Clinical InvestigationAtorvastatin for high-risk statin-naïve patients undergoing noncardiac surgery: The Lowering the Risk of Operative Complications Using Atorvastatin Loading Dose (LOAD) randomized trial
Section snippets
Trial design
The LOAD trial was an investigator-initiated, multicenter, pragmatic, randomized (concealed) controlled trial of atorvastatin vs placebo in high-risk patients undergoing noncardiac surgery. Participants, health care providers, data collectors, clinical outcomes adjudicators, and the study statistician were blinded to whether patients received atorvastatin or placebo. All centers (see Appendix 1) obtained approval from their institution review board before randomizing a patient, and all patients
Patients
From a total of 648 patients enrolled in the study between April 2013 and June 2015, 1 patient withdrew their informed consent. Of the overall study population, 328 were assigned to atorvastatin, and 320 to placebo. The 30-day follow-up was complete for 642 (99.1%) of the 648 patients (Fig. 1).
The baseline clinical characteristics were well balanced between the atorvastatin and the placebo groups (Table I), except for the following characteristics: there was a higher proportion of women and
Discussion
In this multicenter exploratory randomized trial involving high-risk statin-naïve patients undergoing noncardiac surgery, statin therapy did not significantly reduce the risk of major vascular events 30 days after surgery. Nevertheless, the point estimates for the main study outcomes are suggestive of a possible beneficial effect of moderate size, but the wide CIs did not allow us to infer reliably if statin use resulted in either a reduction or an increase in any of the outcomes examined.
Authors' contributions
Otavio Berwanger, Renato D. Lopes, and Lucas Damiani had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
OB conceived, designed, and supervised the study; obtained funding; analyzed and interpreted the data; drafted and revised the manuscript; and was co-chair of the steering committee. PGMBS participated in the design and supervision of the study, was member of the clinical events classification committee, and
Disclosures
All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare the following: no support from any organization for the submitted work, no financial relationships to any organizations that might have an interest in the submitted work in the previous 3 years, and no other relationships or activities that could appear to have influenced the submitted work.
Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study;
References (21)
- et al.
An estimation of the global volume of surgery: a modelling strategy based on available data
Lancet
(2008) - et al.
Atorvastatin decreases C-reactive protein–induced inflammatory response in pulmonary artery smooth muscle cells by inhibiting nuclear factor-kappab pathway
Cardiovasc Ther
(2010) - et al.
Hmg-coa reductase inhibitor, fluvastatin, has cholesterol-lowering independent “direct” effects on atherosclerotic vessels in high cholesterol diet–fed rabbits
Pharmacol Res
(2003) - et al.
Atorvastatin pretreatment improves outcomes in patients with acute coronary syndromes undergoing early percutaneous coronary intervention: results of the ARMYDA-ACS randomized trial
J Am Coll Cardiol
(2007) - et al.
Reduction in cardiovascular events after vascular surgery with atorvastatin: a randomized trial
J Vasc Surg
(2004) - et al.
Evidence of pre-procedural statin therapy a meta-analysis of randomized trials
J Am Coll Cardiol
(2010) - et al.
Efficacy and safety of ldl-lowering therapy among men and women: meta-analysis of individual data from 174,000 participants in 27 randomised trials
Lancet
(2015) - et al.
The effects of lowering ldl cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials
Lancet
(2012) - et al.
Cardiac complications in patients undergoing major noncardiac surgery
N Engl J Med
(2015) - et al.
Effects of preoperative statin therapy on cytokines after cardiac surgery
Thorac Cardiovasc Surg
(2006)
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Clinical trial registration: Clinicaltrials.gov Identifier: NCT01543555
Funding/Support: This study was funded by the Brazilian Ministry of Health in Partnership with Hospital do Coracao–“Programa Hospitais de Excelencia a Servico do SUS” (Brazilian Public Health System)–PROADI-SUS” and study drugs were provided by “EMS Indústria Farmaceutica.” These sources had no role in study design and had no influence on the study execution, analyses, final manuscript writing, and decision about publication, all of which were the responsibility of the Trial Steering Committee. The authors declare that they have no competing interests.
Charles J. Davidson, MD served as guest editor for this article.