血管紧张素II受体拮抗剂与心力衰竭:血管紧张素转换酶抑制剂仍是一线选择。

Angiotensin II receptor antagonists and heart failure: angiotensin-converting-enzyme inhibitors remain the first-line option.

出版信息

Prescrire Int. 2005 Oct;14(79):180-6.

DOI:
Abstract

(1) Some angiotensin-converting-enzyme inhibitors (ACE inhibitors) reduce mortality in patients with heart failure (captopril, enalapril, ramipril and trandolapril), and in patients with recent myocardial infarction and heart failure or marked left ventricular dysfunction (captopril, ramipril and trandolapril). (2) Angiotensin II receptor antagonists, otherwise known as angiotensin receptor blockers, have haemodynamic effects similar to ACE inhibitors, but differ in their mechanism of action and certain adverse effects. (3) Five clinical trials have evaluated angiotensin II receptor antagonists (candesartan, losartan and valsartan) in terms of their effect on mortality and on the risk of clinical deterioration in patients with symptomatic heart failure, but without severe renal failure, hyperkalemia or hypotension. In these trials, candesartan and valsartan were used at much higher doses than those recommended for the treatment of arterial hypertension. (4) In patients with heart failure who were not taking an angiotensin II receptor antagonist or an ACE inhibitor at enrollment, no significant difference was found between losartan and captopril in terms of mortality or the risk of clinical deterioration. (5) In patients with heart failure who had stopped taking an ACE inhibitor because of adverse effects, candesartan had no effect on mortality as compared with placebo, but it did reduce the risk of clinical deterioration (3 fewer hospitalisations per year per 100 patients). However, candesartan was associated with adverse effects such as renal failure and hyperkalemia, especially in patients who had experienced these same adverse effects while taking an ACE inhibitor. (6) In patients with heart failure who were already taking an ACE inhibitor, adjunctive candesartan or valsartan treatment did not influence mortality in comparison to the addition of a placebo. Adding candesartan or valsartan reduced the risk of hospitalisation (between 1 and 3 fewer hospitalisations per year per 100 patients), but increased the risk of renal failure and hyperkalemia. (7) In patients with heart failure and incapacitating dyspnea despite ACE inhibitor + diuretic combination therapy, there are no trials comparing the addition of an angiotensin II receptor antagonist versus spironolactone. Adjunctive spironolactone therapy prevents 5 to 6 deaths per year per 100 patients in this setting. (8) In patients with heart failure who do not have markedly altered cardiac contractility, candesartan appears to have no clinical advantages over placebo. (9) In some of these trials, mortality was higher with angiotensin II receptor antagonist therapy than with placebo among patients who were already taking a betablocker. (10) Two trials have compared an angiotensin II receptor antagonist with an ACE inhibitor in patients with recent myocardial infarction who had heart failure or an altered left ventricular ejection fraction, but who did not have hypotension or severe renal failure. However, there are no placebo-controlled randomised trials assessing the effects of angiotensin II receptor antagonists on mortality. (11) In patients with recent myocardial infarction, these trials showed no difference in mortality between angiotensin II receptor antagonist treatment (losartan or valsartan) and captopril. They did not rule out the possibility that these angiotensin II receptor antagonists are moderately less effective than captopril. Adding valsartan to ongoing captopril therapy did not reduce mortality or morbidity as compared with placebo, but did increase the risk of adverse effects. (12) Overall, these trials confirm the advantage of angiotensin II receptor antagonists over ACE inhibitors with respect to some adverse effects (cough, skin rash, etc.). However, the two drug classes share certain serious adverse effects such as hyperkalemia, renal failure and hypotension. In one trial, angioedema was less frequent with angiotensin II receptor antagonist therapy (one less case per 500 patients).

摘要

(1) 一些血管紧张素转换酶抑制剂(ACE抑制剂)可降低心力衰竭患者(卡托普利、依那普利、雷米普利和群多普利)以及近期心肌梗死合并心力衰竭或明显左心室功能障碍患者(卡托普利、雷米普利和群多普利)的死亡率。(2) 血管紧张素II受体拮抗剂,又称血管紧张素受体阻滞剂,具有与ACE抑制剂相似的血流动力学效应,但作用机制和某些不良反应有所不同。(3) 五项临床试验评估了血管紧张素II受体拮抗剂(坎地沙坦、氯沙坦和缬沙坦)对有症状心力衰竭患者(无严重肾衰竭、高钾血症或低血压)死亡率和临床恶化风险的影响。在这些试验中,坎地沙坦和缬沙坦的使用剂量远高于治疗动脉高血压的推荐剂量。(4) 在入组时未服用血管紧张素II受体拮抗剂或ACE抑制剂的心力衰竭患者中,氯沙坦和卡托普利在死亡率或临床恶化风险方面未发现显著差异。(5) 在因不良反应而停用ACE抑制剂的心力衰竭患者中,与安慰剂相比,坎地沙坦对死亡率无影响,但确实降低了临床恶化风险(每100例患者每年住院次数减少3次)。然而,坎地沙坦与肾衰竭和高钾血症等不良反应相关,尤其是在服用ACE抑制剂时曾出现过这些相同不良反应的患者中。(6) 在已经服用ACE抑制剂的心力衰竭患者中,与加用安慰剂相比,辅助使用坎地沙坦或缬沙坦治疗对死亡率无影响。加用坎地沙坦或缬沙坦可降低住院风险(每100例患者每年住院次数减少1至3次),但增加了肾衰竭和高钾血症的风险。(7) 在尽管接受ACE抑制剂 + 利尿剂联合治疗仍有严重呼吸困难的心力衰竭患者中,尚无比较加用血管紧张素II受体拮抗剂与螺内酯的试验。在这种情况下,辅助使用螺内酯治疗可使每100例患者每年预防5至6例死亡。(8) 在心脏收缩力无明显改变的心力衰竭患者中,坎地沙坦似乎比安慰剂无临床优势。(9) 在其中一些试验中,在已经服用β受体阻滞剂的患者中,血管紧张素II受体拮抗剂治疗组的死亡率高于安慰剂组。(10) 两项试验比较了血管紧张素II受体拮抗剂与ACE抑制剂对近期心肌梗死合并心力衰竭或左心室射血分数改变但无低血压或严重肾衰竭患者的影响。然而,尚无评估血管紧张素II受体拮抗剂对死亡率影响的安慰剂对照随机试验。(11) 在近期心肌梗死患者中,这些试验表明血管紧张素II受体拮抗剂治疗(氯沙坦或缬沙坦)与卡托普利在死亡率方面无差异。它们并未排除这些血管紧张素II受体拮抗剂的疗效略低于卡托普利的可能性。在正在进行的卡托普利治疗中加用缬沙坦与安慰剂相比,并未降低死亡率或发病率,但确实增加了不良反应的风险。(12) 总体而言,这些试验证实了血管紧张素II受体拮抗剂在某些不良反应(咳嗽、皮疹等)方面优于ACE抑制剂。然而,这两类药物都有某些严重不良反应,如高钾血症、肾衰竭和低血压。在一项试验中,血管紧张素II受体拮抗剂治疗引起的血管性水肿较少见(每500例患者少1例)。

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