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[高血压治疗的回顾性研究与展望]

[Retrospective studies and prospects of therapy for hypertension].

作者信息

Maisch B, Brilla C, Kruse T, Noll B, Bethge C

机构信息

Abteilung Innere Medizin-Schwerpunkt Kardiologie-der Philipps-Universität Marburg.

出版信息

Herz. 1995 Dec;20(6):370-89.

PMID:8582697
Abstract

Future trends in hypertensive treatment have to rely on our past and present experience with antihypertensive drugs as well as on emerging concepts of blood pressure regulation, on which some new drugs in the "pipeline" are based. Early detection of hypertension, before organ manifestations particularly in the heart, the kidney and the vessels occur, remain mandatory since in most of the patients with mild and moderate hypertension the high blood pressure is not diagnosed at all or treated inadequately. Prevention of cardiac, vascular, renal or metabolic complications has always been better for the patient and less costly than their repair or reparation. Our present treatment goals have often not reached far enough. Normalisation of blood pressure demonstrates only surrogate efficacy of our treatment. Our ultimate goal has to be improvement of total or cerebrovascular or cardiovascular and cardiac mortality. Important steps on that road are the prevention or reparation of cardiac hypertrophy, of the increased extracellular matrix and collagen deposition, the conservation of vascular integrity including both coronary and systemic microangiopathy and macroangiopathy. For the patient this means integrated care of his associated disorders that is of coronary artery disease, diabetes mellitus, lipid disorders, overweight and the metabolic syndrome. True health efficacy (= reduction of total or cerebro- and cardiovascular mortality) has been demonstrated so far only by blood pressure reduction with diuretics (thiazides) and beta-blockers in long term studies, whereas sufficient surrogate efficacy, the lowering of blood pressure, has been demonstrated with almost all the others drugs either in mono- or in combinationtherapy. Together with ACE-inhibitors, which have demonstrated their prognostic value in patients with heart failure of different causes, thiazides (as the most representative diuretic) and betablockade can be considered first line drugs in the treatment of hypertension. Long-term mortality trials for ACE-inhibitors in hypertension are needed, however, to prove that the anticipated benefit from the heart failure megatrials can also be taken for granted for hypertensive patients without coronary artery disease as well. All other drugs should not or not yet be considered first line medication, although treatment behavior in the US and in Europe shows wide-spread use of calcium antagonists in short- and long-acting dihydropyridine type hypertensive patients. No peer reviewed journal has so far published a randomized double-blind trial with the endpoint of total or cardiovascular mortality in hypertension using calcium antagonists. A recent case control study, as well as the preliminary data from MIDAS and GLANT, for which event rates are available in abstract form, suggest that short acting calcium-antagonists of the dihydropyridine type, though controlling blood pressure well, are not reducing mortality but show a trend to increase cardiovascular events particularly when given in higher doses. In contrast the unpublished data from a Chinese megatrial with dihydropyridines (STONE) demonstrate effective blood pressure reduction and benefit in mortality in a population that differs from patients in Europe and in the USA because of the low prevalence of coronary artery disease. No randomized, double blindly acquired data on mortality as the primary end of antihypertensive treatment are yet available for verapamil, diltiazem and the new class of longer acting calciumantagonists. Only when speculating from trials with calcium antagonists in coronary artery disease e.g. the DAVIT II study, one could imagine so far that prognostic benefit may be expected from drugs that do not or very little activate the adrenergic and the renin-angiotensin-aldosterone system and the baroreceptors and reduce or at least maintain heart rate. The need for double blind, randomized trials with the different Ca-antagonists is obvious, before a further w

摘要

高血压治疗的未来趋势必须依赖于我们过去和现在使用抗高血压药物的经验,以及血压调节的新观念,一些处于研发阶段的新药正是基于这些观念。在器官出现病变,尤其是心脏、肾脏和血管病变之前尽早发现高血压仍然至关重要,因为在大多数轻度和中度高血压患者中,高血压根本未被诊断出来或治疗不充分。预防心脏、血管、肾脏或代谢并发症对患者来说始终比修复这些并发症更好,成本也更低。我们目前的治疗目标往往还不够远大。血压正常化仅显示了我们治疗的替代疗效。我们的最终目标必须是降低全因死亡率、脑血管或心血管及心脏死亡率。在这条道路上的重要步骤包括预防或修复心脏肥大、细胞外基质增加和胶原沉积,保护血管完整性,包括冠状动脉和全身微血管及大血管病变。对患者来说,这意味着综合治疗其相关疾病,即冠状动脉疾病、糖尿病、脂质紊乱、超重和代谢综合征。到目前为止,在长期研究中,只有通过使用利尿剂(噻嗪类)和β受体阻滞剂降低血压才显示出真正的健康疗效(即降低全因死亡率、脑血管和心血管死亡率),而几乎所有其他药物无论是单药治疗还是联合治疗都显示出足够的替代疗效,即降低血压。与已在不同病因心力衰竭患者中证明其预后价值的ACE抑制剂一起,噻嗪类(作为最具代表性的利尿剂)和β受体阻滞剂可被视为高血压治疗的一线药物。然而,需要进行ACE抑制剂治疗高血压的长期死亡率试验,以证明心力衰竭大型试验中预期的益处也能理所当然地适用于无冠状动脉疾病的高血压患者。所有其他药物不应或尚未被视为一线药物,尽管在美国和欧洲的治疗行为显示,钙拮抗剂在短效和长效二氢吡啶类高血压患者中广泛使用。到目前为止,尚无同行评审期刊发表过以高血压患者全因或心血管死亡率为终点的随机双盲试验。最近一项病例对照研究以及MIDAS和GLANT的初步数据(事件发生率可从摘要形式获取)表明,二氢吡啶类短效钙拮抗剂虽然能很好地控制血压,但并不能降低死亡率,反而显示出增加心血管事件的趋势,尤其是在高剂量使用时。相比之下,一项中国关于二氢吡啶类药物的大型试验(STONE)未发表的数据表明,在一个因冠状动脉疾病患病率低而与欧美患者不同的人群中,该药物能有效降低血压并对死亡率有益。对于维拉帕米、地尔硫䓬和新型长效钙拮抗剂,尚无关于以死亡率作为抗高血压治疗主要终点的随机双盲数据。只有从冠状动脉疾病中使用钙拮抗剂的试验(如DAVIT II研究)进行推测,目前可以想象,对于那些不激活或很少激活肾上腺素能和肾素 - 血管紧张素 - 醛固酮系统以及压力感受器并降低或至少维持心率的药物,可能预期有预后益处。在进一步推广使用不同的钙拮抗剂之前,显然需要进行双盲、随机试验。

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