How do ACE inhibitors, AIIRAs, and DRIs compare in effectiveness?

ACE inhibitors and AIIRAs have similar effects on important outcomes, including reducing risk of cardiovascular events and death and improving renal function and quality of life symptoms. This is found when ACE inhibitors and AIIRAs are given in combination, and when one or the other drug is used alone. The benefits are found in patients with heart disease, high blood pressure, diabetic and nondiabetic proteinuria, and chronic kidney disease. No studies were found that directly compared the effectiveness of aliskiren (DRI) to either an ACE inhibitor or an AIIRA. [details]

For detailed comparisons between DRIs, AIIRAs, and ACE inhibitors, please see the Drug Class Review.

How do ACE inhibitors, AIIRAs, and DRIs compare in harms?

Overall, fewer patients experienced cough and withdrawal with AIIRAs than with ACE inhibitors. Low blood pressure is more common when AIIRAs and ACE inhibitors are used in combination . No studies were found that directly compared the harms between aliskiren (DRI) and either an ACI inhibitor or an AIIRA. [details]

How does the direct renin inhibitor, aliskiren, compare in effectiveness and harms?

There are two studies available at this time:

• In patients with heart failure and hypertension taking either an ACE inhibitor or AIIRA, there is no significant difference between the addition of either aliskiren or placebo in serum creatine levels, adverse events, or withdrawal rates. [details]
• When added to losartan (AIIRA) in patients with diabetic nephropathy, aliskiren was superior to placebo in decreasing the urinary albumin:creatinine ratio and increasing the number of patients who achieved a 50% or greater reduction in albuminuria, but did not improve risk of death. There were no significant differences between aliskiren and placebo in risk of withdrawal or any harms outcomes. [details]

Does age or other patient factors influence effectiveness or harms?

For heart failure, there is no significant difference between ACE inhibitors and AIIRAs based on age, ejection fraction, and extent of heart failure. Among patients on prior beta-blocker therapy, however, there was a significantly higher risk of all-cause mortality or heart failure-related mortality and hospital admissions with losartan (AIIRA) than with captopril (ACE inhibitor).

For high blood pressure, the rate of cough is significantly lower for eprosartan than enalapril, regardless of age (above or below 65 years) and race (black or non-black).

When added to losartan (AIIRA) in patients with diabetic nephropathy, greater improvements in kidney function (lowered the albumin:creatinine ratio) were found for aliskiren over placebo, regardless of gender, age, or race.

Data are limited for chronic kidney disease and proteinuria not caused by diabetes. [details]

Direct renin inhibitors included in this review

Angiotensin II receptor blockers included in this review

Angiotensin converting enzyme inhibitors included in this review

Further information

This PubMed Clinical Q&A was reviewed by Kimberly Peterson, MS.

For the full report and evidence tables, please see:
Norris S, Weinstein J, Peterson K, et al. Drug Class Review: Direct Renin Inhibitors, Angiotensin Converting Enzyme Inhibitors, and Angiotensin II Receptor Blockers: Final Report [Internet]. Portland (OR): Oregon Health & Science University; 2010 Jan. Available at: http://www.ncbi.nlm.nih.gov/books/NBK47119/.