Angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) appear most effective in preventing end-stage renal disease (ESRD) in patients with diabetes and kidney disease, although no regimen to lower blood pressure seems to prolong survival, a recent analysis has found.
Researchers performed a network meta-analysis of randomized trials comparing the effects of oral blood pressure-lowering agents in adults who had diabetic kidney disease. The primary outcomes were all-cause mortality and ESRD; secondary safety and cardiovascular outcomes were also assessed. All drug regimens were ranked comparatively against placebo. The study results were published online on May 23 by The Lancet.
Overall, 157 studies involving 43,256 patients were included in the meta-analysis. The mean patient age was 52.5 years. The drug classes compared with placebo or standard treatment were ACE inhibitors, ARBs, aldosterone antagonists, beta-blockers, calcium-channel blockers, endothelin inhibitors, and renin inhibitors. None of the drug regimens examined appeared to be more effective in reducing all-cause mortality. ESRD was significantly less likely in patients treated with an ARB and an ACE inhibitor (odds ratio, 0.62; 95% CI, 0.43 to 0.90) and in those treated with only an ARB (odds ratio, 0.77; 95% CI, 0.65 to 0.92) versus those treated with placebo.
Hyperkalemia and acute kidney injury did not appear to increase significantly with any regimen (calcium-channel blocker, beta-blocker, ACE inhibitor plus diuretic, endothelin inhibitor, diuretic, renin inhibitor, ARB, ACE inhibitor, aldosterone antagonist, and ACE inhibitor plus ARB for hyperkalemia; ACE inhibitor plus calcium-channel blocker, calcium-channel blocker, ACE inhibitor, renin inhibitor, endothelin inhibitor, ARB, aldosterone antagonist, and ACE inhibitor plus ARB for acute kidney injury). However, the authors noted that ACE inhibitor plus ARB was the regimen with the highest odds ratios for these 2 outcomes (odds ratios, 2.69 [95% CI, 0.97 to 7.47] and 2.69 [95% CI, 0.98 to 7.38]).
The authors noted that their study had limited primary data, that data for the ESRD outcome came mainly from patients with macroalbuminuria and patients with type 2 diabetes, and that acute kidney injury was not well defined, among other limitations. They concluded that based on available evidence, lowering blood pressure in adults with diabetes and kidney disease does not appear to improve survival but that ACE inhibitors and ARBs, together or alone, appear most effective in preventing ESRD in this population.
"However, we must consider the potential harms of these treatments in individual patients," the authors wrote. "Surveillance for treatment-related acute kidney injury and hyperkalaemia is important, as is better standardisation of the definitions of these adverse events and improved understanding of their outcomes, particularly in the context of future trials." They also noted that their results don't support the use of beta-blockers, calcium-channel blockers, renin inhibitors, or diuretic monotherapy in this patient population.
The authors of an accompanying comment said that the results "reignite the debate" about the utility of dual renin-angiotensin-aldosterone system (RAAS) blockade and said that the findings will help researchers design future trials examining this question. The comment authors pointed out that preventive treatments for end-stage kidney failure are urgently needed in diabetic patients.
"Screening for albuminuria and prompt initiation of lifestyle and pharmacological interventions is likely to prevent progression of chronic kidney disease and cardiovascular disease," they wrote. "Addition of dual ACE inhibitor and ARB treatment to this multifactorial management approach—if confirmed to be efficacious and cost effective—might further improve patients' outcomes in regions of the world where careful selection of patients and close monitoring are possible."