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Telmisartan as effective as ramipril, better tolerated

Friday, April 04 2008 | Comments

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What's This? By Nancy Stanley

New data from the ONTARGET trial show that telmisartan is as effective as ramipril at reducing cardiovascular risk while resulting in fewer side effects. However, the combination of telmisartan and ramipril does not reduce cardiovascular risk more than ramipril alone and has increased side effects.

Researchers performed the double-blind, double-dummy study to determine whether telmisartan was noninferior to ramipril and whether the combination of telmisartan and ramipril was superior to ramipril alone in reducing the composite endpoint of cardiovascular death, myocardial infarction, stroke, and chronic heart failure hospitalization. After a 3-week, single-blind run-in period, the researchers randomized 25,620 patients aged >=55 years with coronary heart disease or diabetes to receive telmisartan, ramipril, or a combination of the 2 drugs.

Median follow-up was 56 months.

There was no significant difference between the 2 drugs in the primary endpoint (relative risk, 1.01; 95% CI, 0.94-1.09; P=.0038), which was below the predefined noninferiority boundary of 1.13 of the upper confidence limit. The outcome of cardiovascular death, MI, and stroke was also similar between the patients receiving telmisartan or ramipril (RR, 0.99; 95% CI, 0.91-1.07; P=.0009)

Decreases from baseline in systolic blood pressure were 6.0 mm Hg with ramipril, 6.9 mm Hg with telmisartan, and 8.4 mm Hg with the combination of the 2 drugs, while the respective decreases in diastolic BP were 4.6 mm Hg, 5.2 mm Hg, and 6.0 mm Hg.

Telmisartan was better tolerated than ramipril was, as shown by the significantly lower overall rates of permanent study drug discontinuation (P=.02). As for the reasons for stopping the study medications, hypotension was significantly more common with telmisartan versus ramipril (P=.0001), rates of syncope were similar with either therapy, but cough was significantly less common with telmisartan than it was with ramipril (P<.0001). In addition, angioedema was significantly reduced by 60% with telmisartan relative to ramipril (P=.0115).

Data also showed that there was no incremental benefit of the combination of the 2 drugs as compared with ramipril alone. Even in patient subgroups, there was no evidence of statistical heterogeneity.

Significantly more patients in the combination group than in the ramipril group stopped medications (P<.0001). Hypotension was nearly 3-fold higher with the combination group than with the ramipril group (RR, 2.75; P<.0001), while syncope was nearly doubled with the combination treatment (RR, 1.95 P=.032). Cough was no different between the 2 groups. However, diarrhea and renal impairment were more common with the combination group, "which fits in with the concept that intensive blockade of the renin-angiotensin system has an effect on the GI system," Dr. Salim Yusuf, lead researcher, noted.

"Therefore, the clinical implication is that telmisartan is a reasonable alternative to ramipril and is slightly better tolerated," he concluded.

"Combination therapy, though, is not recommended because it doesn't improve outcomes and has more side effects," Dr. Yusuf added.

This study was partially funded by Boehringer Ingelheim GmbH. (Presentation 407-1.)

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