In a subgroup of high-risk Asians, telmisartan was non-inferior to ramipril and better tolerated in the prevention of cardiovascular events

Antonio L Dans, Koon Teo, Peggy Gao, Jyh-Hong Chen, Kim Jae-Hyung, Khalid Yusoff, Suphachai Chaithiraphan, Jun Zhu, Liu Lisheng, Salim Yusuf, Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial Investigators, Antonio L Dans, Koon Teo, Peggy Gao, Jyh-Hong Chen, Kim Jae-Hyung, Khalid Yusoff, Suphachai Chaithiraphan, Jun Zhu, Liu Lisheng, Salim Yusuf, Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial Investigators

Abstract

Background and objectives: Results of the recently published ONTARGET study (The Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial) showed that telmisartan (80 mg/day) was non-inferior to ramipril (10 mg/day) in reducing cardiovascular events. Clinicians in Asia doubt tolerability of these doses for their patients. We therefore analyzed data from this study and a parallel study TRANSCEND (Telmisartan Randomized Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease). Our objectives were to compare Asians and non-Asians with respect to the following: 1) Effectiveness of telmisartan vs. ramipril in reducing cardiovascular events;2) Proportions who reached the full dose of telmisartan, ramipril or placebo; and3) Proportions of overall discontinuations, and discontinuations due to adverse effects.

Method: The ONTARGET study randomized 25,620 patients at risk of cardiovascular events to ramipril, telmisartan, or their combination. The primary composite endpoint was death caused by cardiovascular disease, acute MI, stroke, and hospitalization because of congestive heart failure. TRANSCEND randomized 5926 high-risk patients with a history of intolerance to ACE-inhibitors to telmisartan or placebo. The primary outcome was the same. In this substudy, we compared Asians and non-Asians as to how well they tolerated telmisartan (given in both studies) and ramipril (given in ONTARGET).

Results: 1) Telmisartan was non-inferior to ramipril in lowering the primary endpoint among Asians (RR = 0.92; 95% CI: 0.74, 1.13); 2) more Asians achieved the full dose of either drug; 3) less withdrew (overall); and 4) less withdrew for adverse effects. Furthermore, telmisartan was better tolerated than ramipril. This advantage was greater among Asians.

Conclusion and significance: Although Asians had lower BMI than non-Asians, Asians tolerated both drugs better. Regulatory agencies require reporting of safety and effectiveness data by ethnicity, but few comply with this requirement. This study shows that safety data in ethnic subgroups can help assess applicability of results to specific populations.

Trial registration: ClinicalTrials.gov NCT00153101.

Conflict of interest statement

Competing Interests: Except for Peggy Gao, all the authors have received research funds from the sponsors, grants for travel to scientific meetings, and honoraria for lectures. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials, as detailed online in the guide for authors.

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