Results of the ONTARGET and TRANSCEND studies: an update and discussion.
The renin angiotensin aldosterone system (RAAS) plays an important role in the pathophysiology of cardiovascular disease. Angiotensin converting enzyme inhibitors (ACEi) have proven benefit in reducing cardiovascular events in patients at high risk. Angiotensin receptor blockers (ARB) have been demonstrated to have benefit in the management of heart failure and to be non-inferior to ACEi in patients with left ventricular dysfunction after a myocardial infarction (MI). Yet until now, there has been no trial to support the use of the ARB for vascular protection. The ONTARGET study showed that the ARB telmisartan conserved 95% of the vascular protective properties of the ACEi ramipril, given at similar doses to a similar patient group as had been previously shownin the HOPE study to benefit from ACE inhibition with ramipril. The TRANSCEND study in a similar population of patients who were intolerant of ACEi despite the primary endpoint being neutral, showed a trend to a benefit for the combined secondary endpoint of cardiovascular death, MI and stroke, with excellent tolerance of the ARB. The reasons for neutral result of the TRANSCEND study result include an underpowered study, and pre-treatment with a RAAS inhibitor in a high proportion of patients. These studies indicate that an ARB can be used for vascular protection in high risk individuals in the place of an ACEi. However ACEi will probably remain the first choice due to the greater body of supportive evidence.
St Michael's Hospital, and University of Toronto, Toronto, Ontario, Canada. fitchettd@smh.toronto.on.ca
David
D
Fitchett
D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D002986:Clinical Trials as Topic; D004359:Drug Therapy, Combination; D019317:Evidence-Based Medicine; D006801:Humans; D008875:Middle Aged; D009203:Myocardial Infarction / Q000517:prevention & control; D018579:Patient Selection; D017410:Practice Guidelines as Topic; D012084:Renin-Angiotensin System / Q000187:drug effects*; D012107:Research Design; D018570:Risk Assessment; D020521:Stroke / Q000517:prevention & control; D016896:Treatment Outcome
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors