1. The long-term impact of renin-angiotensin system (RAS) inhibition on cardiorenal outcomes (LIRICO): A randomized, controlled trial
- Author
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Saglimbene, V., Palmer, S. C., Ruospo, M., Natale, P., Maione, A., Nicolucci, A., Vecchio, M., Tognoni, G., Craig, J. C., Pellegrini, F., Lucisano, G., Hegbrant, J., Ariano, R., Lamacchia, O., Sasso, A., Morano, S., Filardi, T., De Cosmo, S., Pugliese, G., Procaccini, D. A., Gesualdo, L., Palasciano, G., Johnson, D. W., Tonelli, M., Strippoli, G. F. M., Cignarelli, M., Di Mauro, M. D., Tonolo, G., Adinolfi, L. E., Gigante, A., Carboni, L., Anichini, R., Marino, C., Querques, M., Manfrini, S., Cianciaruso, B., Grandaliano, Giuseppe, Prato, S. D., Giorgino, F., Perin, P. C., Malberti, F., Nardo, A., Invitti, C., Panettieri, I., Bono-mini, M., Sesti, G., Altomare, E., Giordano, R., Iacono, A., Lusenti, T., Jovane, C., Zavaroni, I., Vernaglione, L., Grosso, J., Stratta, P., Andriani, A., Montanaro, A., Ciaula, A. D., Triolo, G., Santoro, A., Spada, S., Benedetto, A. D., Borzi, V., Tortul, C., Schiavoni, M., Cavalera, C., Iannarelli, R., Mileti, G., Tardi, S., Di Rosa, S., Saglimbene, V, Palmer, Ruospo, S. C., Natale, M., Maione, P., Nicolucci, A., Vecchio, A., Tognoni, M., Craig, G, Pellegrini, J. C., Lucisano, F., Hegbrant, G., Ariano, J., Lamacchia, R., Sasso, O., Morano, A., Filardi, S., Cosmo, De, Pugliese, Pier Paolo, Procaccini, G., Gesualdo, D. A., Palasciano, L., Johnson, G., Tonelli, D. W., Strippoli, M., Cignarelli, G. F. M., Mauro, Di, Tonolo, M. D., G, Adinolfi, Le, Gigante, A., Carboni, L., Anichini, R., Marino, Concetta, Querques, M., Manfrini, Cianciaruso, S., Grandaliano, B., Prato, G., Giorgino, S. D., Perin, F., Malberti, P. C., Nardo, F., Invitti, A. n., Cavalera, C., Iannarelli, C., Mileti, R., Tardi, G., and Rosa, Di
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Male ,Angiotensin-Converting Enzyme Inhibitors ,030204 cardiovascular system & hematology ,albuminuria ,clinical trial ,diabetic nephropathy ,end-stage renal disease ,mortality ,renin angiotensin system ,urologic and male genital diseases ,law.invention ,Renin-Angiotensin System ,0302 clinical medicine ,Randomized controlled trial ,Risk Factors ,law ,Settore MED/14 - NEFROLOGIA ,030212 general & internal medicine ,General Medicine ,Middle Aged ,Cardiovascular disease ,female genital diseases and pregnancy complications ,Treatment Outcome ,Cardiovascular Diseases ,Nephrology ,Hypertension ,Drug Therapy, Combination ,Female ,medicine.symptom ,medicine.drug ,medicine.medical_specialty ,Combination therapy ,End stage renal disease ,Angiotensin Receptor Antagonists ,03 medical and health sciences ,Clinical Research ,Internal medicine ,Diabetes Mellitus ,medicine ,Albuminuria ,Humans ,Adverse effect ,Aged ,business.industry ,Discontinuation ,Clinical trial ,ACE inhibitor ,business ,chronic kidney disease - 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. Copyright © 2018 by the American Society of Nephrology 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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- 2018