ONTARGET results a boon to Asian patients

Medical Tribune June 2008 SFXV

David Brill

The results of the ONTARGET trial should give doctors more confidence in prescribing angiotensin receptor blockers (ARBs) to patients who cannot tolerate angiotensin converting enzyme (ACE) inhibitors – something that is more common among Asian patients, according to a Singapore cardiologist.

One study of 111 patients found ACE inhibitor intolerance among Chinese patients to be as high as 53 percent, whereas the incidence appears to be lower among Caucasian patients.[Am J Cardio 1995 May 1;75(14):967-8]

The reasons for this discrepancy are currently unknown, according to Dr. Bernard Kwok, senior consultant at the National Heart Centre, Singapore and one of the ONTARGET investigators in the region. He speculates that it could result from genetic differences.

Around 33 percent of heart failure patients at Kwok’s center develop cough in response to ACE inhibitor therapy, although this reaction usually disappears within 2 weeks of switching to an ARB. However, until recently, there was a lack of data to support the use of ARBs as an alternative for these patients.

“Finally, ONTARGET tells us that this is the correct thing to do and, more importantly, it tells us that telmisartan should be the preferred ARB in this case,” said Kwok.

The trial found that telmisartan was non-inferior to the ACE inhibitor ramipril in reducing cardiovascular events among high-risk patients without heart failure. Some 4,000 of the study’s 25,620 subjects came from Asian countries, including China, Singapore and Malaysia.

“The patients who were studied in ONTARGET … are very representative of the type of patients that we see on a daily basis,” said Kwok.

“We can no longer say ‘oh this study was done in Americans or Europeans so the results may not apply to Asians.’ These results should apply globally.”

The study also demonstrated that telmisartan was better tolerated than ramipril. The drug was associated with significantly lower rates of cough (1.1 percent compared to 4.2 percent) – the most common side effect of ACE inhibitors – and angioedema (.1 percent compared to .3 percent).

Despite these findings Kwok does not believe that ARBs should become first-line therapy for all cardiac patients, owing to the greater cost-effectiveness of ACE inhibitors. ARBs should be reserved for those who cannot take ACE inhibitors, he said.

The results of ONTARGET were presented earlier this year at the annual meeting of the American College of Cardiology and subsequently published in the New England Journal of Medicine. The efficacy of ARBs had been previously documented in subgroups of patients such as those with heart failure and hypertension, but had not been established in the broader-
risk population included in the study.

Future trials are likely to assess the role of ARBs in other subgroups such as patients who have
had a myocardial infarction, said Kwok.