Bateman D N, Colin-Jones D, Hartz S, Langman M, Logan R F, Mant J, Murphy M, Paterson K R, Rowsell R, Thomas S, Vessey M
Wolfson Unit of Clinical Pharmacology, University of Newcastle upon Tyne, Newcastle upon Tyne, UK.
Gut. 2003 Jul;52(7):942-6. doi: 10.1136/gut.52.7.942.
The long term safety of potent gastric acid suppressive therapy has yet to be established.
General practice record review at a median interval of 26 months followed by retrieval of details of all deaths within four years using the UK National Health Service Central Registers in 17 936 patients prescribed omeprazole in 1993-1995. Death rates were compared with general population rates.
Records of 17 489 patients (97.5%) were examined. A total of 12 703 patients received further scripts for antisecretory drugs, 8097 for omeprazole only (65.6%): 3097 patients have died. All cause mortality was higher in the first year (observed/expected (O/E) 1.44 (95% confidence intervals (CI) 1.34-1.55); p<0.0001) but had fallen to population expectation by the fourth year. There were significant mortality increases in the first year, falling to or below population expectation by the fourth year, for deaths ascribed to neoplasms (1.82 (95% CI 1.58-2.08); p<0.0001), circulatory diseases (1.27 (95% CI 1.13-1.43); p<0.0001), and respiratory diseases (1.37 (95% CI 1.12-1.64); p<0.001). Increased mortality ascribed to digestive diseases (2.56 (95% CI 1.87-3.43); p<0.0001) persisted, although reduced. Increased mortality rates for cancers of the stomach (4.06 (95% CI 2.60-6.04); p<0.0001), colon and rectum (1.40 (95% CI 0.84-2.18); p=0.075), and trachea, bronchus, and lung (1.64 (95% CI 1.19-2.19); p<0.01) seen in the first year had disappeared by the fourth year but that for cancer of the oesophagus had not (O/E 7.35 (95% CI 5.20-10.09) (p<0.0001) in year 1; 2.88 (95% CI 1.62-4.79) (p<0.001) in year 4). Forty of 78 patients dying of oesophageal cancer had the disease present at registration. Twenty seven of those remaining cases had clinical evidence of Barrett's disease, stricture, ulcer, or oesophagitis at registration (O/E 3.30 (95% CI 2.17-4.80)). Six deaths occurred in patients with hiatal hernia or reflux only (O/E 1.02 (95% CI 0.37-2.22)) and five in patients without oesophageal disease (O/E 0.77 (95% CI 0.25-1.80)). No relationships were detected with numbers of omeprazole scripts received.
Increases in mortality associated with treatment are due to pre- existing illness, including pre-existing severe oesophageal disease. There was no evidence of an increased risk of oesophageal adenocarcinoma in those without oesophageal mucosal damage recorded at registration.
强效胃酸抑制疗法的长期安全性尚未确立。
对普通医疗记录进行回顾，中位间隔时间为26个月，随后使用英国国家医疗服务体系中央登记处检索1993 - 1995年开具奥美拉唑处方的17936例患者在四年内所有死亡的详细信息。将死亡率与普通人群的死亡率进行比较。
检查了17489例患者的记录（97.5%）。共有12703例患者接受了抗分泌药物的后续处方，仅接受奥美拉唑的有8097例（65.6%）；3097例患者死亡。全因死亡率在第一年较高（观察值/预期值（O/E）1.44（95%置信区间（CI）1.34 - 1.55）；p<0.0001），但到第四年已降至人群预期水平。归因于肿瘤（1.82（95%CI 1.58 - 2.08）；p<0.0001）、循环系统疾病（1.27（95%CI 1.13 - 1.43）；p<0.0001）和呼吸系统疾病（1.37（95%CI 1.12 - 1.64）；p<0.001）的死亡率在第一年显著增加，到第四年降至或低于人群预期水平。归因于消化系统疾病的死亡率增加（2.56（95%CI 1.87 - 3.43）；p<0.0001）仍然存在，尽管有所降低。第一年观察到的胃癌（4.06（95%CI 2.60 - 6.04）；p<0.0001）、结肠和直肠癌（1.40（95%CI 0.84 - 2.18）；p = 0.075）以及气管、支气管和肺癌（1.64（95%CI 1.19 - 2.19）；p<0.01）的死亡率增加在第四年已消失，但食管癌的死亡率增加未消失（第一年O/E 7.35（95%CI 5.20 - 10.09）（p<0.0001）；第四年2.88（95%CI 1.62 - 4.79）（p<0.001））。78例死于食管癌的患者中有40例在登记时就患有该疾病。其余病例中有27例在登记时有巴雷特病、狭窄、溃疡或食管炎的临床证据（O/E 3.30（95%CI 2.17 - 4.80））。6例死亡发生在仅有食管裂孔疝或反流的患者中（O/E 1.02（95%CI 0.37 - 2.22）），5例死亡发生在无食管疾病的患者中（O/E 0.77（95%CI 0.25 - 1.80））。未发现与接受奥美拉唑处方的数量之间存在关联。
与治疗相关的死亡率增加是由于既往存在的疾病，包括既往存在的严重食管疾病。在登记时未记录食管黏膜损伤的患者中，没有证据表明食管腺癌风险增加。
