The long-term impact of renin-angiotensin system (RAS) inhibition on cardiorenal outcomes (LIRICO): A randomized, controlled trial

Valeria Saglimbene, Suetonia C. Palmer, Marinella Ruospo, Patrizia Natale, Ausilia Maione, Antonio Nicolucci, Mariacristina Vecchio, Gianni Tognoni, Jonathan C. Craig, Fabio Pellegrini, Giuseppe Lucisano, Jörgen Hegbrant, Rosario Ariano, Olga Lamacchia, Antonio Sasso, Susanna Morano, Tiziana Filardi, Salvatore De Cosmo, Giuseppe Pugliese, Deni A. ProcacciniLoreto Gesualdo, Giuseppe Palasciano, David W. Johnson, Marcello Tonelli, Giovanni F.M. Strippoli, Long-Term Impact of RAS Inhibition on Cardiorenal Outcomes (LIRICO) Investigators, Fabio Malberti

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27 Citations (Scopus)


Background The comparative effectiveness of treatment with angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), or their combination in people with albuminuria and cardiovascular risk factors is unclear. Methods In a multicenter, randomized, open label, blinded end point trial, we evaluated the effectiveness on cardiovascular events of ACE or ARB monotherapy or combination therapy, targeting BP,130/80 in patients with moderate or severe albuminuria and diabetes or other cardiovascular risk factors. End points included a primary composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and hospitalization for cardiovascular causes and a revised end point of all-cause mortality. Additional end points included ESRD, doubling of serum creatinine, albuminuria, eGFR, BP, and adverse events. Results Because of slow enrollment, the trial was modified and stopped 41% short of targeted enrollment of 2100 participants, corresponding to 35% power to detect a 25% reduced risk in the primary outcome. Our analysis included 1243 adults, with median follow-up of 2.7 years. Efficacy outcomes were similar between groups (ACE inhibitor versus ARB, ACE inhibitor versus combination, ARB versus combination) as were rates of serious adverse events. The rate of permanent discontinuation for ARB monotherapy (6.3%) was significantly lower than for ACE inhibitor monotherapy (15.7%) or combined therapy (18.3%). Conclusions Patients may tolerate ARB monotherapy better than ACE inhibitor monotherapy. However, data from this trial and similar trials, although as yet inconclusive, show no trend suggesting differences in mortality and renal outcomes with ACE inhibitors or ARBs as dual or monotherapy in patients with albuminuria and diabetes or other cardiovascular risk factors.

Original languageEnglish
Pages (from-to)2890-2899
Number of pages10
JournalJournal of The American Society of Nephrology
Issue number12
Publication statusPublished - Dec 2018


  • angiotensin-converting enzyme (ACE) inhibitors
  • angiotensin receptor blockers (ARBs)
  • clinical trials
  • albuminuria
  • diabetes
  • cardiovascular risk factors


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