Telmisartan Fails as Substitute for ACE Inhibitors

The angiotensin receptor blocker telmisartan (Micardis) failed to significantly prevent ischemic events among patients who cannot tolerate angiotensin-converting enzyme (ACE) inhibitors, researchers found. After almost five years of treatment, telmisartan reduced the primary outcome by just 8% (P=0.22), Koon K. Teo, M.B., Ph.D., of McMaster University in Hamilton, Ontario, reported at the European Society of Cardiology. The findings were simultaneously published online by The Lancet.

The TRANSCEND (Telmisartan Randomized AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease) trial randomized 2,954 high-risk patients to 80 mg telmisartan and 2,972 to placebo.

All patients had confirmed cardiovascular disease or diabetes and were ACE-inhibitor intolerant. Median age of patients was 67; 75% were taking aspirin, and more than half were taking a beta blocker, a statin, or both.

After a median follow-up of 56 months, 465 patients in the telmisartan group (15.7%) experienced the primary composite endpoint of cardiovascular death, myocardial infarction, stroke, or hospitalization for heart failure compared with 504 patients (16.9%) in the placebo group, a difference which was not significant (HR 0.92, 95% CI 0.81 to 1.05).

Dr. Teo said that the main secondary endpoint — reducing a composite of cardiovascular-caused death, myocardial infarction, and stroke — was achieved. Treatment with telmisartan resulted in a 13% decrease in these events compared with placebo (HR 0.87, 95% CI 0.76 to 1.00, P=0.0475), he said.

He reported that 384 patients (13%) on telmisartan experienced the endpoint compared with 440 (14.8%) of those on placebo. However, this difference became non-signi?cant after statistical adjustments were made for multiple comparisons (P=0.068).

None of these endpoints were individually significant.

Telmisartan did reduce hospitalizations for cardiovascular reasons and left-ventricular hypertrophy, and fewer patients had the combination of macrovascular and microvascular events plus microalbuminuria.

In a commentary, also published in The Lancet, Toni L. Ripley, Pharm.D., and Donald Harrison, Ph.D., of the University of Oklahoma College of Pharmacy in Oklahoma City, noted that although the TRANSCEND findings "are too limited to reach definitive conclusions, the clinical effect of angiotensin-receptor blockers seems less robust than that of angiotensin-converting-enzyme inhibitors."

They pointed out that the higher use of lipid-lowering therapy, ß blockers, and antiplatelet drugs in TRANSCEND compared with other studies, re?ects the current standard of care and would be expected to lower event rates and in?uence the size of the effect from additional therapies.

Drs. Ripley and Harrison concluded that ACE-inhibitors "should remain the preferred renin-active agent to prevent vascular events in patients with or at high-risk for cardiovascular events."

Karl Swedberg, M.D., of the University of Gothenburg in Sweden, and discussant at the session at which the TRANSCEND trial was presented, said the failure of telmisartan to perform at least as well as an ACE-inhibitor in the trial was mystifying.

He noted that telmisartan effectiveness compared with placebo appeared to emerge only after at least six months of therapy.
"Primary preventive vascular effects by angiotensin receptor blocker therapy are at best modest," said Dr. Swedberg said. "ACE-inhibitors should remain the first-line therapy for vascular protection."

Although he noted that the receptor blockers have not been found superior to ACE-inhibition, he said that the use of telmisartan and other angiotensin receptor blockers still appears reasonable as an alternative in ACE-inhibitor-intolerant patients.

Practice Pearls:

* Explain to interested patients that in this study telmisartan (Micardis) did not work any better as an alternative to ACE-inhibitors than placebo.

* Note, however, that there are several other angiotensin receptor blockers that may prove better in preventing events than telmisartan.

European Society of Cardiology 2008/The Lancet: TRANSCEND investigators "Effects of the angiotensin-receptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: a randomized controlled trial" Lancet 2008; Published online Aug. 31.

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