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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 林珍芳助理教授 | |
dc.contributor.author | Dan Wei Choo | en |
dc.contributor.author | 朱丹惟 | zh_TW |
dc.date.accessioned | 2021-06-17T01:18:58Z | - |
dc.date.available | 2022-09-14 | |
dc.date.copyright | 2017-09-14 | |
dc.date.issued | 2017 | |
dc.date.submitted | 2017-08-11 | |
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Taiwan’s National Health Insurance Research Database: administrative health care database as study object in bibliometrics. Scientometrics 2010;86:365-80. 40. Lin H-C, Xirasagar S, Tsao N-W, Hwang Y-T, Kuo N-W, Lee H-C. Volume–outcome relationships in coronary artery bypass graft surgery patients: 5-year major cardiovascular event outcomes. The Journal of Thoracic and Cardiovascular Surgery 2008;135:923-30. 41. Post PN, Kuijpers M, Ebels T, Zijlstra F. The relation between volume and outcome of coronary interventions: a systematic review and meta-analysis. European Heart Journal 2010;31:1985-92. 42. Rubin DB. Estimating causal effects from large data sets using propensity scores. Annals of internal medicine 1997;127:757-63. 43. Austin PC. Primer on statistical interpretation or methods report card on propensity-score matching in the cardiology literature from 2004 to 2006: a systematic review. Circulation Cardiovascular quality and outcomes 2008;1:62-7. 44. Suissa S. Immortal time bias in observational studies of drug effects. Pharmacoepidemiol Drug Saf 2007;16:241-9. 45. Suissa S. Immortal time bias in pharmaco-epidemiology. Am J Epidemiol 2008;167:492-9. 46. Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014;129:S1-45. 47. Bruckert E, Hayem G, Dejager S, Yau C, Begaud B. Mild to moderate muscular symptoms with high-dosage statin therapy in hyperlipidemic patients--the PRIMO study. Cardiovasc Drugs Ther 2005;19:403-14. 48. Lin ZF, Wang CY, Shen LJ, Hsiao FY, Lin Wu FL. Statin Use and the Risk for Incident Diabetes Mellitus in Patients with Acute Coronary Syndrome after Percutaneous Coronary Intervention: A Population-Based Retrospective Cohort Study in Taiwan. Can J Diabetes 2016;40:264-9. 49. Fruchart JC, Brewer HB, Jr., Leitersdorf E. Consensus for the use of fibrates in the treatment of dyslipoproteinemia and coronary heart disease. Fibrate Consensus Group. Am J Cardiol 1998;81:912-7. 50. Pauriah M, Elder DH, Ogston S, et al. High-potency statin and ezetimibe use and mortality in survivors of an acute myocardial infarction: a population-based study. Heart 2014;100:867-72. 51. Lee E, Ryan S, Birmingham B, et al. Rosuvastatin pharmacokinetics and pharmacogenetics in white and Asian subjects residing in the same environment. Clin Pharmacol Ther 2005;78:330-41. 52. Birmingham BK, Bujac SR, Elsby R, et al. Rosuvastatin pharmacokinetics and pharmacogenetics in Caucasian and Asian subjects residing in the United States. Eur J Clin Pharmacol 2015;71:329-40. 53. Tzeng TB, Schneck DW, Birmingham BK, et al. Population pharmacokinetics of rosuvastatin: implications of renal impairment, race, and dyslipidaemia. Curr Med Res Opin 2008;24:2575-85. 54. Birmingham BK, Bujac SR, Elsby R, et al. Impact of ABCG2 and SLCO1B1 polymorphisms on pharmacokinetics of rosuvastatin, atorvastatin and simvastatin acid in Caucasian and Asian subjects: a class effect? Eur J Clin Pharmacol 2015;71:341-55. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/67067 | - |
dc.description.abstract | 研究背景:
近期的研究指出,血液中高濃度的三酸甘油酯會提高發生心血管疾病之風險。然而,ACCORD-Lipid 研究中併用fibrate與simvastatin的治療結果顯示,因心血管疾病死亡、心肌梗塞與中風在primary composite outcome上並無顯著差異。因缺乏密集、長期且大規模之急性冠心症病人之資料,使得併用fibrate與statin所帶來的益處尚待討論。也由於臨床上關於併用fibrate來治療急性冠心症病人的治療效果之資料相當稀少,故本研究將以回溯性世代研究之方法來探討此議題。 研究目的: 以一個大型的世代資料,比較第一次住院之急性冠心症病人併用statin與fibrate或只服用statin的情況下在死亡、再入院與冠狀動脈重建術之風險差異。 研究方法: 此世代研究的資料來源為2005年至2011年臺灣健保資料庫。作者自臺灣健保資料庫中選取在2006年1月1 日至2010年12月31日此期間內,第一次因急性冠心症入院的病人為研究族群。本研究利用傾向分數配對的方法來矯正兩組比較組之間潛在的選擇性偏差。並使用time-varying multivariable Cox proportional hazards regression model來分析併用fibrate對於statin使用者的全死因死亡率、因急性冠心症的再入院率以及冠狀動脈重建術的影響。 研究結果: 本研究共收納29,328個病人(平均年齡62歲,女性佔23%),作者從中挑選出2,545個併用statin與fibrate之急性冠心症病人(佔總人數8.68%),與26,738個只單一服用statin的急性冠心症病人(佔總人數91.32%)。為期六年的追蹤期(追蹤期之中位數為3.22年),有3,201個病人死亡。(死亡為主要試驗指標)併用statin與fibrate相較於單一使用statin,其死亡之多變數校正危險比為0.54(95%信賴區間為0.45-0.65)。在用了time-varying multivariable Cox proportional模型後,併用statin與fibrate相較於單一使用statin,其全因死亡之多變數校正危險比為0.93 (95%信賴區間為0.78-1.12)。在配對後的世代,併用statin與fibrate相較於單一使用statin的族群,其死亡之多變數校正危險比為0.54(95%信賴區間為0.44-0.67)。然而,在使用time-varying方法後,併用statin與fibrate,其死亡之多變數校正危險比為0.99(95%信賴區間為0.80-1.23)。再入院率及冠狀動脈重建術之比率在用time-varying方法後,危險比變成1.01(95%信賴區間為0.89-1.14)及1.05(95%信賴區間為0.91-1.21)。相似的結果也可以在配對世代中發現。此研究也發現併用fibrate與statin的治療方法與高血脂症有顯著的交互作用。在有高血脂症共病的次族群中,他的全死因死亡率為0.69(95%信賴區間為95% CI, 0.50-0.94)。在敏感度分析中得到的結果與主要研究結果是一致的。 研究結論: 併用fibrate 與 statin的治療方法並不能顯著降低急性冠心症病人之全死因死亡率、再入院率及冠狀動脈重建術之比率。然而,在共病為高血脂症的急性冠心症病人,卻發現併用fibrate 與 statin能為該次族群帶能顯著的益處。 | zh_TW |
dc.description.abstract | Background:
Recent data indicates that high levels of TG are correlated with a higher risk of CVD. However, the ACCORD-Lipid study which fibrate was used in combination with simvastatin showed the non-significant difference in the primary composite outcome of CV mortality, nonfatal MI, and nonfatal stroke. In the absence of extensive, long-term and large-scale data in hospitalized ACS patients, the benefit of a fibrate in combination with statin remains equivocal. Owing to the scarcity of clinical outcome data on fibrate and statin combination use in ACS patients, a new user design retrospective cohort study was conducted. Objective: To compare the mortality, re-hospitalization for ACS, and revascularization risk among a large cohort of first hospitalized ACS patients receiving statin plus fibrate combination in comparison to those who used statin monotherapy. Method: This nationwide cohort study was based on data obtained from the full population data of Taiwan National Health Insurance Research Database (NHIRD) from 2005 to 2011. We identified all ACS patients who were first hospitalized for ACS between January 1, 2006, and December 31, 2010, from the NHIRD. A propensity score matching approach was used to create a matched cohort for further adjusting forpotential selection bias between statin-alone and statin-plus-fibrate groups. The effect of adding fibrate on statin users on all-cause mortality, re-hospitalization for ACS and revascularization was analyzed by time-varying multivariable Cox proportional hazards regression model. Results: In the original cohort, 29,328 patients (mean age of 62 years, 23% female) were included, we identified 2,545 (8.68%) ACS patients who received statin and fibrate while 26,783 (91.32%) ACS patients who received statin only during the study period. During the 6-year follow-up period with a mean of 3.22 years, 3201 subjects (10.9%) reached the primary endpoint- all-cause mortality. The multivariate-adjusted hazard ratios (HRs) of all-cause mortality of statin-plus-fibrate group was 0.54 (95% CI, 0.45-0.65) compared with the statin-alone group. After using a time-varying multivariable Cox proportional model, the HR for all-cause mortality of statin-plus-fibrate group was 0.93 (95% CI, 0.78-1.12) compared with the statin-alone group. In the matched cohort, the multivariate adjusted HR for all-cause mortality of statin-plus-fibrate group was 0.54 (95% CI, 0.44-0.67) compared with statin-alone group. However, the multivariate-adjusted HR for all-cause mortality of statin-plus-fibrate became 0.99 (95% CI, 0.80-1.23) after using a time-varying approach. The HRs for re-hospitalization and revascularization of statin-plus-fibrate group changed to 1.01 (95% CI, 0.89-1.14) and 1.05(95% CI, 0.91-1.21) respectively after using a time-varying method. Similar trends were revealed in the matched cohort. A significant interaction effect was noticed which were the interaction of combination therapy and hyperlipidemia (P = 0.04). In the subgroup of patients with hyperlipidemia, the time-varying adjusted HR for all-cause mortality was 0.69 (95% CI, 0.50-0.94). The sensitivity analysis showed similar results of HRs for all-cause mortality. Conclusion The combination therapy of fibrate and statin did not reduce all-cause mortality, re-hospitalization for ACS and revascularization significantly. However, a significant interaction was found in ACS patients with comorbidity of hyperlipidemia, and the significant benefit was shown in this subgroup. | en |
dc.description.provenance | Made available in DSpace on 2021-06-17T01:18:58Z (GMT). No. of bitstreams: 1 ntu-106-R05451003-1.pdf: 2014522 bytes, checksum: f3907b739a5c678a8d886b9242b09fb7 (MD5) Previous issue date: 2017 | en |
dc.description.tableofcontents | 誌謝 i
中文摘要 ii ABSTRACT iv CONTENTS vii LIST OF FIGURES x LIST OF TABLES xi Chapter 1 Introduction 1 Chapter 2 Literature Review 3 2.1 Acute Coronary Syndrome 3 2.2 Secondary Prevention of Acute Coronary Syndrome 3 2.3 Lipid Profile Control in Patients with Acute Coronary Syndrome 4 2.3.1 The Association between Low-Density Lipoprotein Cholesterol Lowering Agents and Acute Coronary Syndrome 4 2.3.2 The Association between Triglyceride and Acute Coronary Syndrome 5 2.4 The Efficacy and Safety of Fibrates 7 2.4.1 Efficacy of Fibrates as a Monotherapy 7 2.4.2 Efficacy of Fibrates in Combination with Statins 8 2.4.3 Safety Profile of Fibrates in Combination with Statins 9 2.5 Knowledge gap 11 2.5.1 What Is Known 11 2.5.2 What Is Needed 11 Chapter 3 Objectives 12 Chapter 4 Methods 13 4.1 Data Source 13 4.2 Study Design 14 4.2.1 Study Population 14 4.2.2 Covariate 15 4.2.3 Exposure and Outcome Measurement 16 4.2.4 Propensity Score 17 4.2.5 Statistical Analysis 17 4.3 Sensitivity Analyses 19 Chapter 5 Results 20 5.1 Study Cohort Enrollment 20 5.2 Baseline Characteristics 21 5.2.1 Original Cohort and Matched Cohort of Primary Outcome 21 5.2.2 Original Cohort and Matched Cohort of Secondary Outcomes 22 5.2.3 Combination Therapy Users 23 5.3 Percentages of Prescription and Daily Doses of Fibrates and Statins 24 5.4 Outcomes 25 5.4.1 Primary and Secondary Outcomes in the Original and Matched Cohort 25 5.4.2 Primary Outcome and Secondary Outcomes in the Original Cohort Whose Medication Possession Ratio exceeding 0.8 27 5.4.3 Timing to Add Fibrates 28 5.4.4 Dose-response Relationship 28 5.5 Subgroup Analysis 29 5.6 Sensitivity Analysis 30 Chapter 6 Discussion 31 6.1 Key Findings 31 6.2 Interpretations 31 6.2.1 Effectiveness of Combining Statin and Fibrate in ACS Population 31 6.2.2 Heterogeneity of the Combination Therapy of Fibrate and Statin 32 6.2.3 Daily Doses of Statins in ACS Population 33 6.3 Strengths and Limitations 34 Chapter 7 Conclusion 36 Figures 37 Tables 44 REFERENCE 75 | |
dc.language.iso | en | |
dc.title | 急性冠心症患者併用fibrates與statins類藥物之效用 | zh_TW |
dc.title | Effectiveness of a Combination of Fibrates and Statins in Patients with Acute Coronary Syndrome | en |
dc.type | Thesis | |
dc.date.schoolyear | 105-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 蕭斐元副教授,簡國龍教授 | |
dc.subject.keyword | 急性冠心症,併用藥物,全死因死亡率,再入院率, | zh_TW |
dc.subject.keyword | Fibrates,Statins,Acute Coronary Syndrome,Combination Therapy,All-cause Mortality,Rehospitalization, | en |
dc.relation.page | 78 | |
dc.identifier.doi | 10.6342/NTU201702963 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2017-08-12 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 臨床藥學研究所 | zh_TW |
顯示於系所單位: | 臨床藥學研究所 |
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