摘要
心血管及腎臟疾病的病理機轉可以用cardiorenovascular continuum的模型來解釋，它的過程包含從危險因子的暴露到內皮細胞功能不良、動脈粥狀硬化、心室肥大、白蛋白尿、心肌梗塞、到最終的心臟及腎臟衰竭。腎素－血管張力素－醛固酮系統在每一個步驟都扮演關鍵的角色，因此它的阻斷劑理當能反轉或改善疾病的進展。然而，各個阻斷劑都有本身的缺陷，因此合併使用多個不同機轉的阻斷劑理論上可以達到更完全地抑制效果。這個議題在過去十年已經被熱烈地討論，且某些研究報告是有好處的。然而，最近的資料卻對這種合併不同機轉藥物的複方治療的效果和安全性提出質疑。RESOLVD、Val HeFT、CHARM-added研究顯示合併ACEI加ARB的治療在心臟衰竭的患者可以改善某些臨床預後，但在VALLIANT研究卻發現在心肌梗塞後併發心臟衰竭的患者使用ACEI加ARB並沒有益處，ONTARGET研究也發現在心血管疾病高危險群使用ACEI加ARB並沒有改善心血管及腎臟的預後。此外，大部分的研究都發現這樣處方會增加高血鉀的風險。RALES和EPHESUS研究顯示在收縮性心臟衰竭患者給予標準的藥物治療後，加上醛固酮拮抗劑可以改善心臟衰竭住院及死亡的風險。最後，腎素直接抑制劑為新的治療的選擇，可惜最近的研究結果令人失望，它的臨床效果也還未被建立。總結來說，合併多種不同腎素－血管張力素－醛固酮系統阻斷劑的複方治療目前不建議常規地使用，除非患者的心臟衰竭在標準藥物治療後症狀仍未改善，這時使用雙重藥物治療或許可以改善某些心臟衰竭的臨床預後。
並列摘要
The pathologic mechanism of cardiovascular and renal disease could be explained by the model of cardiorenovascular continuum. It comprises a process from exposure of risk factors to endothelial dysfunction, atherosclerosis, ventricular hypertrophy, albuminuria, myocardial infarction, and finally heart and renal failure. The renin-angiotensin-aldosterone system (RAAS) plays a central role in all steps along this process. Therefore, its blockade could reasonably reverse or prevent disease progression. However, because individual blockade has their limitations, combination of drugs with different mechanisms could theoretically have more complete inhibition of RAAS. This issue has been discussed in the past decade and benefits have been reported in some studies. However, recent data has raised some controversies about the efficacy and safety of combination therapy. The RESOLVD, Val HeFT and CHARM-added studies have shown the combination of ACEI and ARB was associated with reduction of the morbidity in patients with heart failure. But the VALLIANT study did not find further benefit with ACEI and ARB in patients with acute myocardial infarction complicated by heart failure. The ONTARGET study also failed to show combination benefit of ACEI and ARB in cardiovascular and renal outcome in patient with high cardiovascular risk. Besides, increased risk of hyperkalemia was reported in most studies. The RALES and EPHESUS studies have shown the addition of an aldosterone antagonist to standard heart failure therapy conferred powerful relative risk reductions for both morbidity and mortality in systolic heart failure patients. Finally, direct renin inhibitor, as a novel RAAS blockade, may provide additional therapeutic choice. However, the recent data were disappointing and its role has yet to be established. In conclusion, combined therapy with different RAAS blockade should not be routinely used. In patients with heart failure with incomplete neuroendocrine inhibition and refractory symptoms, dual therapy might benefit in certain end points.
延伸閱讀
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