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Randomized Controlled Trial
. 2018 Nov 1;3(11):1113-1118.
doi: 10.1001/jamacardio.2018.3408.

Timing of Loading Dose of Atorvastatin in Patients Undergoing Percutaneous Coronary Intervention for Acute Coronary Syndromes: Insights From the SECURE-PCI Randomized Clinical Trial

Renato D Lopes  1   2 , Pedro G M de Barros E Silva  1   3 , Isabella de Andrade Jesuíno  3 , Eliana Vieira Santucci  3 , Lilian Mazza Barbosa  1 , Lucas Petri Damiani  3 , Renato Hideo Nakagawa Santos  3 , Ligia Nasi Laranjeira  3 , Frederico Toledo Campo Dall Orto  4 , Pedro Beraldo de Andrade  5 , Igor Ribeiro de Castro Bienert  6 , John H Alexander  2 , Christopher B Granger  2 , Otavio Berwanger  3
Affiliations
Randomized Controlled Trial

Timing of Loading Dose of Atorvastatin in Patients Undergoing Percutaneous Coronary Intervention for Acute Coronary Syndromes: Insights From the SECURE-PCI Randomized Clinical Trial

Renato D Lopes et al. JAMA Cardiol. .

Erratum in

Abstract

Importance: Loading doses of atorvastatin did not show reduction on clinical outcomes in the overall population of patients with acute coronary syndrome (ACS) enrolled in the Statins Evaluation in Coronary Procedures and Revascularization (SECURE-PCI) trial, but a potential benefit was identified in patients who subsequently underwent percutaneous coronary intervention (PCI).

Objectives: To determine whether periprocedural loading doses of atorvastatin are associated with decreased 30-day major adverse cardiovascular events (MACE) in patients with ACS undergoing PCI according to type of ACS and timing of atorvastatin administration before PCI.

Design, setting, and participants: Secondary analysis of a multicenter, double-blind, placebo-controlled, randomized clinical trial conducted at 53 sites that enrolled 4191 patients with ACS intended to be treated with PCI between April 18, 2012, and October 06, 2017.

Interventions: Patients were randomized to 2 loading doses of 80 mg of atorvastatin or matching placebo before and 24 hours after a planned PCI. By protocol, all patients (regardless of treatment group) received 40 mg of atorvastatin for 30 days starting 24 hours after the second dose of study medication.

Main outcomes and measures: The primary outcome was MACE through 30 days, composed by all-cause mortality, myocardial infarction, stroke, and unplanned coronary revascularization. Cox regression models adjusting for key baseline characteristics were used to assess the association between atorvastatin and MACE in patients undergoing PCI.

Results: From the overall trial population, 2710 (64.7%) underwent PCI (650 women [24.0%]; mean [SD] age, 62 [11.3] years). Loading atorvastatin was associated with reduced MACE at 30 days by 28% in the PCI group (adjusted hazard ratio [HR], 0.72; 95% CI 0.54-0.97; P = .03). Loading dose of atorvastatin was administered less than 12 hours before PCI in 2548 patients (95.3%) (45.1% < 2 hours and 54.3% between 2 and 12 hours). There was no significant interaction between treatment effect and timing of study drug administration. The treatment effect of loading atorvastatin was more pronounced in patients with ST-segment elevation myocardial infarction than in patients with non-ST-segment elevation ACS (adjusted HR, 0.59; 95% CI, 0.38-0.92; P = .02; HR, 0.85; 95% CI, 0.58-1.27; P = .43, respectively).

Conclusions and relevance: In patients with ACS undergoing PCI, periprocedural loading doses of atorvastatin appeared to reduce the rate of MACE at 30 days, most clearly in patients with ST-segment elevation myocardial infarction. This beneficial effect seemed to be preserved and consistent, irrespective of the timing of atorvastatin administration, including within 2 hours before PCI.

Trial registration: clinicaltrials.gov Identifier: NCT01448642.

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Conflict of interest statement

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Alexander reports personal fees from AstraZeneca, Janssen Pharmaceuticals, Merck, Novo Nordisk Pharmaceuticals, Pfizer, Portola Pharmaceuticals, VA Cooperative Studies Program, and Zafgen; grants and personal fees from Bristol Myers Squibb; and grants from Boehringer Ingelheim, CryoLife, CSL Behring, US National Institutes of Health, US Food and Drug Administration, Tenax Therapeutics, VoluMetrix, and Sanofi outside the submitted work. Dr Berwanger reports grants and personal fees from AstraZeneca, Bayer, and Boehringer-Ingelheim; grants from Amgen and Roche Diagnosis; and personal fees from NovoNordisk and Novartis outside the submitted work. Dr Granger reports personal fees from Abbvie, Boston Scientific, Gilead Science, Medscape, Medtronic Inc, Merck, Novo Nordisk, Roche Diagnostics, Rho Pharmaceuticals, Sirtex, and Verseon; grants from Apple and Medtronic Foundation; and grants and personal fees from Bayer, Boehringer Ingelheim, Bristol Myers Squibb, GlaxoSmithKline, Janssen Phamaceutical, Novartis, and Pfizer outside the submitted work. Drs Jesuino, Laranjeira, Santos, and Santucci report grants from Program to Support Institutional Development of Universal System from the Brazilian Ministry of Health during the conduct of the study. Dr Lopes reports grants from Amgen; personal fees from Bayer, Boehringer Ingleheim, and Portola; and grants and personal fees from Bristol Myers Squibb, GlaxoSmithKline, Pfizer, and Sanofi-Aventis outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Analysis of Treatment Effect According to the Timing of Atorvastatin Before Percutaneous Coronary Intervention (PCI)
A, 52 Patients did not receive study drug before PCI (25 atorvastatin and 27 placebo). B, 22 Patients did not receive study drug before PCI (10 atorvastatin and 12 placebo). C, 28 Patients did not receive study drug before PCI (14 atorvastatin and 14 placebo).
Figure 2.
Figure 2.. Cumulative Incidence of Primary Outcome
Composite of all-cause mortality, acute myocardial infarction, stroke, and unplanned coronary revascularization in the percutaneous coronary intervention (PCI) population according to previous use of statin or not (P = .71 for interaction between treatment effect and previous use of statin). MACE indicates major adverse cardiovascular event.
See this image and copyright information in PMC

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