Timing of Loading Dose of Atorvastatin in Patients Undergoing Percutaneous Coronary Intervention for Acute Coronary Syndromes

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 Fromtheoveralltrialpopulation,2710(64.7%)underwentPCI(650women[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 atorvastatinwasadministeredlessthan12hoursbeforePCIin2548patients(95.3%)(45.1% < 2hours 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, primarily in patients with ST-segment elevation myocardial infarction. This beneficial effect seemed to be preserved and consistent, regardless of timing of atorvastatin administration, including within 2 hours before PCI. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01448642

Associação entre Terapia com Estatinas e Menor Incidência de Hiperglicemia em Pacientes Internados com Síndromes Coronarianas Agudas

“… 8 Contudo, um ensaio randomizado mais amplo, o SECURE-PCI, não detectou uma redução em eventos isquêmicos pós SCA com atorvastatina precoce na dose de 80 mg, 9 apesar do potencial benefício no subgrupo de pacientes submetidos à ICP após a randomização. 30 …”

“… 8 However, a larger randomized study, the SECURE-PCI trial, did not find a decrease in ischemic events after ACS with an 80 mg loading dose of atorvastatin, 9 despite a potential benefit in the subgroup of patients who were submitted to PCI after randomization. 30 …”

A Prospective, Randomized, Open-Label Trial of Atorvastatin versus Rosuvastatin in the Prevention of Contrast-Induced Acute Kidney Injury, Worsened Renal Function at 30 Days, and Clinical Events After Acute Coronary Angiography: the PRATO-ACS-2 Study

“…Atorvastatin and rosuvastatin are both high-intensity statins recommended by current guidelines as first-line therapy in ACS patients [3]. The correct timing of statin administration during the index event is still being debated [3, 33, 34]. Originally, statin prescription was recommended at discharge after an episode of ACS [35].…”

“…The time of administration was further anticipated in the first PRATO-ACS trial involving statin-naive patients with NSTEACS; early on-admission rosuvastatin resulted in a significantly lower incidence of AKI and improved 30-day and 6-month clinical outcomes, which was statistically significant in patients subjected to PCI [4]. A very recent randomized trial in 4,191 patients with ACS and a planned invasive strategy showed short-term (30 days) clinical benefits of a preprocedural high-dose atorvastatin load only in patients subjected to PCI and in patients with STEMI [33]. The present PRATO-ACS 2 study shows that early on-admission (prior to angiographic procedures) high-intensity statins provide important protection especially regarding renal function that leads to overall clinical benefits at 30 days and 12 months, with impressive better outcome in patients who do not develop AKI or WRF, irrespectively of the choice of statin.…”

Elevated levels of circulating soluble ST2 at discharge predict late adverse ventricular remodeling in patients with ST-segment elevation myocardial infarction

“…Even though early functionally restored revascularization effectively prevents alterations in ventricular architecture and thereby stop developing early adverse cardiac remodeling, there is no compelling evidence that late adverse cardiac remodeling could be effectively prevented by restoring coronary blood flow beyond the use of peri-procedural and post-procedural drugs (i.e., statins, double anti-platelet therapy, abciximab, tirofiban, ACE inhibitors, etc.) [9][10][11][12] . In this context, biomarkers would be a useful tool to indicate whether candidates for PCI are at high risk of poor clinical outcomes relating to late adverse cardiac remodeling and whether they should be treated by an alternative method.…”