The New England Journal of Medicine has published the results of the ONTARGET Study. The study compared ramipril, telmisartan or the combination of both drugs in patients at high risk of vascular events.
The study recruited 25,620 patients who were then randomised to treatment with ramipril 10mg, an angiotensin converting enzyme inhibitor (ACEI), telmisartan 80mg, an angiotensin receptor blocker (ARB), or both drugs. Baseline characteristics were similar for age, gender, ethnicity, blood pressure, smoking history and drug treatment. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, stroke, or hospitalization for heart failure and follow up was for a median of 56 months.
The primary outcome occurred in 16.5% of patients taking ramipril, 16.7% of patients taking telmisartan and 16.3% of patients taking both drugs. Statistically, there were no differences between the groups. In terms of adverse reactions and discontinuations, there was more cough in the ramipril group compared to telmisartan but fewer cases of hypotensive symptoms. The group taking the combination were more likely to discontinue treatment with higher rates of hypotensive symptoms and cough.
The authors conclude that, "telmisartan was equivalent to ramipril in patients with vascular disease or high risk diabetes and was associated with less angioedema. The combination of the two drugs was associated with more adverse events without an increase in benefit".
To date, this is the largest comparative study of an ACEI and an ARB. It confirms that ARBs are no better than ACEIs in prevention of cardiovascular events. The higher acquisition cost of ARBs must be weighed very carefully against the small advantage of lower incidence of cough. This study also indicates that using a combination of ACEI and ARB is not justified in routine practice and is only likely to be appropriate in patients with heart failure as indicated by the CHARM-Added study.
Action: Clinicians should ensure that ACEIs are used in preference to ARBs and that ARBs are only used in cases of genuine intolerance to ACEIs. The combined use of ACEI and ARB is not justified in routine practice.