Holzgreve H, Middeke M
University of Munich, Medizinische Poliklinik, Germany.
Drugs. 1992;44 Suppl 1:67-73. doi: 10.2165/00003495-199200441-00013.
Several long term trials using traditional antihypertensive therapy with diuretics and beta-blockers have shown that antihypertensive therapy reduces the overall risk of cardiovascular complications. However, even after several years of therapy the cardiovascular risk in hypertensive patients cannot be lowered to that in the normotensive population. Antihypertensive therapy can reduce the incidence of cerebrovascular complications in patients with hypertension by about 65%. However, the effect of such therapy in preventing coronary events has been disappointing, as these events are 3 to 4 times more common than cerebrovascular complications in hypertensive patients. It is now apparent that adverse pharmacological effects of diuretics and beta-blockers on lipid metabolism persist for many years. Thus, treatment with these agents constitutes a new risk factor for coronary heart disease and may, at least in part, explain the failure of traditional antihypertensive therapy to reduce the incidence of myocardial infarction and sudden death as effectively as that of cerebrovascular accidents. On the other hand, titration of these antihypertensive agents to the lowest possible dose in order to avoid metabolic alterations and subjective adverse effects has frequently resulted in the administration of subtherapeutic doses, particularly for hydrochlorothiazide. Until comparative long term clinical trials with older and newer antihypertensive agents and morbidity and mortality as end-points are completed, the debate on first-line drugs for antihypertensive treatment will not be satisfactorily resolved.
几项使用利尿剂和β受体阻滞剂进行传统抗高血压治疗的长期试验表明，抗高血压治疗可降低心血管并发症的总体风险。然而，即使经过数年治疗，高血压患者的心血管风险仍无法降至正常血压人群的水平。抗高血压治疗可使高血压患者脑血管并发症的发生率降低约65%。然而，这种治疗在预防冠心病事件方面的效果却令人失望，因为在高血压患者中，这些事件的发生率比脑血管并发症高3至4倍。现在很明显，利尿剂和β受体阻滞剂对脂质代谢的不良药理作用会持续多年。因此，使用这些药物进行治疗构成了冠心病的一个新的危险因素，并且至少在一定程度上可以解释传统抗高血压治疗在降低心肌梗死和猝死发生率方面不如降低脑血管意外发生率有效的原因。另一方面，为了避免代谢改变和主观不良反应而将这些抗高血压药物滴定至尽可能低的剂量，常常导致给予低于治疗剂量的药物，尤其是氢氯噻嗪。在以 older和更新的抗高血压药物以及发病率和死亡率作为终点的比较长期临床试验完成之前，关于抗高血压治疗一线药物的争论将无法得到令人满意的解决。
