進階搜尋


  查詢北醫館藏
系統識別號 U0007-1704200714554163
論文名稱(中文) 高血壓病人進行血管收縮素接受器阻斷劑相同療效藥品替代之評估
論文名稱(英文) ARB therapeutic interchange evaluation in patients with hypertension
校院名稱 臺北醫學大學
系所名稱(中) 藥學研究所
系所名稱(英) Graduate Institute of Pharmacy
學年度 93
學期 2
出版年 94
研究生(中文) 黃子芸
研究生(英文) Tzu-yun Huang
學號 M301092022
學位類別 碩士
語文別 中文
口試日期
論文頁數 117頁
口試委員 指導教授-何意
指導教授-簡淑真
中文關鍵字 相同療效藥品替代  治療相等性藥品  血管收縮素接受器阻斷劑  高血壓 
英文關鍵字 therapeutic interchange  therapeutic equivalents  angiotensin Ⅱ receptor blockers  hypertension 
學科別分類
中文摘要 研究目的:評估高血壓病人從其他血管收縮素接受器阻斷劑(ARBs)換成candesartan之後對治療結果的影響,評估藥品替代之後的療效、安全性和病人滿意度。療效評估包括換藥前後的血壓變化和達目標血壓值的人數比率,安全性則是評估病人將藥物換成candesartan是否產生副作用或嚴重不良反應。 研究方法:這是非隨機分派(non-randomized)、開放性(open labeled)且自我比較(self-controlled)的研究。依據收案條件納入2004年8月至2004年11月所有使用candesartan的門診病人,開始進入研究過程。研究進行的時間從2004年8月至2005年5月止,為期九個月。在藥物替換成candesartan之後,分別在第2至4週、12週、24週,評估病人回醫院門診測量的血壓,及換藥之前病歷的血壓紀錄,換藥後2至4週、12週和24週的血壓分別和換藥之前的血壓比較,評估其療效。除了評估血壓值,也評估病人達到目標血壓值的人數比率,比較換藥前和換藥後符合目標血壓值的人數比率。副作用是以電話訪談的方式進行追蹤,詢問是否產生副作用或發生嚴重不良反應,在第2至4週、12週和24週分別進行第一次、第二次和第三次評估,並調查病人對於換藥結果的滿意度。收集紀錄病人的血壓值和副作用資料並加以整理,之後進行統計分析。 研究結果:依據納入和排除標準共納入了586位病人,而最後有494位病人納入本研究,進行第一次的電話訪談。訪談的494人中其平均年齡為61.7±12.4歲,有53%是男性,47%是女性。換藥前、換藥後2至4週、12週和24週,病人的血壓值分別為143.3/86.1, 140.8/84.1, 137.9/82.9和137.0/82.6 mmHg,和換藥前比較具有明顯的差異(p<0.01)。病人達到目標血壓值的人數及其比率,換藥前是142人(37%),換藥後2至4週是142人(37%),換藥後12週是160人(41%),和換藥前比較並沒有明顯差異,而換藥後24週是182人(47%),和換藥前比較具有顯著差異(p<0.01)。產生副作用的比率在藥品替代之後2至4週、12週和24週分別為103人(21%),26人(6%)和4人(1%),換藥後12週及24週的副作用發生率和換藥後2至4週比較,有明顯降低(p<0.001),而換藥後24週的副作用發生率和12週比較,也有明顯降低(p=0.001),故三次病人產生的副作用發生率明顯減少。然而,有68人(15%)由於副作用或血壓控制不滿意停用candesartan,換成其他降血壓藥治療。藥品替代之後2至4週、12週和24週的滿意度分別為494位病人中有428人(87%)滿意、425位病人中有400人(94%)滿意和389位病人中有378人(97%)滿意,三組之間的滿意度並沒有顯著差異。 結論:本研究納入494位病人,其中有389人(79%)完成三次評估,約八成的病人持續使用candesartan至少六個月以上,而且有更好的降血壓效果,大多數的副作用是在病人換藥後2至4週產生,隨著藥品使用時間的延長而自行緩解,並沒有產生任何嚴重的不良反應,符合臨床上藥品有效性和安全性的要求,而且近九成的病人滿意candesartan的治療結果,顯示candesartan適合作為其他血管收縮素接受器阻斷劑治療高血壓的替代藥品。
英文摘要 Objective: To evaluate clinical outcomes of subjects whose therapy was converted from other ARBs to candesartan, determine the efficacy and safety of candesartan in patients with hypertension, and patients’ satisfaction. Efficacy analysis was the changes in blood pressure and number of patients meeting their goal blood pressure before and after therapeutic interchange. Safety analysis was to evaluate if patients have side effects or severe adverse drug reaction. Methods: A non-randomized, open-labeled and self-controlled study. All eligible outpatients taking candesartan entered into the study from August 2004 to November 2004. After converting to candesartan, baseline and blood pressure during 2 to 4-week, 12-week and 24-week clinic visits were compared to assess efficacy. The rate of subjects attaining blood pressure goal after conversion were compared to baseline. Side effects were followed up by telephone interview at 2 to 4, 12 and 24 weeks. Patients’ satisfaction with outcome of therapeutic interchange was assessed. The values of blood pressure and side effects were recorded and collected. Results: Eligible outpatients were 586 patients, and 494 patients were enrolled in the study and completed the first evaluation by telephone interview. The 494 interviewed patients had a mean age of 61.7 ± 12.4 years, 53% were male and 47% were female. Mean baseline blood pressure, 2 to 4 - week, 12 - week, and 24 - week after drug conversion were 143.3/86.1, 140.8/84.1, 137.9/82.9, and 137.0/82.6 mmHg, respectively(p<0.01 vs. baseline). The rate of subjects achieving blood pressure goal were 142(37%)at baseline, 142(37%)at 2 to 4 weeks, and 160(41%)at 12 weeks(p values no significant difference vs. baseline)and 182(47%)at 24 weeks(p< 0.01 vs. baseline), respectively. The incidence of side effects at 2 to 4 weeks, 12 weeks and 24 weeks were 21%(n=103), 6%(n=26), and 1%(n=4), respectively(p<0.001 vs. 2 to 4 weeks, p=0.001 vs. 12 weeks). Sixty-eight(15% of all subjects)discontinued candesartan due to side effects or unsatisfying blood pressure. Patients’ satisfaction at 2 to 4, 12, and 24 weeks were 428(87%) of the 494 patients, 400(94%)of the 425 patients and 378(97%)of the 389 patients, respectively(P>0.05 vs. 2 to 4 weeks). Conclusions: There were 494 patients enrolled in the study and 389 (79%)patients completed the study. Patients who can tolerate the conversion from ARBs to candesartan at least six months achieved better blood pressure control. Most side effects appeared during 2 to 4 weeks and resolved steadily with time, and no serious adverse drug reactions happened. Approximately 90 percentages of patients were satisfied with clinical outcomes of therapeutic interchange. Candesartan is an appropriate substitution for other angiotensin Ⅱ receptor blockers.
論文目次 內容目錄 Ⅰ 表目錄 Ⅲ 圖目錄 Ⅴ 附錄目錄 Ⅵ 中文摘要 Ⅶ Abstract Ⅸ 第一章 前言 1 第二章 文獻回顧 4 第一節 高血壓簡介 4 第二節 相同療效藥品替代 8 第三節 Angiotensin II receptor blockers (ARBs) 23 第四節 Candesartan cilexetil (Blopress?)的介紹 27 第三章 研究目的 44 第四章 研究方法 45 第一節 研究設計 45 第二節 研究對象 45 第三節 研究過程 46 第四節 研究資料收集 48 第五節 資料處理與統計分析 51 第五章 研究結果 53 第一節 研究對象基本資料 55 第二節 臨床結果 61 第三節 病人換藥分析 73 第六章 討論 75 第一節 研究對象 75 第二節 相同療效藥品替代的研究 77 第三節 療效評估 77 第四節 安全性評估 82 第五節 滿意度評估 90 第六節 研究限制 92 第七章 結論 94 參考文獻 95 附錄一 血管收縮素接受器阻斷劑的相同療效藥品替代 104 附錄二 電話訪談內容 105 附錄三 Candesartan副作用記錄表 106
參考文獻 1. Compton A. Pharmacy practice issues: Therapeutic Interchange. In: Dipiro JT. Encyclopedia of Clinical Pharmacy, 2003:860-868. 2. Saffel D. Outcomes Based Therapeutic Interchange: An ACE Inhibitor Interchange Program. Consult Pharm 1999;14:65-71. 3. Guidelines for therapeutic interchange. American College of Clinical Pharmacy. Pharmacotherapy 1993;13(3):252-6. 4. Carroll NV. Formularies and therapeutic interchange: the health care setting makes a difference. Am J Health Syst Pharm 1999;56(5):467-72. 5. Guidelines for Implementing Therapeutic Interchange in Long-Term Care. American Society of Consultant Pharmacists. 1997. http://www.ascp.com/public/pr/guidelines/therapeutic.shtml 6. Schachtner JM, Guharoy R, Medicis JJ, Newman N, Speizer R. Prevalence and cost savings of therapeutic interchange among U.S. hospitals. Am J Health Syst Pharm 2002;59(6):529-33. 7.中央健康保險局http://www.nhi.gov.tw/ 8.行政院衛生署國民健康局http://www.bhp.doh.gov.tw/BHP/do/chinese/home 9. Gainor C. Pharmacologic and liability considerations of therapeutic interchange with low-molecular-weight heparins. Hospital Pharmacy 2003;38:652-8. 10. Chobanian AV, Bakris GL, Black HR, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA 2003;289(19):2560-72. 11. AMA policy on drug formularies and therapeutic interchange in inpatient and ambulatory patient care settings. American Medical Association. Am J Hosp Pharm 1994;51(14):1808-10. 12. Tran F, Boggie DT, Delattre ML, Schaefer MG, Morreale AP, Plowman BK. Therapeutic interchange involving replacement of rofecoxib or celecoxib with valdecoxib. Am J Health Syst Pharm 2004;61(13):1391-4. 13. Steiner MA, Yorgason RZ, Vermeulen LC, Theisen J. Patient outcomes after therapeutic interchange of dolasetron for granisetron. Am J Health Syst Pharm 2003;60(10):1023-8. 14. Sodorff MM, Galt KA, Galt MA, Turner PD, Lambrecht JE. Patient perceptions of a proton pump inhibitor therapeutic interchange program across the continuum of care. Pharmacotherapy 2002;22(4):500-12. 15. Lomaestro BM. Therapeutic interchange of fluoroquinolones at a medical center. Am J Health Syst Pharm 2001;58(10):904-7. 16. Condra LJ, Morreale AP, Stolley SN, Marcus D. Assessment of patient satisfaction with a formulary switch from omeprazole to lansoprazole in gastroesophageal reflux disease maintenance therapy. Am J Manag Care 1999;5(5):631-8. 17. Grace KA, Swiecki J, Hyatt R, et al. Implementation of a therapeutic-interchange clinic for HMG-CoA reductase inhibitors. Am J Health Syst Pharm 2002;59(11):1077-82. 18. Hilleman DE, Wurdeman RL, Lenz TL. Therapeutic change of HMG-CoA reductase inhibitors in patients with coronary artery disease. Pharmacotherapy 2001;21(4):410-5. 19. Ito MK, Lin JC, Morreale AP, et al. Effect of pravastatin-to-simvastatin conversion on low-density-lipoprotein cholesterol. Am J Health Syst Pharm 2001;58(18):1734-9. 20. Taylor AJ, Grace K, Swiecki J, et al. Lipid-lowering efficacy, safety, and costs of a large-scale therapeutic statin formulary conversion program. Pharmacotherapy 2001;21(9):1130-9. 21. Patel RJ, Gray DR, Pierce R, Jafari M. Impact of therapeutic interchange from pravastatin to lovastatin in a Veterans Affairs Medical Center. Am J Manag Care 1999;5(4):465-74. 22. Hilleman DE, Reyes AP, Wurdeman RL, Faulkner M. Efficacy and safety of a therapeutic interchange from high-dose calcium channel blockers to a fixed-dose combination of amlodipine/benazepril in patients with moderate-to-severe hypertension. J Hum Hypertens 2001;15(8):559-65. 23. Clay DR, Bourg MP, Lawrence DB. Outcomes of an amlodipine-to-felodipine therapeutic interchange program. Am J Health Syst Pharm 2000;57(17):1604-7. 24. Walters JP, Noel HANPP, Folstad JP, Kapadia VP, White CMP. Prospective Evaluation of the Therapeutic Interchange of Felodipine ER for Amlodipine in Patients With Hypertension. Hospital Pharmacy 2000;35(1):48-51. 25. Hilleman DE. Outcomes and cost savings of an ACE inhibiotr therapeutic interchange. J Managed Care Pharm 1997;3:219-23. 26. Graham MR, Allcock NM. Irbesartan substitution for valsartan or losartan in treating hypertension. Annals of Pharmacotherapy 2002;36(12):1840-4. 27. Porcellati C, Omboni S. Switching from ACE inhibitors, beta-blockers, calcium antagonists or diuretics to candesartan improves efficacy and tolerability. Blood Press 2002;11(5):310-9. 28. Wurdeman RL, Mooss AN, Mohiuddin SM, Lucas BD, Jr., Ryschon KL, Hilleman DE. Comparison of 24-hour ambulatory blood pressure data in hypertensive patients switched from nifedipine-GITS to nifedipine-CC. Pharmacotherapy 1999;19(1):94-100. 29. Rodgers JE, Patterson JH. Angiotensin II-receptor blockers: clinical relevance and therapeutic role. Am J Health Syst Pharm 2001;58(8):671-83. 30. Mimran A, Ribstein J. Angiotensin receptor blockers: pharmacology and clinical significance. J Am Soc Nephrol 1999;10 Suppl 12:S273-7. 31. Burnier M, Maillard M. The comparative pharmacology of angiotensin II receptor antagonists. Blood Press Suppl 2001;1:6-11. 32. Burnier M. Angiotensin II type 1 receptor blockers. Circulation 2001;103(6):904-12. 33. Song JC, White CM. Pharmacologic, pharmacokinetic, and therapeutic differences among angiotensin II receptor antagonists. Pharmacotherapy 2000;20(2):130-9. 34. Unger T. Differences among angiotensin II type 1 receptor blockers: characteristics of candesartan cilexetil. Blood Press Suppl 2000;1:14-8. 35. Nishikawa K, Naka T, Chatani F, Yoshimura Y. Candesartan cilexetil: a review of its preclinical pharmacology. J Hum Hypertens 1997;11 Suppl 2:S9-17. 36. See S, Stirling AL. Candesartan cilexetil: an angiotensin II-receptor blocker. Am J Health Syst Pharm 2000;57(8):739-46. 37. Easthope SE, Jarvis B. Candesartan cilexetil: an update of its use in essential hypertension. Drugs 2002;62(8):1253-87. 38. Stoukides CA, McVoy HJ, Kaul AF. Candesartan cilexetil: an angiotensin II receptor blocker. Ann Pharmacother 1999;33(12):1287-98. 39. Gleiter CH, Morike KE. Clinical pharmacokinetics of candesartan. Clin Pharmacokinet 2002;41(1):7-17. 40. Gavras H. Update on the clinical pharmacology of candesartan cilexetil. Am J Hypertens 2000;13(1 Pt 2):25S-30S. 41. Elmfeldt D, George M, Hubner R, Olofsson B. Candesartan cilexetil, a new generation angiotensin II antagonist, provides dose dependent antihypertensive effect. J Hum Hypertens 1997;11 Suppl 2:S49-53. 42. Sever P. Candesartan cilexetil: a new, long-acting, effective angiotensin II type 1 receptor blocker. J Hum Hypertens 1997;11 Suppl 2:S91-5. 43. Bell TP, DeQuattro V, Lasseter KC, et al. Effective dose range of candesartan cilexetil for systemic hypertension. Candesartan Cilexetil Study Investigators. Am J Cardiol 1999;83(2):272-5, A6. 44. Reif M, White WB, Fagan TC, et al. Effects of candesartan cilexetil in patients with systemic hypertension. Candesartan Cilexetil Study Investigators. Am J Cardiol 1998;82(8):961-5. 45. Meredith PA. Clinical comparative trials of angiotensin II type 1 (AT1)-receptor blockers. Blood Press Suppl 2001(3):11-7. 46. Meredith P. Achieving quality 24-h blood pressure control with candesartan cilexetil. Blood Press Suppl 2000;1:23-6. 47. Heuer HJ, Schondorfer G, Hogemann AM. Twenty-four hour blood pressure profile of different doses of candesartan cilexetil in patients with mild to moderate hypertension. J Hum Hypertens 1997;11 Suppl 2:S55-6. 48. Sever PS. Key features of candesartan cilexetil and a comparison with other angiotensin II receptor antagonists. J Hum Hypertens 1999;13 Suppl 1:S3-10; discussion S33-4. 49. Andersson OK, Neldam S. The antihypertensive effect and tolerability of candesartan cilexetil, a new generation angiotensin II antagonist, in comparison with losartan. Blood Press 1998;7(1):53-9. 50. Andersson OK, Neldam S. A comparison of the antihypertensive effects of candesartan cilexetil and losartan in patients with mild to moderate hypertension. J Hum Hypertens 1997;11 Suppl 2:S63-4. 51. Cuspidi C, Muiesan ML, Valagussa L, et al. Comparative effects of candesartan and enalapril on left ventricular hypertrophy in patients with essential hypertension: the candesartan assessment in the treatment of cardiac hypertrophy (CATCH) study. J Hypertens 2002;20(11):2293-300. 52. Zanchetti A, Omboni S. Comparison of candesartan versus enalapril in essential hypertension. Italian Candesartan Study Group. Am J Hypertens 2001;14(2):129-34. 53. Ogihara T, Arakawa K. Clinical efficacy and tolerability of candesartan cilexetil. Candesartan Study Groups in Japan. J Hum Hypertens 1999;13 Suppl 1:S27-31; discussion S33-4. 54. Franke H. Antihypertensive effects of candesartan cilexetil, enalapril and placebo. J Hum Hypertens 1997;11 Suppl 2:S61-2. 55. Zanchetti A, Omboni S, Di Biagio C. Candesartan cilexetil and enalapril are of equivalent efficacy in patients with mild to moderate hypertension. J Hum Hypertens 1997;11 Suppl 2:S57-9. 56. Sever P, Holzgreve H. Long-term efficacy and tolerability of candesartan cilexetil in patients with mild to moderate hypertension. J Hum Hypertens 1997;11 Suppl 2:S69-73. 57. McInnes GT, O'Kane KP, Jonker J, Roth J. The efficacy and tolerability of candesartan cilexetil in an elderly hypertensive population. J Hum Hypertens 1997;11 Suppl 2:S75-80. 58. Belcher G, Hubner R, George M, Elmfeldt D, Lunde H. Candesartan cilexetil: safety and tolerability in healthy volunteers and patients with hypertension. J Hum Hypertens 1997;11 Suppl 2:S85-9. 59. Elmfeldt D, Olofsson B, Meredith P. The relationships between dose and antihypertensive effect of four AT1-receptor blockers. Differences in potency and efficacy. Blood Press 2002;11(5):293-301. 60. Yamamoto S, Kawashima T, Kunitake T, Koide S, Fujimoto H. The effects of replacing dihydropyridine calcium-channel blockers with angiotensin II receptor blocker on the quality of life of hypertensive patients. Blood Press Suppl 2003;2:22-8. 61. Ostergren J. Candesartan for the treatment of hypertension and heart failure. Expert Opin Pharmacother 2004;5(7):1589-97. 62. Pfeffer MA, Swedberg K, Granger CB, et al. Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme. Lancet 2003;362(9386):759-66. 63. McMurray JJ, Ostergren J, Swedberg K, et al. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors: the CHARM-Added trial. Lancet 2003;362(9386):767-71. 64. Granger CB, McMurray JJ, Yusuf S, et al. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARM-Alternative trial. Lancet 2003;362(9386):772-6. 65. Yusuf S, Pfeffer MA, Swedberg K, et al. Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved Trial. Lancet 2003;362(9386):777-81. 66. Smith KS, Briceland LL, Nightingale CH, Quintiliani R. Formulary conversion of cefoxitin usage to cefotetan: experience at a large teaching hospital. Dicp 1989;23(12):1024-30. 67. Martinusen S, Chen D, Frighetto L, Bunz D, Stiver HG, Jewesson PJ. Comparison of cefoxitin and ceftizoxime in a hospital therapeutic interchange program. Cmaj 1993;148(7):1161-9. 68. Goldwater SH, Milkovich G, Morrison AJ, Jr., Lindgren B. Comparison of therapeutic interchange with standard educational tools for influencing fluoroquinolone prescribing. Am J Health Syst Pharm 2001;58(18):1740-5. 69. Fudge KA, Moore KA, Schneider DN, Sherrin TP, Wellman GS. Change in prescribing patterns of intravenous histamine2-receptor antagonists results in significant cost savings without adversely affecting patient care. Ann Pharmacother 1993;27(2):232-7. 70. Chase SL, Peterson AM, Wordell CJ. Therapeutic-interchange program for oral histamine H2-receptor antagonists. Am J Health Syst Pharm 1998;55(13):1382-6. 71. Kinnon AL, Bourne J, Blizzard S. Outcome analysis of a formulary transition from nifedipine at a Veterans Affairs Medical Center. J Managed Care Pharm 1999;5:425-8. 72. Gustin G, White WB, Taylor S, Daragjati C. Clinical outcome of a mandatory formulary switch for dihydropyridine calcium channel blocker therapy at a Veteran's Administration Medical Center. Am J Hypertens 1996;9(4 Pt 1):312-6. 73. Nadel HL. Formulary conversion from glipizide to glyburide: A cost-minimization analysis. Hospital Pharmacy 1995;30:467-469;472-474. 74. Whalen CR, Watson TL, Baize T, Ball A. Formulary management of colony-stimulating factors. Am J Health Syst Pharm 2002;59(7 Suppl 2):S21-7. 75. Stock AJ, Kofoed L. Therapeutic interchange of fluoxetine and sertraline: experience in the clinical setting. Am J Hosp Pharm 1994;51(18):2279-81. 76. Michel MC, Bohner H, Koster J, Schafers R, Heemann U. Safety of telmisartan in patients with arterial hypertension: an open-label observational study. Drug Saf 2004;27(5):335-44. 77. Neutel JM. Safety and efficacy of angiotensin II receptor antagonists. Am J Cardiol 1999;84(2A):13K-17K. 78. Simon TA, Gelarden RT, Freitag SA, Kassler-Taub KB, Davies R. Safety of irbesartan in the treatment of mild to moderate systemic hypertension. Am J Cardiol 1998;82(2):179-82. 79. Oparil S, Dyke S, Harris F, et al. The efficacy and safety of valsartan compared with placebo in the treatment of patients with essential hypertension. Clin Ther 1996;18(5):797-810. 80. Goldberg AI, Dunlay MC, Sweet CS. Safety and tolerability of losartan potassium, an angiotensin II receptor antagonist, compared with hydrochlorothiazide, atenolol, felodipine ER, and angiotensin-converting enzyme inhibitors for the treatment of systemic hypertension. Am J Cardiol 1995;75(12):793-5.
論文全文使用權限
  • 不同意授權瀏覽/列印電子全文服務。


  • 若您有任何疑問,請與我們聯絡!
    臺北醫學大學 圖書館 簡莉婷
    E-mail:etds@tmu.edu.tw
    Tel:(02) 2736-1661 ext.2519
    Fax:(02) 2737-5446