Otavio Berwanger1, Pedro G M de Barros E Silva2, Roberto Ramos Barbosa3, Dalton Bertolim Precoma4, Estêvão Lanna Figueiredo5, Ludhmila Abrahão Hajjar6, Cleber Dario Pinto Kruel7, Carolina Alboim7, Adail Paixão Almeida8, Marianna Deway Andrade Dracoulakis9, Hugo Vargas Filho10, Maria José Carvalho Carmona11, Lília Nigro Maia12, João Bosco de Oliveira Filho13, Jose Francisco Kerr Saraiva14, Rafael M Soares15, Lucas Damiani15, Denise Paisani15, Alessandra A Kodama15, Beatriz Gonzales15, Dimas T Ikeoka15, Philip J Devereaux16, Renato D Lopes17. 1. Research Institute-Hospital do Coracao (HCOR), São Paulo, Brazil. Electronic address: oberwanger@hcor.com.br. 2. Research Institute-Hospital do Coracao (HCOR), São Paulo, Brazil; Brazilian Clinical Research Institute (BCRI), São Paulo, Brazil. 3. Santa Casa de Vitória, Vitória, Espírito Santo, Brazil. 4. Hospital Angelina Caron, Campina Grande do Sul, Paraná, Brazil. 5. Hospital Lifecenter, Belo Horizonte, Minas Gerais, Brazil. 6. Instituto do Câncer do estado de São Paulo (ICESP), Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, São Paulo, Brazil. 7. Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil. 8. Hospital Unimec, Vitória da Conquista, Bahia, Brazil. 9. Hospital da Bahia, Salvador, Bahia, Brazil. 10. Hospital São Vicente de Paulo, Passo Fundo, Rio Grande do Sul, Brazil. 11. Divisão de Anestesia Instituto Central-Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil. 12. Hospital de Base-São José do Rio Preto, São Paulo, Brazil. 13. Instituto de Medicina Integral Prof. Fernando Figueira - IMIP, Recife, Pernambuco, Brazil. 14. Hospital e Maternidade Celso Pierro, Campinas, São Paulo, Brazil. 15. Research Institute-Hospital do Coracao (HCOR), São Paulo, Brazil. 16. Population Health Research Institute (PHRI), Hamilton, Canada. 17. Brazilian Clinical Research Institute (BCRI), São Paulo, Brazil; Duke Clinical Research Institute, Durham, NC.
Abstract
Preliminary evidence suggests that statins may prevent major perioperative vascular complications. METHODS: We randomized 648 statin-naïve patients who were scheduled for noncardiac surgery and were at risk for a major vascular complication. Patients were randomized to a loading dose of atorvastatin or placebo (80 mg anytime within 18hours before surgery), followed by a maintenance dose of 40 mg (or placebo), started at least 12hours after the surgery, and then 40 mg/d (or placebo) for 7days. The primary outcome was a composite of all-cause mortality, nonfatal myocardial injury after noncardiac surgery, and stroke at 30days. RESULTS: The primary outcome was observed in 54 (16.6%) of 326 patients in the atorvastatin group and 59 (18.7%) of 316 patients in the placebo group (hazard ratio [HR] 0.87, 95% CI 0.60-1.26, P=.46). No significant effect was observed on the 30-day secondary outcomes of all-cause mortality (4.3% vs 4.1%, respectively; HR 1.14, 95% CI 0.53-2.47, P=.74), nonfatal myocardial infarction (3.4% vs 4.4%, respectively; HR 0.76, 95% CI 0.35-1.68, P=.50), myocardial injury after noncardiac surgery (13.2% vs 16.5%; HR 0.79, 95% CI 0.53-1.19, P=.26), and stroke (0.9% vs 0%, P=.25). CONCLUSION: In contrast to the prior observational and trial data, the LOAD trial has neutral results and did not demonstrate a reduction in major cardiovascular complications after a short-term perioperative course of statin in statin-naïve patients undergoing noncardiac surgery. We demonstrated, however, that a large multicenter blinded perioperative statin trial for high-risk statin-naïve patients is feasible and should be done to definitely establish the efficacy and safety of statin in this patient population.
RCT Entities:
Preliminary evidence suggests that statins may prevent major perioperative vascular complications. METHODS: We randomized 648 statin-naïve patients who were scheduled for noncardiac surgery and were at risk for a major vascular complication. Patients were randomized to a loading dose of atorvastatin or placebo (80 mg anytime within 18hours before surgery), followed by a maintenance dose of 40 mg (or placebo), started at least 12hours after the surgery, and then 40 mg/d (or placebo) for 7days. The primary outcome was a composite of all-cause mortality, nonfatal myocardial injury after noncardiac surgery, and stroke at 30days. RESULTS: The primary outcome was observed in 54 (16.6%) of 326 patients in the atorvastatin group and 59 (18.7%) of 316 patients in the placebo group (hazard ratio [HR] 0.87, 95% CI 0.60-1.26, P=.46). No significant effect was observed on the 30-day secondary outcomes of all-cause mortality (4.3% vs 4.1%, respectively; HR 1.14, 95% CI 0.53-2.47, P=.74), nonfatal myocardial infarction (3.4% vs 4.4%, respectively; HR 0.76, 95% CI 0.35-1.68, P=.50), myocardial injury after noncardiac surgery (13.2% vs 16.5%; HR 0.79, 95% CI 0.53-1.19, P=.26), and stroke (0.9% vs 0%, P=.25). CONCLUSION: In contrast to the prior observational and trial data, the LOAD trial has neutral results and did not demonstrate a reduction in major cardiovascular complications after a short-term perioperative course of statin in statin-naïve patients undergoing noncardiac surgery. We demonstrated, however, that a large multicenter blinded perioperative statin trial for high-risk statin-naïve patients is feasible and should be done to definitely establish the efficacy and safety of statin in this patient population.
Authors: Nathaniel R Smilowitz; Gabriel Redel-Traub; Anais Hausvater; Andrew Armanious; Joseph Nicholson; Christian Puelacher; Jeffrey S Berger Journal: Cardiol Rev Date: 2019 Nov/Dec Impact factor: 2.644
Authors: Alessandro Putzu; Carolina Maria Pinto Domingues de Carvalho E Silva; Juliano Pinheiro de Almeida; Alessandro Belletti; Tiziano Cassina; Giovanni Landoni; Ludhmila Abrahao Hajjar Journal: Ann Intensive Care Date: 2018-09-27 Impact factor: 6.925