Dose-response relationships between individual nonaspirin nonsteroidal anti-inflammatory drugs (NANSAIDs) and serious upper gastrointestinal bleeding: a meta-analysis based on individual patient data

被引:174
作者
Lewis, SC [1 ]
Langman, MJS
Laporte, JR
Matthews, JNS
Rawlins, MD
Wiholm, BE
机构
[1] Newcastle Univ, Wolfson Unit Clin Pharmacol, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England
[2] Univ Birmingham, Dept Med, Birmingham B15 2TT, W Midlands, England
[3] Univ Autonoma Barcelona, CSU Vall Hebron, Inst Catala Farmacol, E-08193 Barcelona, Spain
[4] Huddinge Hosp, Karolinska Inst, Dept Clin Pharmacol, S-14186 Huddinge, Sweden
关键词
diclofenac; dose-response; ibuprofen; indomethacin; ketoprofen; meta-analysis of individual patient data; naproxen; non-aspirin nonsteroidal anti-inflammatory drugs; paracetamol (acetaminophen); piroxicam; upper gastrointestinal bleeding;
D O I
10.1046/j.1365-2125.2002.01636.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Aims To define by amalgamation of data obtained in contemporaneous case-control studies, the risks associated with individual nonaspirin nonsteroidal anti-inflammatory drugs (NANSAIDs) according to doses used. Methods Meta-analysis of individual patient data from three retrospective case-control studies using similar data collection protocols was carried out in hospitals in Catalonia, England, Scotland and Sweden. 2472 cases of upper gastrointestinal bleeding and 5877 controls were studied. Main outcome measures were risks associated with individual NANSAIDs according to dose used and the period of time for which they were given. Results Ibuprofen showed the lowest odds ratio (OR = 1.7; 95% confidence interval 1.1, 2.5), followed by diclofenac (4.9; 3.3, 7.1), indomethacin (6.0; 3.6, 10.0), naproxen (9.1; 6.0-13.7), piroxicam (13.1; 7.9-21.8) and ketoprofen (34.9; 12.7, 96.5). Striking dose-response relationships were seen with four to eight-fold increases in risk within conventionally used dose ranges for all except ketoprofen, where numbers were too few to allow dose analysis. Across the class, risk was highest during the first week of use (11.7; 6.5, 21.0), decreased thereafter with continuing use (5.6; 4.6, 7.0), and fell to 3.2 (2.1, 5.1) 1 week after discontinuing use. Concurrent use of more than one NANSAID substantially increased risk. Conclusions The risk of upper gastrointestinal bleeding with NANSAIDs varies twenty-fold depending on the drug, and by three to seven-fold depending on the dose chosen. Risk is maximal during the first week and decreases thereafter. Paracetamol (acetaminophen) is not associated with upper gastrointestinal bleeding at any dose and should be the first-line analgesic wherever possible.
引用
收藏
页码:320 / 326
页数:7
相关论文
共 21 条
  • [1] BELTON KJ, 1994, PERSPECTIVES PHARMAC
  • [2] Randomised trial of eradication of Helicobacter pylori before non-steroidal anti-inflammatory drug therapy to prevent peptic ulcers
    Chan, FKL
    Sung, JJY
    Chung, SCS
    To, KF
    Yung, MY
    Leung, VKS
    Lee, YT
    Chan, CSY
    Li, EKM
    Woo, J
    [J]. LANCET, 1997, 350 (9083) : 975 - 979
  • [3] Committee on the Safety of Medicines/Medicines Control Agency, 1994, CURRENT PROBLEMS PHA, V20, P9
  • [4] Peptic ulcer bleeding in the elderly: relative roles of Helicobacter pylori and non-steroidal anti-inflammatory drugs
    Cullen, DJE
    Hawkey, GM
    Greenwood, DC
    Humphreys, H
    Shepherd, V
    Logan, RFA
    Hawkey, CJ
    [J]. GUT, 1997, 41 (04) : 459 - 462
  • [5] Randomised controlled trial of Helicobacter pylori eradication in patients on non-steroidal anti-inflammatory drugs:: HELP NSAIDs study
    Hawkey, CJ
    Tulassay, Z
    Szczepanski, L
    van Rensburg, CJ
    Filipowicz-Sosnowska, A
    Lanas, A
    Wason, CM
    Peacock, RA
    Gillon, KRW
    [J]. LANCET, 1998, 352 (9133) : 1016 - 1021
  • [6] VARIABILITY IN THE RISK OF MAJOR GASTROINTESTINAL COMPLICATIONS FROM NONASPIRIN NONSTEROIDAL ANTIINFLAMMATORY DRUGS
    HENRY, D
    DOBSON, A
    TURNER, C
    [J]. GASTROENTEROLOGY, 1993, 105 (04) : 1078 - 1088
  • [7] Variability in risk of gastrointestinal complications with individual non-steroidal anti-inflammatory drugs: Results of a collaborative meta-analysis
    Henry, D
    Lim, LLY
    Rodriguez, LAG
    Gutthann, SP
    Carson, JL
    Griffin, M
    Savage, R
    Logan, R
    Moride, Y
    Hawkey, C
    Hill, S
    Fries, JT
    [J]. BRITISH MEDICAL JOURNAL, 1996, 312 (7046) : 1563 - 1566
  • [8] NONSTEROIDAL ANTIINFLAMMATORY DRUG-USE IN RELATION TO MAJOR UPPER GASTROINTESTINAL-BLEEDING
    KAUFMAN, DW
    KELLY, JP
    SHEEHAN, JE
    LASZLO, A
    WIHOLM, BE
    ALFREDSSON, L
    KOFF, RS
    SHAPIRO, S
    [J]. CLINICAL PHARMACOLOGY & THERAPEUTICS, 1993, 53 (04) : 485 - 494
  • [9] RISKS OF BLEEDING PEPTIC-ULCER ASSOCIATED WITH INDIVIDUAL NONSTEROIDAL ANTIINFLAMMATORY DRUGS
    LANGMAN, MJS
    WEIL, J
    WAINWRIGHT, P
    LAWSON, DH
    RAWLINS, MD
    LOGAN, RFA
    MURPHY, M
    VESSEY, MP
    COLINJONES, DG
    [J]. LANCET, 1994, 343 (8905) : 1075 - 1078
  • [10] UPPER GASTROINTESTINAL-BLEEDING IN RELATION TO PREVIOUS USE OF ANALGESICS AND NONSTEROIDAL ANTIINFLAMMATORY DRUGS
    LAPORTE, JR
    CARNE, X
    VIDAL, X
    MORENO, V
    JUAN, J
    [J]. LANCET, 1991, 337 (8733) : 85 - 89