Valeria Saglimbene1,2, Suetonia C Palmer3, Marinella Ruospo2, Patrizia Natale2,4, Ausilia Maione5, Antonio Nicolucci6, Mariacristina Vecchio7, Gianni Tognoni6, Jonathan C Craig1,8, Fabio Pellegrini9, Giuseppe Lucisano6, Jörgen Hegbrant2, Rosario Ariano10, Olga Lamacchia11, Antonio Sasso12, Susanna Morano13, Tiziana Filardi13, Salvatore De Cosmo14, Giuseppe Pugliese15, Deni A Procaccini16, Loreto Gesualdo4, Giuseppe Palasciano17, David W Johnson18, Marcello Tonelli19, Giovanni F M Strippoli20,2,4,21. 1. Sydney School of Public Health, Faculty of Medicine and Health, Sydney, Australia. 2. Medical Scientific Office, Diaverum Renal Services Group, Lund, Sweden. 3. Department of Medicine, University of Otago Christchurch, Christchurch, New Zealand. 4. Emergency and Organ Transplantation and. 5. Freelance Consultant (formerly Department of Clinical Pharmacology and Epidemiology, Consorzio Mario Negri Sud, S Maria Imbaro, Chieti, Italy. 6. Center for Outcomes Research and Clinical Epidemiology, Pescara, Italy. 7. Department of Hydration and Health, Danone Research, Palaiseau, France. 8. College of Medicine and Public Health, Flinders University, Health Sciences Building, Adelaide 5001, South Australia. 9. Worldwide Medical, Biogen, Cambridge, Massachusetts. 10. Department of Nephrology and Dialysis, Azienda Ospedaliera Instituti Ospedalieri di Cremona, Cremona, Italy. 11. Department of Endocrinology, Azienda Ospedaliera Universitaria Foggia, Foggia, Italy. 12. Department of Medicine, Ospedale Civile S. Pellegrino, Trani, Italy. 13. Department of Clinical Sciences, Azienda Policlinico Umberto I-Università La Sapienza, Rome, Italy. 14. Department of Medical Sciences, Scientific Institute Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy. 15. Department of Clinical and Molecular Medicine, "La Sapienza" University, Rome, Italy. 16. Division of Nephrology, University of Foggia, Foggia, Italy; Departments of. 17. Internal Medicine, University of Bari, Bari, Italy. 18. Department of Nephrology, University of Queensland at Princess Alexandra Hospital, Brisbane, Australia. 19. Research Office of the Vice-President, Cumming School of Medicine, University of Calgary, Calgary, Canada; and. 20. Sydney School of Public Health, Faculty of Medicine and Health, Sydney, Australia; gfmstrippoli@gmail.com. 21. Diaverum Academy, Bari, Italy.
Abstract
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.
RCT Entities:
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.
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