ACE-inhibition and angiotensin II receptor blockers in chronic heart failure: pathophysiological consideration of the unresolved battle.
Reducing the effects of angiotensin II by blockade of AT1-receptors may be superior to inhibition of angiotensin II formation by angiotensin converting enzyme (ACE) inhibitors in chronic heart failure (CHF) patients. However, the results of several trials did not fulfil this expectation. In both ELITE II with symptomatic CHF patients and in OPTIMAAL involving high risk patients after acute myocardial infarction, angiotensin II type I (AT1) receptor blocker (ARB) losartan did not prove to be superior to captopril. There are several potential reasons, why ARBs did not fare better than ACE inhibitors. Although AT1-receptor blockade may block the effects of non-ACE pathways of tissue angiotensin II formation, no clinical evidence is available that a more powerful inhibition of the tissue renin-angiotensin system brings improved survival. The choice of patients for clinical trials of HF therapy is not based on the level of neurohumoral activation. Thus, the more effective attenuation of angiotensin II action with ARBs may not bring additional benefits. The potential antiremodeling effect of ARBs through the stimulation of AT2 receptors by angiotensin II could be counterbalanced by a failure of AT1-receptor blockers to enhance bradykinin, nitric oxide and prostacyclin formation with antigrowth properties. Although ACE-inhibitors seem to have slightly better results at present than AT1 blockers in the battle on heart failure patient, future trials will decide which is the definitive winner.
Simko
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F
Simko
J
J
Fabryova
M
M
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D002908:Chronic Disease; D002986:Clinical Trials as Topic; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D019808:Losartan / Q000494:pharmacology / Q000627:therapeutic use; D012084:Renin-Angiotensin System / Q000502:physiology
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D019808:Losartan