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Update in Therapeutic Approaches to Plaque Stabilization

  • Nonstatin Drugs (WB Borden, Section Editor)
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Abstract

Increasing pathological insights have highlighted the role of plaque instability in the pathogenesis of acute ischemic syndromes. These studies have identified a specific plaque phenotype, characterized by large burden, expansive arterial wall remodeling, and greater composition of lipid, inflammatory, and necrotic material, as the disease most likely to rupture and provoke acute ischemia. Accordingly, considerable efforts have been made to develop more effective strategies to identify patients more likely to harbor such lesions and to passivate this disease from both a prophylactic and a therapeutic perspective. The approaches to management of plaque stabilization are reviewed.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Lloyd-Jones D, Adams R, Carnethon M, De Simone G, Ferguson TB, Flegal K, et al. Heart disease and stroke statistics – 2009 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2009;119:e21–181.

    Article  PubMed  Google Scholar 

  2. Turnbull F. Effects of different blood-pressure-lowering regimens on major cardiovascular events: results of prospectively-designed overviews of randomised trials. Lancet. 2003;362:1527–35.

    Article  CAS  PubMed  Google Scholar 

  3. Cholesterol Treatment Trialists’ (CTT) Collaboration. 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.

    Article  Google Scholar 

  4. Sacks FM, Pfeffer MA, Moye LA, Rouleau JL, Rutherford JD, Cole TG, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. N Engl J Med. 1996;335:1001–9.

    Article  CAS  PubMed  Google Scholar 

  5. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. 1994;344:1381–9.

  6. MRC/BHF Heart Protection. Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360:7–22.

    Article  Google Scholar 

  7. Downs JR, Clearfield M, Weis S, Whitney E, Shapiro DR, Beere PA, et al. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFcaps/Texcaps. AirForce/Texas Coronary Atherosclerosis Prevention Study. JAMA. 1998;279:1615–22.

    Article  CAS  PubMed  Google Scholar 

  8. Perk J, De Backer G, Gohlke H, Graham I, Reiner Z, Verschuren M, 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 (constituted by representatives of nine societies and by invited experts). Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur Heart J. 2012;33:1635–701.

    Article  CAS  PubMed  Google Scholar 

  9. Falk E, Nakano M, Bentzon JF, Finn AV, Virmani R. Update on acute coronary syndromes: the pathologists' view. Eur Heart J. 2013;34:719–28. This is a review of the latest pathology findings about vulnerable plaque.

    Article  CAS  PubMed  Google Scholar 

  10. Davies MJ. The pathophysiology of acute coronary syndromes. Heart. 2000;83:361–6.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Borén J, Gustafsson M, Skålén K, Flood C, Innerarity TL. Role of extracellular retention of low density lipoproteins in atherosclerosis. Curr Opin Lipidol. 2000;11:451–6.

    Article  PubMed  Google Scholar 

  12. Libby P, Okamoto Y, Rocha VZ, Folco E. Inflammation in atherosclerosis: transition from theory to practice. Circ J. 2010;74:213–20.

    Article  CAS  PubMed  Google Scholar 

  13. Tsimikas S, Miller YI. Oxidative modification of lipoproteins: mechanisms, role in inflammation and potential clinical applications in cardiovascular disease. Curr Pharm Des. 2011;17:27–37.

    Article  CAS  PubMed  Google Scholar 

  14. Steinberg D. The LDL, modification hypothesis of atherogenesis: an update. J Lipid Res. 2009;50(Suppl):S376–81.

    PubMed Central  PubMed  Google Scholar 

  15. Ghosh S. Macrophage cholesterol homeostasis and metabolic diseases: critical role of cholesteryl ester mobilization. Expert Rev Cardiovasc Ther. 2011;9:329–40.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Chikani G, Zhu W, Smart EJ. Lipids: potential regulators of nitric oxide generation. Am J Physiol Endocrinol Metab. 2004;287:E386–9.

    Article  CAS  PubMed  Google Scholar 

  17. Huo Y, Xia L. P-selectin glycoprotein ligand-1 plays a crucial role in the selective recruitment of leukocytes into the atherosclerotic arterial wall. Trends Cardiovasc Med. 2009;19:140–5.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Eriksson EE. Mechanisms of leukocyte recruitment to atherosclerotic lesions: future prospects. Curr Opin Lipidol. 2004;15:553–8.

    Article  CAS  PubMed  Google Scholar 

  19. Leskinen MJ, Kovanen PT, Lindstedt KA. Regulation of smooth muscle cell growth, function and death in vitro by activated mast cells—a potential mechanism for the weakening and rupture of atherosclerotic plaques. Biochem Pharmacol. 2003;66:1493–8.

    Article  CAS  PubMed  Google Scholar 

  20. Falk E, Shah PK, Fuster V. Coronary plaque disruption. Circulation. 1995;92:657–71.

    Article  CAS  PubMed  Google Scholar 

  21. Narula J, Garg P, Achenbach S, Motoyama S, Virmani R, Strauss HW. Arithmetic of vulnerable plaques for noninvasive imaging. Nat Clin Pract Cardiovasc Med. 2008;5:S2–10.

    Article  PubMed  Google Scholar 

  22. Kolodgie FD, Burke AP, Farb A, Gold HK, Yuan J, Narula J, et al. The thin-cap fibroatheroma: a type of vulnerable plaque: the major precursor lesion to acute coronary syndromes. Curr Opin Cardiol. 2001;16:285–92.

    Article  CAS  PubMed  Google Scholar 

  23. Tan NY, Li JM, Stocker R, Khachigian LM. Angiotensin II-inducible smooth muscle cell apoptosis involves the angiotensin II type 2 receptor, GATA-6 activation, and FasL-Fas engagement. Circ Res. 2009;105:422–30.

    Article  CAS  PubMed  Google Scholar 

  24. Geng YJ, Henderson LE, Levesque EB, Muszynski M, Libby P. Fas is expressed in human atherosclerotic intima and promotes apoptosis of cytokine-primed human vascular smooth muscle cells. Arterioscler Thromb Vasc Biol. 1997;17:2200–8.

    Article  CAS  PubMed  Google Scholar 

  25. Lee E, Grodzinsky AJ, Libby P, Clinton SK, Lark MW, Lee RT. Human vascular smooth muscle cell-monocyte interactions and metalloproteinase secretion in culture. Arterioscler Thromb Vasc Biol. 1995;15:2284–9.

    Article  CAS  PubMed  Google Scholar 

  26. Kodali R, Hajjou M, Berman AB, Bansal MB, Zhang S, Pan JJ, et al. Chemokines induce matrix metalloproteinase-2 through activation of epidermal growth factor receptor in arterial smooth muscle cells. Cardiovasc Res. 2006;69:706–15.

    Article  CAS  PubMed  Google Scholar 

  27. Ambrose JA, Tannenbaum MA, Alexopoulos D, Hjemdahl-Monsen CE, Leavy J, Weiss M, et al. Angiographic progression of coronary artery disease and the development of myocardial infarction. J Am Coll Cardiol. 1998;12:56–62.

    Article  Google Scholar 

  28. Giroud D, Li JM, Urban P, Meier B, Rutishauer W. Relation of the site of acute myocardial infarction to the most severe coronary arterial stenosis at prior angiography. Am J Cardiol. 1992;69:729–32.

    Article  CAS  PubMed  Google Scholar 

  29. Little WC, Constantinescu M, Applegate RJ, Kutcher MA, Burrows MT, Kahl FR, et al. Can coronary angiography predict the site of a subsequent myocardial infarction in patients with mild-to-moderate coronary artery disease? Circulation. 1988;78:1157–66.

    Article  CAS  PubMed  Google Scholar 

  30. Corti R, Fuster V, Badimon JJ. Pathogenetic concepts of acute coronary syndromes. J Am Coll Cardiol. 2003;41(4 Suppl S):7S–14.

    Article  CAS  PubMed  Google Scholar 

  31. Kannel WB. Range of serum cholesterol values in the population developing coronary artery disease. Am J Cardiol. 1995;76:69C–77.

    Article  CAS  PubMed  Google Scholar 

  32. Kannel WB. Elevated systolic blood pressure as a cardiovascular risk factor. Am J Cardiol. 2000;85:251–5.

    Article  CAS  PubMed  Google Scholar 

  33. Tyroler HA. Serum lipoproteins as risk factors: recent epidemiologic studies in individuals with and without prevalent cardiovascular disease. Eur Heart J. 1990;11 Suppl H:21–5.

    Article  CAS  PubMed  Google Scholar 

  34. Linton MF, Fazio S. A practical approach to risk assessment to prevent coronary artery disease and its complications. Am J Cardiol. 2003;92:19i–26.

    Article  PubMed  Google Scholar 

  35. Ridker PM, Cook N. Clinical usefulness of very high and very low levels of C-reactive protein across the full range of Framingham Risk Scores. Circulation. 2004;109:1955–9.

    Article  PubMed  Google Scholar 

  36. Koenig W, Khuseyinova N, Löwel H, Trischler G, Meisinger C. Lipoprotein-associated phospholipase A2 adds to risk prediction of incident coronary events by C-reactive protein in apparently healthy middle-aged men from the general population: results from the 14-year follow-up of a large cohort from southern Germany. Circulation. 2004;110:1903–8.

    Article  CAS  PubMed  Google Scholar 

  37. Mallat Z, Steg PG, Benessiano J, Tanguy ML, Fox KA, Collet JP, et al. Circulating secretory phospholipase A2 activity predicts recurrent events in patients with severe acute coronary syndromes. J Am Coll Cardiol. 2005;46:1249–57.

    Article  CAS  PubMed  Google Scholar 

  38. Baldus S, Heeschen C, Meinertz T, Zeiher AM, Eiserich JP, Münzel T, et al. Myeloperoxidase serum levels predict risk in patients with acute coronary syndromes. Circulation. 2003;108:1440–5.

    Article  CAS  PubMed  Google Scholar 

  39. Belhassen L, Carville C, Pelle G, Monin JL, Teiger E, Duval-Moulin AM, et al. Evaluation of carotid artery and aortic intima-media thickness measurements for exclusion of significant coronary atherosclerosis in patients scheduled for heart valve surgery. J Am Coll Cardiol. 2002;39:1139–44.

    Article  PubMed  Google Scholar 

  40. Arad Y, Spadaro LA, Goodman K, Newstein D, Guerci AD. Prediction of coronary events with electron beam computed tomography. J Am Coll Cardiol. 2000;36:1253–60.

    Article  CAS  PubMed  Google Scholar 

  41. Motoyama S, Sarai M, Harigaya H, Anno H, Inoue K, Hara T, et al. Computed tomographic angiography characteristics of atherosclerotic plaques subsequently resulting in acute coronary syndrome. J Am Coll Cardiol. 2009;54:49–57.

    Article  PubMed  Google Scholar 

  42. Kurra V, Lieber ML, Sola S, Kalahasti V, Hammer D, Gimple S, et al. Extent of thoracic aortic atheroma burden and long-term mortality after cardiothoracic surgery: a computed tomography study. JACC Cardiovasc Imaging. 2010;3:1020–9.

    Article  PubMed  Google Scholar 

  43. Mintz GS, Nissen SE, Anderson WD, Bailey SR, Erbel R, Fitzgerald PJ, et al. American College of Cardiology clinical expert consensus document on standards for acquisition, measurement and reporting of intravascular ultrasound studies (IVUS). A report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents. J Am Coll Cardiol. 2001;37:1478–92.

    Article  CAS  PubMed  Google Scholar 

  44. Nicholls SJ, Hsu A, Wolski K, Hu B, Bayturan O, Lavoie A, et al. Intravascular ultrasound-derived measures of coronary atherosclerotic plaque burden and clinical outcome. J Am Coll Cardiol. 2010;55:2399–407. This article describes the relationship between intravascular ultrasound measures and clinical outcomes.

    Article  PubMed  Google Scholar 

  45. Stone GW, Maehara A, Lansky AJ, de Bruyne B, Cristea E, Mintz GS, et al. A prospective natural-history study of coronary atherosclerosis. N Eng J Med. 2011;364:226–35. This article describes the relationship between virtual histology intravascular ultrasound measures and clinical outcomes.

    Article  CAS  Google Scholar 

  46. Jang IK, Bouma BE, Kang DH, Park SJ, Park SW, Seung KB, et al. Visualization of coronary atherosclerotic plaques in patients using optical coherence tomography: comparison with intravascular ultrasound. J Am Coll Cardiol. 2002;39:604–9.

    Article  PubMed  Google Scholar 

  47. Gardner CM, Tan H, Hull E, Lisauskas JB, Sum ST, Meese TM, et al. Detection of lipid core coronary plaques in autopsy specimens with a novel catheter‐based near‐infrared spectroscopy system. JACC Cardiovasc Imaging. 2008;1:638–48.

    Article  PubMed  Google Scholar 

  48. Stamler J, Wentworth D, Neaton JD. Is relationship between serum cholesterol and risk of premature death from coronary heart disease continuous and graded? Findings in 356,222 primary screenees of the Multiple Risk Factor Intervention Trial (MRFIT). JAMA. 1986;256:2823–8.

    Article  CAS  PubMed  Google Scholar 

  49. Bustos C, Hernández-Presa MA, Ortego M, Tuñón J, Ortega L, Pérez F, et al. HMG-CoA reductase inhibition by atorvastatin reduces neointimal inflammation in a rabbit model of atherosclerosis. J Am Coll Cardiol. 1998;32:2057–64.

    Article  CAS  PubMed  Google Scholar 

  50. de Lemos JA, Blazing MA, Wiviott SD, Lewis EF, Fox KA, White HD, et al. Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes: phase Z of the A to Z trial. JAMA. 2004;292:1307–16.

    Article  PubMed  Google Scholar 

  51. Cannon CP, Braunwald E, McCabe CH, Rader DJ, Rouleau JL, Belder R, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med. 2004;350:1495–504.

    Article  CAS  PubMed  Google Scholar 

  52. Nissen SE, Tuzcu EM, Schoenhagen P, Brown BG, Ganz P, Vogel RA, et al. Effect of intensive compared with moderate lipid-lowering therapy on progression of coronary atherosclerosis: a randomized controlled trial. JAMA. 2004;291:1071–80.

    Article  CAS  PubMed  Google Scholar 

  53. Nissen SE, Nicholls SJ, Sipahi I, Libby P, Raichlen JS, Ballantyne CM, et al. Effect of very high- intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial. JAMA. 2006;295:1556–65.

    Article  CAS  PubMed  Google Scholar 

  54. Nicholls SJ, Ballantyne CM, Barter PJ, Chapman MJ, Erbel RM, Libby P, et al. Effect of two intensive statin regimens on progression of coronary disease. N Engl J Med. 2011;365:2078–87. This article describes the benefits of potent statin therapy for plaque progression.

    Article  CAS  PubMed  Google Scholar 

  55. Nasu K, Tsuchikane E, Katoh O, Tanaka N, Kimura M, Ehara M, et al. Effect of fluvastatin on progression of coronary atherosclerotic plaque evaluated by virtual histology intravascular ultrasound. JACC Cardiovasc Interv. 2009;2:689–96.

    Article  PubMed  Google Scholar 

  56. Nissen SE, Tuzcu EM, Schoenhagen P, Crowe T, Sasiela WJ, Tsai J, et al. Statin therapy, LDL cholesterol, C-reactive protein, and coronary artery disease. N Engl J Med. 2005;352:29–38.

    Article  CAS  PubMed  Google Scholar 

  57. McKenney JM, Koren MJ, Kereiakes DJ, Hanotin C, Ferrand AC, Stein EA. Safety and efficacy of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 serine protease, SAR236553/REGN727, in patients with primary hypercholesterolemia receiving ongoing stable atorvastatin therapy. J Am Coll Cardiol. 2012;59:2344–53.

    Article  CAS  PubMed  Google Scholar 

  58. Blake GJ, Otvos JD, Rifai N, Ridker PM. Low-density lipoprotein particle concentration and size as determined by nuclear magnetic resonance spectroscopy as predictors of cardiovascular disease in women. Circulation. 2002;106:1930–7.

    Article  CAS  PubMed  Google Scholar 

  59. Kuller L, Arnold A, Tracy R, Otvos J, Burke G, Psaty B, et al. Nuclear magnetic resonance spectroscopy of lipoproteins and risk of coronary heart disease in the Cardiovascular Health Study. Arterioscler Thromb Vasc Biol. 2002;22:1175–80.

    Article  CAS  PubMed  Google Scholar 

  60. Benn M, Nordestgaard BG, Jensen GB, Tybjaerg-Hansen A. Improving prediction of ischemic cardiovascular disease in the general population using apolipoprotein B: the Copenhagen City Heart Study. Arterioscler Thromb Vasc Biol. 2007;27:661–70.

    Article  CAS  PubMed  Google Scholar 

  61. Miller M, Cannon CP, Murphy SA, Qin J, Ray KK, Braunwald E. Impact of triglyceride levels beyond low-density lipoprotein cholesterol after acute coronary syndrome in the PROVE IT-TIMI 22 trial. J Am Coll Cardiol. 2008;51:724–30.

    Article  CAS  PubMed  Google Scholar 

  62. Anuurad E, Boffa MB, Koschinsky ML, Berglund L. Lipoprotein (a): a unique risk factor for cardiovascular disease. Clin Lab Med. 2006;26:751–72.

    Article  PubMed  Google Scholar 

  63. Berglund L, Ramakrishnan R. Lipoprotein (a): an elusive cardiovascular risk factor. Arterioscler Thromb Vasc Biol. 2004;24:2219–26.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  64. Boffa MB, Marcovina SM, Koschinsky ML. Lipoprotein (a) as a risk factor for atherosclerosis and thrombosis: mechanistic insights from animal models. Clin Biochem. 2004;37:333–43.

    Article  CAS  PubMed  Google Scholar 

  65. Barter P, Gotto AM, LaRosa JC, Maroni J, Szarek M, Grundy SM, et al. HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events. N Engl J Med. 2007;357:1301–10.

    Article  CAS  PubMed  Google Scholar 

  66. Jafri H, Alsheikh-Ali AA, Karas RH. Meta-analysis: statin therapy does not alter the association between low levels of high-density lipoprotein cholesterol and increased cardiovascular risk. Ann Intern Med. 2010;153:800–8.

    Article  PubMed  Google Scholar 

  67. Nicholls SJ, Cutri B, Worthley SG, Kee P, Rye KA, Bao S, et al. Impact of short-term administration of high-density lipoproteins and atorvastatin on atherosclerosis in rabbits. Arterioscler Thromb Vasc Biol. 2005;25:2416–21.

    Article  CAS  PubMed  Google Scholar 

  68. AIM-HIGH Investigators. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med. 2011;365:2255–67.

    Article  Google Scholar 

  69. Barter PJ, Caulfield M, Eriksson M, Grundy SM, Kastelein JJ, Komajda M, et al. Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med. 2007;357:2109–22.

    Article  CAS  PubMed  Google Scholar 

  70. Nissen SE, Tardif JC, Nicholls SJ, Revkin JH, Shear CL, Duggan WT, et al. Effect of torcetrapib on the progression of coronary atherosclerosis. N Engl J Med. 2007;356:1304–16.

    Article  CAS  PubMed  Google Scholar 

  71. Schwartz GG, Olsson AG, Abt M, Ballantyne CM, Barter PJ, Brumm J, et al. Effects of dalcetrapib in patients with a recent acute coronary syndrome. N Engl J Med. 2012;367:2089–99.

    Article  CAS  PubMed  Google Scholar 

  72. Nicholls SJ, Brewer HB, Kastelein JJ, Krueger KA, Wang MD, Shao M, et al. Effects of the CETP inhibitor evacetrapib administered as monotherapy or in combination with statins on HDL and LDL cholesterol: a randomized controlled trial. JAMA. 2011;306:2099–109. This article describes the efficacy and safety of a novel cholesteryl ester transfer protein inhibitor, evacetrapib.

    Article  CAS  PubMed  Google Scholar 

  73. Nissen SE, Tsunoda T, Tuzcu EM, Schoenhagen P, Cooper CJ, Yasin M, et al. Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial. JAMA. 2003;290:2292–300.

    Article  CAS  PubMed  Google Scholar 

  74. Waksman R, Torguson R, Kent KM, Pichard AD, Suddath WO, Satler LF, et al. A first-in-man, randomized, placebo-controlled study to evaluate the safety and feasibility of autologous delipidated high-density lipoprotein plasma infusions in patients with acute coronary syndrome. J Am Coll Cardiol. 2010;55:2727–35. This article describes favorable effects of HDL infusion therapy on coronary atherosclerosis.

    Article  PubMed  Google Scholar 

  75. Tardif JC, Grégoire J, L’Allier PL, Ibrahim R, Lespérance J, Heinonen TM, et al. Effects of reconstituted high-density lipoprotein infusions on coronary atherosclerosis: a randomized controlled trial. JAMA. 2007;297:1675–82.

    Article  PubMed  Google Scholar 

  76. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo Jr JL, et al. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003;289:2560–72.

    Article  CAS  PubMed  Google Scholar 

  77. Heart Outcomes Prevention Evaluation Study Investigators. Effects of an angiotensin-converting- enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med. 2000;342:145–53.

    Article  Google Scholar 

  78. European Trial on Reduction of Cardiac Events With Perindopril in Stable Coronary Artery Disease Investigators. Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study). Lancet. 2003;362:782–8.

    Article  Google Scholar 

  79. Mason RP. Mechanisms of plaque stabilization for the dihydropyridine calcium channel blocker amlodipine: review of the evidence. Atherosclerosis. 2002;165:191–9.

    Article  CAS  PubMed  Google Scholar 

  80. Lewington S, Clarke R, Qizilbash N, Peto R, Collins R. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. 2002;360:1903–13.

    Article  PubMed  Google Scholar 

  81. Nicholls SJ, Bakris GL, Kastelein JJ, Menon V, Williams B, Armbrecht J, et al. Effect of aliskiren on progression of coronary disease in patients with prehypertension: the AQUARIUS randomized clinical trial. JAMA. 2013;310:1135–44.

    Article  CAS  PubMed  Google Scholar 

  82. Nicholls SJ, Tuzcu EM, Kalidindi S, Wolski K, Moon KW, Sipahi I, et al. Effect of diabetes on progression of coronary atherosclerosis and arterial remodeling: a pooled analysis of 5 intravascular ultrasound trials. J Am Coll Cardiol. 2008;52:255–62.

    Article  CAS  PubMed  Google Scholar 

  83. Huxley R, Barzi F, Woodward M. Excess risk of fatal coronary heart disease associated with diabetes in men and women: meta-analysis of 37 prospective cohort studies. BMJ. 2006;332:73–8.

    Article  PubMed Central  PubMed  Google Scholar 

  84. Boyle PJ. Diabetes mellitus and macrovascular disease: mechanisms and mediators. Am J Med. 2007;120:S12–7.

    Article  CAS  PubMed  Google Scholar 

  85. Nasu K, Tsuchikane E, Katoh O, Fujita H, Surmely JF, Ehara M, et al. Plaque characterisation by virtual histology intravascular ultrasound analysis in patients with type 2 diabetes. Heart. 2008;94:429–33.

    Article  CAS  PubMed  Google Scholar 

  86. Action to Control Cardiovascular Risk in Diabetes Study Group. Effect of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358:2545–59.

    Article  Google Scholar 

  87. ADVANCE Collaborative Group. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358:2560–72.

    Article  Google Scholar 

  88. Duckworth W, Abraira C, Moritz T, Reda D, Emanuele N, Reaven PD, et al. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med. 2009;360:129–39.

    Article  CAS  PubMed  Google Scholar 

  89. White WB, Cannon CP, Heller SR, Nissen SE, Bergenstal RM, Bakris GL, et al. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med. 2013;369:1327–35.

    Article  CAS  PubMed  Google Scholar 

  90. Scirica BM, Bhatt DL, Braunwald E, Steg PG, Davidson J, Hirshberg B, et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med. 2013;369:1317–26.

    Article  CAS  PubMed  Google Scholar 

  91. Ridker PM, Cannon CP, Morrow D, Rifai N, Rose LM, McCabe CH, et al. C-reactive protein levels and outcomes after statin therapy. N Engl J Med. 2005;352:20–8.

    Article  CAS  PubMed  Google Scholar 

  92. Anthera Pharmaceuticals. VISTA-16 trial: evaluation of safety and efficacy of short-term A-002 treatment in subjects with acute coronary syndrome. 2010–2012. http://clinicaltrials.gov/ct2/show/NCT01130246/.

  93. Serruys PW, García-García HM, Buszman P, Erne P, Verheye S, Aschermann M, et al. Effects of the direct lipoprotein-associated phospholipase A2 inhibitor darapladib on human coronary atherosclerotic plaque. Circulation. 2008;118:1172–82.

    Article  CAS  PubMed  Google Scholar 

  94. O’Donoghue ML, Braunwald E, White HD, Serruys P, Steg PG, Hochman J, et al. Study design and rationale for the Stabilization of pLaques usIng Darapladib-Thrombolysis in Myocardial Infarction (SOLID-TIMI 52) trial in patients after an acute coronary syndrome. Am Heart J. 2011;162:613–9.

    Article  PubMed  Google Scholar 

  95. Ormiston JA, Serruys PW. Bioabsorbable coronary stents. Circ Cardiovasc Interv. 2009;2:255–60.

    Article  CAS  PubMed  Google Scholar 

  96. Wald DS, Morris JK, Wald NJ, Chase AJ, Edwards RJ, Hughes LO, et al. Randomized trial of preventive angioplasty in myocardial infarction. N Engl J Med. 2013;369:1115–23.

    Article  CAS  PubMed  Google Scholar 

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Stephen J. Nicholls is a consultant to AstraZeneca, Merck, Takeda, Roche, CSL Behring, Boehringer Ingelheim, Novartis, Omthera, and Atheronova.

Yu Kataoka declares that he has no conflict of interest.

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  1. South Australian Health and Medical Research Institute, PO Box 11060, Adelaide, SA, 5001, Australia

    Stephen J. Nicholls & Yu Kataoka

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  1. Stephen J. Nicholls
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Correspondence to Stephen J. Nicholls.

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Nicholls, S.J., Kataoka, Y. Update in Therapeutic Approaches to Plaque Stabilization. Curr Atheroscler Rep 16, 392 (2014). https://doi.org/10.1007/s11883-013-0392-y

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