CHICAGO — Telmisartan is as effective as ramipril in reducing vascular events in high-risk patients, but combining the two drugs provides no incremental benefit and increases side effects.
That was the key message of ONTARGET (the Ongoing Telmisartan Alone and in Combination With Ramipril Global End Point Trial), a 25,620-patient megatrial presented by Dr. Salim Yusuf at the annual meeting of the American College of Cardiology.
ONTARGET was designed to answer two clinically relevant questions: Is the angiotensin-receptor blocker (ARB) telmisartan an effective alternative to ramipril in the 20%–30% of patients who can't tolerate an angiotensin-converting enzyme (ACE) inhibitor because of cough, angioedema, or other side effects? And does combining two blockers of the renin-angiotensin system provide additional risk reduction?
“We found that combining the two led to some harm. This is important because there are a significant number of people out there who use combination therapy, either to have greater blood pressure lowering or to protect the kidney,” said Dr. Yusuf, lead investigator in ONTARGET and director of the Population Health Research Institute at McMaster University, Hamilton, Ont.
ONTARGET participants had vascular disease or high-risk diabetes at entry, but no heart failure. They were randomly assigned in double-blind fashion to receive 10 mg/day of ramipril, 80 mg/day of telmisartan, or both.
The primary composite end point in ONTARGET was cardiovascular death, stroke, MI, or hospitalization for heart failure. At a median follow-up of 56 months, this end point had occurred in 16.5% of the ramipril group, 16.7% in the telmisartan arm, and—to the investigators' surprise—16.3% on combination therapy. They had expected combined therapy to perform best.
Moreover, the combined therapy group had significantly higher rates of renal dysfunction, hypotensive symptoms, and diarrhea—and a 20% greater relative risk of treatment discontinuation.
Telmisartan was slightly better tolerated than ramipril, but patients known to be intolerant of ACE inhibitors were excluded from the study. They were assigned instead to TRANSCEND (the Telmisartan Randomized Assessment Study in Ace-Intolerant Subjects With Cardiovascular Disease), a placebo-controlled trial to be presented later this year at the European Society of Cardiology meeting. Dr. Yusuf reported receiving consulting fees from Boehringer Ingelheim, the ONTARGET sponsor.
A significant number of people use combination therapy, said Dr. Salim Yusuf. Vivian E. Lee/Elsevier Global Medical News