Preview

Современная ревматология

Расширенный поиск

КЛИНИЧЕСКИЕ РЕКОМЕНДАЦИИ «Рациональное применение нестероидных противовоспалительных препаратов (НПВП) в клинической практике»

https://doi.org/10.14412/1996-7012-2015-1-4-23

Аннотация

Представлена новая редакция клинических рекомендаций «Рациональное применение нестероидных противовоспалительных препаратов (НПВП) в клинической практике», подготовленных Ассоциацией ревматологов России, Российским обществом по изучению боли, Российской гастроэнтерологической ассоциацией, Российским кардиологическим обществом, Ассоциацией травматологов-ортопедов России, Ассоциацией междисциплинарной медицины, Российской ассоциацией паллиативной медицины. В нашей стране НПВП являются важнейшим и наиболее популярным классом анальгетиков. В отличие от мировой практики российские врачи достаточно редко рекомендуют парацетамол как препарат «первой линии» для купирования умеренной или сильной боли, отдавая предпочтение НПВП; использование опиоидных анальгетиков при неонкологических заболеваниях сведено к минимуму из-за жестких ограничений.

НПВП эффективны и удобны в использовании, однако они далеко не безопасны – прием этих препаратов в ряде случаев может приводить к развитию серьезных осложнений со стороны желудочно-кишечного тракта, сердечно-сосудистой системы, почек и др. Поэтому применение НПВП должно включать обязательный контроль нежелательных реакций, а выбор конкретного препарата для каждого клинического случая должен основываться на объективной оценке соотношения его эффективности и безопасности. В последние годы опубликованы свежие данные об использовании НПВП при различных заболеваниях, а на российском фармакологическом рынке появилось несколько новых представителей этой лекарственной группы.

Все это определило необходимость создания новой редакции рекомендаций по рациональному использованию НПВП. Они основаны на положениях, имеющих высокий уровень доказательности и подтвержденных результатами хорошо организованных клинических и масштабных популяционных исследований, а также их метаанализом. Рекомендации предназначены для врачей всех специальностей.

 

Об авторах

А. Е. Каратеев
ФГБНУ НИИР им. В.А. Насоновой
Россия

д.м.н., заведующий лабораторией гастроэнтерологических проблем у пациентов с ревматическими заболеваниями,

115522, Москва, Каширское шоссе, 34А



Е. Л. Насонов
ФГБНУ НИИР им. В.А. Насоновой; Ассоциация ревматологов России
Россия

академик РАН, д.м.н., профессор, директор,

115522, Москва, Каширское шоссе, 34А;

президент



Н. Н. Яхно
ГБОУ ВПО «Первый МГМУ им. И.М. Сеченова» Минздрава России; Российское общество по изучению боли
Россия

академик РАМН, д.м.н., профессор, заведующий научно-исследовательским отделом неврологии НИЦ, профессор кафедры нервных болезней и нейрохирургии лечебного факультета, директор Научно-образовательного клинического центра неврологии,

119991, Москва, ул. Трубецкая, 8, стр. 2;

президент,

Москва, Россия



В. Т. Ивашкин
ГБОУ ВПО «Первый МГМУ им. И.М. Сеченова» Минздрава России; Российская гастроэнтерологическая ассоциация
Россия

академик РАН, д.м.н., профессор, заведующий кафедрой пропедевтики внутренних болезней, директор Клиники пропедевтики внутренних болезней, гастроэнтерологии и гепатологии им. В.Х. Василенко,

119991, Москва, ул. Трубецкая, 8, стр. 2;

президент,

 Москва, Россия



Н. В. Чичасова
ИПО ГБОУ ВПО «Первый МГМУ им. И.М. Сеченова» Минздрава России
Россия

д.м.н., профессор кафедры ревматологии,

119991, Москва, ул. Трубецкая, 8, стр. 2



Л. И. Алексеева
ФГБНУ НИИР им. В.А. Насоновой
Россия

д.м.н., руководитель отдела метаболических заболеваний костей и суставов c центром профилактики остеопороза Минздрава России,

115522, Москва, Каширское шоссе,



Ю. А. Карпов
ФГБНУ «Российский кардиологический научно-производственный комплекс» Минздрава России; Российское кардиологическое общество
Россия

д.м.н., профессор, первый заместитель гене- рального директора, заместитель генерального директора по науке,

121552, Москва, ул. 3-я Черепковская, 15А;

вице-президент,

Москва, Россия



М. А. Евсеев
ГБУ «Городская клиническая больница №52» ДЗ Москвы
Россия

д.м.н., профессор, заведующий 2-м хирургическим отделением,

 123182, Москва, ул. Пехотная, 3



М. Л. Кукушкин
ФГБНУ «НИИ общей патологии и патофизиологии»; Российское общество по изучению боли
Россия

д.м.н., профессор, руководитель лаборато- рии фундаментальных и прикладных проблем боли,

 125315, Москва, ул. Балтийская, 8;

ответственный секретарь,

Москва, Россия



А. Б. Данилов
ИПО ГБОУ ВПО «Первый МГМУ им. И.М. Сеченова» Минздрава России
Россия

д.м.н., профессор кафедры нервных болезней,

119991, Москва, ул. Трубецкая, 8, стр. 2



О. В. Воробьева
ИПО ГБОУ ВПО «Первый МГМУ им. И.М. Сеченова» Минздрава России
Россия

д.м.н. профессор кафедры нервных болезней,

119991, Москва, ул. Трубецкая, 8, стр. 2



А. В. Амелин
ГБОУ ВПО «Санкт-Петербургский государственный медицинский университет им. И.П. Павлова» Минздрава России; Институт фармакологии им. А.В. Вальдмана
Россия

д.м.н., профессор кафедры неврологии и нейро- хирургии с клиникой,

197022, Санкт-Петербург, ул. Льва Толстого, 6/8

заведующий лабораторией нейрофизиологии и фармакологии боли,

Санкт-Петербург, Россия 



Д. С. Новикова
ФГБНУ НИИР им. В.А. Насоновой
Россия

д.м.н., ведущий научный сотрудник лаборатории инструментальной и ультразвуковой диагностики,

115522, Москва, Каширское шоссе, 34А



О. М. Драпкина
ГБОУ ВПО «Первый МГМУ им. И.М. Сеченова» Минздрава России
Россия

д.м.н., профессор кафедры пропедевтики внутренних болезней,

119991, Москва, ул. Трубецкая, 8, стр. 2



С. С. Копенкин
ГБОУ ВПО «РНИМУ им. Н.И. Пирогова» Минздрава России
Россия

к.м.н., доцент кафедры травматологии, ортопедии и военно-полевой хирургии,

 117997, Москва, ул. Островитянова, 1



Г. Р. Абузарова
Центр паллиативной помощи онкологическим больным при ФГБНУ «МНИОИ им. П.А. Герцена» Минздрава России
Россия

д.м.н., руководитель Центра,

125284, Москва, 2-й Боткинский проезд, 3



Литература

1. Шостак НА, Рябкова АА, Савельев ВС, Малярова ЛН. Желудочно-кишечное кровотечение как осложнение гастропатий, связанных с приемом нестероидных противовоспалительных препаратов. Терапевтический архив. 2003;(5):70–4. [Shostak NA, Ryabkova AA, Savel'ev VS, Malyarova LN. Gastrointestinal bleeding as a complication of gastropathy associated with use of nonsteroidal anti-inflammatory drugs. Terapevticheskii arkhiv. 2003;(5):70–4. (In Russ.)].

2. Евсеев МА. НПВП-индуцированные гастродуоденальные язвы, осложненные кровотечением. Русский медицинский журнал. 2006;(15):1099–107. [Evseev MA. NSAID-induced gastroduodenal ulcer complicated by bleeding. Russkii meditsinskii zhurnal. 2006;(15):1099–107. (In Russ.)].

3. Гельфанд БР, Проценко ДН, Бабаянц АВ, Каратеев АЕ. Острые кровотечения из верхних отделов желудочно-кишечного тракта: от эпидемиологии до формирования концепции консервативной терапии. Инфекции в хирургии. 2013;(4):11–7. [Gel'fand BR, Protsenko DN, Babayants AV, Karateev AE. Severe bleeding from the upper parts of the gastrointestinal tract: from epidemiology to the formation of the concept of conservative therapy. Infektsii v khirurgii. 2013;(4):11–7. (in Russ.)].

4. Harirforoosh S, Asghar W, Jamali F. Adverse Effects of Nonsteroidal Antiinflammatory Drugs: An Update of Gastrointestinal, Cardiovascular and Renal Complications. J Pharm Pharm Sci. 2013;16(5):821–47.

5. Lee C, Straus WL, Balshaw R, et al. A comparison of the efficacy and safety of nonsteroidal antiinflammatory agents versus acetaminophen in the treatment of osteoarthritis: a meta-analysis. Arthritis Rheum. 2004 Oct 15;51(5):746–54.

6. Chen YF, Jobanputra P, Barton P, et al. Cyclooxygenase-2 selective nonsteroidal antiinflammatory drugs (etodolac, meloxicam, celecoxib, rofecoxib, etoricoxib, valdecoxib and lumiracoxib) for osteoarthritis and rheumatoid arthritis: a systematic review and economic evaluation. Health Technol Assess. 2008 Apr;12(11):1–278, iii.

7. Stam W, Jansen J, Taylor S. Efficacy of etoricoxib, celecoxib, lumiracoxib, nonselective NSAIDs, and acetaminophen in osteoarthritis: a mixed treatment comparison. Open Rheumatol J. 2012;6:6–20. doi: 10.2174/1874312901206010006. Epub 2012 Apr 3.

8. Sieper J, Klopsch T, Richter M, et al. Comparison of two different dosages of celecoxib with diclofenac for the treatment of active ankylosing spondylitis: results of a 12-week randomised, double-blind, controlled study. Ann Rheum Dis. 2008 Mar;67(3):323–9. Epub 2007 Jul 6.

9. Roelofs PD, Deyo RA, Koes BW, Scholten RJ, van Tulder MW. Nonsteroidal anti-inflammatory drugs for low back pain. Cochrane Database Syst Rev. 2008 Jan 23;(1):CD000396. doi: 10.1002/14651858.CD000396.pub3.

10. Derry S, Moore RA. Single dose oral celecoxib for acute postoperative pain in adults. Cochrane Database Syst Rev. 2013 Oct 22;10:CD004233. doi: 10.1002/14651858.CD004233.pub4.

11. Moore RA, Derry S, McQuay HJ. Discontinuation rates in clinical trials in musculoskeletal pain: meta-analysis from etoricoxib clinical trial reports. Arthritis Res Ther. 2008;10(3):R53. doi: 10.1186/ar2422. Epub 2008 May 8.

12. Combe B, Velicitat P, Garzon N, Bluhmki E. Comparison of intramuscular and oral meloxicam in rheumatoid arthritis patients. Inflamm Res. 2001 Mar;50 Suppl 1:S10–6.

13. Neighbor ML, Puntillo KA. Intramuscular ketorolac vs oral ibuprofen in emergency department patients with acute pain. Acad Emerg Med. 1998 Feb;5(2):118–22.

14. Shrestha M, Morgan DL, Moreden JM, et al. Randomized double-blind comparison of the analgesic efficacy of intramuscular ketorolac and oral indomethacin in the treatment of acute gouty arthritis. Ann Emerg Med. 1995 Dec;26(6):682–6.

15. Tramer MR, Williams JE, Carroll D, et al. Comparing analgesic efficacy of nonsteroidal anti-inflammatory drugs given by different routes in acute and chronic pain: a qualitative systematic review. Acta Anaesthesiol Scand. 1998; 42(1):71–9.

16. Orlando A, Marrone C, Nicoli N, et al. Fatal necrotising fasciitis associated with intramuscular injection of nonsteroidal antiinflammatory drugs after uncomplicated endoscopic polypectomy. J Infect. 2007 Mar;54(3):e145–8. Epub 2006 Oct 17.

17. Verfaillie G, Knape S, Corne L. A case of fatal necrotizing fasciitis after intramuscular administration of diclofenac. Eur J Emerg Med. 2002 Sep;9 (3):270–3.

18. Rossi L, Conen D. Intramuscular injections-an outdated form of administration? 6 cases of Staphylococcus aureus sepsis following intramuscular injections. [Article in German]. Schweiz Med Wochenschr. 1995 Aug 8;125(31–32):1477–82.

19. Rotman-Pikielny P, Levy Y, Eyal A, Shoenfeld Y. Pyomyositis or «injectiositis»–Staphylococcus aureus multiple abscesses following intramuscular injections. Isr Med Assoc J. 2003 Apr;5(4):295–6.

20. Frick S, Cerny A. Necrotizing fasciitis due to Streptococcus pneumoniae after intramuscular injection of nonsteroidal antiinflammatory drugs: report of 2 cases and review. Clin Infect Dis. 2001 Sep 1;33(5):740–4. Epub 2001 Aug 6.

21. Bjordal J, Klovning A, Ljunggren A, Slordal L. Short-term efficacy of pharmacotherapeutic interventions in osteoarthritic knee pain: A meta-analysis of randomised placebo-controlled trials. Eur J Pain. 2007 Feb;11(2):125–38. Epub 2006 May 8.

22. Pincus T, Koch G, Lei H, et al. Patient Preference for Placebo, Acetaminophen (paracetamol) or Celecoxib Efficacy Studies (PACES): two randomised, double blind, placebo controlled, crossover clinical trials in patients with knee or hip osteoarthritis. Ann Rheum Dis. 2004 Aug;63(8):931–9. Epub 2004 Apr 13.

23. Daniels SE, Bandy DP, Christensen SE, et al. Evaluation of the dose range of etoricoxib in an acute pain setting using the postoperative dental pain model. Clin J Pain. 2011 Jan;27(1):1–8.

24. DeLemos B, Xiang J, Benson C, et al. Tramadol hydrochloride extended-release once-daily in the treatment of osteoarthritis of the knee and/or hip: a double-blind, randomized, dose-ranging trial. Am J Ther. 2011 May;18(3):216–26. doi: 10.1097/MJT.0b013e3181cec307.

25. Innes G, Croskerry P, Worthington J, et al. Ketorolac versus acetaminophencodeine in the emergency department treatment of acute low back pain. J Emerg Med. 1998 Jul–Aug;16(4):549–56.

26. O'Donnell JB, Ekman EF, Spalding WM, et al. The effectiveness of a weak opioid medication versus a cyclo-oxygenase-2 (COX-2) selective nonsteroidal anti-inflammatory drug in treating flare-up of chronic low-back pain: results from two randomized, double-blind, 6-week studies. J Int Med Res. 2009 Nov–Dec;37(6):1789–802.

27. Кукушкин МЛ. Алгоритмы диагностики и лечения боли в спине. Русский медицинский журнал. 2014;(11):844–48. [Kukushkin ML. Algorithms for diagnosis and treatment of back pain. Russkii meditsinskii zhurnal. 2014;(11):844–48. (In Russ.).]

28. Malanga G, Wolff E. Evidence-informed management of chronic low back pain with nonsteroidal anti-inflammatory drugs, muscle relaxants, and simple analgesics. Spine J. 2008 Jan–Feb;8(1):173–84. doi: 10.1016/j.spinee.2007.10.013.

29. Kuritzky L, Samraj GP. Nonsteroidal anti-inflammatory drugs in the treatment of low back pain. J Pain Res. 2012;5:579–90. doi: 10.2147/JPR.S6775. Epub 2012 Nov 28.

30. White AP, Arnold PM, Norvell DC, et al. Pharmacologic management of chronic low back pain: synthesis of the evidence. Spine (Phila Pa 1976). 2011 Oct 1;36(21 Suppl):S131–43. doi: 10.1097/BRS.0b013e31822f178f.

31. De Oliveira GS Jr, Agarwal D, Benzon HT. Perioperative single dose ketorolac to prevent postoperative pain: a metaanalysis of randomized trials. Anesth Analg. 2012 Feb;114(2):424–33. doi: 10.1213/ANE.0b013e3182334d68. Epub 2011 Sep 29.

32. Cepeda MS, Carr DB, Miranda N, et al. Comparison of morphine, ketorolac, and their combination for postoperative pain: results from a large, randomized, doubleblind trial. Anesthesiology. 2005 Dec;103(6):1225–32.

33. McDaid C, Maund E, Rice S, et al. Paracetamol and selective and nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) for the reduction of morphinerelated side effects after major surgery: a systematic review. Health Technol Assess. 2010 Mar;14(17):1–153, iii-iv. doi: 10.3310/hta14170.

34. Vardy J, Agar M. Nonopioid drugs in the treatment of cancer pain. J Clin Oncol. 2014 Jun 1;32(16):1677–90. doi: 10.1200/JCO.2013.52.8356. Epub 2014 May 5.

35. Rodriguez MJ, Contreras D, Galvez R, et al. Double-blind evaluation of short-term analgesic efficacy of orally administered dexketoprofen trometamol and ketorolac in bone cancer pain. Pain. 2003 Jul;104(1–2):103–10.

36. Mercadante S, Fulfaro F, Casuccio A. A randomised controlled study on the use of anti-inflammatory drugs in patients with cancer pain on morphine therapy: effects on dose-escalation and a pharmacoeconomic analysis. Eur J Cancer. 2002 Jul;38(10):1358–63.

37. Pannuti F, Robustelli della Cuna G, Ventaffrida V, et al. A double-blind evaluation of the analgesic efficacy and toxicity of oral ketorolac and diclofenac in cancer pain. The TD/10 recordati Protocol Study Group. Tumori. 1999 Mar–Apr;85(2):96–100.

38. McNicol E, Strassels SA, Goudas L, et al. NSAIDS or paracetamol, alone or combined with opioids, for cancer pain. Cochrane Database Syst Rev. 2005 Jan 25;(1):CD005180.

39. Luyten FP, Geusens P, Malaise M, et al. A prospective randomised multicentre study comparing continuous and intermittent treatment with celecoxib in patients with osteoarthritis of the knee or hip. Ann Rheum Dis. 2007 Jan;66(1):99–106. Epub 2006 Jun 30.

40. Strand V, Simon LS, Dougados M, et al. Treatment of osteoarthritis with continuous versus intermittent celecoxib. J Rheumatol. 2011 Dec;38(12):2625–34. doi: 10.3899/jrheum.110636. Epub 2011 Nov 1.

41. Blachier M, Canoui-Poitrine F, Dougados M, et al. Factors associated with radiographic lesions in early axial spondyloarthritis. Results from the DESIR cohort. Rheumatology (Oxford). 2013 Sep;52(9):1686–93. doi: 10.1093/rheumatology/ket207. Epub 2013 Jun 13.

42. Poddubnyy D, van der Heijde D. Therapeutic controversies in spondyloarthritis: nonsteroidal anti-inflammatory drugs. Rheum Dis Clin North Am. 2012 Aug;38(3):601–11. doi: 10.1016/j.rdc.2012.08.005. Epub 2012 Sep 15.

43. Wanders A, Heijde Dv, Landewe R, et al. Nonsteroidal anti-inflammatory drugs reduce radiographic progression in patients with ankylosing spondylitis: a randomized clinical trial. Arthritis Rheum. 2005, 52(6):1756–1765.

44. Altman R., Barthel H. Topical therapies for osteoarthritis. Drugs. 2011 Jul 9;71(10):1259–79. doi: 10.2165/11592550-000000000-00000.

45. Baraf HS, Gloth FM, Barthel HR, et al. Safety and efficacy of topical diclofenac sodium gel for knee osteoarthritis in elderly and younger patients: pooled data from three randomized, double-blind, parallel-group, placebo-controlled, multicentre trials. Drugs Aging. 2011 Jan 1;28(1):27–40. doi: 10.2165/11584880-000000000-00000.

46. Derry S, Moore RA, Rabbie R. Topical NSAIDs for chronic muscoloskeletal pain in adults. Cochrane Database Syst Rev. 2012 Sep 12;9:CD007400. doi: 10.1002/14651858.CD007400.pub2.

47. Sostres C, Gargallo CJ, Lanas A. Nonsteroidal anti-inflammatory drugs and upper and lower gastrointestinal mucosal damage. Arthritis Res Ther. 2013;15 Suppl 3:S3. doi: 10.1186/ar4175. Epub 2013 Jul 24.

48. Lain L. Proton pump inhibitor co-therapy with nonsteroidal anti-inflammatory drugs – nice or necessary? Rev Gastroenterol Disord. 2004;4 Suppl 4:S33–41.

49. Fries JF, Murtagh KN, Bennett M, et al. The rise and decline of nonsteroidal antiinflammatory drag-associated gastropathy in rheumatoid arthritis. Arthritis Rheum. 2004 Aug;50(8):2433–40.

50. Brooks J, Warburton R, Beales IL. Prevention of upper gastrointestinal haemorrhage: current controversies and clinical guidance. Ther Adv Chronic Dis. 2013 Sep;4(5):206–22. doi:10.1177/2040622313492188.

51. Scheiman JM. The use of proton pump inhibitors in treating and preventing NSAIDinduced mucosal damage. Arthritis Res Ther. 2013;15 Suppl 3:S5. doi: 10.1186/ar4177. Epub 2013 Jul 24.

52. Maiden L, Thjodleifsson B, Seigal A, et al. Long-term effects of nonsteroidal antiinflammatory drugs and cyclooxygenase-2 selective agents on the small bowel: a crosssectional capsule enteroscopy study. Clin Gastroenterol Hepatol. 2007 Sep;5(9):1040–5. Epub 2007 Jul 10.

53. Adebayo D, Bjarnason I. Is nonsteroidal anti-inflammatory drug (NSAID) enteropathy clinically more important than NSAID gastropathy? Postgrad Med J. 2006 Mar;82(965):186–91.

54. Goldstein JL, Eisen GM, Lewis B. et al. Small bowel mucosal injury is reduced in healthy subjects treated with celecoxib compared with ibuprofen plus omeprazole, as assessed by video capsule endoscopy. Aliment Pharmacol Ther. 2007 May 15;25(10):1211–22.

55. Hawkey CJ, Ell C, Simon B, et al. Less small-bowel injury with lumiracoxib compared with naproxen plus omeprazole. Clin Gastroenterol Hepatol. 2008 May;6(5):536–44. doi: 10.1016/j.cgh.2007.12.023. Epub 2008 Jan 31.

56. Sands G, Shell B, Zhang R. Adverse events in patients with blood loss: a pooled analysis of 51 clinical studies from the celecoxib clinical trial database. Open Rheumatol J. 2012;6:44–9. doi: 10.2174/1874312901206010044. Epub 2012 May 11.

57. Mallen SR, Essex MN, Zhang R. Gastrointestinal tolerability of NSAIDs in elderly patients: a pooled analysis of 21 randomized clinical trials with celecoxib and nonselective NSAIDs. Curr Med Res Opin. 2011 Jul;27(7):1359–66. doi: 10.1185/03007995.2011.581274. Epub 2011 May 12.

58. Lanas A. A review of the gastrointestinal safety data – a gastroenterologist's perspective. Rheumatology (Oxford). 2010 May;49 Suppl 2:ii3–10. doi: 10.1093/rheumatology/keq058.

59. Насонов ЕЛ. Анальгетическая терапия в ревматологии: путешествие между Сциллой и Харибдой. Клиническая фармакология и терапия 2003;12(1):64–9. [Nasonov EL. Analgesic therapy in rheumatology: a journey between Scylla and Charybdis. Klinicheskaya farmakologiya i terapiya 2003;12(1):64–9. (In Russ.)].

60. Harris RC, Breyer MD. Update on Cyclooxygenase-2 Inhibitors. Clin J Am Soc Nephrol. 2006 Mar;1(2):236–45. Epub 2006 Feb 1.

61. Cheng HF Harris RC. Cyclooxygenases, the kidney, and hypertension. Hypertension. 2004 Mar;43(3):525–30. Epub 2004 Jan 19.

62. Singh G, Miller JD, Lee FH, et al. Pevalence of cardiovascular disease risk factors among US adults with self-reported osteoarthritis: data from the Third National Health and Nutrition Examination survey. Am J Manag Care. 2002 Oct;8(15 Suppl):S383–91.

63. Harley C, Wagner S. The prevalence of cardiovascular risk factors in parients prescribing anti-inflammatory drugs; data from managed care. Clin Ther. 2003 Jan;25(1):139–49.

64. Curhan GC, Willett WC, Rosner B, Stampfer MJ. Frequency оf analgestic use and risk of hypertension in younger woman. Arch Intern Med. 2002 Oct 28;162(19):2204–8.

65. Forman JP, Stampfer MJ, Curhan GC. Non-narcotic analgetic dose and risk of incident hypertension in US women. Hypertension. 2005 Sep;46(3):500–7. Epub 2005 Aug 15.

66. Silverstein FE, Faich G, Goldstein JL, et al. Gastrointestinal toxicity with celecoxib versus nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: a randomized controlled trial. Celecoxid long-term arthritis safety study. JAMA. 2000 Sep 13;284(10):1247–55.

67. Singh G, Fort JG, Goldstein JL, et al. Celecoxib versus naproxen and diclofenac in osteoarthritis patients: SUCCESS-1 study. Am J Med. 2006 Mar;119 (3):255–66.

68. Cannon C., Curtis S., FitzGerald G., 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, 18; 368(9549): 1771–1781.

69. Chan CC1, Reid CM, Aw TJ, et al. Do COX-2 inhibitors raise blood pressure more than nonselective NSAIDs and placebo? An updated meta-analysis. J Hypertens. 2009 Dec;27(12):2332–41. doi: 10.1097/HJH.0b013e3283310dc9.

70. Brown J, Dollery C, Valdes G. Interaction of nonsteroidal anti-inflammatory drugs with antihypertensove and diuretic agents. Am J Med. 1986 Aug 25;81(2B):43–57.

71. Durao V, Prata MM, Goncalves LM. Modification of antihypertensive effect of beta-adrenoreceptor-blocking agents by inhibition of endogenous prostaglandin synthesis. Lancet. 1977 Nov 12;2(8046):1005–7.

72. Oates JA. Antagonism of antihypertensive drug therapy by nonsteroidal anti-inflammatory drugs. Hypertension. 1988 Mar;11(3 Pt 2):II4–6.

73. Quilley J, Duchin KL, Hudes EM, McGiff JC. The antihypertensive effect of captopril in essential hypertension. Relationship to prostaglandins and kallikreinkinin system. J Hypertens. 1987 Feb;5(1):121–8.

74. Salvetti A, Pedrinalli R, Magagna A, Ugenti P. Differential effects of selective and non-selective prostaglandin-synthesis inhibition on pharmacological response to captopril in patients with essential hypertension. Clin.Sci. 1982;63:261–3.

75. Watkins J, Abbott EC, Hensby CN, et al. Attenuation of hypotensive effect of propranalol and thiaside diuretics by indomethacin. Br Med J. 1980 Sep 13;281(6242):702–5.

76. Polonia J, Boaventura I, Gama G, et al. Influence of nonsteroidal anti-inflammatory drugs on renal function and 24-hour blood pressure-reducing effects of enalapril and nifedipine gastrointestinal therapeutic system in hypertensive patients. J Hypertens. 1995 Aug;13(8):925–31.

77. Wong DG, Spence JD, Lamki L, et al. Effect of nonsteroidal anti-inflammatory drugs on control of hypertension of betablockers and diuretics. Lancet. 1986 May 3;1(8488):997–1001.

78. Ylitalo P, Pitkä jä rvi T, Pyykö nen ML, et al. Inhibition of prostaglandin synthesis by indomethacin interacts with the antihypertensive effect of atenolol. Clin Pharmacol Ther. 1985 Oct;38(4):443–9.

79. Baez MA, Alvarez CR, Weidler DJ. Effects of the non-steroidal anti-inflammatory drugs, piroxicam or sulindac, on the antihypertensive action of propranolol and verapamil. J Hypertens Suppl. 1987 Dec;5(5):S563–6.

80. Cinquegrani MP, Liang CS. Antihypertensive effects of pinacidil in patients with and without indomethacin pretreatment. Clin Exp Hypertens A. 1988;10(3):411–31. 81. Hardy BG, Bartle WR, Myers M, et al. Effects of indomethacin on the pharmakokinetics of felodipine. Br J Clin Pharmacol. 1988 Nov;26(5):557–62.

81. Houston MC, Weir M, Gray J, et al. The effects of nonsteroidal anti-inflammatory drugs on blood pressure of patients with hypertension controlled by verapamil. Arch Intern Med. 1995 May 22;155(10):1049–54.

82. Klassen D, Goodfriend TL, Schuna AA, et al. Assesment of Blood pressure during treatment with naproxen of ibuprofen in hypertensive patients treated with hydrochlorthiazide. J Clin Pharmacol. 1993 Oct;33(10):971–8.

83. White WB, Kent J, Taylor A, et al. Effects of celecoxib on ambulatory blood pressure in hypertensive patients on ACE inhibitors. Hypertension. 2002 Apr;39(4):929–34.

84. Whelton A, Fort JG, Puma JA, et al. SUCCESS VI Study Group. Cyclooxygenase-2-specific inhibitors and cardiorenal function: a randomized, controlled trial of celecoxib and rofecoxib in older hypertensive osteoarthritis patients. Am J Ther. 2001 Mar-Apr;8(2):85–95.

85. Whelton A, White WB, Bello AE, et al. SUCCESS VII Investigators. Effects of celecoxib and rofecoxib on blood pressure and edema in patients ≥ 65 years of age with systolic hypertension and osteoarthritis. Am J Cardiol. 2002 Nov 1;90 (9):959–63.

86. Sowers JR, White WB, Pitt B, et al. The effects of cycloxygenase-2 inhibitors and nonsteroidal anti-inflammatory therapy on 24-houar blood pressure in patients with hypertension, osteoarthritis, and type 2 diabetes mellitus. Arch Intern Med. 2005 Jan 24;165(2):161–8.

87. Dilger K, Herrlinger C, Peters J, et al. Effects of celecoxib and diclofenac on blood pressure, renal function, and vasoactive prostanoids in young and elderly subjects. J Clin Pharmacol. 2002 Sep;42(9):985–94.

88. Cheng Y, Austin SC, Rocca B, et al. Role of prostacyclin in the cardiovascular response to thromboxane A2. Science. 2002 Apr 19;296(5567):539–41.

89. Grosser T, Fries S, FitzGerald GA.. Biological basis for the cardiovascular consequences of COX-2 inhibition: therapeutic challenes an opportunities. J Clin Invest. 2006 Jan;116(1):4–15.

90. Schaeverbeke T, Heloire F, Deray G. How to watch over a patient treated with a NSAID in relation to the cardiovascular and renal risk? Presse Med. 2006 Sep;35 Suppl 1:41–6.

91. Laine L, White WB, Rostom A, Hochberg M. COX-2 Selective Inhibitors in the Treatment of Osteoarthritis. Semin Arthritis Rheum. 2008 Dec;38(3):165–87. doi: 10.1016/j.semarthrit.2007.10.004. Epub 2008 Jan 4.

92. Gislason GH, Jacobsen S, Rasmussen JN, et al. Risk of death or reinfarction associated with the use of selective cyclooxygenase-2 inhibitors and nonselective nonsteroidal antiinflammatory drugs after acute myocardial infarction. Circulation. 2006 Jun 27;113(25):2906–13. Epub 2006 Jun 19.

93. Catella-Lawson F, Reilly MP, Kapoor SC, et al. Cyclooxygenase inhibitors and the antiplatelet effect of aspirin. N Engl J Med. 2001 Dec 20;345(25):1809–17.

94. Capone ML, Sciulli MG, Tacconelli S, et al. Pharmacodynamic interaction of naproxen with low-dose aspirin in healthy subjects. J Am Coll Cardiol. 2005 Apr 19;45(8):1295–301.

95. van Solingen RM, Rosenstein ED, Mihailescu G, et al. Comparison of the effects of ketoprofen on platelet function in the presence and absence of aspirin. Am J Med. 2001 Sep;111(4):285–9.

96. Wilner KD, Rushing M, Walden C, et al. Celecoxib does not affect the antiplatelet activity of aspirin in healthe volunteers. J Clin Pharmacol. 2002 Sep;42(9):1027–30.

97. Van Ryn J, Kink-Eiband M, Kuritsch I, et al. Meloxicam does not affect the antiplatelet effect of aspirin in healthy male and female volunteers. J Clin Pharmacol. 2004 Jul;44(7):777–84.

98. MacDonald T., Wei L. Effect of ibuprofen on cardioprotective effect of aspirin. Lancet 2003;361:573–574

99. Garcia Rodriguez LA, Varas-Lorenzo C, Maguire A, Gonzalez-Perez A. Nonsteroidal anti-inflammatory drugs and the risk of myocardial infarction in the general population. Circulation. 2004 Jun 22;109(24):3000–6. Epub 2004 Jun 14.

100. Kurth T, Glynn RJ, Walker AM, et al. Inhibition of clinical benefit of aspirin on first myocardial infarction by nonsteroidal antiinflammatory drugs. Circulation. 2003 Sep 9;108(10):1191–5. Epub 2003 Aug 25.

101. Hudson M, Baron M, Rahme E, Pilote L. Ibuprofen may abrogate the benefits of aspirin when used for secondary prevention of myocardial infarction. J Rheumatol. 2005 Aug;32(8):1589–93.

102. Curtis JP, Wang Y, Portnay EL, et al. Aspirin, ibuprofen, and mortality after myocardial infarction. BMJ. 2003 Dec 6;327(7427):1322–3.

103. Patel TN, Goldberg KC. Use of aspirin and ibuprofen compared with aspirin alone and the risk of myocardial infarction. Arch Intern Med. 2004 Apr 26;164(8):852–6.

104. Singh G, Graham D, Wang H, et al. Concominant aspirin use reduces the risk of acute myocardial infarction in users of cyclooxygenase-2 selective and some nonselective nonsteroidal anti-inflammatory drugs. Ann Rheum Dis 2006; 65 (Suppl. II): 61 (OP0024 abst)

105. Scott PA, Kingsley GH, Scott DL. Nonsteroidal anti-inflammatory drugs and cardiac failure: meta-analyses of observational studies and randomised controlled trials. Eur J Heart Fail. 2008 Nov;10(11):1102–7. doi: 10.1016/j.ejheart.2008.07.013. Epub 2008 Aug 29.

106. Hudson M., Richard H., Pilote L. Different in outcome of patients with congestive heart failure prescribed celecoxib, rofecoxib, or nonsteroidal anti-inflammatory drugs: population based study. BMJ 2005 Jun 11; 330 (7504): 1370

107. Bernatsky S, Hudson M, Suissa S. Antirheumatic drug use and risk of hospitalisation for congestive heart failure in rheumatoid arthritis. Rheumatology (Oxford). 2005 May;44(5):677–80. Epub 2005 Mar 22.

108. Mamdani M, Juurlink DN, Lee DS, et al. Cyclo-oxygenase-2 inhibitors versus nonselective nonsteroidal anti-inflammatory drugs and congestive heart failure outcomes in eldery patients: a population-based cohort study. Lancet. 2004 May 29;363(9423):1751–6.

109. Garcia Rodriguez LA, Hernandez-Diaz S. Nonsteroidal anti-inflammatory drugs as a trigger of clinical heart failure. Epidemiology. 2003 Mar;14(2):240–6.

110. Harirforoosh S, Jamali F. Renal adverse effects of nonsteroidal anti-inflammatory drugs. Expert Opin Drug Saf. 2009 Nov;8(6):669–81. doi: 10.1517/14740330903311023.

111. Huerta C, Castellsague J, Varas-Lorenzo C, Garcia Rodriguez LA. Nonsteroidal anti-inflammatory drugs and risk of ARF in the general population. Am J Kidney Dis. 2005 Mar;45(3):531–9.

112. Nawaz FA, Larsen CP, Troxell ML. Membranous nephropathy and nonsteroidal anti-inflammatory agents. Am J Kidney Dis. 2013 Nov;62(5):1012–7. doi: 10.1053/j.ajkd. 2013.03.045. Epub 2013 Jun 14.

113. Möller B, Pruijm M, Adler S, et al. Chronic NSAID use and long-term decline of renal function in a prospective rheumatoid arthritis cohort study. Ann Rheum Dis. 2013 Dec 19. doi: 10.1136/annrheumdis-2013-204078. [Epub ahead of print]

114. Nderitu P, Doos L, Jones PW, et al. Nonsteroidal anti-inflammatory drugs and chronic kidney disease progression: a systematic review. Fam Pract. 2013 Jun;30(3):247–55. doi: 10.1093/fampra/cms086. Epub 2013 Jan 8.

115. Souter A. Controversies in the perioperative use of nonsteroidal anti-inflammatory drugs. Anesth Analg. 1994 Dec;79(6):1178–90.

116. Strom BL, Berlin JA, Kinman JL, et al. Parenteral ketorolac and the risk of gastrointestinal and operative site bleeding. A postmarketing surveillance study. JAMA. 1996 Feb 7;275(5):376–82.

117. Weber EW, Slappendel R, Durieux ME, et al. COX 2 selectivity of nonsteroidal antiinflammatory drugs and perioperative blood loss in hip surgery. A randomized comparison of indomethacin and meloxicam. Eur J Anaesthesiol. 2003 Dec;20(12):963–6.

118. Bricker SR, Savage ME, Hanning CD.. Perioperative blood loss and nonsteroidal anti-inflammatory drugs: an investigation using diclofenac in patients undergoing transurethral resection of the prostate. Eur J Anaesthesiol. 1987 Nov;4(6):429–34.

119. Wierod FS1, Frandsen NJ, Jacobsen JD, et al. Risk of haemorrhage from transurethral prostatectomy in acetylsalicylic acid and NSAID-treated patients. Scand J Urol Nephrol. 1998 Apr;32(2):120–2.

120. Nikanne E, Kokki H, Salo J, Linna TJ. Celecoxib and ketoprofen for pain management during tonsillectomy: a placebo-controlled clinical trial. Otolaryngol Head Neck Surg. 2005 Feb;132(2):287–94.

121. Moiniche S, Romsing J, Dahl JB, Tramer MR.. Nonsteroidal anti-inflammatory drugs and the risk of operative site bleeding after tonsillectomy: A quantitative systematic review. Anesth Analg. 2003 Jan;96(1):68–77.

122. Forrest JB, Camu F, Greer IA, et al. Ketorolac, diclofenac, and ketoprofen are equally safe for pain relief after major surgery. Br J Anaesth. 2002 Feb;88(2):227–33.

123. Friedman RJ, Kurth A, Clemens A, et al. Dabigatran etexilate and concomitant use of nonsteroidal anti-inflammatory drugs or acetylsalicylic acid in patients undergoing total hip and total knee arthroplasty: no increased risk of bleeding. Thromb Haemost. 2012 Jul;108(1):183–90. doi: 10.1160/TH11-08-0589. Epub 2012 May 3.

124. Elia N, Lysakowski C, Tramer MR. Does multimodal analgesia with acetaminophen, nonsteroidal anti-inflammatory drugs, or selective cyclooxygenase-2 inhibitors and patient-controlled analgesia morphine offer advantages over morphine alone? Metaanalyses of randomized trials. Anesthesiology. 2005 Dec;103(6):1296–304.

125. Unzueta A, Vargas HE. Non-steroidal anti-inflammatory drug-induced hepatoxicity. Clin Liver Dis. 2013 Nov;17(4):643–56, ix. doi: 10.1016/j.cld.2013.07.009. Epub 2013 Sep 4.

126. Bessone F. Nonsteroidal anti-inflammatory drugs: What is the actual risk of liver damage? World J Gastroenterol. 2010 Dec 7;16(45):5651–61.

127. Laine L, Goldkind L, Curtis SP, et al. How common is diclofenac-associated liver injury? Analysis of 17,289 arthritis patients in a long-term prospective clinical trial. Am J Gastroenterol. 2009 Feb;104(2):356–62. doi: 10.1038/ajg.2008.149. Epub 2009 Jan 27.

128. Sanchez-Matienzo D, Arana A, Castellsague J, Perez-Gutthann S. Hepatic disorders in patient treated with COX-2 selective inhibitors or nonselective NSAIDs: A case/noncase analysis of spontaneous reports. Clin Ther. 2006 Aug;28(8):1123–32.

129. Traversa G, Bianchi C, Da Cas R, et al. Cohort study of hepatotoxity associated with nimesulide and other nonsteroidal antiinflammatory drugs. BMJ. 2003 Jul 5;327(7405):18–22.

130. Gulmez SE, Larrey D, Pageaux GP, et al. Transplantation for acute liver failure in patients exposed to NSAIDs or paracetamol (acetaminophen): the multinational casepopulation SALT study. Drug Saf. 2013Feb;36(2):135–44. doi: 10.1007/s40264-012-0013-7.

131. Каратеев АЕ. Российский опыт применения нимесулида: обзор клинических испытаний. Consilium medicum. 2011;13(9):89-95. [Karateev AE. The Russian experience in the use of nimesulide: clinical trials review. Consilium medicum. 2011;13(9):89–95. (In Russ.)].

132. Каратеев АЕ, Алексеева ЛИ, Братыгина ЕА, Аширова ТБ. Оценка частоты развития побочных эффектов при длительном применении нимесулида в реальной клинической практике. Русский Медицинский Журнал. 2009;17(21):1466–72. [Karateev AE, Alekseeva LI, Bratygina EA,

133. Ashirova TB. Evaluation of the frequency of adverse effects with long-term use of nimesulide in real clinical practice. Russkii Meditsinskii Zhurnal. 2009;17(21):1466–72. (In Russ.)].

134. Andres E, Maloisel F. Idiosyncratic drug-induced agranulocytosis or acute neutropenia. Curr Opin Hematol. 2008 Jan;15(1):15–21.

135. Hamerschlak N, Cavalcanti AB. Neutropenia, agranulocytosis and dipyrone. Sao Paulo Med J. 2005 Sep 1;123(5):247–9. Epub 2005 Dec 8.

136. Mourad AA, Bahna S. Hypersensitivities to nonsteroidal anti-inflammatory drugs. Expert Rev Clin Immunol. 2014 Sep;10(9):1263–8. doi: 10.1586/1744666X.2014.946905. Epub 2014 Aug 4.

137. Kowalski ML, Asero R, Bavbek S, et al. Classification and practical approach to the diagnosis and management of hypersensitivity to nonsteroidal anti-inflammatory drugs. Allergy. 2013 Oct;68(10):1219–32. doi: 10.1111/all.12260. Epub 2013 Oct 5.

138. White AA, Stevenson DD. Aspirin-exacerbated respiratory disease: update on pathogenesis and desensitization. Semin Respir Crit Care Med. 2012 Dec;33(6):588–94. doi: 10.1055/s-0032-1325618. Epub 2012 Oct 9.

139. Simon RA. Adverse respiratory reactions to aspirin and nonsteroidal anti-inflammatory drugs. Curr Allergy Asthma Rep. 2004 Jan;4(1):17–24.

140. Crofford LJ. Use of NSAIDs in treating patients with arthritis. Arthritis Res Ther. 2013;15 Suppl 3:S2. doi: 10.1186/ar4174. Epub 2013 Jul 24.

141. Bhala N, Emberson J, Merhi A, et al. Vascular and upper gastrointestinal effects of nonsteroidal anti-inflammatory drugs: metaanalyses of individual participant data from randomised trials. Lancet. 2013 Aug 31;382(9894):769–79. doi: 10.1016/S0140-6736(13)60900-9. Epub 2013 May 30.

142. Burmester G, Lanas A, Biasucci L, et al. The appropriate use of nonsteroidal antiinflammatory drugs in rheumatic disease: opinions of a multidisciplinary European expert panel. Ann Rheum Dis. 2011 May;70(5):818–22. doi: 10.1136/ard.2010.128660. Epub 2010 Sep 10.

143. Singh G, Triadafilopoulos S. Appropriative choice of proton pump inhibitor therapy in the prevention and management of NSAID-related gastrointestinal damage. Int J Clin Pract. 2005 Oct;59(10):1210–7.

144. Lanas A, Tornero J, Zamorano JL. Assessment of gastrointestinal and cardiovascular risk in patients with osteoarthritis who require NSAIDs: the LOGICA study. Ann Rheum Dis. 2010 Aug;69(8):1453–8. doi: 10.1136/ard.2009.123166. Epub 2010 May 24.

145. Malfertheiner P, Megraud F, O'Morain CA, et al. Management of Helicobacter pylori infection – the Maastricht IV/ Florence Consensus Report. Gut. 2012 May;61(5):646–64. doi: 10.1136/gutjnl-2012-302084.

146. Conroy RM, Pyorala K, Fitzgerald AP, et al. SCORE project group. Estimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE project. Eur Heart J. 2003 Jun;24(11):987–1003.

147. Wang PS, Avorn J, Brookhart MA, et al. Effects of noncardiovascular comorbidities on anti-hypertensive use in elderly hypertensives. Hypertension. 2005 Aug;46(2):273–9. Epub 2005 Jun 27.

148. Moore A, Makinson G, Li C. Patientlevel pooled analysis of adjudicated gastrointestinal outcomes in celecoxib clinical trials: meta-analysis of 51,000 patients enrolled in 52 randomized trials. Arthritis Res Ther. 2013 Jan 8;15(1):R6. doi: 10.1186/ar4134.

149. Chan FK, Lanas A, Scheiman J, et al. Celecoxib versus omeprazole and diclofenac in patients with osteoarthritis and rheumatoid arthritis (CONDOR): a randomised trial. Lancet. 2010 Jul 17;376(9736):173–9. doi: 10.1016/S0140-6736(10)60673-3. Epub 2010 Jun 16.

150. Castellsague J, Riera-Guardia N, Calingaert B, et al. Individual NSAIDs and upper gastrointestinal complications: a systematic review and meta-analysis of observational studies (the SOS project). Drug Saf. 2012 Dec 1;35(12):1127–46. doi: 10.2165/11633470-000000000-00000.

151. Laine L, Curtis SP, Cryer B, et al. Assessment of upper gastrointestinal safety of 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. 2007 Feb 10;369(9560):465–73.

152. Laine L, Curtis SP, Langman M, et al. Lower gastrointestinal events in a double-blind trial of the cyclo-oxygenase-2 selective inhibitor etoricoxib and the traditional nonsteroidal antiinflammatory drug diclofenac. Gastroenterology. 2008 Nov;135(5):1517–25. doi: 10.1053/j.gastro.2008.07.067. Epub 2008 Aug 3.

153. Singh G, Lanes S, Triadafilopoulos G. Risk of serious upper gastrointestinal and cardiovascular tromboembolic complications with meloxicam. Am J Med. 2004 Jul 15;117(2):100–6.

154. Trelle S, Reichenbach S, Wandel S, et al. Cardiovascular safety of nonsteroidal antiinflammatory drugs: network meta-analysis. BMJ. 2011 Jan 11;342:c7086. doi: 10.1136/bmj.c7086.

155. Varas-Lorenzo C, Riera-Guardia N, Calingaert B, et al. Myocardial infarction and individual nonsteroidal anti-inflammatory drugs meta-analysis of observational studies. Pharmacoepidemiology and Drug Safety, 2013; 22: 559–570 DOI: 10.1002/pds Published online 25 April 2013 in Wiley Online Library (wileyonlinelibrary.com)

156. Каратеев АЕ. Шесть ножей в спину ингибиторам протонной помпы. Научно-практическая ревматология. 2013;51(3):332–40. [Karateev AE. Six stabs in the back of proton pump inhibitors. Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practice. 2013;51(3):332–40. (In Russ.).] DOI: http://dx.doi.org/10.14412/1995-4484-2013-1509

157. Ikeda Y, Shimada K, Teramoto T, et al. Low-dose aspirin for primary prevention of cardiovascular events in Japanese patients 60 years or older with atherosclerotic risk factors: a randomized clinical trial. JAMA. 2014 Dec 17;312(23):2510–20. doi: 10.1001/jama.2014.15690.

158. Brotons C, Benamouzig R, Filipiak KJ, et al. A Systematic Review of Aspirin in Primary Prevention: Is It Time for a New Approach? Am J Cardiovasc Drugs. 2014 Dec 12. [Epub ahead of print]

159. Hennekens CH, Dalen JE. Aspirin in the primary prevention of cardiovascular disease: Current knowledge and future research needs. Trends Cardiovasc Med. 2014 Nov;24(8):360–6. doi: 10.1016/j.tcm.2014.08.006. Epub 2014 Sep 1.

160. Strand V. Are COX-2 inhibitors preferable to nonselective nonsteroidal anti-inflammatory drugs in patients with risk of cardiovascular events taking low-dose aspirin? Lancet. 2007 Dec 22;370(9605):2138–51.

161. Scheiman JM, Yeomans ND, Talley NJ, et al. Prevention of ulcer by esomeprazole in at-risk patients using nonselective NSAIDs or COX-2 inhibitor. Am J Gastroenterol. 2006 Apr;101(4):701–10. Epub 2006 Feb 22.

162. Chan FK, Wong VW, Suen BY, et al. Combination of a cyclo-oxygenase-2 inhibitor and a proton-pump inhibitor for prevention of recurrent ulcer bleeding in patients at very high risk: a double-blind, randomised trial. Lancet. 2007 May 12;369(9573):1621–6.


Рецензия

Просмотров: 37989


Creative Commons License
Контент доступен под лицензией Creative Commons Attribution 4.0 License.


ISSN 1996-7012 (Print)
ISSN 2310-158X (Online)