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ACE inhibitors but not angiotensin II receptor blockers cut deaths and major cardiovascular events in diabetes patients

Angiotensin-converting enzyme inhibitors (ACEIs) reduce deaths and major cardiovascular events in patients with diabetes mellitus whereas angiotensin II receptor blockers (ARBs) lack these benefits, a meta-analysis has found.

The pooled analysis of 35 randomised controlled trials suggests that ACEIs should be considered as first-line therapy to limit excess mortality and morbidity in this population, say the study authors writing in JAMA Internal Medicine (online, 31 March 2014).

X-ray showing heart failure

Source: Vesna Njagulj /

Angiotensin II receptor blockers reduced the risk of heart failure in patients with diabetes

Steve McGlynn, specialist principal pharmacist (cardiology) at NHS Greater Glasgow and Clyde, told PJ Online that “although it is difficult to not agree with the authors’ headline conclusion, there are a lot of interesting data when the trials are grouped on the basis of the comparators used and the clinical outcomes studied to show the variability of results within the trials included in the analysis”. He added: “The lack of benefit of the ARBs on outcomes other than heart failure, despite the prevalence of hypertension in the study groups, is of particular interest.”

The meta-analysis was undertaken by Jianghua Chen, from The First Affiliated Hospital, Zhejiang, China, and colleagues. It included 23 clinical trials that compared ACEIs with placebo or active drug in a total of 32,827 patients and 13 trials that compared ARBs with no therapy in 23,867 patients.

In the meta-analysis, ACEIs reduced the risks of all-cause mortality, CV death, major CV events, myocardial infarction and heart failure, with risk ratios of 0.87 (95 per cent confidence interval 0.78-0.98), 0.83 (CI 0.70-0.99), 0.86 (CI 0.77-0.95), 0.79 (CI 0.65-0.95), and 0.81 (CI 0.71-0.93), respectively.

ARBs had no effect on any of these endpoints, with the exception of heart failure, which had a risk ratio of 0.70 versus no treatment (CI 0.59-0.82). Neither ACEIs nor ARBs reduced the risk of stroke.

The impact of ACEI treatment on all-cause mortality and CV death was similar irrespective of patients’ age, baseline blood pressure or level of proteinuria, the type of diabetes mellitus and the type of ACEI used.

The researchers say that there is a plausible biological rationale for the different cardioprotective effects of these two classes of drug. Angiotensin-(1-7) and bradykinin antagonism occur with ACEIs but not ARBs. “The selectivity of ARBs might not necessarily be an advantage,” they write.

Citation: The Pharmaceutical Journal DOI: 10.1211/PJ.2014.11137045

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