issues are noted: (1) the subjects were healthier than most people over age 80 years; (2) only one third had isolated systolic hypertension, the usual form of hypertension in the elderly; (3) only half reached the goal of 150/80 mm Hg; and (4) therapy was limited to the diuretic indapamide and the angiotensin-converting enzyme (ACE) inhibitor perindopril.Nonetheless, the outcome data are very impressive and will call for extension of drug treatment to patients at any age who are not suffering from terminal illness or severe dementia. The suggestive evidence that ACE inhibition may reduce the risk of Alzheimer disease by increasing degradation of amyloid-9 will likely add to the rush toward ACE inhibitor therapy in the elderly.The Misleading TrialThe Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial (ONTARGET) compared an ACE inhibitor with an angiotensin receptor blocker (ARB) and with a combination of the ACE inhibitor and the ARB.2 The trial was patterned after the Heart Outcomes Prevention Evaluation Trial10 with the same principal investigators. It was designed to show noninferiority of the ARB to the ACE inhibitor, which was shown. In particular, the equal cardioprotection by the 2 agents should settle the claim than ARBs are less effective than ACE inhibitors for myocardial protection. The combination was associated with more progressive renal dysfunction, likely from excessive lowering of blood pressure in vulnerable patients.In view of the equivalence of the 2 drugs, a not-surprising result, the major issue leading clinicians to choose one or the other would logically depend on adverse effects. In ONTARGET, the incidence of the most common adverse effect of ACE inhibitors, cough, was reported in only 4.2% to be the cause for discontinuation of the ACE inhibitor, whereas the same dose of the same ACE inhibitor was the cause for discontinuation in 7.3% of the Heart Outcomes Prevention Evaluation Trial (both 4.2% and 7.3% are below the usual reported incidence of cough, 10% to 15%, but the larger incidences are for the occurrence of cough and not the cause of discontinuation of treatment).Why the lower incidence of ACE inhibitorinduced cough? The reasons are obvious and should have at least been mentioned in the discussion of ONTARGET if not taken into account in establishing the protocol. These are as follows: (1) 60% of enrollees were already on an ACE inhibitor, weeding out those who were intolerant; (2) those who were known to be intolerant to an ACE inhibitor were shunted to a parallel study, Telmisartan Randomized Assessment Study in ACE Intolerant Subjects With Cardiovascular Disease, which has not yet been published; and (3) ramipril was given for a 3- to 4-week run-in so that, again, those who were quickly intolerant of an ACE inhibitor were not enrolled.Thus, the major adverse effect of ACE inhibitors was minimized by design, negating the well-known lesser adverse effect profile of ARBs. This may be the reason why the editorialist commenting on ONTARGET stated, "ARBs have more side effects than ACE inhibitors,"11 despite the common knowledge that they do not.12The Unpublished Trial Results of the Avoiding Cardiovascular Events Through Combination Therapy