Worsening renal function during renin-angiotensin-aldosterone system inhibitor initiation and long-term outcomes in patients with left ventricular systolic dysfunction.
OBJECTIVE
Impaired renal function is associated with worse clinical outcomes in patients with LV systolic dysfunction (LVSD) and heart failure. Renin-angiotensin-aldosterone system (RAAS) inhibitors provide clinical benefit in these settings and often worsen renal function. It is not clear whether worsening renal function (WRF) in patients exposed to these agents predicts a worse prognosis or merely reflects the pharmacological action of the drug on the kidney.


RESULTS
We performed a meta-analysis of all RAAS inhibitor LVSD trials reporting on outcomes according to WRF (as per individual study definition) in both active intervention and placebo groups. Five major studies (SOLVD, SAVE, RALES, Val-HeFT and EPHESUS) contributed, with 20 573 patients. Compared with placebo, RAAS inhibitors reduced all-cause mortality overall [n = 20 573, relative risk ratio (RR) 0.91, 95% confidence interval (CI) 0.86-0.95, P = 0.0003], in the group with no WRF (n = 18 209, RR 0.91, 95% CI 0.83-0.99, P = 0.04), and in the WRF group (n = 2364, RR 0.72, 95% CI 0.62-0.84, P < 0.0001). Compared with no WRF, WRF was associated with increased all-cause mortality; however, this was less in the RAAS inhibitor group (n = 8905, RR 1.22, 95% CI 1.10-1.36, P = 0.0003) than in the placebo group (n = 9304, RR 1.52, 95% CI 1.37-1.69, P < 0.00001).


CONCLUSIONS
WRF shortly after randomization is associated with worsened outcomes compared with no WRF; however, the reduction in all-cause mortality associated with the use of RAAS inhibitors was significantly greater in the presence of WRF than in the no WRF group. Clinicians should not be deterred from using RAAS inhibitors in the setting of WRF.
Centre of Cardiovascular Research & Education in Therapeutics, School of Public Health and Preventive Medicine, Monash University, Victoria, 3004, Australia.
Hannah
H
Clark
Henry
H
Krum
Ingrid
I
Hopper
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D018450:Disease Progression; D005500:Follow-Up Studies; D014943:Global Health; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006801:Humans; D015994:Incidence; D007668:Kidney / Q000187:drug effects*; D011379:Prognosis; D051437:Renal Insufficiency / Q000453:epidemiology / Q000209:etiology / Q000503:physiopathology; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013997:Time Factors; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy* / Q000503:physiopathology
D000806:Angiotensin-Converting Enzyme Inhibitors
Angiotensin receptor blocker; Heart failure; Mineralocorticoid receptor antagonists; RAAS inhibitors; Renal impairment; Worsening renal function