TRANSCEND Study Misses Primary Endpoint

August 31, 2008 by Scott P. Williams [mailto:swilliams@perfuse.org]

ESC Congress 2008- Munich, DE: Researchers from McMaster University reported that the angiotensin-receptor blocker (ARB), telmisartan, while well tolerated by patients and associated with a modest reduction in the secondary outcome of cardiovascular death, myocardial infarction, and stroke, failed to meet its primary endpoint. These results were presented by Dr. Koon Teo, on behalf of the TRANSCEND (Telmisartan Randomized AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease) Study investigators, as part of the Hot Line at the ESC 2008 Congress. The full results were published online today in The Lancet.

The TRANSCEND Study was composed of 5926 patients who are unable to tolerate angiotensin-converting enzyme (ACE) inhibitors. Following a three-week run-in period patients were randomized to either 80 mg/day of telmisartan (n=2954) or placebo (n=2972). Patients were recruited at 630 centers located in 40 countries. The duration of follow up was a median of 56 months, with a maximum and minimum of 64 and 51 months, respectively.

Telmisartan was well tolerated by patients. 23.8% (n=705) of patients in the placebo group permanently discontinued study drug compared to 21.6% (n=639) of patients who received telmisartan (p=0.055). The most frequent reason for study drug discontinuation was hypotensive symptoms, which was more frequent in patients who received telmisartan (0.54% [n=16] vs. 0.98% [n=29]). Patients who received telmisartan had a lower mean blood pressure than patients who received placebo in this study.

The trial’s primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, stroke, or hospitalization for heart failure. 17.0% (n=504) of patients who received placebo sustained this composite outcome compared to 15.7% (n=465) of patients who received telmisartan (hazard ratio 0.92, 95% CI 0.81–1.05, p=0.216). 14.8% (n=440) of patients in the placebo group and 13.0% (n=384) of patients in the telmisartan group suffered a secondary efficacy outcome, a composite of cardiovascular death, myocardial infarction, and stroke (0.87, 0.76–1.00, p=0.048 unadjusted; p=0.068 after adjustment for multiplicity of comparisons and overlap with primary endpoint).

The TRANSCEND Study investigators call telmisartan’s lack of effect on hospitalization for heart failure “unexpected and puzzling” and consider this an area in need of further research.

The statistically significant 13% reduction in the composite occurrence of cardiovascular death, myocardial infarction, and stroke suggests thattelmisartan could prove valuable in reducing the occurrence of major cardiovascular events among patients who are unable to tolerate the standard therapy of ACE inhibitors.

The TRANSCEND Study was supported by a grant from Boehringer Ingelheim. Additionally, Dr. S. Yusuf was supported by the Heart and Stroke Foundation of Ontario, and a Senior Scientist Award from the Canadian Institutes of Health Research.

Reviewed by C. Michael Gibson, M.S., M.D.