Efficacy of LDL-C lowering therapy in patients with non-ST-segment elevation acute coronary syndrome: a meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

HE Xiaoling , LIU Tianyao , PAN Yilong ,  LI Xiaodong

Department of Cardiology, The Shengjing Hospital, China Medical University, Shenyang, 110000, P.R.China;

Corresponding author：

LI Xiaodong, Email: lixd189hos@163.com

Keywords：

Low-density lipoprotein-cholesterol; Non-ST-segment-elevation acute coronary syndromes; Major adverse cardiac events; RCTs; Meta analysis

DOI：

10.7507/1672-2531.201609068

Video：

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Objective To investigate the efficacy of LDL-C lowering treatment on NSTE-ACS, and to analyze the target LDL-C level for clinical treatment. Methods PubMed, EMbase, the Cochrane Central Register of Controlled Trials, Web of Science databases were searched up to January 2016 for randomized controlled trials assessing the effects of LDL-C lowering therapy on major adverse cardiac events (MACE) in patients with NSTE-ACS. Two reviewers independently screened litertures, extracted data and assessed the risk of bias of included studies, and then meta-analysis was performed by using Stata12.0 and RevMan 5.3 software. Result A total of 12 RCT including 4 702 individuals with NATE-ACS were included. The results of meta-analysis showed that, compared with the control group, the statin group could significantly reduced the risk of MACE (RR=0.68, 95% CI 0.549 to 0.834,P=0.000). With 18.68 months of follow-up, patients in target LDL-C level from over 70 mg/dL to less than 100 mg/dL group had lower risk of MACE than other LDL-C level group. When LDL-C lower 20% to 40% than baseline with 28.99 months follow-up, patients in target of LDL-C level from over 70 mg/dL to less than 100 mg/dL group had lowest risk of MACE (RR=20.143, 95% CI 6.946 to 58.414,P=0.000). Conclusion LDL-C lower treatment can lower the risk of MACE in patients with NSTE-ACS. Patients in target LDL-C level from over 70 mg/dL to less than 100 mg/dL group have relatively low risk of MACE, in which patients who lower 20% to 40% LDL-C than baseline will get more benefits from LDL-C lowering therapy.

Citation： HE Xiaoling, LIU Tianyao, PAN Yilong, LI Xiaodong. Efficacy of LDL-C lowering therapy in patients with non-ST-segment elevation acute coronary syndrome: a meta-analysis. Chinese Journal of Evidence-Based Medicine, 2017, 17(5): 550-556. doi: 10.7507/1672-2531.201609068 Copy

1.	Sherbet DP, Garg P, Brilakis ES, et al. Low-density lipoprotein cholesterol: how low can we go? Am J Cardiovasc Drugs, 2013, 13(4): 225-232.
2.	Meier P, Fröhlich GM, Meller S, et al. Selection and timing for invasive therapy in non-ST-segment-elevation acute coronary syndrome. Expert Rev Cardiovasc Ther, 2013, 11(4): 437-445.
3.	Mihos CG, Santana O. Pleiotropic effects of the HMG-CoA reductase inhibitors. Int J Gen Med, 2011, 4: 261-271.
4.	Bays HE, Neff D, Tomassini JE, et al. Ezetimibe: cholesterol lowering and beyond. Expert Rev Cardiovasc Ther, 2008, 6(4): 447-470.
5.	Gao WQ, Feng QZ, Li YF, et al. Systematic study of the effects of lowering low-density lipoprotein-cholesterol on regression of coronary atherosclerotic plaques using intravascular ultrasound. BMC Cardiovasc Disord, 2014, 14: 60.
6.	Cholesterol Treatment Trialists’ (CTT) Collaboration., Fulcher J, O’Connell R, et al. Efficacy and safety of LDL-lowering therapy among men and women: meta-analysis of individual data from 174, 000 participants in 27 randomised trials. Lancet, 2015, 385(9976): 1397-1405.
7.	Catapano AL. Perspectives on low-density lipoprotein cholesterol goal achievement. Curr Med Res Opin, 2009, 25(2): 431-447.
8.	Chinwong D, Patumanond J, Chinwong S, et al. Clinical indicators for recurrent cardiovascular events in acute coronary syndrome patients treated with statins under routine practice in Thailand: an observational study. BMC Cardiovasc Disord, 2015, 15: 55.
9.	Banerjee S, Kahali D, Banerjee A, et al. LDL cholesterol: should guidelines include targets? Expert Rev Cardiovasc Ther, 2014, 12(3): 285-290.
10.	Kanadaşi M, Cayli M, Demirtaş M, et al. The effect of early statin treatment on inflammation and cardiac events in acute coronary syndrome patients with low-density lipoprotein cholesterol. Heart Vessels, 2006, 21(5): 291-297.
11.	Dohi T, Miyauchi K, Okazaki S, et al. Early intensive statin treatment for six months improves long-term clinical outcomes in patients with acute coronary syndrome (Extended-ESTABLISH trial): a follow-up study. Atherosclerosis, 2010, 210(2): 497-502.
12.	Sato H, Kinjo K, Ito H, et al. Osaka Acute Coronary Insufficiency Study (OACIS)-LIPID Study Investigators. Effect of early use of low-dose pravastatin on major adverse cardiac events in patients with acute myocardial infarction: the OACIS-LIPID Study. Circ J, 2008, 72(1): 17-22.
13.	Tsunoda R, Sakamoto T, Kojima S, et al. Recurrence of angina pectoris after percutaneous coronary intervention is reduced by statins in Japanese patients. J Cardiol, 2011, 58(3): 208-215.
14.	Lee CH, de Feyter P, Serruys PW, et al. Beneficial effects of fluvastatin following percutaneous coronary intervention in patients with unstable and stable angina: results from the Lescol intervention prevention study (LIPS). Heart, 2004, 90(10): 1156-1161.
15.	Gao Y, Jia ZM, Sun YJ, et al. Effect of high-dose rosuvastatin loading before percutaneous coronary intervention in female patients with non-ST-segment elevation acute coronary syndrome. Chin Med J (Engl), 2012, 125(13): 2250-2254.
16.	Zhao SP, Yu BL, Peng DQ, et al. The effect of moderate-dose versus double-dose statins on patients with acute coronary syndrome in China: Results of the CHILLAS trial. Atherosclerosis, 2014, 233(2): 707-712.
17.	Jang Y, Zhu J, Ge J, et al. Preloading with atorvastatin before percutaneous coronary intervention in statin-naïve Asian patients with non-ST elevation acute coronary syndromes: A randomized study. J Cardiol, 2014, 63(5): 335-343.
18.	Gibson CM, Pride YB, Hochberg CP, et al. Effect of intensive statin therapy on clinical outcomes among patients undergoing percutaneous coronary intervention for acute coronary syndrome. PCI-PROVE IT: A PROVE IT-TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22) Substudy. J Am Coll Cardiol, 2009, 54(24): 2290-2295.
19.	Izawa A, Kashima Y, Miura T, et al. ALPS-AMI Investigators. Assessment of lipophilic vs. hydrophilic statin therapy in acute myocardial infarction-ALPS-AMI study. Circ J, 2015, 79(1): 161-168.
20.	Lablanche JM, Leone A, Merkely B, et al. Comparison of the efficacy of rosuvastatin versus atorvastatin in reducing apolipoprotein B/apolipoprotein A-1 ratio in patients with acute coronary syndrome: results of the CENTAURUS study. Arch Cardiovasc Dis, 2010, 103(3): 160-169.
21.	Zou YC, Hu DY, Yang XC, et al. Lipid-lowering efficacy and safety of varying doses of Simvastatin in patients with early stage acute coronary syndromes: one-year follow-up study. Chin Med J (Engl), 2003, 116(6): 853-856.
22.	Ye Y, Zhao X, Zhai G, et al. Effect of high-dose statin versus low-dose statin plus ezetimibe on endothelial function: a meta-analysis of randomized trials. J Cardiovasc Pharmacol Ther, 2012, 17(4): 357-365.
23.	Grigore L, Raselli S, Garlaschelli K, et al. Effect of treatment with pravastatin or ezetimibe on endothelial function in patients with moderate hypercholesterolemia. Eur J Clin Pharmacol, 2013, 69(3): 341-346.
24.	Settergren M, Böhm F, Rydén L, et al. Cholesterol lowering is more important than pleiotropic effects of statins for endothelial function in patients with dysglycaemia and coronary artery disease. Eur Heart J, 2008, 29(14): 1753-1760.
25.	Stone NJ, Robinson J, Lichtenstein AH, et al. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation, 2014, 129(25 Suppl 2): S1-45.
26.	Roffi M, Gencer B, Storey RF, et al. Clinical Perspectives and Pearls from the 2015 ESC NSTE-ACS Guidelines. Curr Cardiol Rep, 2016, 18(5): 48.
27.	Chinwong S, Patumanond J, Chinwong D, et al. Reduction in total recurrent cardiovascular events in acute coronary syndrome patients with low-density lipoprotein cholesterol goal <70 mg/dL: a real-life cohort in a developing country. Ther Clin Risk Manag, 2016, 12: 353-360.
28.	Chinwong D, Patumanond J, Chinwong S, et al. Low-density lipoprotein cholesterol of less than 70 mg/dL is associated with fewer cardiovascular events in acute coronary syndrome patients: a real-life cohort in Thailand. Ther Clin Risk Manag, 2015, 11: 659-667.
29.	Lee VW, Chau RY, Cheung HY, et al. How low should we target the LDL goal to improve survival for acute coronary syndrome patients in Hong Kong? BMC Cardiovasc Disord, 2015, 15: 117.

1. Sherbet DP, Garg P, Brilakis ES, et al. Low-density lipoprotein cholesterol: how low can we go? Am J Cardiovasc Drugs, 2013, 13(4): 225-232.
2. Meier P, Fröhlich GM, Meller S, et al. Selection and timing for invasive therapy in non-ST-segment-elevation acute coronary syndrome. Expert Rev Cardiovasc Ther, 2013, 11(4): 437-445.
3. Mihos CG, Santana O. Pleiotropic effects of the HMG-CoA reductase inhibitors. Int J Gen Med, 2011, 4: 261-271.
4. Bays HE, Neff D, Tomassini JE, et al. Ezetimibe: cholesterol lowering and beyond. Expert Rev Cardiovasc Ther, 2008, 6(4): 447-470.
5. Gao WQ, Feng QZ, Li YF, et al. Systematic study of the effects of lowering low-density lipoprotein-cholesterol on regression of coronary atherosclerotic plaques using intravascular ultrasound. BMC Cardiovasc Disord, 2014, 14: 60.
6. Cholesterol Treatment Trialists’ (CTT) Collaboration., Fulcher J, O’Connell R, et al. Efficacy and safety of LDL-lowering therapy among men and women: meta-analysis of individual data from 174, 000 participants in 27 randomised trials. Lancet, 2015, 385(9976): 1397-1405.
7. Catapano AL. Perspectives on low-density lipoprotein cholesterol goal achievement. Curr Med Res Opin, 2009, 25(2): 431-447.
8. Chinwong D, Patumanond J, Chinwong S, et al. Clinical indicators for recurrent cardiovascular events in acute coronary syndrome patients treated with statins under routine practice in Thailand: an observational study. BMC Cardiovasc Disord, 2015, 15: 55.
9. Banerjee S, Kahali D, Banerjee A, et al. LDL cholesterol: should guidelines include targets? Expert Rev Cardiovasc Ther, 2014, 12(3): 285-290.
10. Kanadaşi M, Cayli M, Demirtaş M, et al. The effect of early statin treatment on inflammation and cardiac events in acute coronary syndrome patients with low-density lipoprotein cholesterol. Heart Vessels, 2006, 21(5): 291-297.
11. Dohi T, Miyauchi K, Okazaki S, et al. Early intensive statin treatment for six months improves long-term clinical outcomes in patients with acute coronary syndrome (Extended-ESTABLISH trial): a follow-up study. Atherosclerosis, 2010, 210(2): 497-502.
12. Sato H, Kinjo K, Ito H, et al. Osaka Acute Coronary Insufficiency Study (OACIS)-LIPID Study Investigators. Effect of early use of low-dose pravastatin on major adverse cardiac events in patients with acute myocardial infarction: the OACIS-LIPID Study. Circ J, 2008, 72(1): 17-22.
13. Tsunoda R, Sakamoto T, Kojima S, et al. Recurrence of angina pectoris after percutaneous coronary intervention is reduced by statins in Japanese patients. J Cardiol, 2011, 58(3): 208-215.
14. Lee CH, de Feyter P, Serruys PW, et al. Beneficial effects of fluvastatin following percutaneous coronary intervention in patients with unstable and stable angina: results from the Lescol intervention prevention study (LIPS). Heart, 2004, 90(10): 1156-1161.
15. Gao Y, Jia ZM, Sun YJ, et al. Effect of high-dose rosuvastatin loading before percutaneous coronary intervention in female patients with non-ST-segment elevation acute coronary syndrome. Chin Med J (Engl), 2012, 125(13): 2250-2254.
16. Zhao SP, Yu BL, Peng DQ, et al. The effect of moderate-dose versus double-dose statins on patients with acute coronary syndrome in China: Results of the CHILLAS trial. Atherosclerosis, 2014, 233(2): 707-712.
17. Jang Y, Zhu J, Ge J, et al. Preloading with atorvastatin before percutaneous coronary intervention in statin-naïve Asian patients with non-ST elevation acute coronary syndromes: A randomized study. J Cardiol, 2014, 63(5): 335-343.
18. Gibson CM, Pride YB, Hochberg CP, et al. Effect of intensive statin therapy on clinical outcomes among patients undergoing percutaneous coronary intervention for acute coronary syndrome. PCI-PROVE IT: A PROVE IT-TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22) Substudy. J Am Coll Cardiol, 2009, 54(24): 2290-2295.
19. Izawa A, Kashima Y, Miura T, et al. ALPS-AMI Investigators. Assessment of lipophilic vs. hydrophilic statin therapy in acute myocardial infarction-ALPS-AMI study. Circ J, 2015, 79(1): 161-168.
20. Lablanche JM, Leone A, Merkely B, et al. Comparison of the efficacy of rosuvastatin versus atorvastatin in reducing apolipoprotein B/apolipoprotein A-1 ratio in patients with acute coronary syndrome: results of the CENTAURUS study. Arch Cardiovasc Dis, 2010, 103(3): 160-169.
21. Zou YC, Hu DY, Yang XC, et al. Lipid-lowering efficacy and safety of varying doses of Simvastatin in patients with early stage acute coronary syndromes: one-year follow-up study. Chin Med J (Engl), 2003, 116(6): 853-856.
22. Ye Y, Zhao X, Zhai G, et al. Effect of high-dose statin versus low-dose statin plus ezetimibe on endothelial function: a meta-analysis of randomized trials. J Cardiovasc Pharmacol Ther, 2012, 17(4): 357-365.
23. Grigore L, Raselli S, Garlaschelli K, et al. Effect of treatment with pravastatin or ezetimibe on endothelial function in patients with moderate hypercholesterolemia. Eur J Clin Pharmacol, 2013, 69(3): 341-346.
24. Settergren M, Böhm F, Rydén L, et al. Cholesterol lowering is more important than pleiotropic effects of statins for endothelial function in patients with dysglycaemia and coronary artery disease. Eur Heart J, 2008, 29(14): 1753-1760.
25. Stone NJ, Robinson J, Lichtenstein AH, et al. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation, 2014, 129(25 Suppl 2): S1-45.
26. Roffi M, Gencer B, Storey RF, et al. Clinical Perspectives and Pearls from the 2015 ESC NSTE-ACS Guidelines. Curr Cardiol Rep, 2016, 18(5): 48.
27. Chinwong S, Patumanond J, Chinwong D, et al. Reduction in total recurrent cardiovascular events in acute coronary syndrome patients with low-density lipoprotein cholesterol goal <70 mg/dL: a real-life cohort in a developing country. Ther Clin Risk Manag, 2016, 12: 353-360.
28. Chinwong D, Patumanond J, Chinwong S, et al. Low-density lipoprotein cholesterol of less than 70 mg/dL is associated with fewer cardiovascular events in acute coronary syndrome patients: a real-life cohort in Thailand. Ther Clin Risk Manag, 2015, 11: 659-667.
29. Lee VW, Chau RY, Cheung HY, et al. How low should we target the LDL goal to improve survival for acute coronary syndrome patients in Hong Kong? BMC Cardiovasc Disord, 2015, 15: 117.

Chinese Journal of Evidence-Based Medicine

Efficacy of LDL-C lowering therapy in patients with non-ST-segment elevation acute coronary syndrome: a meta-analysis

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