LDL lowering after acute coronary syndrome: Is lower better?

Current Treatment Options in Cardiovascular Medicine

Volumn 15, Issue 1, 2013, Pages 33-40

  Reddy, Gautam ^a   Bittner, Vera ^b  

^a University of Alabama at Birmingham   (United States)

^b University of Alabama at Birmingham and Birmingham Veterans Affairs Medical Center   (United States)

Author keywords

Acute coronary syndrome; Coronary heart disease; Low density lipoprotein cholesterol; Secondary prevention; Statins

Indexed keywords

HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; LOW DENSITY LIPOPROTEIN CHOLESTEROL; PLACEBO; SIMVASTATIN;

ACUTE CORONARY SYNDROME; ACUTE HEART FAILURE; APHERESIS; CARDIOVASCULAR RISK; CEREBROVASCULAR ACCIDENT; CHOLESTEROL BLOOD LEVEL; DIABETES MELLITUS; DRUG SAFETY; DRUG USE; DRUG WITHDRAWAL; HEART INFARCTION; HIGH RISK PATIENT; HUMAN; HYPERCHOLESTEROLEMIA; MYOPATHY; PRACTICE GUIDELINE; REVIEW; RHABDOMYOLYSIS; RISK FACTOR; RISK REDUCTION; SIDE EFFECT; UNSTABLE ANGINA PECTORIS;

EID: 84873092591     PISSN: 10928464     EISSN: 15343189     Source Type: Journal    
DOI: 10.1007/s11936-012-0221-6     Document Type: Review

References (40)

1. Kolansky DM. Acute coronary syndromes: morbidity, mortality, and pharmaco-economic burden. Am J Manag Care. 2009;15(2 Suppl):S36-41.
2. Kannel WB, Castelli WP, Gordon T, et al. Serum cholesterol, lipoproteins, and the risk of CHD. The Framingham study. Ann Intern Med. 1971;74:1-12.
3. Neaton JD, Wentworth D. Serum cholesterol, blood pressure, cigarette smoking, and death from CHD. Overall findings and differences by age for 316,099 white men. Multiple Risk Factor Intervention Trial Research Group. Arch Intern Med. 1992;152:56-64.
4. Baigent C, Blackwell L, Emberson J, Cholesterol Treatment Trialists' (CTT) Collaboration, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376:1670-81. One of the most extensive meta-analyses of major statin trials to date, showing incremental benefits with progressive LDL-C lowering even below 1.8 mmol/L with no increase in overall mortality below this level.
5. Baigent C, Keech A, Kearney PM, Blackwell L, Cholesterol Treatment Trialists' (CTT) Collaborators, et al. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet. 2005;366:1267-78.
6. O'Keefe Jr JH, Cordain L, Harris WH, et al. Optimal low-density lipoprotein is 50 to 70 mg/dL: lower is better and physiologically normal. J Am Coll Cardiol. 2004;43:2142-6.
7. Taylor F, Ward K, Moore TH et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2011;(1):CD004816.
8. Redberg RF, Katz MH. Healthy men should not take statins. JAMA. 2012;307:1491-2.
9. Smith Jr SC, Benjamin EJ, Bonow RO, et al. AHA/ACCF Secondary Prevention and Risk Reduction Therapy for Patients with Coronary and other Atherosclerotic Vascular Disease: 2011 update: a guideline from the American Heart Association and American College of Cardiology Foundation. Circulation. 2011;124:2458-73.
10. Perk J, De Backer G, Gohlke H, et al. European Guidelines on cardiovascular disease prevention in clinical practice (version 2012): the Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice. Eur J Prev Cardiol. 2012;19:585-667.
11. Vondrakova D, Ostadal P, Kruger A. Immediate effect of intensive atorvastatin therapy on lipid parameters in patients with acute coronary syndrome. Lipids Health Dis. 2010;9:71.
12. Di Sciascio G, Patti G, Pasceri V, et al. Efficacy of atorvastatin reload in patients on chronic statin therapy undergoing percutaneous coronary intervention: results of the ARMYDA-RECAPTURE (Atorvastatin for Reduction of Myocardial Damage During Angioplasty) Randomized Trial. J Am Coll Cardiol. 2009;54:558-65.
13. Shimojima M, Kawashiri MA, Nitta Y, et al. Rapid changes in plaque composition and morphology after intensive lipid lowering therapy: study with serial coronary CT angiography. Am J Cardiovasc Dis. 2012;2(2):84-8. Study describing the effects of intensive lipid lowering therapy on plaque morphology. Describes morphologic changes consistent with increased plaque stability as early as 3 weeks after initiation of statin therapy.
14. Otagiri K, Tsutsui H, Kumazaki S, et al. Early intervention with rosuvastatin decreases the lipid components of the plaque in acute coronary syndrome: analysis using integrated backscatter IVUS. Circ J. 2011;75:633-41.
15. Takarada S, Imanishi T, Ishibashi K, et al. The effect of lipid and inflammatory profiles on the morphological changes of lipid-rich plaques in patients with non-ST-segment elevated acute coronary syndrome: follow-up study by optical coherence tomography and intravascular ultrasound. JACC Cardiovasc Interv. 2010;3:766-72. Studied the effects of intensive lipid lowering therapy on plaque morphology using intravascular imaging. Remarkable findings include the correlation of fibrous cap thickness with hs-CRP levels but not with LDL-C/HDL-C ratio, suggesting that the pleiotropic effects of statins in suppressing inflammation plays a role in in vivo stabilization of plaque. Total atheroma volume did correlate with the LDL-C/HDL-C ratio demonstrating the effects of intensive lipid lowering on plaque regression.
16. Otsuka F, Hibi K, Kusama I, et al. Impact of statin pretreatment on the incidence of plaque rupture in ST-elevation acute myocardial infarction. Atherosclerosis. 2010;213:505-11. Studied the effects of statin pretreatment of the propensity of plaque rupture on presentation using intravascular ultrasound. Showed a decrease in the incidence of plaque rupture in patients treated with statins compared to those who were not, again suggesting that statins decrease the incidence of plaque rupture in vivo.
17. 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;96:611-16.
18. Cannon CP, Braunwald E, McCabe CH, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med. 2004;350:1495-504.
19. 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;295:2046-56.
20. Hulten E, Jackson JL, Douglas K, et al. The effect of early, intensive statin therapy on acute coronary syndrome: a meta-analysis of randomized controlled trials. Arch Intern Med. 2006;166:1814-21.
21. Vale N, Nordmann AJ, Schwartz GG et al. Statins for acute coronary syndrome. Cochrane Database Syst Rev. 2011;(6):CD006870. Review of trials comparing acute statin therapy to usual care or placebo for acute coronary syndromes, assessing risks and benefits of this intervention. Showed significant reduction in unstable angina at 4 months and a trend towards reduction in major cardiovascular events at 4 months as well.
22. Afilalo J, Majdan AA, Eisenberg MJ. Intensive statin therapy in acute coronary syndromes and stable CHD: a comparative meta-analysis of randomised controlled trials. Heart. 2007;93:914-21.
23. Wiviott SD, Cannon CP, Morrow DA, et al. PROVE IT-TIMI 22 Investigators. Can low-density lipoprotein be too low? The safety and efficacy of achieving very low low-density lipoprotein with intensive statin therapy: a PROVE IT-TIMI 22 substudy. J Am Coll Cardiol. 2005;46:1411-6.
24. Murphy SA, Cannon CP, Wiviott SD, et al. Reduction in recurrent cardiovascular events with intensive lipid-lowering statin therapy compared with moderate lipid-lowering statin therapy after acute coronary syndromes from the PROVE IT-TIMI 22 trial. J Am Coll Cardiol. 2009;54:2358-62. Analysis of the PROVE-IT trial, examining reduction in recurrent cardiovascular events after ACS. Trials of lipid lowering in this setting have typically used reduction in first events after the initial ACS as measures of effect, but this was the first analysis to specifically look at reductions in recurrent events with statin therapy.
25. Lee K, Jeong M, Kim H, 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;58:1664-71. Propensity matched analysis of patients with LDL-C levels < 70 mg/dL, with one cohort receiving statins and one receiving usual care with lifestyle modification, demonstrating continued benefit of lipid lowering therapy for secondary prevention in patients with already low LDL-C levels.
26. Armitage J. The safety of statins in clinical practice. Lancet. 2007;370:1781-90.
27. Law M, Rudnicka AR. Statin safety: a systematic review. Am J Cardiol. 2006;97:52C-60C.
28. Sattar N, Preiss D, Murray HM, et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet. 2010;375:735-42.
29. Bersot TP. Drug therapy for hypercholesterolemia and dyslipidemia. In: Brunton LL, Chabner BA, Knollmann BC, editors. Goodman & Gilman's the pharmacological basis of therapeutics, vol. Chapter 31. 12th ed. New York: McGraw-Hill; 2011.
30. FDA Drug Safety Communication: Important safety label changes to cholesterol-lowering statin drugs. Available at http://www.fda.gov/Drugs/ DrugSafety/ucm293101.htm.
31. FDA Drug Safety Communication: New restrictions, contraindications, and dose limitations for simvastatin to reduce the risk of muscle injury. Available at http://www.fda.gov/Drugs/DrugSafety/ucm256581.htm.
32. Hackam DG, Woodward M, Newby LK, et al. Statins and intracerebral hemorrhage: collaborative systematic review and meta-analysis. Circulation. 2011;124:2233-42. Comprehensive reassessment of risk of intracerebral hemorrhage with statin therapy, including in populations with cerebrovascular disease, which suggests that intracerebral hemorrhage is not a concern with statin therapy.
33. Jukema JW, Cannon CP, de Craen AJ, et al. The controversies of statin therapy: weighing the evidence. J Am Coll Cardiol. 2012;60:875-81. Recent review of evidence examining side effects of statins that found no increase in cancer incidence or cognitive decline with statin use, but corroborated the small increase in incident diabetes mellitus with this therapy.
34. Smith Jr SC, Allen J, Blair SN, et al. AHA/ACC guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease: 2006 update. Circulation. 2006;113:2363-72.
35. National Cholesterol Education Program (NCEP) Expert Panel. Summary of the second report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel II). JAMA. 1993;269:3015-23.
36. Grundy SM, Cleeman JI, Merz CN, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines. J Am Coll Cardiol. 2004;44:720-32.
37. Melloni C, Shah BR, Ou FS, et al. Lipid-lowering intensification and low-density lipoprotein cholesterol achievement from hospital admission to 1-year follow-up after an acute coronary syndrome event: results from the Medications ApplIed aNd SusTAINed Over Time (MAINTAIN) registry. Am Heart J. 2010;160:1121-9. 1129.1. Registry data demonstrating an increase in statin prescriptions on discharge after ACS but indicating suboptimal use of intensive lipid lowering therapy on discharge and failure to achieve guidelines goals in many cases.
38. Javed U, Deedwania PC, Bhatt DL, et al. Use of intensive lipid-lowering therapy in patients hospitalized with acute coronary syndrome: An analysis of 65,396 hospitalizations from 344 hospitals participating in Get With The Guidelines (GWTG). Am Heart J. 2011;161:418-424.e1-3. Registry data again demonstrating suboptimal prescription of intensive lipid lowering therapy after ACS.
39. Visser ME, Witztum JL, Stroes ES, Kastelein JJ. Antisense oligonucleotides for the treatment of dyslipidaemia. Eur Heart J. 2012;33:1451-8. Concise review of new LDL-C lowering therapies including the antisense oligonucleotides and preprotein convertase subtilin kexin inhibitors currently in development.
40. Plaque Regression and Progenitor Cell Mobilization with Intensive Lipid Elimination Regimen. Available at http://clinicaltrials.gov/ct2/show/ NCT01004406.