Effect of Loading Dose of Atorvastatin Prior to Planned Percutaneous Coronary Intervention on Major Adverse Cardiovascular Events in Acute Coronary Syndrome: The SECURE-PCI Randomized Clinical Trial

Abstract

Importance: The effects of loading doses of statins on clinical outcomes in patients with acute coronary syndrome (ACS) and planned invasive management remain uncertain.

Objective: To determine if periprocedural loading doses of atorvastatin decrease 30-day major adverse cardiovascular events (MACE) in patients with ACS and planned invasive management.

Design, setting, and participants: Multicenter, double-blind, placebo-controlled, randomized clinical trial conducted at 53 sites in Brazil among 4191 patients with ACS evaluated with coronary angiography to proceed with a percutaneous coronary intervention (PCI) if anatomically feasible. Enrollment occurred between April 18, 2012, and October 6, 2017. Final follow-up for 30-day outcomes was on November 6, 2017.

Interventions: Patients were randomized to receive 2 loading doses of 80 mg of atorvastatin (n = 2087) or matching placebo (n = 2104) before and 24 hours after a planned PCI. All patients 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, defined as a composite of all-cause mortality, myocardial infarction, stroke, and unplanned coronary revascularization through 30 days.

Results: Among the 4191 patients (mean age, 61.8 [SD, 11.5] years; 1085 women [25.9%]) enrolled, 4163 (99.3%) completed 30-day follow-up. A total of 2710 (64.7%) underwent PCI, 333 (8%) underwent coronary artery bypass graft surgery, and 1144 (27.3%) had exclusively medical management. At 30 days, 130 patients in the atorvastatin group (6.2%) and 149 in the placebo group (7.1%) had a MACE (absolute difference, 0.85% [95% CI, -0.70% to 2.41%]; hazard ratio, 0.88; 95% CI, 0.69-1.11; P = .27). No cases of hepatic failure were reported; 3 cases of rhabdomyolysis were reported in the placebo group (0.1%) and 0 in the atorvastatin group.

Conclusions and relevance: Among patients with ACS and planned invasive management with PCI, periprocedural loading doses of atorvastatin did not reduce the rate of MACE at 30 days. These findings do not support the routine use of loading doses of atorvastatin among unselected patients with ACS and intended invasive management.

Trial registration: clinicaltrials.gov Identifier: NCT01448642.

Figure 1.. Flow of Participants Through the Statins Evaluation in Coronary Procedures and Revascularization Trial

PCI indicates percutaneous coronary intervention. Considering the pragmatic nature of the study, not all sites collected complete and detailed information of patients who would be eligible but not randomized because of lack of adequate time to obtain informed consent. Patients who were lost to 30-day follow-up or withdrew consent were censored at hospital discharge in the time-to-event analysis.

Figure 2.. Cumulative Incidence of the Primary Outcome

HR indicates hazard ratio; NSTEMI, non–ST-segment elevation myocardial infarction; STEMI, ST-segment elevation myocardial infarction. The combined primary outcome of major adverse cardiovascular events (MACE) included all-cause mortality, acute myocardial infarction, stroke, and unplanned coronary revascularization occurrence in all patients. Panels B-D show primary outcome occurrence in patients who underwent percutaneous coronary intervention (PCI) and in patients who did not undergo PCI. There were 4 patients (2 in each group) for whom information regarding PCI could not be obtained. These patients were not included in the subgroup analyses (PCI and no PCI subgroups). P=.04 for interaction between PCI and non-PCI and P=.13 for interaction between groups in panels C and D.

Figure 3.. Subgroup Analysis of the Primary Outcome

NSTEMI indicates non–ST-segment elevation myocardial infarction; STEMI, ST-segment elevation myocardial infarction. Size of the data markers indicates size of hazard ratios. P values were calculated by interaction parameters in the Cox regression model. ^aAmong patients undergoing PCI, 2643 (98%) received a stent.