ARBs as effective as ACEIs for treating patients at risk of MI, stroke, CV morbidity and total mortality

A recent meta-analysis of published blinded randomised controlled trials comparing angiotensin II receptor blockers (ARBs) to angiotensin-converting enzyme inhibitors (ACEIs) has found that these two first-line antihypertensives, related by their association with altering the renin-angiotensin system, have equivalent efficacy in the treatment of patients at risk of a number of cardiovascular events.1 This is the first time a study has compared ARBs and ACEIs for their effect on reducing the risk of a generic suite of cardiovascular conditions based on a healthy patient population and adds weight to the argument that there is no evidence basis in selecting an ACEI over an ARB to achieve greater cardioprotective benefit.

The study, which included six previously published trials including VALIANT (valsartan in acute myocardial infarction study) and ONTARGET (the ongoing telmisartan alone and in combination with ramipril global endpoint trial) compared a range of ARBs and ACEIs to generate a composite dataset that included 31,632 patients randomised to ARBs and 18,292 patients randomised to ACEIs.

Cardiologist Paul Langton said:

"The ONTARGET study clearly shows equivalence of the ARB telmisartan with ramipril, the ACEI with arguably the best evidence of benefit in this population."

The comparisons within the meta-analysis included both ARB vs. ACEI directly, and ARB plus ACEI vs. ACEI, principally because of the inclusion of ONTARGET within the dataset.¹ Whilst VALIANT and ONTARGET comprised a large proportion of the overall patient population within the dataset, the authors of the study performed rigorous statistical analyses to ensure that no single study influenced the overall outcome on a pooled results basis.

It should be noted that the meta-analysis only included studies that assessed for risk of myocardial infarction, stroke, cardiovascular morbidity and overall mortality.¹ Thus, other cardiovascular events and outcomes such as congestive cardiac failure were omitted. Additionally, a comparison of the blood pressure reducing effects of ARBs vs ACEIs could not be included because these values were not available in several of the studies included within the meta-analysis.¹

Results from the meta-analysis found that there was no statistically significant difference between ARBs and ACEIs in terms of their protective benefit for myocardial infarction, cardiovascular morbidity and total mortality. In terms of protection against stroke as an outcome, ARBs achieved an 8% improvement compared to ACEIs for their protective benefit when compared overall. An independent analysis that examined this same relationship for ARB vs. ACEI and ARB plus ACEI vs. ACEI found a similar relationship, although the results of that study were statistically insignificant.¹

Dr Langton said that though historically ARBs have been associated with an increased risk of myocardial infarction, this is an outdated view "based on a limited and arguably unbalanced analysis of selective studies."

Thus, it can be concluded that in general terms there is equivalence between ARBs and ACEIs in their protective benefit against adverse cardiovascular events, including cardiovascular related morbidity and mortality, although the competitive inhibition of angiotensin II receptors by ARBs appears to provide additional cerebrovascular protective benefits. However, the authors do note that this effect may be class related. In contrast to findings from ONTARGET, this meta-analysis concludes that the use of ARBs is not associated with an increased risk of myocardial infarction when compared with ACEIs.¹

Dr Langton said sales figures of anti-hypertensives show a huge uptake of ARBs since their introduction and ARBs should be a valid first line choice in preference to ACEIs as an antihypertensive.

He said, "This will be recommended in the new European HTN guidelines and possibly the forthcoming JNC-8 guidelines from the US; diuretics may well shift to second or third line."

Reference

1. Reboldi G, Angeli F, Cavallini C, Gentile G, Mancia G, Verdecchia P. Comparison between angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on the risk of myocardial infarction, stroke and death: A meta-analysis. J Hypertens. 2008; 26(7): 1282-9.