Conclusions and Limitations

AIIRA drugs are not significantly different from, nor are they inferior to, ACE-I drugs for a broad range of patient-important effectiveness outcomes. These include cardiovascular events, mortality, quality of life, renal function, and symptoms. This conclusion applies to both monotherapy and combination therapy with ACE-Is and ARBs, and across a broad range of populations including those with heart disease, diabetic proteinuria, nondiabetic proteinuria, chronic kidney disease, and hypertension. Combination therapy with an ACE-I and an ARB, does, however, produce a reduction in proteinuria in nondiabetic proteinuria or chronic kidney disease. Rates of cough and withdrawal were generally less with ARBs than ACE-Is, and hypotension was more common with combination therapy.

Aliskirin administered with an ACE-I or ARB decreased mean urinary albumin-to-creatinine ratio in 1 study, but did not improve other renal outcomes or withdrawal rates in either available study.

There are a number of important limitations for this review. Although we attempted to compare specific ACE-Is with specific ARBs, few studies were available for many if these comparisons. If there are important intra-class differences among ACE-Is or ARBs, then valid conclusions about inter-class comparisons are limited.

Additionally, little evidence was available for evaluating inter-class differences between DRI, ACE-I and AIIRA drugs in subgroups based on age, sex, race, other medications or co-morbidities. For example, only 3 trials (< 5%) evaluated the impact of race on treatment effects, which did not provide sufficient evidence to reliably determine the comparative effectiveness and harms for most comparisons.

The data and conclusions concerning populations with cardiovascular disease including heart failure are likely applicable to broad clinical populations due to the large sample size and relatively unselected populations in a number of these trials. For populations with hypertension, nondiabetic proteinuria, chronic kidney disease, and diabetic nephropathy, the small trials with selected populations may not be applicable to populations seen in general clinical practice.