Johnson A G
University Department of Medicine, University of Queensland, Brisbane, Australia.
Drugs Aging. 1998 Jan;12(1):17-27. doi: 10.2165/00002512-199812010-00003.
The use of nonsteroidal anti-inflammatory drugs (NSAIDs) and antihypertensive medication increases with age to 26% and > 50%, respectively, among the elderly. Overall, 12 to 15% of elderly individuals take at least 1 NSAID and an antihypertensive medication concurrently. A large case-control study of older individuals demonstrated that recent users of NSAIDs had a 1.7-fold increase in risk of initiating antihypertensive therapy compared with non-users. A community-based epidemiological study revealed that NSAID use significantly predicted the presence of hypertension (odds ratio 1.4, 95% confidence interval 1.1 to 1.7) in the elderly. Furthermore, among those taking antihypertensive agents in the 65+ Rural Health Study, in Iowa, US, individuals also taking NSAIDs had a mean systolic blood pressure (BP) 4.9 mm Hg higher than non-users of NSAIDs. The hypertensive effect of NSAIDs varies depending on the specific NSAID used and the type of antihypertensive agent, if they are taken concurrently. While the results of randomised, controlled trials in the elderly have been conflicting, 2 meta-analyses involving younger adults have revealed that NSAID use produces a clinically significant increment in mean BP of 5.0 mm Hg, which is most marked in patients with controlled hypertension. Stratification by NSAID type has revealed that piroxicam and indomethacin had the greatest, and sulindac the least, pressor effect. While the mechanisms) of the pressor effect remain speculative, salt and water retention, caused by several factors operating in parallel, coupled with an increased total peripheral vascular resistance via increased renal endothelin-1 synthesis, are potentially important. A 5 to 6 mm Hg increase in diastolic BP maintained over a few years may be associated with a 67% increase in total stroke occurrence and a 15% increase in events associated with coronary heart disease. Clinicians should strive to avoid excessive use of NSAID treatment and consider alternative, well-tolerated therapeutic options, including simple analgesics and physical therapy. For patients who require concomitant NSAID and antihypertensive treatment, clinicians should be aware of the greater hypertensive effect of indomethacin and piroxicam compared with alternative NSAIDs, and the potential for relatively greater antagonism by NSAIDs of the BP-lowering effect of beta-blockers compared with other antihypertensives. Finally, the progress of each patient should be monitored by careful BP measurement particularly during the initiation of NSAID therapy.
在老年人中,非甾体抗炎药(NSAIDs)和抗高血压药物的使用比例分别增至26%和超过50%。总体而言,12%至15%的老年人同时服用至少一种NSAIDs和一种抗高血压药物。一项针对老年人的大型病例对照研究表明,与未使用者相比,近期使用NSAIDs的人开始抗高血压治疗的风险增加了1.7倍。一项基于社区的流行病学研究显示,在老年人中,使用NSAIDs可显著预测高血压的存在(比值比为1.4,95%置信区间为1.1至1.7)。此外,在美国爱荷华州65岁及以上农村健康研究中,正在服用抗高血压药物的人群中,同时服用NSAIDs的个体的平均收缩压比未使用NSAIDs的个体高4.9毫米汞柱。NSAIDs的高血压作用因所使用的具体NSAIDs和抗高血压药物类型(如果同时服用)而异。虽然针对老年人的随机对照试验结果存在矛盾,但两项涉及年轻人的荟萃分析显示,使用NSAIDs会使平均血压临床上显著升高5.0毫米汞柱,这在血压得到控制的患者中最为明显。按NSAIDs类型分层显示,吡罗昔康和吲哚美辛的升压作用最大,而舒林酸的升压作用最小。虽然升压作用的机制仍属推测,但由多种因素共同作用导致的盐和水潴留,以及通过增加肾内皮素-1合成导致的总外周血管阻力增加,可能很重要。舒张压持续数年升高5至6毫米汞柱可能与中风总发生率增加67%以及冠心病相关事件增加15%有关。临床医生应努力避免过度使用NSAIDs治疗,并考虑选择耐受性良好的替代治疗方案,包括简单的镇痛药和物理治疗。对于需要同时使用NSAIDs和抗高血压治疗的患者,临床医生应意识到与其他NSAIDs相比,吲哚美辛和吡罗昔康具有更大的高血压作用,并且与其他抗高血压药物相比,NSAIDs对β受体阻滞剂降压作用具有相对更大的拮抗作用。最后,应通过仔细测量血压来监测每位患者的病情进展,尤其是在开始NSAIDs治疗期间。