Tuesday, August 24, 2010

ACE-i - a wonder drug for Heart failure

ACE-inhibitors have long been used in heart failure due to their many beneficial effects.  Angiotensin II has shown to activate growth factors in myocardium. So blocking the RAAS with ace-i helps with regression of LV hypertrophy. As we all know, LVH is associated with increased incidence of heart failure, MI or sudden cardiac death. ace-i as we all know....are related to cough due to to inhibition of bradykinin degradation. But this is also the reason how it improves insulin sensitivity, as bradykinin increases Insulin dependent glucose uptake by cells.

With regards to clinical outcomes in patients with Heart failure, how do ace-i perform?
In 1987, CONSENSUS trial was published in NEJM. 260 patients with NYHA class 3 & 4 heart failure were randomised to enalapril Vs placebo. Cardiovascular mortality was reduced by 30% in enalapril group. There was also a significant decrease in cardiac size, and in NYHA symptoms. 7 pts in enalapril group had to stop it due to hypotension Vs none in placebo arm.

In 1991, SOLVD trial was published in NEJM. 2500 pts with LVEF < 35% and NYHA class 2 & 3 were randomised to enalapril Vs placebo. Follow up for 3.5 years. Enalapril had a 15% reduction in mortality compared to placebo. But in this study patients with creatinine >2 mg/dl or who had a tendency to increased creatinine during the run-in phase ,were excluded from the study.
In both the above studies ..the reduction in deaths were largely due to reduction in deaths due to pump failure.

In 1992, AIRE study was published in LANCET. 2000 pts were randomised to receive Enalapril Vs placebo 3-10 days after an acute MI and showing signs of Heart failure. F/U for 6 mon - 1 year. There was a 27% risk reduction in mortality, with enalapril compared to placebo. The beneficial effect was evident as early as in 30 days. An AIRE extension study (AIREX) found that the benefit extended upto 3 years after the study.

Then in 2000, HOPE trial was published in NEJM! 9000 high risk pts (age > 55) with evidence of vascular disease( CAD, PVD, stroke) or diabetes with 1 additional risk(HTN, hyperlipidemia, smoking ) were randomised to Ramipril Vs placebo. F/U for 5 years. There was a 22% reduction in cardiovascular mortality with Ramipril compared to placebo. Note that 7% of Ramipril patients stopped it due to cough.

All these studies(and many more) have shown beyond doubt, the usefulness of ACE- inhibitors along the whole spectrum of heart failure. As we all are aware of, they also have a renoprotective effect (thats an extensive topic!!). It has become such a wonder medication for Cardiologists, Internist, nephrologist, endocrinologists.........


  1. HOwever,studies has shown effect only for 40 mg,so I think you should stress that

  2. Thanks for the good point you brought up.

    This is my take on the dose. ....It is important to titrate the dose to what has been used in studies. Different studies used different medications( HOPE - 10mg Ramipril, SOLVD - 2.5 to 20mg Enalapril, CONSENSUS - 2.5 to 40mg Enalapril. But the best dose for a patient will be the dose that is tolerable, without major side effects( in this case....hypotension).For example SOLVD excluded pts..who had hypotension to Enalapril,during the run in phase!

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