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Feb 4, 2013

No use of ACE and ARB combination.

In year 2009 Lancet retracted its previous publication of the year 2003 COOPERATE (Combination treatment of angiotensin-II receptor blocker and angiotensin-converting-enzyme inhibitor in non-diabetic renal disease) it’s says that its lead author, Naoyuki Nakao, appears to have engaged in serious scientific misconduct. COOPERATE trial showed benfit of combining ACE and ARB

Nephrologists favor this combination as combination reduces the protinuria, but this combination is associated with increased renal failure see below.

New Meta analysis

Now a new meta-analysis, with first author Dr Harikrishna Makani (St Luke's Hospital, New York), published BMJ Jan 28, 2013, states that there is no benfit of combining ACE and ARB

This new Meta analysis contained 68405 patients from 33 randomized controlled trials treated for a mean duration of one year.

Combination therapy is associated with significant reduction heart failure admission but there is no mortality benfit. Heart failure admission reduction has come from studies which contained patients with heart failure (hazard ratio 0.77; 95% CI 0.68-0.88) but in studies with patients without heart failure there was less benfit in terms of heart failure admission i.e. Hazard ratio neared value 1 (HR 0.91; 0.82-1.01).

On contrary combination therapy is associated with increased incidence of hyperkalemia 55%, increased incidence of hypotension 66%, increased incidence of renal failure 41%.

Previous trials

The Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) trials published in year 2003 showed benfit of combination in terms of mortality reduction and also reduction in hospital admission. CHARM trial benfit of patients with preserved LV systolic function was not convincing

ONTARGET trial showed that the combination was associated with a doubling of serum creatinine, increased risk of dialysis, and motility, compared with using either agent alone.

In the year 2009 Canadian Hypertension Education Program (CHEP) published in Feb 2, 2009 in the Journal of the American College of Cardiology, urged physician and patients not use combination of ACE and ARB.