Hydrophilic vs lipophilic statins in coronary artery disease: A meta-analysis of randomized controlled trials

Authors:

Ibadete Bytyçi, MD | Gani Bajraktari, MD, PhD, FESC, FAAC | Deepak L. Bhatt, MD, MPH, FACC, FAHA, FSCAI, FESC | Charity J. Morgan, MD, PhD | Ali Ahmed, MD, MPH | Wilbert S. Aronow, MD | Maciej Banach, MD, PhD, FNLA, FAHA, FESC, FASA | on behalf ofLipid and Blood Pressure Meta-analysis Collaboration (LBPMC) Group
First published: March 13, 2017 |https://doi.org/10.1016/j.jacl.2017.03.003

Abstract:

Introduction

Some available experimental studies have reported that hydrophilic statins might have advantages compared with lipophilic statins in patients with coronary artery disease (CAD). Therefore, we performed a meta-analysis of randomized controlled trials (RCTs) investigating the potential differences of lipophilic and hydrophilic statins in patients with CAD.

Methods

We systematically searched selected electronic databases up to September 2016 to select RCTs, which compared clinical outcomes of hydrophilic vs lipophilic statins. Primary endpoints were cardiovascular (CV) events: major adverse cardiac events, myocardial infarction, cardiac revascularization, stroke, CV death, CV hospitalization, and all-cause mortality. Secondary endpoints were safety parameters: drug discontinuation, statin-associated muscle symptoms and alanine aminotransferase level increase.

Results

A total of 11,697 patients from 11 RCTs, randomly allocated to lipophilic (n = 5736) or hydrophilic statins (n = 5961), with a mean follow-up 14 months, were included in the meta-analysis. In comparison with hydrophilic, the lipophilic statins showed similar risk reduction for major adverse cardiac events (relative risk = 0.969, 95% confidence interval [CI], 0.835–1.125, P = .682), myocardial infarction (0.880, 95% CI: 0.731–1.058, P = .174), CV death (0.757, 95% CI: 0.486–1.180, P = .219), and all-cause mortality (0.797, 95% CI: 0.590–1.075, P = .137), as well as cardiac revascularization, stroke, drug discontinuation, and statin-associated muscle symptoms. CV hospitalization was lower (0.789, 95% CI: 0.643–0.969, P = .024) and alanine aminotransferase elevation was higher (2.689, 95% CI: 1.841–3.954, P ≤ .001) in lipophilic than in hydrophilic-treated patients.

Conclusions

In conclusion, similarity between hydrophilic and lipophilic statins holds between various clinical CAD settings.

  1. Munnur R.K., Nerlekar N., Wong D.T.
    Imaging of coronary atherosclerosis in various susceptible groups.
    Cardiovasc Diagn Ther. 2016; 6: 382-395
  2. Nichols M., Townsend N., Scarborough P., Rayner M.
    Cardiovascular disease in Europe 2014: epidemiological update.
    Eur Heart J. 2014; 35: 2950-2959
  3. Ferreira-González I.
    The epidemiology of coronary heart disease.
    Rev Esp Cardiol (Engl Ed). 2014; 67: 139-144
  4. McNamara R.L., Spatz E.S., Kelley T.A., et al.
    Standardized outcome measurement for patients with coronary artery disease: consensus from the International Consortium for Health Outcomes Measurement (ICHOM).
    J Am Heart Assoc. 2015; 4: e001767
  5. Tamis-Holland J.E., O’Gara P.
    Highlights from the 2013 ACCF/AHA guidelines for the management of ST-elevation myocardial infarction and beyond.
    Clin Cardiol. 2014; 37: 252-259
  6. Levine G.N., Bates E.R., Blankenship J.C., et al.
    2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions.
    J Am Coll Cardiol. 2011; 58: e44-e122
  7. Roffi M. ,Gencer B., Storey R.F., Andreotti F., Patrono C.
    Clinical perspectives and pearls from the 2015 ESC NSTE-ACS guidelines.
    Curr Cardiol Rep. 2016; 18: 48
  8. Sahebkar A., Serban C., Mikhailidis D.P.
    Lipid and Blood Pressure Meta-analysis Collaboration (LBPMC) Group
    Association between statin use and plasma D-dimer levels. A systematic review and meta-analysis of randomised controlled trials.
    Thromb Haemost. 2015; 114: 546-557
  9. Germershausen J.I., Hunt V.M., Bostedor R.G., Bailey P.J., Karkas J.D., Alberts A.W.
    Tissue selectivity of the cholesterol-lowering agents lovastatin, simvastatin and pravastatin in rats in vivo.
    Biochem Biophys Res Commun. 1989; 158: 667-675
  10. McKenney J.M.
    Pharmacologic characteristics of statins.
    Clin Cardiol. 2003; 26: III32-III38
  11. Zhou Q., Liao J.K.
    Pleiotropic effects of statins. – Basic research and clinical perspectives -.
    Circ J. 2010; 74: 818-826
  12. Ichihara K., Satoh K.
    Disparity between angiographic regression and clinical event rates with hydrophobic statins.
    Lancet. 2002; 359: 2195-2198
  13. Satoh K., Ichihara K.
    Lipophilic HMG-CoA reductase inhibitors increase myocardial stunning in dogs.
    J Cardiovasc Pharmacol. 2000; 35: 256-262
  14. Yun K.H., Jeong M.H., Oh S.K., 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
  15. Hiro T., Kimura T., Morimoto T., et al.
    Effect of intensive statin therapy on regression of coronary atherosclerosis in patients with acute coronary syndrome: a multicenter randomized trial evaluated by volumetric intravascular ultrasound using pitavastatin versus atorvastatin (JAPAN-ACS [Japan assessment of pitavastatin and atorvastatin in acute coronary syndrome] study).
    J Am Coll Cardiol. 2009; 54: 293-302
  16. Vilahur G., Casani L., Peña E., et al.
    HMG-CoA reductase inhibition prior reperfusion improves reparative fibrosis post-myocardial infarction in a preclinical experimental model.
    Int J Cardiol. 2014; 175: 528-538
  17. Sahebkar A., Serban C., Ursoniu S., et al.
    Lipid and Blood Pressure Meta-analysis Collaboration (LBPMC) Group
    The impact of statin therapy on plasma levels of von Willebrand factor antigen. Systematic review and meta-analysis of randomised placebo-controlled trials.
    Thromb Haemost. 2016; 115: 520-532
  18. Arnaboldi L., Corsini A.
    Do structural differences in statins correlate with clinical efficacy?.
    Curr Opin Lipidol. 2010; 21: 298-304
  19. Backes J.M., Howard P.A., Ruisinger J.F., Moriarty P.M.
    Does simvastatin cause more myotoxicity compared with other statins?.
    Ann Pharmacother. 2009; 43: 2012-2020
  20. Kim M.C., Ahn Y., Jang S.Y., et al.
    Comparison of clinical outcomes of hydrophilic and lipophilic statins in patients with acute myocardial infarction.
    Korean J Intern Med. 2011; 26: 294-303
  21. Maruyama T., Takada M., Nishibori Y. ,et al.
    Comparison of preventive effect on cardiovascular events with different statins. -The CIRCLE study-.
    Circ J. 2011; 75: 1951-1959
  22. Moher D., Liberati A., Tetzlaff J., Altman D.G., Group P.
    Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.
    BMJ. 2009; 339: b2535
  23. Higgins JPT, Green S. Cochrane Handbook for systematic reviews of intervention Version. 5.1.0. The Cochrane Collaboration, 2011. Available at: www.cochrane–handbook.org.
  24. Hozo S.P., Djulbegovic B., Hozo I.
    Estimating the mean and variance from the median, range, and the size of a sample.
    BMC Med Res Methodol. 2005; 5: 13
  25. Higgins J.P., Thompson S.G., Deeks J.J., Altman D.G.
    Measuring inconsistency in meta analyses.
    BMJ. 2003; 327: 557-560
  26. Sterne J.A., Egger M., Smith G.D.
    Systematic reviews in health care: investigating and dealing with publication and other biases in meta-analysis.
    BMJ. 2001; 323: 101-105
  27. Cannon C.P., Braunwald E., McCabe C.H., et al.
    Intensive versus moderate lipid lowering with statins after acute coronary syndromes.
    N Engl J Med. 2004; 350: 1495-1504
  28. Nissen S.E., Tuzcu E.M., Schoenhagen P., et al.
    Effect of intensive compared with moderate lipid-lowering therapy on progression of coronary atherosclerosis: a randomized controlled trial.
    JAMA. 2004; 291: 1071-1080
  29. Deedwania P., Stone P.H., Bairey Merz C.N., et al.
    Effects of intensive versus moderate lipid-lowering therapy on myocardial ischemia in older patients with coronary heart disease: results of the Study Assessing Goals in the Elderly (SAGE).
    Circulation. 2007; 115: 700-707
  30. Sakamoto T., Kojima S., Ogawa H., et al.
    MUSASHI-AMI Investigators
    Usefulness of hydrophilic vs lipophilic statins after acute myocardial infarction: subanalysis of MUSASHI-AMI.
    Circ J. 2007; 71: 1348-1353
  31. Hall A.S., Jackson B.M., Farrin A.J., et al., SPACE ROCKET Trial Group
    A randomized, controlled trial of simvastatin versus rosuvastatin in patients with acute myocardial infarction: the Secondary Prevention of Acute Coronary Events–Reduction of Cholesterol to Key European Targets Trial.
    Eur J Cardiovasc Prev Rehabil. 2009; 16: 712-721
  32. Lablanche J.M., Leone A., Merkely B., et al., CENTAURUS investigators
    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: 160-169
  33. Nicholls S.J., Ballantyne C.M., Barter P.J., et al.
    Effect of two intensive statin regimens on progression of coronary disease.
    N Engl J Med. 2011; 365: 2078-2087
  34. Pitt B., Loscalzo J., Monyak J., Miller E., Raichlen J.
    Comparison of lipid-modifying efficacy of rosuvastatin versus atorvastatin in patients with acute coronary syndrome (from the LUNAR study).
    Am J Cardiol. 2012; 109: 1239-1246
  35. Sardella G., Lucisano L., Mancone M., et al.
    Comparison of high reloading ROsuvastatin and Atorvastatin pretreatment in patients undergoing elective PCI to reduce the incidence of MyocArdial periprocedural necrosis. The ROMA II trial.
    Int J Cardiol. 2013; 168: 3715-3720
  36. Suh J.W., Cha M.J., Lee S.P., et al.
    Relationship between statin type and responsiveness to clopidogrel in patients treated with percutaneous coronary intervention: a subgroup analysis of the CILON-T trial.
    J Atheroscler Thromb. 2014; 21: 140-150
  37. Izawa A., Kashima Y., Miura T., et al., ALPS-AMI
    Assessment of lipophilic vs. hydrophilic statin therapy in acute myocardial infarction – ALPS-AMI study.
    Circ J. 2015; 79: 161-168
  38. Chitose T., Sugiyama S., Sakamoto K., et al.
    Effect of a hydrophilic and a hydrophobic statin on cardiac salvage after ST-elevated acute myocardial infarction – a pilot study.
    Atherosclerosis. 2014; 237: 251-258
  39. Khurana S., Gupta S., Bhalla H., Nandwani S., Gupta V.
    Comparison of anti-inflammatory effect of atorvastatin with rosuvastatin in patients of acute coronary syndrome.
    J Pharmacol Pharmacother. 2015; 6: 130-135
  40. van Vliet A.K., van Thiel G.C., Huisman R.H., Moshage H., Yap S.H., Cohen L.H.
    Different effects of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors on sterol synthesis in various human cell types.
    Biochim Biophys Acta. 1995; 1254: 105-111
  41. Banach M., Serban C., Ursoniu S., et al.
    Statin therapy and plasma coenzyme Q10 concentrations – A systematic review and meta-analysis of placebo-controlled trials.
    Pharmacol Res. 2015; 99: 329-336
  42. Carnicka S., Adameova A., Ravingerova T., et al.
    Distinct effects of acute pretreatment with lipophilic and hydrophilic statins on myocardial stunning, arrhythmias and lethal injury in the rat heart subjected to ischemia/reperfusion.
    Physiol Res. 2011; 60: 825-830
  43. Liu Y., Liu Y.H., Tan N., et al.
    Comparison of the efficacy of rosuvastatin versus atorvastatin in preventing contrast induced nephropathy in patient with chronic kidney disease undergoing percutaneous coronary intervention.
    PLoS One. 2014; 9: e111124
  44. Bulhak A.A., Gourine A.V., Gonon A.T., Sjoquist P.O., Valen G., Pernow J.
    Oral pre-treatment with rosuvastatin protects porcine myocardium from ischaemia/reperfusion injury via a mechanism related to nitric oxide but not to serum cholesterol level.
    Acta Physiol Scand. 2005; 183: 151-159
  45. Lefer A.M., Scalia R., Lefer D.J.
    Vascular effects of HMG CoA-reductase inhibitors (statins) unrelated to cholesterol lowering: new concepts for cardiovascular disease.
    Cardiovasc Res. 2001; 49: 281-287
  46. Wolfrum S., Grimm M., Heidbreder M., et al.
    Acute reduction of myocardial infarct size by a hydroxymethyl glutaryl coenzyme A reductase inhibitor is mediated by endothelial nitric oxide synthase.
    J Cardiovasc Pharmacol. 2003; 41: 474-480
  47. Scalia R., Gooszen M.E., Jones S.P., et al.
    Simvastatin exerts both anti-inflammatory and cardioprotective effects in apolipoprotein E-deficient mice.
    Circulation. 2001; 103: 2598-2603
  48. Sahebkar A., Kotani K., Serban C., et al.
    Statin therapy reduces plasma endothelin-1 concentrations: a meta-analysis of 15 randomized controlled trials.
    Atherosclerosis. 2015; 241: 433-442
  49. Serban C., Sahebkar A., Ursoniu S., et al.
    A systematic review and meta-analysis of the effect of statins on plasma asymmetric dimethylarginine concentrations.
    Sci Rep. 2015; 5: 9902
  50. Bulhak A., Roy J., Hedin U., Sjöquist P.O., Pernow J.
    Cardioprotective effect of rosuvastatin in vivo is dependent on inhibition of geranylgeranyl pyrophosphate and altered RhoA membrane translocation.
    Am J Physiol Heart Circ Physiol. 2007; 292: H3158-H3163
  51. Hobbs F.D., Banach M., Mikhailidis D.P., Malhotra A., Capewell S.
    Is statin-modified reduction in lipids the most important preventive therapy for cardiovascular disease? A pro/con debate.
    BMC Med. 2016; 14: 4
  52. Banach M., Rizzo M., Toth P.P., et al.
    Statin intolerance – an attempt at a unified definition. Position paper from an International Lipid Expert Panel.
    Arch Med Sci. 2015; 11: 1-23

© 2023 Lipid and Blood Pressure Meta-Analysis Collaboration Group All Rights Reserved

Site map