Korean Circ J.  2019 May;49(5):419-433. 10.4070/kcj.2018.0341.

Benefit of Early Statin Initiation within 48 Hours after Admission in Statin-Naïve Patients with Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention

• Kim MC
• Ahn Y
• Cho JY
• Lee KH
• Sim DS
• Yoon NS
• Yoon HJ
• Kim KH
• Hong YJ
• Park HW
• Kim JH
• Jeong MH
• Cho JG
• Park JC
• Chang K
• Seung KB

• KMID: 2444961
• DOI: http://doi.org/10.4070/kcj.2018.0341

Abstract

BACKGROUND AND OBJECTIVES
Although current guidelines recommend early initiation of statin in patients with acute myocardial infarction (AMI), there is no consensus for optimal timing of statin initiation.
METHODS
A total of 3,921 statin-naïve patients undergoing percutaneous coronary intervention were analyzed, and divided into 3 groups according to statin initiation time: group 1 (statin initiation <24 hours after admission), group 2 (24-48 hours) and group 3 (≥48 hours). We also made 3 stratified models to reduce bias: model 1 (<24 hours vs. ≥24 hours), model 2 (<48 hours vs. ≥48 hours) and model 3 (<24 hours vs. 24-48 hours). The endpoint was major adverse cardiac events (MACE; composite of cardiac death, myocardial infarction and target-vessel revascularization) during median 3.8 years.
RESULTS
During follow-up, incidence of MACE was lower in early statin group in both model 1 (14.3% vs. 18.4%, hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.66-0.91; p=0.002) and model 2 (14.6% vs. 19.7%, HR, 0.81; 95% CI, 0.67-0.97; p=0.022). After propensity-score matching, results remained unaltered. Statin initiation <24 hours reduced MACE compared to statin initiation ≥24 hours in model 1. Statin initiation <48 hours also reduced MACE compared to statin initiation later in model 2. However, there was no difference in incidence of MACE between statin initiation <24 hours and 24-48 hours) in model 3.
CONCLUSIONS
Early statin therapy within 48 hours after admission in statin-naïve patients with AMI reduced long-term clinical outcomes compared with statin initiation later. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02385682

Keyword

Myocardial infarction; Hydroxymethylglutaryl-CoA reductase inhibitors; Percutaneous coronary intervention

MeSH Terms

Bias (Epidemiology)
Consensus
Death
Follow-Up Studies
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors*
Incidence
Myocardial Infarction*
Percutaneous Coronary Intervention*
Hydroxymethylglutaryl-CoA Reductase Inhibitors

Figure

• 

  Figure 1 Kaplan-Meier curves for cumulative incidence of cardiac death, myocardial infarction or TVR in patients who received statin <24 hours vs. ≥24 hours (A), <48 hours vs. ≥48 hours (B), and <24 hours vs. 24–48 hours (C) after admission.AMI = acute myocardial infarction; MI = myocardial infarction; TVR = target-vessel revascularization.

• 

  Figure 2 Subgroup analysis of major adverse cardiac events in model 2 (<48 hours vs. ≥48 hours).CI = confidence interval; DM = diabetes mellitus; GFR = glomerular filtration rate; LAD = left anterior descending; LCX = left circumflex; LM = left main; LVEF = left ventricular ejection fraction; NSTEMI = non-ST-segment elevation myocardial infarction; RCA = right coronary artery; STEMI = ST-segment elevation myocardial infarction.

Reference

1. Ibanez B, James S, Agewall S, et al. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: the task force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2018; 39:119–177. PMID: 28886621.

2. Roffi M, Patrono C, Collet JP, et al. 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: task force for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2016; 37:267–315. PMID: 26320110.

3. O'Gara PT, Kushner FG, Ascheim DD, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013; 61:e78–140. PMID: 23256914.

4. Amsterdam EA, Wenger NK, Brindis RG, et al. 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014; 64:e139–228. PMID: 25260718.

5. Kim MC, Ahn Y, Cho KH, et al. Early statin therapy within 48 hours decreased one-year major adverse cardiac events in patients with acute myocardial infarction. Int Heart J. 2011; 52:1–6. PMID: 21321460.

6. Li YH, Wu HL, Yang YH, Tsai HS, Chao TH. Effect of early versus late in-hospital initiation of statin therapy on the clinical outcomes of patients with acute coronary syndrome. Int Heart J. 2007; 48:677–688. PMID: 18160760.

7. Fonarow GC, Wright RS, Spencer FA, et al. Effect of statin use within the first 24 hours of admission for acute myocardial infarction on early morbidity and mortality. Am J Cardiol. 2005; 96:611–616. PMID: 16125480.

8. Aronow HD, Novaro GM, Lauer MS, et al. In-hospital initiation of lipid-lowering therapy after coronary intervention as a predictor of long-term utilization: a propensity analysis. Arch Intern Med. 2003; 163:2576–2582. PMID: 14638557.

9. Lenderink T, Boersma E, Gitt AK, et al. Patients using statin treatment within 24 h after admission for ST-elevation acute coronary syndromes had lower mortality than non-users: a report from the first Euro Heart Survey on acute coronary syndromes. Eur Heart J. 2006; 27:1799–1804. PMID: 16820364.

10. Newby LK, Kristinsson A, Bhapkar MV, et al. Early statin initiation and outcomes in patients with acute coronary syndromes. JAMA. 2002; 287:3087–3095. PMID: 12069671.

11. Briel M, Schwartz GG, Thompson PL, et al. Effects of early treatment with statins on short-term clinical outcomes in acute coronary syndromes: a meta-analysis of randomized controlled trials. JAMA. 2006; 295:2046–2056. PMID: 16670413.

12. Choo EH, Chang K, Ahn Y, et al. Benefit of β-blocker treatment for patients with acute myocardial infarction and preserved systolic function after percutaneous coronary intervention. Heart. 2014; 100:492–499. PMID: 24395980.

13. Kim MC, Cho JY, Jeong HC, et al. Impact of postdischarge statin withdrawal on long-term outcomes in patients with acute myocardial infarction. Am J Cardiol. 2015; 115:1–7. PMID: 25456863.

14. Cutlip DE, Windecker S, Mehran R, et al. Clinical end points in coronary stent trials: a case for standardized definitions. Circulation. 2007; 115:2344–2351. PMID: 17470709.

15. Kurth T, Walker AM, Glynn RJ, et al. Results of multivariable logistic regression, propensity matching, propensity adjustment, and propensity-based weighting under conditions of nonuniform effect. Am J Epidemiol. 2006; 163:262–270. PMID: 16371515.

16. Lee CH, Lee SH, Park JS, et al. Impact of statin usage patterns on outcomes after percutaneous coronary intervention in acute myocardial infarction: Korea Working Group on Myocardial Infarction registry (KorMI) study. J Geriatr Cardiol. 2014; 11:93–99. PMID: 25009557.

17. Rosenson RS, Farkouh ME, Mefford M, et al. Trends in use of high-intensity statin therapy after myocardial infarction, 2011 to 2014. J Am Coll Cardiol. 2017; 69:2696–2706. PMID: 28571633.

18. Liu Z, Xu Y, Hao H, et al. Efficacy of high intensity atorvastatin versus moderate intensity atorvastatin for acute coronary syndrome patients with diabetes mellitus. Int J Cardiol. 2016; 222:22–26. PMID: 27448700.

19. Cannon CP, Blazing MA, Giugliano RP, et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015; 372:2387–2397. PMID: 26039521.

20. Lee KH, Jeong MH, Kim HM, et al. Benefit of early statin therapy in patients with acute myocardial infarction who have extremely low low-density lipoprotein cholesterol. J Am Coll Cardiol. 2011; 58:1664–1671. PMID: 21982310.

21. Sposito AC, Santos SN, de Faria EC, et al. Timing and dose of statin therapy define its impact on inflammatory and endothelial responses during myocardial infarction. Arterioscler Thromb Vasc Biol. 2011; 31:1240–1246. PMID: 21372302.

22. Grundy SM, Cleeman JI, Merz CN, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation. 2004; 110:227–239. PMID: 15249516.

23. Kenaan M, Seth M, Aronow HD, et al. Preprocedural statin use in patients undergoing percutaneous coronary intervention. Am Heart J. 2014; 168:110–116.e3. PMID: 24952867.

24. Ko DT, Wijeysundera HC, Yun L, Austin PC, Cantor WJ, Tu JV. Effectiveness of preprocedural statin therapy on clinical outcomes for patients with stable coronary artery disease after percutaneous coronary interventions. Circ Cardiovasc Qual Outcomes. 2011; 4:459–466. PMID: 21712520.

25. Greque GV, Serrano CV Jr, Strunz CM, et al. Preprocedural statin therapy, inflammation, and myocardial injury in low-risk stable coronary artery disease patients submitted to coronary stent implantation. Catheter Cardiovasc Interv. 2016; 87:222–229. PMID: 23592528.

26. Kim JS, Kim J, Choi D, et al. Efficacy of high-dose atorvastatin loading before primary percutaneous coronary intervention in ST-segment elevation myocardial infarction: the STATIN STEMI trial. JACC Cardiovasc Interv. 2010; 3:332–339. PMID: 20298994.

27. Yun KH, Jeong MH, Oh SK, et al. The beneficial effect of high loading dose of rosuvastatin before percutaneous coronary intervention in patients with acute coronary syndrome. Int J Cardiol. 2009; 137:246–251. PMID: 18706705.

28. Patti G, Pasceri V, Colonna G, 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; 49:1272–1278. PMID: 17394957.

29. Hwang D, Kim HK, Lee JM, et al. Effects of statin intensity on clinical outcome in acute myocardial infarction patients. Circ J. 2018; 82:1112–1120. PMID: 29491327.