Elsevier

American Heart Journal

Volume 184, February 2017, Pages 88-96
American Heart Journal

Clinical Investigation
Atorvastatin for high-risk statin-naïve patients undergoing noncardiac surgery: The Lowering the Risk of Operative Complications Using Atorvastatin Loading Dose (LOAD) randomized trial

https://doi.org/10.1016/j.ahj.2016.11.001Get rights and content

Background

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 18 hours before surgery), followed by a maintenance dose of 40 mg (or placebo), started at least 12 hours after the surgery, and then 40 mg/d (or placebo) for 7 days. The primary outcome was a composite of all-cause mortality, nonfatal myocardial injury after noncardiac surgery, and stroke at 30 days.

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.

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;

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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.

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