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老年患者长期用药的潜在药物相互作用及其影响因素分析

泰然健康网
2024-12-11 18:43

摘要:

背景药物-药物相互作用(drug-drug interactions， DDIs)是导致药物不良反应的因素，识别和避免DDIs对于优化老年患者药物治疗效果十分必要。

目的分析老年患者长期用药中潜在的具有临床意义的DDIs发生情况及相关影响因素，为老年药物合理使用提供依据。

方法 2018年12月 - 2020年3月、2021年5月 - 2022年4月，在北京三个社区≥65岁的老年人群中开展横断面研究，使用《老年人潜在的具有临床意义的DDIs国际共识清单》评估患者长期用药中的DDIs发生情况，通过logistic回归分析DDIs的危险因素。

结果共纳入老年患者683例，年龄[Md(IQR)：84(79 ~ 88)]岁，至少发生1种潜在DDIs的患者202例(29.6%)。其中药品使用的种类越多，发生潜在DDIs的概率越高(与2 ~ 4种相比：5 ~ 9种，OR=2.751，95% CI：1.627 ~ 4.652，P＜0.001；10 ~ 14种，OR=5.006，95% CI：2.813 ~ 8.907，P＜0.001；≥15种，OR=11.27，95% CI：5.140 ~ 24.711，P＜0.001)，衰弱状态(OR=1.757，95% CI：1.184 ~ 2.606，P=0.005)、有潜在不适当用药(OR=2.722，95% CI：1.863 ~ 3.976，P＜0.001)、有心血管疾病(OR=6.759，95% CI：1.549 ~ 29.501，P=0.011)者发生潜在DDIs的概率更高。最常见的潜在DDIs为同时使用两种以上保钾药，所有与非甾体抗炎药有关的药物相互作用中，患者均使用了阿司匹林。

结论社区老年人用药中潜在的具有临床意义的DDIs多见，应特别关注多药、衰弱、具有心血管疾病、有潜在不适当用药的老年患者DDIs发生情况，加强潜在DDIs的相关风险监测，以优化药物治疗效果，减少不良结局。

Abstract:

Background Drug-drug interactions (DDIs) are one of the factors for adverse drug reactions. It is necessary to identify and avoid DDIs to optimize the efficacy of drug therapy in elderly patients.

Objective To study the prevalence of potentially clinically significant DDIs and related influencing factors in elderly patients in the communities, and provide evidence for rational drug use in the elderly.

Methods A cross-sectional study was conducted from December 2018 to April 2022 in a cohort of older adults ≥65 years old in three communities in Beijing. The occurrence of potential DDIs in patients' long-term medication use was assessed using the International Consensus List of Potentially Clinically Significant DDIs in Older People, and risk factors for potential DDIs were analyzed by Logistic regression.

Results A total of 683 elderly patients with a median age (interquartile spacing) of 84 (79 - 88) years were included, and 202 (29.6%) patients had at least one potential DDIs. The more the number of drugs used, the higher the probability of potential DDIs (compared with 2-4: 5-9, OR=2.751, 95%CI: 1.627-4.652, P<0.001; 10-14, OR=5.006, 95% CI: 2.813-8.907, P<0.001; ≥15, OR=11.27, 95% CI: 5.140-24.711, P<0.001). Patients in frail status (OR=1.757, 95% CI: 1.184-2.606, P=0.005), with PIM (OR=2.722, 95% CI: 1.863-3.976, P<0.001), and cardiovascular disease (OR=6.759, 95% CI: 1.549-29.501, P=0.011) had a higher risk of potential DDIs. The most common potential DDIs were the concomitant use of more than two potassium-preserving drugs, and aspirin was used by patients in all potential DDIs related to NSAIDs.

Conclusion Potentially clinically significant DDIs are common in elderly patients in the community. Special attention should be paid to the occurrence of DDIs in elderly patients with polypharmacy, frailty, cardiovascular disease, and PIM, and to enhancing the monitoring of risks associated with potential DDIs to optimize pharmacotherapy outcomes and reduce adverse outcomes.

表 1 研究对象基本特征(例，%)

Table 1 Characteristics of the participants (n, %)

　指标总体(n=683)无潜在DDIs (n=481)有潜在DDIs (n=202)χ2值P值性别4.1740.041　女性445(65.2)325(73)120(27.0)　男性238(34.8)156(65.5)82(34.5)年龄Md(IQR)：84(79，88)岁27.1480.000　65 ~ 69岁93(13.6)82(88.2)11(11.8)　70 ~ 79岁90(13.2)72(80)18(20.0)　80 ~ 89岁410(60.0)275(67.1)135(32.9)　90 ~ 99岁90(13.2)52(57.8)38(42.2)BMI(24.34 ± 3.47) kg·m-20.9850.321　＜28.5 kg·m-2588(86.1)410(69.7)178(30.3)　≥28.5 kg·m-295(13.9)71(74.7)24(25.3)受教育程度0.3860.534　初中及以下496(72.6)346(69.8)150(30.2)　初中以下187(27.4)135(72.2)52(27.8)婚姻状况0.2080.901　已婚438(64.2)311(71)127(29.0)　丧偶242(35.4)168(69.4)74(30.6)　离异分居3(0.4)2(66.7)1(33.3)照护情况4.4050.111　家人同住477(69.8)346(72.5)131(27.5)　专人照护133(19.5)84(63.2)49(36.8)　独居73(10.7)51(69.9)22(30.1)收入6.3630.012　≤5000元169(24.7)132(78.1)37(21.9)　＞5000元514(75.3)349(67.9)165(32.1)吸烟史1.5120.470　从不590(86.4)413(70)177(30)　已戒烟74(10.8)56(75.7)18(24.3)　吸烟19(2.8)12(63.2)7(36.8)1年内饮酒史0.0110.915　无620(90.8)437(70.5)183(29.5)　有63(9.2)44(69.8)19(30.2)药品数量Md(IQR)：6(4，10)种104.2470.000　1 ~ 4种238(34.8)214(89.9)24(10.1)　5 ~ 9种260(38.1)181(69.6)79(30.4)　10 ~ 14种134(19.6)71(53)63(47)　≥15种51(7.5)15(29.4)36(70.6)1年内住院29.5620.000　无482(70.6)369(76.6)113(23.4)　有201(29.4)112(55.7)89(44.3)CCI评分Md(IQR)：3(1，4)10.2590.006　0 ~ 2330(48.3)245(74.2)85(25.8)　3 ~ 5257(37.6)181(70.4)76(29.6)　≥696(14.1)55(57.3)41(42.7)衰弱评分Md(IQR)：5(2，8)57.765＜0.001　　0 ~ 5355(52.0)289(81.4)66(18.6)　6 ~ 7136(19.9)92(67.6)44(32.4)　8 ~ 999(14.5)56(56.6)43(43.4)　10 ~ 1159(8.6)32(54.2)27(45.8)　≥1234(5.0)12(35.3)22(64.7)PIM48.618＜0.001　　无383(56.1)311(81.2)72(18.8)　有300(43.9)170(56.7)130(43.3)神经系统疾病7.9800.005　无610(89.3)440(72.1)170(27.9)　有73(10.7)41(56.2)32(43.8)心脑血管疾病15.536＜0.001　　无47(6.9)45(95.7)2(4.3)　有636(93.1)436(68.6)200(31.4)消化系统疾病0.2530.615　无264(38.7)183(69.3)81(30.7)　有419(61.3)298(71.1)121(28.9)高血脂0.0510.821　无192(28.1)134(69.8)58(30.2)　有491(71.9)347(70.7)144(29.3)糖尿病4.1820.041　无351(51.4)235(67.0)116(33.0)　有332(48.6)246(74.1)86(25.9)　

表 2 社区老年人群潜在具有临床意义的DDIs的发生例次及风险(n=202)

Table 2 Incidence and risk of potentially clinically significant DDIs (n=202)

共识编号DDI组合发生例次/(例次，%)相互作用风险 DDI-21同时使用≥2种保钾药物105(51.98)高血钾症DDI-23ACEI/ARB + 口服NSAIDs90(44.55)肾功能恶化及高血钾血压控制改变DDI-37阿普唑仑或地西泮或咪达唑仑或三唑仑
或唑吡坦或佐匹克隆 + CYP3A4抑制剂76(37.62)过度的镇静和长时间的催眠作用DDI-24利尿剂 + 口服NSAIDs36(17.82)肾功能恶化、高钾血症和充血性心力衰竭改变了血压控制DDI-27辛伐他汀 + 氨氯地平29(14.36)严重的肌病和横纹肌溶解，可导致急性肾衰竭和死亡DDI-18利伐沙班 + P-gp抑制剂或CYP3A4-抑制剂12(5.94)出血DDI-20抗血小板药物 + 口服NSAIDs9(4.45)出血、胃肠道毒性(炎症、溃疡、穿孔)
降低了阿司匹林的心脏保护作用DDI-12口服抗凝剂 + 抗血小板药物6(2.97)出血DDI-30钙通道阻滞剂 + CYP3A4抑制剂6(2.97)钙通道阻滞剂作用增强DDI-36同时使用3种中枢作用药物6(2.97)摔倒和骨折的风险增加，认知能力受损DDI-11口服抗凝剂 + 口服NSAIDs4(1.98)出血、胃肠道出血和毒性(如炎症、溃疡和穿孔)DDI-26阿托伐他汀或辛伐他汀
或洛伐他汀 + 维拉帕米或地尔硫卓3(1.49)严重的肌病和横纹肌溶解，
可导致急性肾衰竭和死亡DDI-50乙酰胆碱酯酶抑制剂 + 降低心率的药物3(1.49)心跳过缓DDI-57同时使用≥2种抗胆碱能药物3(1.49)抗胆碱能效应包括认知能力下降DDI-6地高辛 + 噻嗪类或袢利尿剂2(0.99)地高辛毒性；可能导致严重的致命心律失常后果DDI-22ACEI或ARB或保钾利尿剂 + 钾补充剂2(0.99)高血钾症DDI-25他汀类药物 + 吉非贝齐2(0.99)严重的肌病和横纹肌溶解，可导致急性肾衰竭和死亡DDI-32β -阻滞剂 + 维拉帕米或地尔硫卓2(0.99)潜在的严重心血管不良反应，包括
充血性心力衰竭、严重低血压、心绞痛加重、
心室停搏、窦性停搏、心脏传导阻滞DDI-39口服NSAIDs + SSRI或SNRI2(0.99)出血、消化道出血DDI-65同时使用2种降钾药物(如b2激动剂、噻嗪类、
环型利尿剂、皮质类固醇)2(0.99)低钾血症、QT间期延长和尖端扭转型心动过速DDI-7维生素k拮抗剂 + 贝特类1(0.50)出血DDI-10维生素k拮抗剂 + 胺碘酮1(0.50)出血DDI-16达比加群 + P-gp抑制剂1(0.50)出血DDI-56口服或肠外皮质类固醇
+ 口服NSAIDs1(0.50)胃肠道溃疡或出血DDI-66SSRI + 袢利尿剂或噻嗪类利尿剂1(0.50)低钠血症，直立性低血压

表 3 社区老年人群涉及潜在的DDIs最多的药物类别和具体药物

Table 3 The most frequent drug classes and drugs involved in potential DDIs

　药品类别使用人数/例发生相关DDIs例数/(例，%)涉及DDIs最多的药品/例钙离子通道阻滞剂337105(31.16)氨氯地平(79)，硝苯地平(21)血管紧张素Ⅱ受体拮抗剂19084(44.21)厄贝沙坦(33)，氯沙坦钾(20)口服非甾体抗炎药23791(38.40)阿司匹林(91)，塞来昔布(2)利尿剂 8846(52.27)氢氯噻嗪(25)，螺内酯(15)他汀类14934(22.82)辛伐他汀(30)，阿托伐他汀(4)血管经张素转化酶抑制剂 2919(65.52)贝那普利(9)，培哚普利(4)

表 4 老年长期用药潜在DDIs关联因素的logistics分析

Table 4 Logistics analysis of potential DDIs for long-term use in the elderly

　变量OR95% CIP值药品数量　2 ~ 4种1.000　5 ~ 9种2.7511.627 ~ 4.652＜0.001　10 ~ 14种5.0062.813 ~ 8.907＜0.001　≥15种11.2705.140 ~ 24.711＜0.001衰弱(衰弱评分≥5)1.7571.184 ~ 2.6060.005有PIM2.7221.863 ~ 3.976＜0.001有心血管疾病6.7591.549 ~ 29.5010.011有糖尿病0.5950.405 ~ 0.8750.008 [1]

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