口試委員 指導教授-高雅慧
中文關鍵字 非類固醇抗發炎劑  第二型環氧酉每抑制劑  阿斯匹靈  交互作用  不良反應  老年人  栓塞性中風  藥物流行病學 
英文關鍵字 NSAIDs  Coxibs, aspirin  interaction  adverse effect  elderly  ischemic stroke  pharmacoepidemiology 
中文摘要 研究背景:近年來許多文獻指出非類固醇抗發炎劑及選擇性第二型環氧酶抑制劑具心血管不良反應,此事件不但引起公眾的關注也導致二種選擇性第二型環氧酶抑制劑自全球市場下市。除此之外,近年來也有研究指出同時使用aspirin與非類固醇抗發炎劑具交互作用,而影響aspirin預防中風的效果。雖然已有許多國外文獻佐證,但是,前逋風險在臺灣的實證評估仍然闕如。有鑑於台灣健保資料庫是包含全國人口就醫資訊的申報檔案,具有族群代表性;其資料品質若經系統性的評估,更可作為醫療相關議題研究的寶貴材料。
研究方法:利用橫斷性研究評估健保資料之效度,以一家醫學中心的資料為標準,擷取在1999年因栓塞性中風的老年人之出院病歷摘要,臨床檢驗結果及住院與第一次門診的醫囑,以評估栓塞性中風診斷及aspirin處方之效度。其次,我們以回溯性重疊病例對照研究利用全民健保資料研究老年人使用非類醇抗發炎劑及選擇性第二型環氧酶抑制劑與中風之相關性。研究族群為2000年1月1日至2003年12月31日因栓塞性中風而住院大於65歲以上的老年患者,並且於出院後曾處方過一次任何一種非類固醇抗發炎劑者。定義病例組為因栓塞性中風再次住院的患者,以年齡、性別、第一次住院時間及追蹤時間配對出1比3的對照組,評估栓塞性中風事件發生時仍在非類固醇抗發炎劑或選擇性第二型環氧酶抑制劑的使用情形,依中風事件之日期為指標日期區分為正在使用,最近曾使用與過去曾使用者之相關危險性;同時利用分層分析評估aspirin與非類固醇抗發炎劑之交互作用的影響,並進行敏感性分析使本研究更具可信度。統計方法以條件性邏輯性回歸模式控制共變項因子後分析非類固醇抗發炎劑使用與中風之相關性,本研究以SAS 9.1版為統計軟體。
研究結果:在效度分析部分,自全民健保資料庫共定義出372位患者,其中有364位(97.85%)經由放射線檢查報告及臨床表現確認為因栓塞性中風而入院。以主診斷碼計算之陽性預測值(PPV)為0.98,若包含次診斷之陽性預測值為0.87。而所計算所有的共病症之診斷符合率為48.39%;在個別的共病症中陽性預測值分佈範圍較廣從骨折0.50至結腸癌1.00。出院後第一次門診aspirin處方的陽性預測值較高為0.94,而住院期間的aspirin處方則為0.88。研究老年人使用非類固醇抗發炎劑及選擇性第二型環氧酶抑制劑與中風危險之相關性部分,共納入43,214位為世代追蹤的族群,其中10,238位病例組並且配對出至少有一位的對照組。在基本特質部分,病例組之心血管疾病發生率高於對照組,並且在指標日期正在使用非類固醇抗發炎劑的比例亦較高,分別為4,391 (42.9%)及9,399 (32.8%)。而與過去曾使用者比較,除了celecoxib外,所有正在使用非類固醇抗發炎劑的患者具有較高栓塞性中風復發的機率(OR=1.09,95% CI 0.91 to 1.31),其中以rofecoxib的危險性最高(OR=2.44,95% CI 1.87 to 3.18),其次為diclofenac (OR=1.83,95% CI 1.40 to 2.38)。無論是否併用aspirin,rofecoxib (OR=2.98, 95% CI 1.59 to 5.59)及diclofenac (OR=1.83,95% CI 1.40 to 2.38)皆具有相同的危險性;相對的naproxen (OR=1.61,95% CI 0.81 to 3.19)及ibuprofen (OR=1.55,95% CI 0.96 to 2.52)在併用aspirin時其危險性並不具統計學上之差異。且經由多項敏感性分析確認本研究結果。
研究結論:本研究結果顯示全民健保資料庫在栓塞性中風及aspirin處方具有高的效度,可作為此族群之研究材料來源。在老年人,使用非選擇性非類固醇抗發炎劑及選擇性第二型環氧酶抑制劑rofecoxib (不包含celecoxib)會增加栓塞性中風復發的危險性。在併用aspirin的情形下,除了celecoxib、naproxen及ibuprofen外,使用非類固醇抗發炎劑仍會增加栓塞性中風復發的危險性。
英文摘要 Background: An increased risk of cardiovascular events with non-steroid anti-inflammatory drugs (NSAIDs) and cyclo-oxygenase-2 (COX-2) inhibitors were evident in the literature, which have placed the risk-benefit profile of these COX-2 inhibitors under public scrutiny and two COX-2 inhibitors subsequently been withdrawn from the market. As a result, clinicians have been encouraged to weigh the potential benefits and risks of the NSAIDs prior to prescribing them. Nonetheless, aspirin interaction with other NSAIDs has become new concerns recently. Despite a growing body of literature in this area, very few studies have specifically aimed to examine stroke risk of selective COX-2 inhibitors and NSAIDs in the elderly population in Taiwan. Additionally, the risk resulting from interaction between aspirin, indicated to prevent stroke, and NSAIDs is lacking. Furthermore, although National Health Insurance Research database (NHIRD) provides the longitudinal population data to assess treatment outcomes and drug-disease associations in Taiwan, the data quality of NHIRD has not been systematically evaluated yet.
Objectives: Our study aimed to evaluate the validity of the National Insurance Health Research Database (NHIRD) database in patients with a principal diagnosis of ischemic stroke; to examine the risks of recurrent ischemic stroke among the elderly patients using selective COX-2 inhibitors and other non-steroid anti-inflammatory drugs (NSAIDs); and to investigate the interaction between aspirin and NSAIDs might affect the stroke protective effect of aspirin.
Methods: We conducted a cross-sectional study to evaluate the data quality of NHIRD. This cross-sectional study compares records in NHIRD with those in one medical center. Patients hospitalized for ischemic stroke in 1999 were identified from the two databases. The discharge notes, laboratory data, and medication orders during admission and the first discharge visit were reviewed to validate ischemic stroke diagnoses and aspirin prescribing in NHIRD. Agreement between the two databases in comorbidity of ischemic stroke diagnosis was evaluated using ICD-9 codes. Second, we conducted a retrospective nested case-control study using data from the NHIRD to investigate risk of incident stroke association between NSAIDs/COX-2 inhibitors use and interaction between NSAIDs and aspirin on stroke risk. We identified individuals aged 65 years or older, who were first time hospitalized with ischemic stroke during 1 Jan 2000 to 31 Dec 2003 and who were prescribed any NSAID after discharge. Cases of re-admissions with a major diagnosis of stroke were risk-set matched with three controls for age, sex, calendar year and follow up duration. Current exposure of NSAIDs/coxibs was compared with remote exposure to any NSAIDs. To analyze the effect of NSAIDs on odds of stroke, we employed stratified analyses by aspirin use to evaluate whether NSAIDs/ COX-2 inhibitors antagonize the antiplatelet effects of aspirin. In order to robust our findings, several sensitivity analyses were conducted in this study. Conditional logistic regression models with controlling for all covariates were used to analyze the association between exposure and outcome. All analyses were performed with SAS for Windows, version 9.1.
Results: 372 cases were identified from NHIRD; among them, 364 cases (97.85%) were confirmed as ischemic stroke by radiology examination and clinical presentation. The Positive Predict Value (PPV) was 0.98 among records with this diagnosis in the principle record position and 0.87 in other record positions. The overall agreement of comorbid diagnoses between the two databases was 48.39%. The PPV for selected conditions also varied widely, from 0.50 for fracture to 1.00 for colon cancer. The accuracy of recorded aspirin prescriptions was higher in first post-discharge visits (PPV=0.94) than during hospitalization (PPV=0.88). There were 43,214 patients fulfilled the cohort definition, and 10,238 cases identified with at least 1 matched control were included in the final analysis. As expected, the prevalence of previous cardiovascular admission, and drug use was uniformly increased in cases. A total of 4,391 (42.9%) cases and 9,399 (32.8%) controls had been currently exposed to any NSAIDs before their index date. All current use of NSAIDs, but not celecoxib (OR=1.09, 95% CI 0.91 to 1.31) were associated with higher stroke odds compared with remote users. The risk of ischemic stroke was highest in subjects prescribed rofecoxib (OR=2.44, 95% CI 1.87 to 3.18) followed by diclofenac (OR=1.83, 95% CI 1.63 to 2.05). Both rofecoxib (OR=2.98, 95% CI 1.59 to 5.59) and diclofenac (OR=1.83, 95% CI 1.40 to 2.38) were associated with a statistically significant increase in odds of ischemic stroke, compared with remote users whatever concomitant use of aspirin. In contrast, patients receiving aspirin, naproxen (OR=1.61, 95% CI 0.81 to 3.19) and ibuprofen (OR=1.55, 95% CI 0.96 to 2.52) were not associated with higher rate of ischemic stroke than remote users. Several sensitivity analyses did confirm our findings.
Conclusions: The accuracy of NHIRD in recording ischemic stroke diagnoses and aspirin prescriptions was high, and NHIRD appears to be a valid resource for population research in ischemic stroke. In elderly population, we found a greater risk of ischemic stroke with current use of non-selective NSAIDs and rofecoxib but not celecoxib compared with remote use of any NSAIDs. In those using aspirin, NSAIDs/COX-2 inhibitors, other than celecoxib, naproxen, and ibuprofen, were associated with increased risk of stroke. Additional randomized controlled study is needed to determine the clinical impact of using NSAIDs along with aspirin for stroke prevention.
論文目次 Contents
Chapter 1 Introduction 1
1.1 Statement of Problem 1
1.2 Specific Aims 3
1.3 Significance of This Study 4
Chapter 2 Literature Review 5
2.1 Mechanism of NSAIDs 5
2.1.2 Classification of NSAIDs 8
2.2 Research on NSAIDs Relative Cardiovascular Adverse Effects 12
2.2.1 Mechanism 13
2.2.2 Myocardial infarction 14
2.2.3 Stroke 22
2.3 NSAIDs and Aspirin Interaction 23
2.3.1 Mechanism 23
2.3.2 Clinical data 24
2.4 Clinical Data in Taiwan 25
2.4.1 NSAIDs relative GI complications 26
2.4.2 NSAIDs relative CV complications 27
2.4.3 Pharmaceutical reimbursement guideline 27
2.5 Introduction of NHIRD in Taiwan 28
2.5.1 Background 28
2.5.2 Data protection 28
2.5.3 Structure of NHIRD 29
2.6 Summary of Literature Review 30
Chapter 3 Objectives and hypothesis 31
Chapter 4 Methods 32
4.1 Validation Study 32
4.1.1 Data sources and record linkage 32
4.1.2 Validating diagnoses of ischemic stroke 33
4.1.3 Agreement of comorbid conditions 33
4.1.4 Validity of aspirin exposure 34
4.1.5 Statistical analysis 34
4.2 NSAIDs and Coxibs relative Stroke adverse effect 36
4.2.1 Study design 36
4.2.2 Data source and material 36
4.2.3 Study population and procedure 37
4.2.4 Case definition and exclusion criteria 38
4.2.5 Exposure definition 38
4.2.6 Statistical analysis 39
4.3 Interaction between Aspirin and NSAIDs/coxibs 42
4.3.1 Aspirin exposure definition 42
4.3.2 Statistical analysis 42
4.4 Sensitivity study 42
Chapter 5 Results 44
5.1 Validation study 44
5.2 NSAIDs and Coxibs relative stroke adverse effect 47
5.3 Interaction between aspirin and NSAIDs/Coxibs 48
5.4 Sensitivity study 49
Chapter 6 Discussions 51
6.1 Validation study 51
6.2 NSAIDs and Coxibs relative stroke adverse effect 53
6.3 Interaction between aspirin and NSAIDs/Coxibs 56
Chapter 7 Strength and clinical implication 58
Chapter 8 limitations 60
8.1 Validation study 60
8.2 NSAIDs and Coxibs relative stroke adverse effect 61
Chapter 9 Conclusions 63
References 83
Appendix I ATC code for NSAIDs 90
Appendix II Covariance 91
Appendix III Ethical approval documentation for validation study 92

Index of Table
Table 1 Classification of NSAIDs based on chemical categories 9
Table 2 Classification of NSAIDs by COX-1/COX2 selectivity 12
Table 3 Meta-analysis of observational studies reporting on cardiovascular risks with cyclooxygenase 2 inhibitors 20
Table 4 Meta-analysis of observational studies reporting on cardiovascular risks with non-selective NSAIDs 21
Table 5 Dataset and description on NHIRD in Taiwan 29
Table 6 Agreement in Comorbid Conditions between NHIRD and DNMC, with the Latter as Gold Standard 46
Table 7 Baseline characteristics of cases and matched controls 65
Table 8 Characteristics of controls currently exposed to an individual NSAID (n=28643) 66
Table 9 Characteristics of cases currently exposed to an individual NSAID (N=10238) 67
Table 10 Characteristics of cases and matched controls (uni-variate analysis) 70
Table 11 Multiple-variate analysis of cases and matched controls 71
Table 12 Risk of ischemic stroke with use of NSAIDs compared with remote use of a NSAID 72
Table 13 Risk of ischemic stroke and NSAIDs compared with remote use of a NSAID 74
Table 14 Risk of ischemic stroke with use of NSAIDs compared with remote use of a NSAID 75
Table 15 Sensitivity study (current NSAIDs definition as 0 days) 76
Table 16 Sensitivity study (current NSAIDs definition as 7 days) 77
Table 17 Sensitivity study (current NSAIDs definition as 14 days) 78
Table 18 Sensitivity study (include mortality cases) 79
Table 19 Sensitivity study (restrict follow until 2004) 80
Table 20 Sensitivity study (current use of preferential and non-selective NSAIDs) 81
Table 21 Sensitivity study (aspirin cohort) 82

Index of Figure
Figure 1 Production and Actions of Prostaglandins and Thromboxane 7
Figure 2 Concentrations of NSAIDs required inhibiting the activity of COX-1 and COX-2 by 50 Percent (IC50) in assays of whole blood 10
Figure 3 Schematic picture of the active sites of COX-1 and COX-2 10
Figure 4 Determinable log [IC80 ratio (WHMA-COX-2yCOX-1)] for NSAIDs 11
Figure 5 Effect of NSAIDs and coxibs on platelet-active prostanoids 14
Figure 6 Meta-analysis of randomized trials to compared the effects of different selective COX 2 inhibitors versus placebo on vascular events, myocardial infarction, stroke, and vascular death 18
Figure 7 Meta-analysis of randomized trials to compared the effects of different selective COX 2 inhibitors versus other NSAIDs on vascular events, myocardial infarction, stroke, and vascular death 19
Figure 8 Mechanism of interaction between ibuprofen and aspirin 24
Figure 9 Flow chart of validation study 35
Figure 10 Procedure of Database linkage 40
Figure 11 Flow chart of association with NSAIDs and stroke study 41
Figure 12 Distribution of follow up duration among cases 63
Figure 13 Risk of Ischemic Stroke associated with Interaction between NSAIDs and Aspirin 73
參考文獻 1. Krumholz HM, Ross JS, Presler AH, Egilman DS. What have we learnt from Vioxx? BMJ. 2007;334(7585):120-3. PMCID: 1779871.
2. Mukherjee D, Nissen SE, Topol EJ. Risk of cardiovascular events associated with selective COX-2 inhibitors. JAMA. 2001;286(8):954-9.
3. Solomon DH, Schneeweiss S, Levin R, Avorn J. Relationship between COX-2 specific inhibitors and hypertension. Hypertension. 2004;44(2):140-5.
4. Fischer LM, Schlienger RG, Matter CM, Jick H, Meier CR. Current use of nonsteroidal antiinflammatory drugs and the risk of acute myocardial infarction. Pharmacotherapy. 2005;25(4):503-10.
5. Graham DJ, Campen D, Hui R, Spence M, Cheetham C, Levy G, et al. Risk of acute myocardial infarction and sudden cardiac death in patients treated with cyclo-oxygenase 2 selective and non-selective non-steroidal anti-inflammatory drugs: nested case-control study. Lancet. 2005;365(9458):475-81.
6. Hippisley-Cox J, Coupland C. Risk of myocardial infarction in patients taking cyclo-oxygenase-2 inhibitors or conventional non-steroidal anti-inflammatory drugs: population based nested case-control analysis. BMJ. 2005;330(7504):1366. PMCID: 558288.
7. Levesque LE, Brophy JM, Zhang B. The risk for myocardial infarction with cyclooxygenase-2 inhibitors: a population study of elderly adults. Ann Intern Med. 2005;142(7):481-9.
8. Rahme E, Pilote L, LeLorier J. Association between naproxen use and protection against acute myocardial infarction. Arch Intern Med. 2002;162(10):1111-5.
9. White WB, Faich G, Whelton A, Maurath C, Ridge NJ, Verburg KM, et al. Comparison of thromboembolic events in patients treated with celecoxib, a cyclooxygenase-2 specific inhibitor, versus ibuprofen or diclofenac. Am J Cardiol. 2002;89(4):425-30.
10. Farkouh ME, Kirshner H, Harrington RA, Ruland S, Verheugt FW, Schnitzer TJ, et al. Comparison of lumiracoxib with naproxen and ibuprofen in the Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET), cardiovascular outcomes: randomised controlled trial. Lancet. 2004;364(9435):675-84.
11. Johnsen SP, Larsson H, Tarone RE, McLaughlin JK, Norgard B, Friis S, et al. Risk of hospitalization for myocardial infarction among users of rofecoxib, celecoxib, and other NSAIDs: a population-based case-control study. Arch Intern Med. 2005;165(9):978-84.
12. Sowers JR, White WB, Pitt B, Whelton A, Simon LS, Winer N, et al. The Effects of cyclooxygenase-2 inhibitors and nonsteroidal anti-inflammatory therapy on 24-hour blood pressure in patients with hypertension, osteoarthritis, and type 2 diabetes mellitus. Arch Intern Med. 2005;165(2):161-8.
13. Cannon CP, Curtis SP, FitzGerald GA, Krum H, Kaur A, Bolognese JA, et al. Cardiovascular outcomes with etoricoxib and diclofenac in patients with osteoarthritis and rheumatoid arthritis in the Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) programme: a randomised comparison. Lancet. 2006;368(9549):1771-81.
14. Kearney PM, Baigent C, Godwin J, Halls H, Emberson JR, Patrono C. Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials. BMJ. 2006;332(7553):1302-8. PMCID: 1473048.
15. Bak S, Andersen M, Tsiropoulos I, Garcia Rodriguez LA, Hallas J, Christensen K, et al. Risk of stroke associated with nonsteroidal anti-inflammatory drugs: a nested case-control study. Stroke. 2003;34(2):379-86.
16. Chen LC, Ashcroft DM. Do selective COX-2 inhibitors increase the risk of cerebrovascular events? A meta-analysis of randomized controlled trials. J Clin Pharm Ther. 2006;31(6):565-76.
17. Choi NK, Park BJ, Jeong SW, Yu KH, Yoon BW. Nonaspirin nonsteroidal anti-inflammatory drugs and hemorrhagic stroke risk: the Acute Brain Bleeding Analysis study. Stroke. 2008;39(3):845-9.
18. [Anon]. FDA advises about potential attenuation of anti-platelet effect of low-dose aspirin with concomitant use of ibuprofen. Formulary. 2006;41(11):558-60.
19. Curtis JP, Krumholz HM. The case for an adverse interaction between aspirin and non-steroidal anti-inflammatory drugs: is it time to believe the hype? J Am Coll Cardiol. 2004;43(6):991-3.
20. MacDonald TM, Wei L. Effect of ibuprofen on cardioprotective effect of aspirin. Lancet. 2003;361(9357):573-4.
21. Curtis JP, Krumholz HM. Effect of ibuprofen on cardioprotective effect of aspirin. Lancet. 2003;361(9368):1560; author reply 1.
22. Woodward M, Reid MA. Cardiovascular disease in the Asia-Pacific region: challenges for health research and policy. Med J Aust. 2003;179(2):71-2.
23. Khor GL. Cardiovascular epidemiology in the Asia-Pacific region. Asia Pac J Clin Nutr. 2001;10(2):76-80.
24. Vane JR, Flower RJ, Botting RM. History of aspirin and its mechanism of action. Stroke. 1990;21(12 Suppl):IV12-23.
25. Bjordal JM, Ljunggren AE, Klovning A, Slordal L. Non-steroidal anti-inflammatory drugs, including cyclo-oxygenase-2 inhibitors, in osteoarthritic knee pain: meta-analysis of randomised placebo controlled trials. BMJ. 2004;329(7478):1317. PMCID: 534841.
26. Vane JR. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat New Biol. 1971;231(25):232-5.
27. Simmons DL, Botting RM, Hla T. Cyclooxygenase isozymes: the biology of prostaglandin synthesis and inhibition. Pharmacol Rev. 2004;56(3):387-437.
28. Warner TD, Mitchell JA. Cyclooxygenases: new forms, new inhibitors, and lessons from the clinic. FASEB J. 2004;18(7):790-804.
29. Warner TD, Giuliano F, Vojnovic I, Bukasa A, Mitchell JA, Vane JR. Nonsteroid drug selectivities for cyclo-oxygenase-1 rather than cyclo-oxygenase-2 are associated with human gastrointestinal toxicity: a full in vitro analysis. Proc Natl Acad Sci U S A. 1999;96(13):7563-8. PMCID: 22126.
30. Silverstein FE, Faich G, Goldstein JL, Simon LS, Pincus T, Whelton A, et al. Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: A randomized controlled trial. Celecoxib Long-term Arthritis Safety Study. JAMA. 2000;284(10):1247-55.
31. Bombardier C, Laine L, Reicin A, Shapiro D, Burgos-Vargas R, Davis B, et al. Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. N Engl J Med. 2000;343(21):1520-8.
32. Moore RA, Derry S, Phillips CJ, McQuay HJ. Nonsteroidal anti-inflammatory drugs (NSAIDs), cyxlooxygenase-2 selective inhibitors (coxibs) and gastrointestinal harm: review of clinical trials and clinical practice. BMC Musculoskelet Disord. 2006;7:79. PMCID: 1626078.
33. Ray WA, MacDonald TM, Solomon DH, Graham DJ, Avorn J. COX-2 selective non-steroidal anti-inflammatory drugs and cardiovascular disease. Pharmacoepidemiol Drug Saf. 2003;12(1):67-70.
34. Pairet M. Inhibition of cyclooxygenase-1 and cyclooxygenase-2 analysis of in vitro test systems and their clinical relevance. J Clin Rheumatol. 1998;4(5 Suppl):s17-25.
35. Everts B, Wahrborg P, Hedner T. COX-2-Specific inhibitors--the emergence of a new class of analgesic and anti-inflammatory drugs. Clin Rheumatol. 2000;19(5):331-43.
36. Topol EJ. Failing the public health--rofecoxib, Merck, and the FDA. N Engl J Med. 2004;351(17):1707-9.
37. Topol EJ. Arthritis medicines and cardiovascular events--"house of coxibs". JAMA. 2005;293(3):366-8.
38. Administration FaD. Public Health Advisory - FDA Announces Important Changes and Additional Warnings for COX-2 Selective and Non-Selective Non-Steroidal Anti-Inflammatory Drugs (NSAIDs). 2005.
39. Antman EM, Bennett JS, Daugherty A, Furberg C, Roberts H, Taubert KA. Use of nonsteroidal antiinflammatory drugs: an update for clinicians: a scientific statement from the American Heart Association. Circulation. 2007;115(12):1634-42.
40. Topper JN, Cai JX, Falb D, Gimbrone MA. Identification of vascular endothelial genes differentially responsive to fluid mechanical stimuli: Cyclooxygenase-2, manganese superoxide dismutase, and endothelial cell nitric oxide synthase are selectively up-regulated by steady laminar shear stress. Proceedings of the National Academy of Sciences of the United States of America. 1996;93(19):10417-22.
41. Krotz F, Schiele TM, Klauss V, Sohn HY. Selective COX-2 inhibitors and risk of myocardial infarction. J Vasc Res. 2005;42(4):312-24.
42. Maxwell SR, Payne RA, Murray GD, Webb DJ. Selectivity of NSAIDs for COX-2 and cardiovascular outcome. Br J Clin Pharmacol. 2006;62(2):243-5. PMCID: 1885096.
43. Ray WA, Stein CM, Daugherty JR, Hall K, Arbogast PG, Griffin MR. COX-2 selective non-steroidal anti-inflammatory drugs and risk of serious coronary heart disease. Lancet. 2002;360(9339):1071-3.
44. McGettigan P, Henry D. Cardiovascular risk and inhibition of cyclooxygenase: a systematic review of the observational studies of selective and nonselective inhibitors of cyclooxygenase 2. JAMA. 2006;296(13):1633-44.
45. Layton D, Heeley E, Hughes K, Shakir SA. Comparison of the incidence rates of thromboembolic events reported for patients prescribed rofecoxib and meloxicam in general practice in England using prescription-event monitoring (PEM) data. Rheumatology (Oxford). 2003;42(11):1342-53.
46. Layton D, Hughes K, Harris S, Shakir SA. Comparison of the incidence rates of thromboembolic events reported for patients prescribed celecoxib and meloxicam in general practice in England using Prescription-Event Monitoring (PEM) data. Rheumatology (Oxford). 2003;42(11):1354-64.
47. Andersohn F, Schade R, Suissa S, Garbe E. Cyclooxygenase-2 selective nonsteroidal anti-inflammatory drugs and the risk of ischemic stroke: a nested case-control study. Stroke. 2006;37(7):1725-30.
48. Haag MD, Bos MJ, Hofman A, Koudstaal PJ, Breteler MM, Stricker BH. Cyclooxygenase selectivity of nonsteroidal anti-inflammatory drugs and risk of stroke. Arch Intern Med. 2008;168(11):1219-24.
49. Administration UFaD. New Information for Healthcare Professionals Concomitant Use of Ibuprofen and Aspirin. 2006.
52. Catella-Lawson F, Reilly MP, Kapoor SC, Cucchiara AJ, DeMarco S, Tournier B, et al. Cyclooxygenase inhibitors and the antiplatelet effects of aspirin. N Engl J Med. 2001;345(25):1809-17.
53. Renda G, Tacconelli S, Capone ML, Sacchetta D, Santarelli F, Sciulli MG, et al. Celecoxib, ibuprofen, and the antiplatelet effect of aspirin in patients with osteoarthritis and ischemic heart disease. Clinical Pharmacology & Therapeutics. 2006;80(3):264-74.
54. Ouellet M, Riendeau D, Percival MD. A high level of cyclooxygenase-2 inhibitor selectivity is associated with a reduced interference of platelet cyclooxygenase-1 inactivation by aspirin. Proceedings of the National Academy of Sciences of the United States of America. 2001;98(25):14583-8.
55. MacDonald TM, Wei L. Effect of ibuprofen on cardioprotective effect of aspirin. Lancet. 2003;361(9357):573-4.
56. Ray WA, Stein CM, Hall K, Daugherty JR, Griffin MR. Non-steroidal anti-inflamatory drugs and risk of serious coronary heart disease: an observational cohort study. Lancet. 2002;359(9301):118-23.
57. Farkouh ME, Greenberg JD, Jeger RV, Ramanathan K, Verheugt FW, Chesebro JH, et al. Cardiovascular outcomes in high risk patients with osteoarthritis treated with ibuprofen, naproxen or lumiracoxib. Ann Rheum Dis. 2007;66(6):764-70. PMCID: 1954641.
58. Curtis JP, Wang Y, Portnay EL, Masoudi FA, Havranek EP, Krumholz HM. Aspirin, ibuprofen, and mortality after myocardial infarction: retrospective cohort study. BMJ. 2003;327(7427):1322-3. PMCID: 286319.
59. Garcia Rodriguez LA, Varas-Lorenzo C, Maguire A, Gonzalez-Perez A. Nonsteroidal antiinflammatory drugs and the risk of myocardial infarction in the general population. Circulation. 2004;109(24):3000-6.
60. Liu JY, Chen TJ, Hwang SJ. Concomitant prescription of non-steroidal anti-inflammatory drugs and antacids in the outpatient setting of a medical center in Taiwan: a prescription database study. European Journal of Clinical Pharmacology. 2001;57(6-7):505-8.
61. Chen TJ, Liu JY, Hwang SJ. Non-steroidal anti-inflammatory drug and antacid co-prescription in Taiwan: analysis of national insurance claims. Zhonghua Yi Xue Za Zhi (Taipei). 2002;65(12):588-93.
62. Kao Y-h, Kuo S-c, Jia S-w. Analysis of Drug Consumption and Prescribing Dose in Nhi - Using Non-Steroidal Anti-Inflammatory Drugs and Serum Lipid Reducing Agents as Models. 2002.
63. Huang WF, Hsiao FY, Tsai YW, Wen YW, Shih YT. Cardiovascular events associated with long-term use of celecoxib, rofecoxib and meloxicam in Taiwan: an observational study. Drug Saf. 2006;29(3):261-72.
64. Huang WF, Hsiao FY, Wen YW, Tsai YW. Cardiovascular events associated with the use of four nonselective NSAIDs (etodolac, nabumetone, ibuprofen, or naproxen) versus a cyclooxygenase-2 inhibitor (celecoxib): a population-based analysis in Taiwanese adults. Clin Ther. 2006;28(11):1827-36.
65. NHIRD. Introduction to the National Health Insurance Research Database (NHIRD), Taiwan
66. Jaro MA. Probabilistic linkage of large public health data files. Stat Med. 1995;14(5-7):491-8.
67. Clark DE. Practical introduction to record linkage for injury research. Inj Prev. 2004;10(3):186-91. PMCID: 1730090.
68. Blakely T, Salmond C. Probabilistic record linkage and a method to calculate the positive predictive value. Int J Epidemiol. 2002;31(6):1246-52.
69. Evans JM, MacDonald TM. Record-linkage for pharmacovigilance in Scotland. Br J Clin Pharmacol. 1999;47(1):105-10. PMCID: 2014211.
70. Yang Y-hK, Kuo C-W, Hung H-J, Jia S-W. Classification of pharmaceutical products reimbursed by National Health Insurance by the ATC system. Chinese Pharmaceutical Journal (Taipei). 2002;54(4):283-90.
71. Hall GC, Brown MM, Mo J, MacRae KD. Triptans in migraine: the risks of stroke, cardiovascular disease, and death in practice. Neurology. 2004;62(4):563-8.
72. Leibson CL, Naessens JM, Brown RD, Whisnant JP. ACCURACY OF HOSPITAL DISCHARGE ABSTRACTS FOR IDENTIFYING STROKE. Stroke. 1994;25(12):2348-55.
73. Benesch C, Witter DM, Wilder AL, Duncan PW, Samsa GP, Matchar DB. Inaccuracy of the International Classification of Diseases (ICD-9-CM) in identifying the diagnosis of ischemic cerebrovascular disease. Neurology. 1997;49(3):660-4.
74. Goldstein LB. Accuracy of ICD-9-CM coding for the identification of patients with acute ischemic stroke - Effect of modifier codes. Stroke. 1998;29(8):1602-4.
75. Liu HM, Tu YK, Yip PK, Su CT. Evaluation of intracranial and extracranial carotid steno-occlusive diseases in Taiwan Chinese patients with MR angiography. Preliminary experience. Stroke. 1996;27(4):650-3.
76. Wong KS, Huang YN, Gao S, Lam WWM, Chan YL, Kay R. Intracranial stenosis in Chinese patients with acute stroke. Neurology. 1998;50(3):812-3.
77. Suh DC, Lee SH, Kim KR, Park ST, Lim SM, Kim SJ, et al. Pattern of atherosclerotic carotid stenosis in Korean patients with stroke: Different involvement of intracranial versus extracranial vessels. American Journal of Neuroradiology. 2003;24(2):239-44.
78. O'Malley KJ, Cook KF, Price MD, Wildes KR, Hurdle JF, Ashton CM. Measuring diagnoses: ICD code accuracy. Health Services Research. 2005;40(5):1620-39.
79. Powell H, Lim LLY, Heller RF. Accuracy of administrative data to assess comorbidity in patients with heart disease: an Australian perspective. Journal of Clinical Epidemiology. 2001;54(7):687-93.
80. Preen DB, Holman CDJ, Lawrence DM, Baynham NJ, Semmens JB. Hospital chart review provided more accurate comorbidity information than data from a general practitioner survey or an administrative database. Journal of Clinical Epidemiology. 2004;57(12):1295-304.
81. Peabody JW, Luck J, Jain S, Bertenthal D, Glassman P. Assessing the accuracy of administrative data in health information systems. Medical Care. 2004;42(11):1066-72.
82. Griend JPV, Saseen JJ. Combination antiplatelet agents for secondary prevention of ischemic stroke. Pharmacotherapy. 2008;28(10):1233-42.
83. Caldwell B, Aldington S, Weatherall M, Shirtcliffe P, Beasley R. Risk of cardiovascular events and celecoxib: a systematic review and meta-analysis. J R Soc Med. 2006;99(3):132-40. PMCID: 1383759.
84. Catella-Lawson F, McAdam B, Morrison BW, Kapoor S, Kujubu D, Antes L, et al. Effects of specific inhibition of cyclooxygenase-2 on sodium balance, hemodynamics, and vasoactive eicosanoids. J Pharmacol Exp Ther. 1999;289(2):735-41.
85. Fischer LM, Schlienger RG, Matter CM, Jick H, Meier CR. Current use of nonsteroidal antiinflammatory drugs and the risk of acute myocardial infarction. Pharmacotherapy. 2005;25(4):503-10.
86. Awtry EH, Loscalzo J. Aspirin. Circulation. 2000;101(10):1206-18.
87. Rahme E, Pilote L, LeLorier J. Association between naproxen use and protection against acute myocardial infarction. Archives of Internal Medicine. 2002;162(10):1111-5.
88. Watson DJ, Rhodes T, Cai B, Guess HA. Lower risk of thromboembolic cardiovascular events with naproxen among patients with rheumatoid arthritis. Arch Intern Med. 2002;162(10):1105-10.
89. Mamdani M, Rochon P, Juurlink DN, Anderson GM, Kopp A, Naglie G, et al. Effect of selective cyclooxygenase 2 inhibitors and naproxen on short-term risk of acute myocardial infarction in the elderly. Arch Intern Med. 2003;163(4):481-6.
90. Rodriguez LAG, Varas C, Patrono C. Differential effects of aspirin and non-aspirin nonsteroidal antiinflammatory drugs in the primary prevention of myocardial infarction in postmenopausal women. Epidemiology. 2000;11(4):382-7.
91. Kimmel SE, Berlin JA, Reilly M, Jaskowiak J, Kishel L, Chittams J, et al. The effects of nonselective non-aspirin non-steroidal anti-inflammatory medications on the risk of nonfatal myocardial infarction and their interaction with aspirin. J Am Coll Cardiol. 2004;43(6):985-
92. Tung YC, Chang GM. The Effect of Cuts in Reimbursement on Stroke Outcome A Nationwide Population-Based Study During the Period 1998 to 2007. Stroke. 2010;41(3):504-9.
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