Novel mechanistic and clinical implications concerning the safety of statin discontinuation

Pharmacological Reports

Volumn 63, Issue 4, 2011, Pages 867-879

  Jasińska Stroschein, Magdalena ^a   Owczarek, Jacek ^a   Wejman, Irena ^a   Orszulak Michalak, Daria ^a  

^a MEDICAL UNIVERSITY OF LODZ   (Poland)

Author keywords

HMG CoA reductase inhibitors; Mechanism; Pleiotropic effects; Withdrawal

Indexed keywords

ANGIOTENSIN II; ATORVASTATIN; C REACTIVE PROTEIN; CREATINE KINASE; GELATINASE A; GELATINASE B; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; INTERLEUKIN 6; MEVINOLIN; MONOCYTE CHEMOTACTIC PROTEIN 1; NITRIC OXIDE; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR; PRAVASTATIN; SIMVASTATIN; STROMELYSIN; UBIDECARENONE; VASCULAR CELL ADHESION MOLECULE 1; VON WILLEBRAND FACTOR;

ACUTE CORONARY SYNDROME; ASYMPTOMATIC DISEASE; CARDIOVASCULAR DISEASE; CARDIOVASCULAR RISK; CELL ACTIVITY; CEREBROVASCULAR ACCIDENT; CEREBROVASCULAR DISEASE; CREATINE KINASE BLOOD LEVEL; DISEASE EXACERBATION; DISEASE MARKER; DRUG ACTIVITY; DRUG EFFECT; DRUG EFFICACY; DRUG MECHANISM; DRUG MEGADOSE; DRUG SAFETY; DRUG WITHDRAWAL; ECHOGRAPHY; ENDOTHELIAL DYSFUNCTION; HEMOSTASIS; HUMAN; HYPERLIPIDEMIA; INFLAMMATION; MUSCLE WEAKNESS; MYALGIA; MYOPATHY; NONHUMAN; PLEIOTROPY; PRIMARY PREVENTION; REVIEW; SECONDARY PREVENTION; SIDE EFFECT; SIGNAL TRANSDUCTION; THROMBOCYTE; TREATMENT DURATION; VASCULAR ENDOTHELIUM;

EID: 80053353330     PISSN: 22995684     EISSN: 22995684     Source Type: Journal    
DOI: 10.1016/S1734-1140(11)70602-8     Document Type: Review

References (91)

1. Adams DH, Shaw S: Leucocyte-endothelial interactions and regulation of leucocyte migration. Lancet, 1994, 343, 831-836. (Pubitemid 24147515)
2. Aikawa M, Rabkin E, Sugiyama S, Voglic SJ, Fukumoto Y, Furukawa Y, Shiomi M et al.: An HMG-CoA reductase inhibitor, cerivastatin, suppresses growth of macrophages expressing matrix metalloproteinases and tissue factor in vivo and in vitro. Circulation, 2001, 103, 276-283. (Pubitemid 32095415)
3. Amarenco P, Bogousslavsky J, Callahan A, Goldstein LB, Hennerici M, Rudolph AE, Sillesen H et al.: Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Investigators. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med, 2006, 355, 549-559.
4. Bevilacqua MP, Gimbrone MAJr: Inducible endothelial functions in inflammation and coagulation. Semin Thromb Hemost, 1987, 13, 425-433. (Pubitemid 18007746)
5. Blanco M, Nombela F, Castellanos M, Rodriguez-Yáñez M, García-Gil M, Leira R, Lizasoain I et al.: Statin treatment withdrawal in ischemic stroke: a controlled randomized study. Neurology, 2007, 69, 904-910. (Pubitemid 47329591)
6. Brandes RP, Beer S, Ha T, Busse R: Withdrawal of cerivastatin induces monocyte chemoattractant protein 1 and tissue factor expression in cultured vascular smooth muscle cells. Arterioscler Thromb Vasc Biol, 2003, 23, 1794-1800. (Pubitemid 37254865)
7. Burridge K, Wennerberg K: Rho and Rac take center stage. Cell, 2006, 116, 167-79.
8. Castejon AM, Zollner E, Tristano AG, Cubeddu LX: Upregulation of angiotensin II-AT1 receptors during statin withdrawal in vascular smooth muscle cells. J Cardiovasc Pharmacol, 2007, 50, 708-711. (Pubitemid 350307043)
9. Chen H, Ren JY, Xing Y, Zhang WL, Liu X, Wu P, Wang RJ, Luo Y: Short-term withdrawal of simvastatin induces endothelial dysfunction in patients with coronary artery disease: a dose-response effect dependent on endothelial nitric oxide synthase. Int J Cardiol, 2009, 131, 313-320.
10. Chu CS, Kou HS, Lee CJ, Lee KT, Chen SH, Voon WC, Sheu SH, Lai WT: Effect of atorvastatin withdrawal on circulating coenzyme Q10 concentration in patients with hypercholesterolemia. Biofactors, 2006, 28, 177-184.
11. Chung HK, Lee IK, Kang H, Suh JM, Kim H, Park KC, Kim DW: Statin inhibits interferon-γ-induced expression of intercellular adhesion molecule-1 (ICAM-1) in vascular endothelial and smooth muscle cells. Exp Mol Med, 2002, 34, 451-461. (Pubitemid 36114363)
12. Coleman ML, Olson MF: Rho GTPase signalling pathways in the morphological changes associated with apoptosis. Cell Death Differ, 2002, 9, 493-504. (Pubitemid 34521177)
13. Colivicchi F, Bassi A, Santini M, Caltagirone C: Discontinuation of statin therapy and clinical outcome after ischemic stroke. Stroke, 2007, 38, 2652-2657. (Pubitemid 47493999)
14. Corti R, Osende JI, Fallon JT, Fuster V, Mizsei G, Jneid H, Wright SD et al.: The selective peroxisomal proliferator-activated receptor-γ agonist has an additive effect on plaque regression in combination with simvastatin in experimental atherosclerosis: in vivo study by high-resolution magnetic resonance imaging. J Am Coll Cardiol, 2004, 43, 464-473. (Pubitemid 38167710)
15. Cubeddu LX, Seamon MJ: Statin withdrawal: clinical implications and molecular mechanisms. Pharmacotherapy, 2006, 26, 1288-1296. (Pubitemid 44306889)
16. Dangas G, Smith DA, Unger AH, Shao JH, Meraj P, Fier C, Cohen AM et al.: Pravastatin: an antithrombotic effect independent of the cholesterol-lowering effect. Thromb Haemost, 2000, 83, 688-692. (Pubitemid 30248515)
17. Daskalopoulou SS, Delaney JA, Filion KB, Brophy JM, Mayo NE, Suissa S: Discontinuation of statin therapy following an acute myocardial infarction: a population-based study. Eur Heart J, 2008, 29, 2083-2091.
18. Daskalopoulou SS: When statin therapy stops: implications for the patient. Curr Opin Cardiol, 2009, 24, 454-460.
19. Davies MJ, Gordon JL, Gearing AJ, Pigott R, Woolf N, Katz D, Kyriakopoulos A: The expression of the adhesion molecules ICAM-1, VCAM-1, PECAM, and E-selectin in human atherosclerosis. J Pathol, 1993, 171, 223-229. (Pubitemid 23345967)
20. Echaniz-Laguna A, Mohr M, Tranchant C: Neuromuscular symptoms and elevated creatine kinase after statin withdrawal. N Engl J Med, 2010, 362, 564-565.
21. Endres M, Laufs U: Discontinuation of statin treatment in stroke patients. Stroke, 2006, 37, 2640-2643. (Pubitemid 44454692)
22. Fleming I, Busse R: NO: the primary EDRF. J Mol Cell Cardiol, 1999, 31, 5-14. (Pubitemid 29078214)
23. Fukumoto Y, Libby P, Rabkin E, Hill CC, Enomoto M, Hirouchi Y, Shiomi M: Statins alter smooth muscle cell accumulation and collagen content in established atheroma of watanabe heritable hyperlipidemic rabbits. Circulation, 2001, 103, 993-999. (Pubitemid 32183806)
24. Gregg D, Rauscher FM, Goldschmidt-Clermont PJ: Rac regulates cardiovascular superoxide through diverse molecular interactions: more than a binary GTP switch. Am J Physiol Cell Physiol, 2003, 285, C723-C734. (Pubitemid 37158796)
25. Griendling KK, Murphy TJ, Alexander RW: Molecular biology of the renin-angiotensin system. Circulation, 1993, 87, 1816-1828. (Pubitemid 23165623)
26. Grip O, Janciauskiene S, Lindgren S: Atorvastatin activates PPAR-γ and attenuates the inflammatory response in human monocytes. Inflamm Res, 2002, 51, 58-62. (Pubitemid 34183624)
27. Gueyffier F, Bejan-Angoulvant T: Do we need to assess the effect of treatment withdrawal? The paradigm of life-long prevention. Stroke, 2007, 38, 2629-2630. (Pubitemid 47493994)
28. Hall A: Rho GTPases and the actin cytoskeleton. Science, 1998, 279, 509-514.
29. Heeschen C, Hamm CW, Laufs U, Snapinn S, Böhm M, White HD: Platelet Receptor Inhibition in Ischemic Syndrome Management (PRISM) Investigators. Withdrawal of statins increases event rates in patients with acute coronary syndromes. Circulation, 2002, 105, 1446-1452. (Pubitemid 34263276)
30. Huang CY, Wu TC, Lin WT, Leu HB, Lin CP, Lin SJ, Chen JW: Effects of simvastatin withdrawal on serum matrix metalloproteinases in hypercholesterolaemic patients. Eur J Clin Invest, 2006, 36, 76-84.
31. Huhle G, Abletshauser C, Mayer N, Weidinger G, Harenberg J, Heene DL: Reduction of platelet activity markers in type II hypercholesterolemic patients by a HMG-CoA-reductase inhibitor. Thromb Res, 1999, 95, 229-234. (Pubitemid 29428154)
32. Ii M, Losordo DW: Statins and the endothelium. Vascul Pharmacol, 2007, 46, 1-9. (Pubitemid 44856372)
33. Issemann I, Green S: Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature, 1990, 347, 645-650.
34. Jeremy JY, Rowe D, Emsley AM, Newby AC: Nitric oxide and the proliferation of vascular smooth muscle cells. Cardiovasc Res, 1999, 43, 580-594. (Pubitemid 29369257)
35. Jones CB, Sane DC, Herrington DM: Matrix matalloproteinases: a review of their structure and role in acute coronary syndrome. Cardiovasc Res, 2003, 59, 812-823. (Pubitemid 38366237)
36. Kamal-Bahl SJ, Burke T, Watson D, Wentworth C: Discontinuation of lipid modifying drugs among commercially insured United States patients in recent clinical practice. Am J Cardiol, 2007, 99, 530-534. (Pubitemid 46215558)
37. Kibbe M, Billiar T, Tzeng E: Inducible nitric oxide synthase and vascular injury. Cardiovasc Res, 1999, 43, 650-657. (Pubitemid 29369263)
38. Koh KK: Effects of statins on vascular wall: vasomotor function, inflammation, and plaque stability. Cardiovasc Res, 2000, 47, 648-657.
39. Krysiak R, Okopień B, Herman Z: Effects of HMG-CoA reductase inhibitors on coagulation and fibrinolysis processes. Drugs, 2003, 63, 1821-1854. (Pubitemid 37083030)
40. Kureishi Y, Luo Z, Shiojima I, Bialik A, Fulton D, Lefer DJ, Sessa WC, Walsh K: The HMG-CoA reductase inhibitor simvastatin activates the protein kinase Akt and promotes angiogenesis in normocholesterolemic animals. Nat Med, 2000, 6, 1004-1010.
41. Lai WT, Lee KT, Chu CS, Voon WC, Yen HW, Tsai LY, Sheu SH: Influence of withdrawal of statin treatment on proinflammatory response and fibrinolytic activity in humans: an effect independent on cholesterol elevation. Int J Cardiol, 2005, 98, 459-64.
42. Laufs U, Endres M, Custodis F, Gertz K, Nickenig G, Liao JK, Böhm M: Suppression of endothelial nitric oxide production after withdrawal of statin treatment is mediated by negative feedback regulation of rho GTPase gene transcription. Circulation, 2000, 102, 3104-3110.
43. Laufs U, Gertz K, Huang P, Nickenig G, Böhm M, Dirnagl U, Endres M: Atorvastatin upregulates type III nitric oxide synthase in thrombocytes, decreases platelet activation, and protects from cerebral ischemia in normocholesterolemic mice. Stroke, 2000, 31, 2442-2449.
44. Laufs U, La Fata V, Plutzky J, Liao JK: Upregulation of endothelial nitric oxide synthase by HMG CoA reductase inhibitors. Circulation, 1998, 97, 1129-1135. (Pubitemid 28152885)
45. Laufs U, Liao JK: Post-transcriptional regulation of endothelial nitric oxide synthase mRNA stability by Rho GTPase. J Biol Chem, 1998, 273, 24266-24271. (Pubitemid 28435775)
46. Laufs U, Marra D, Node K, Liao JK: 3-Hydroxy-3-methylglutaryl-CoA reductase inhibitors attenuate vascular smooth muscle proliferation by preventing rho GTPase-induced down-regulation of p27(Kip1). J Biol Chem, 1999, 274, 21926-21931.
47. Law RE, Goetze S, Xi XP, Jackson S, Kawano Y, Demer L, Fishbein MC et al.: Expression and function of PPARγ in rat and human vascular smooth muscle cells. Circulation, 2000, 101, 1311-1318. (Pubitemid 30158620)
48. Li H, Cybulsky MI, Gimbrone MAJr, Libby P: An atherogenic diet rapidly induces VCAM-1, a cytokine-regulatable mononuclear leukocyte adhesion molecule, in rabbit aortic endothelium. Arterioscler Thromb, 1993, 13, 197-204. (Pubitemid 23056792)
49. Li JJ, Fang CH: C-reactive protein is not only an inflammatory marker but also a direct cause of cardiovascular diseases. Med Hypotheses, 2004, 62, 499-506. (Pubitemid 38453349)
50. Li JJ, Li YS, Chu JM, Zhang CY, Wang Y, Huang Y, Chen J et al.: Changes of plasma inflammatory markers after withdrawal of statin therapy in patients with hyperlipidemia. Clin Chim Acta, 2006, 366, 269-273. (Pubitemid 43330994)
51. Libby P: Molecular bases of the acute coronary syndromes. Circulation, 1995, 91, 2844-2850.
52. Lima JA, Desai MY, Steen H, Warren WP, Gautam S, Lai S: Statin-induced cholesterol lowering and plaque regression after 6 months of magnetic resonance imaging-monitored therapy. Circulation, 2004, 110, 2336-2341. (Pubitemid 39407336)
53. Lin R, Liu J, Peng N, Yang G, Gan W, Wang W: Lovastatin reduces nuclear factor kappaB activation induced by C-reactive protein in human vascular endothelial cells. Biol Pharm Bull, 2005, 28, 1630-1634. (Pubitemid 41324122)
54. Littarru GP, Tiano L: Clinical aspects of coenzyme Q10: an update. Nutrition, 2010, 26, 250-254.
55. Macaluso M, Russo G, Cinti C, Bazan V, Gebbia N, Russo A: Ras family genes: an interesting link between cell cycle and cancer. J Cell Physiol, 2002, 192, 125-130. (Pubitemid 34747780)
56. Marin-Garcia J, Goldenthal MJ, Pierpont ME, Ananthakrishnan R: Impaired mitochondrial function in idiopathic dilated cardiomyopathy: biochemical and molecular analysis. J Card Fail, 1995, 1, 285-292.
57. McGinnis B, Olson KL, Magid D, Bayliss E, Korner EJ, Brand DW, Steiner JF: Factors related to adherence to statin therapy. Ann Pharmacother, 2007, 41, 1805-1811. (Pubitemid 350044342)
58. Meda C, Plank C, Mykhaylyk O, Schmidt K, Mayer B: Effects of statins on nitric oxide/cGMP signaling in human umbilical vein endothelial cells. Pharmacol Rep, 2010, 62, 100-112.
59. Mortensen SA, Leth A, Agner E, Rohde M: Dose-related decrease of serum coenzyme Q10 during treatment with HMG-CoA reductase inhibitors. Mol Aspects Med, 1997, 18 Suppl, S137-S144.
60. Newby AC: Dual role of matrix metalloproteinases (matrixins) in intimal thickening and atherosclerotic plaque rupture. Physiol Rev, 2005, 85, 1-31.
61. Nickenig G, Baumer AT, Temur Y, Kebben D, Jockenhovel F, Bohm M: Statin-sensitive dysregulated AT1 receptor function and density in hypercholesterolemic men. Circulation, 1999, 100, 2131-2134.
62. Nickenig G, Roling J, Strehlow K, Schnabel P, Bohm M: Insulin induces upregulation of vascular AT1 receptor gene expression by posttranscriptional mechanisms. Circulation, 1998, 98, 2453-2460. (Pubitemid 28549791)
63. Paiva H, Thelen KM, van Coster R, Smet J, De Paepe B, Mattila KM et al: High-dose statins and skeletal muscle metabolism in humans: a randomized, controlled trial. Clin Pharmacol Ther, 2005, 78, 60-68. (Pubitemid 40956932)
64. Plenz GA, Hofnagel O, Robenek H: Differential modulation of caveolin-1 expression in cells of the vasculature by statins. Circulation, 2004, 109, e7-8.
65. Puccetti L, Pasqui AL, Pastorelli M, Bova G, Di Renzo M, Leo A, Cercignani M et al.: Platelet hyperactivity after statin treatment discontinuation. Thromb Haemost, 2003, 90, 476-482. (Pubitemid 37138773)
66. Rashtchizadeh N, Argani H, Ghorbanihaghjo A, Nezami N, Safa J, Montazer-Saheb S: C-reactive protein level following treatment and withdrawal of lovastatin in diabetic nephropathy. Iran J Kidney Dis, 2009, 3, 93-98.
67. Ridker PM, Rifai N, Pfeffer MA, Sacks FM, Moye LA, Goldman S, Flaker GC: Inflammation, pravastatin, and the risk of coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events (CARE) Investigators. Circulation, 1998, 98, 839-844. (Pubitemid 28397432)
68. Risselada R, Straatman H, van Kooten F, Dippel DW, van der Lugt A, Niessen WJ, Firouzian A et al.: Withdrawal of statins and risk of subarachnoid hemorrhage. Stroke, 2009, 40, 2887-2892.
69. Rosengarten B, Auch D, Kaps M: Effects of initiation and acute withdrawal of statins on the neurovascular coupling mechanism in healthy, normocholesterolemic humans. Stroke, 2007, 38, 3193-3197. (Pubitemid 350175736)
70. Sakai A, Kume N, Nishi E, Tanoue K, Miyasaka M, Kita T: P-selectin and vascular cell adhesion molecule-1 are focally expressed in aortas of hypercholesterolemic rabbits before intimal accumulation of macrophages and T lymphocytes. Arterioscler Thromb Vasc Biol, 1997, 17, 310-316. (Pubitemid 27098189)
71. Schoonjans K, Staels B, Auwerx J: Role of the peroxisome proliferator-activated receptor (PPAR) in mediating the effects of fibrates and fatty acids on gene expression. J Lipid Res, 1996, 37, 907-925. (Pubitemid 26182326)
72. Singh R, Pan S, Mueske CS, Witt T, Kleppe LS, Peterson TE, Slobodova A et al.: Role for tissue factor pathway in murine model of vascular remodeling. Circ Res, 2001, 89, 71-76. (Pubitemid 34135494)
73. Spencer FA, Fonarow GC, Frederick PD, Wright RS, Every N, Goldberg RJ, Gore JM et al.: National Registry of Myocardial Infarction: Early withdrawal of statin therapy in patients with non-ST-segment elevation myocardial infarction: national registry of myocardial infarction. Arch Intern Med, 2004, 164, 2162-2168. (Pubitemid 39410807)
74. Sposito AC, Carvalho LS, Cintra RM, Araújo AL, Ono AH, Andrade JM, Coelho OR, Quinaglia e Silva JC; Brasilia Heart Study Group. Rebound inflammatory response during the acute phase of myocardial infarction after simvastatin withdrawal. Atherosclerosis, 2009, 207, 191-194.
75. Staels B, Fruchart JC: Therapeutic roles of peroxisome proliferator-activated receptor agonists. Diabetes, 2005, 54, 2460-2470. (Pubitemid 41134276)
76. Stoll LL, McCormick ML, Denning GM, Weintraub NL: Antioxidant effects of statins. Drugs Today (Barc), 2004, 40, 975-990.
77. Stone NJ: Stopping statins. Circulation, 2004, 110, 2280-2282.
78. Suzuki T, Nozawa T, Sobajima M, Igarashi N, Matsuki A, Fujii N, Inoue H: Atorvastatin-induced changes in plasma coenzyme Q10 and brain natriuretic peptide in patients with coronary artery disease. Int Heart J, 2008, 49, 423-433.
79. Szmitko PE, Wang CH, Weisel RD, De Almeida JR, Anderson TJ, Verma S: New markers of inflammation and endothelial cell activation: Part I. Circulation, 2003, 108, 1917-1923. (Pubitemid 37296533)
80. Tamai O, Matsuoka H, Itabe H, Wada Y, Kohno K, Imaizumi T: Single LDL apheresis improves endothelium-dependent vasodilatation in hypercholesterolemic humans. Circulation, 1997, 95, 76-82. (Pubitemid 27029946)
81. Taneva E, Borucki K, Wiens L, Makarova R, Schmidt-Lucke C, Luley C, Westphal S: Early effects on endothelial function of atorvastatin 40 mg twice daily and its withdrawal. Am J Cardiol, 2006, 97, 1002-1006.
82. Thomas M, Mann J: Increased thrombotic vascular events after change of statin. Lancet, 1998, 352, 1830-1831. (Pubitemid 28550081)
83. Thomas MK, Narang D, Lakshmy R, Gupta R, Naik N, Maulik SK: Correlation between inflammation and oxidative stress in normocholesterolemic coronary artery disease patients 'on' and 'off' atorvastatin for short time intervals. Cardiovasc Drugs Ther, 2006, 20, 37-44.
84. Tziomalos K, Athyros VG, Mikhailidis DP: Statin discontinuation: an underestimated risk? Curr Med Res Opin, 2008, 24, 3059-3063.
85. van Aelst L, D'Souza-Schorey C: Rho GTPases and signaling networks. Genes Dev, 1997, 11, 2295-2322.
86. Vecchione C, Brandes RP: Withdrawal of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors elicits oxidative stress and induces endothelial dysfunction in mice. Circ Res, 2002, 91, 173-179. (Pubitemid 34827229)
87. Wassmann S, Laufs U, Baumer AT, Muller K, Konkol C, Sauer H, Bohm M et al: Inhibition of geranylgeranylation reduces angiotensin II-mediated free radical production in vascular smooth muscle cells: involvement of angiotensin AT1 receptor expression and Rac1 GTPase. Mol Pharmacol, 2001, 59, 646-654. (Pubitemid 32179945)
88. Weitz-Schmidt G: Lymphocyte function-associated antigen-1 blockade by statins: molecular basis and biological relevance. Endothelium, 2003, 10, 43-47.
89. Yip HK, Hang CL, Fang CY, Hsieh YK, Yang CH, Hung WC, Wu CJ: Level of high-sensitivity C-reactive protein is predictive of 30-day outcomes in patients with acute myocardial infarction undergoing primary coronary intervention. Chest, 2005, 127, 803-808. (Pubitemid 40775508)
90. Yip HK, Youssef AA, Chua S, Hung WC, Chen YH, Yeh KH, Wu CJ, Hang CL: Re-elevation of high-sensitivity C-reactive protein but not the von Willebrand Factor after withdrawing atorvastatin therapy in patients with unstable angina undergoing coronary artery stenting. Int Heart J, 2006, 47, 501-509. (Pubitemid 44463656)
91. Zelvyte I, Dominaitiene R, Crisby M, Janciauskiene S: Modulation of inflammatory mediators and PPARγ and NFκB expression by pravastatin in response to lipoproteins in human monocytes in vitro. Pharmacol Res, 2002, 45, 147-154. (Pubitemid 35425654)