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Abstract: FR-PO1060

Dual Renin-Angiotensin System Blockade: A Meta-Analysis of Cardiovascular and Renal Outcomes

Session Information

Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

  • 1800 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

Authors

  • Vaidya, Satyanarayana R., Emory University School of Medicine, Decatur, Georgia, United States
  • Ali, Waleed, University of chicago, Chicago, Illinois, United States
  • Rajabalan, Ajai S., Emory University School of Medicine, Decatur, Georgia, United States
  • Bailey, James L., Emory University School of Medicine, Decatur, Georgia, United States
Background

Dual renin-angiotensin (RAS) blockade has shown to decrease blood pressure, proteinuria and hospitalization due to heart failure (HF). We intended to evaluate its efficacy and safety in HF, diabetes mellitus (DM), hypertension (HTN), and chronic kidney disease (CKD).

Methods

All randomized trials comparing dual RAS blockade with monotherapy in HF, CKD, DM, and HTN as of January 31, 2019, were identified after searching the PubMed, EMBASE, and CENTRAL databases. Those which compared the dual RAS blockade [Angiotensin converting enzyme inhibitor+ Angiotensin receptor blocker] (ACEI + ARB) or [Direct Renin inhibitor (DRI), aliskiren combined with ACEI or ARB] with monotherapy (ACEI or ARB) were selected. Major outcomes were all-cause and cardiovascular mortality, progression to end-stage renal disease (ESRD), and hospitalization due to HF. Minor outcomes were proteinuria, BP change, renal failure, hyperkalemia, hypotension, and withdrawal due to adverse events.

Results

Eighty-one studies fulfilled the inclusion criteria, yielding 76,866 patients. When compared to monotherapy, the dual RAS blockade reduced blood pressure and proteinuria. In HF subgroup, dual RAS blockade reduced hospitalizations due to HF [relative risk (RR)=0.82, 95% CI0.71-0.94; P=0.004], [number needed to treat (NNT=15)], but had no effect on all-cause mortality (RR=0.98, 95% CI=0.88-1.09; P=0.72) and cardiovascular mortality (RR=0.92, 95% CI=0.79-1.06; P=0.25). Despite a decrease in blood pressure of 11.7 / 7.5 mm Hg in the HTN subgroup and a decrease in proteinuria, dual RAS blockade failed to slow progression to ESRD and was associated with increased rates of renal failure, hyperkalemia, hypotension, and withdrawal due to adverse effects. Neither in DM or CKD were there any outcome benefits.

Conclusion

When compared to monotherapy, dual RAS blockade failed to improve morbidity and mortality in HF, CKD, DM, and hypertension but reduced hospitalizations due to HF. Dual RAS blockade failed to slow progression to ESRD and led to higher withdrawal rates because of adverse effects.

Summary forest plot of outcomes in CKD subgroup