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At a press conference held in Johannesburg on Tuesday, it was revealed that there is no additional protective benefit when the angiotensin II receptor blocker telmisartan and ramipril, an angiotensin-converting enzyme inhibitor, are combined in the treatment of patients at high risk for cardiovascular events.
However, the international ONTARGET trial did establish that telmisartan (80mg) is as protective as, but better tolerated than, ramipril (10mg).
Two drugs interchangeable
Currently, ramipril is the gold standard in reducing cardiovascular death, heart attacks, stroke and hospitalisation for congestive heart failure in a broad cross-section of high-risk cardiovascular patients. But, as a significant percentage of patients experience coughing as a side effect of the drug, researchers have hoped that telmisartan, a drug which has a similar effect while working in a different way, would prove to be an effective alternative.
The ONTARGET trial (conducted over a period of five years in 25 620 patients from around the world) did indeed show that the two drugs work equally well: cardiovascular events occurred in 16.7% of patients receiving telmisartan versus 16.5% of patients receiving ramipril.
In 2000, the HOPE trial showed that the cardiovascular risk for patients treated with ramipril is reduced by approximately 20% compared with placebo. This meant that every fifth serious cardiovascular event in a high-risk group of patients was prevented. A similar effect can now be attributed to telmisartan, with the added benefit that fewer patients experience coughing when using this drug.
According to the ONTARGET researchers, 360 patients in the ramipril treatment arm stopped their treatment because they experienced coughing versus only 93 patients in the telmisartan arm.
"The coughing is a major issue that actually leads people to stop the medication in significant numbers," commented Professor Pinhas Sareli, Honorary Research Associate at the University of the Witwatersrand's Cardiovascular Pathophysiology and Genomics Research Unit. Telmisartan now gives these patients a second option.
Patients using telmisartan were also less inclined to experience angioneurotic oedema - a life-threatening swelling of the throat and airways.
Drug-combo hope shattered
But researchers had hoped that the combination of the two drugs would pack an extra punch. It was anticipated that combining the angiotensin-converting enzyme inhibitor, ramipril, and the angiotensin II receptor blocker, telmisartan, would offer better protection compared to a single drug aimed at blocking the renin-angiotensin system. Since the early 70s, researchers have known that this system plays a primary role in the progression of heart disease.
Unfortunately, however, an added benefit couldn't be found. "Marrying the drugs didn't materialise in terms of a better clinical outcome," Sareli said.
Professor James Ker, Clinical Head at the Department of Internal Medicine of the University of Pretoria, explained that researchers are "extremely interested" to know what blocks angiotensin II – a peptide that causes constriction of blood vessels and which stimulates the release of hormones that increase blood pressure.
Heart disease is the leading cause of death worldwide, causing over 17.5 million deaths per year. In South Africa, it's the second biggest killer behind HIV/Aids and kills around 200 people a day, according to Ker.
Drugs already available in SA
Both telmisartan and ramipril are available – and have, in fact, been used for years – in the public and private health sectors of South Africa. This is the first time, however, that it has been established that the drugs are interchangeable in terms of clinical benefits.
Ramipril is available in the generic form (and also under brand names such as Ramace, Ramiwin, Rampil, Rilace and Tritace), whereas telmisartan is marketed as Micardis.
The results of the ONTARGET trial, which is the largest cardiovascular trial ever undertaken, were released earlier this week at the 57th Annual Scientific Session of the American College of Cardiology in Chicago.
The trial was sponsored by pharmaceutical giant Boehringer Ingelheim, which manufactures Micardis.
- (Carine van Rooyen, April 2008)
Read more: Angiotensin II receptor blockers
