Omboni Stefano, Borghi Claudio
Clinical Research Unit, Italian Institute of Telemedicine, Varese, Italy.
Scientific Research Department of Cardiology, Science and Technology Park for Biomedicine, Sechenov First Moscow State Medical University, Moscow, Russian Federation.
Curr Clin Pharmacol. 2019;14(1):5-15. doi: 10.2174/1574884713666181025145404.
Hypertension and kidney disease often coexist, further increasing the risk of future cardiovascular events. Treatment of hypertensive adults with an angiotensin converting enzyme inhibitor in case of concomitant kidney disease may slow disease progression. The third-generation liphophilic angiotensin converting enzyme inhibitor zofenopril, administered alone or combined with a thiazide diuretic, has proved to be effective in lowering blood pressure in hypertensive patients and to reduce the risk of fatal and non-fatal events in post-acute myocardial infarction and heart failure. In almost three-hundred hypertensive patients with kidney impairment zofenopril administered for 12 weeks showed a similar blood pressure-lowering effect irrespective of the stage of the disease, with larger effects in combination with a thiazide diuretic, particularly in patients with slightly or moderately impaired kidney function. In animal models, zofenopril produced a significant and long-lasting inhibition of kidney angiotensin converting enzyme inhibitor and prevented kidney morphological and functional alterations following kidney ischemia-reperfusion injury. Treatment of hypertensive patients for 18 weeks with a combination of zofenopril 30 mg and hydrochlorothiazide 12.5 mg resulted in a reduction in albumin creatinine ratio of 8.4 mg/g (49.6% reduction from baseline values) and no changes in glomerular filtration rate, variations in line with those obtained in the control group treated with a combination of irbesartan 150 mg and hydrochlorothiazide 12.5 mg. Thus, some preliminary evidence exists to support that relatively long-term treatment with the angiotensin converting enzyme inhibitor zofenopril alone or combined with hydrochlorothiazide is effective in controlling blood pressure and may confer some kidney protection due to ACE inhibition properties.
高血压和肾脏疾病常常并存,进一步增加了未来发生心血管事件的风险。对于伴有肾脏疾病的高血压成人患者,使用血管紧张素转换酶抑制剂进行治疗可能会减缓疾病进展。第三代亲脂性血管紧张素转换酶抑制剂佐芬普利,单独使用或与噻嗪类利尿剂联合使用,已被证明在降低高血压患者血压以及降低急性心肌梗死后和心力衰竭患者的致命和非致命事件风险方面是有效的。在近三百名肾功能不全的高血压患者中,佐芬普利治疗12周显示出相似的降压效果,与疾病阶段无关,与噻嗪类利尿剂联合使用时效果更大,尤其是在轻度或中度肾功能受损的患者中。在动物模型中,佐芬普利对肾脏血管紧张素转换酶产生了显著且持久的抑制作用,并预防了肾脏缺血再灌注损伤后的肾脏形态和功能改变。用30毫克佐芬普利和12.5毫克氢氯噻嗪联合治疗高血压患者18周,导致白蛋白肌酐比值降低8.4毫克/克(较基线值降低49.6%),肾小球滤过率无变化,这些变化与用150毫克厄贝沙坦和12.5毫克氢氯噻嗪联合治疗的对照组所获得的变化一致。因此,有一些初步证据支持,单独使用血管紧张素转换酶抑制剂佐芬普利或与氢氯噻嗪联合进行相对长期的治疗在控制血压方面是有效的,并且由于其对ACE的抑制特性可能会提供一定的肾脏保护作用。