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Statins for the primary prevention of cardiovascular disease - PubMed

  • ️Tue Jan 01 2013

Review

Statins for the primary prevention of cardiovascular disease

Fiona Taylor et al. Cochrane Database Syst Rev. 2013.

Abstract

Background: Reducing high blood cholesterol, a risk factor for cardiovascular disease (CVD) events in people with and without a past history of CVD is an important goal of pharmacotherapy. Statins are the first-choice agents. Previous reviews of the effects of statins have highlighted their benefits in people with CVD. The case for primary prevention was uncertain when the last version of this review was published (2011) and in light of new data an update of this review is required.

Objectives: To assess the effects, both harms and benefits, of statins in people with no history of CVD.

Search methods: To avoid duplication of effort, we checked reference lists of previous systematic reviews. The searches conducted in 2007 were updated in January 2012. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (2022, Issue 4), MEDLINE OVID (1950 to December Week 4 2011) and EMBASE OVID (1980 to 2012 Week 1).There were no language restrictions.

Selection criteria: We included randomised controlled trials of statins versus placebo or usual care control with minimum treatment duration of one year and follow-up of six months, in adults with no restrictions on total, low density lipoprotein (LDL) or high density lipoprotein (HDL) cholesterol levels, and where 10% or less had a history of CVD.

Data collection and analysis: Two review authors independently selected studies for inclusion and extracted data. Outcomes included all-cause mortality, fatal and non-fatal CHD, CVD and stroke events, combined endpoints (fatal and non-fatal CHD, CVD and stroke events), revascularisation, change in total and LDL cholesterol concentrations, adverse events, quality of life and costs. Odds ratios (OR) and risk ratios (RR) were calculated for dichotomous data, and for continuous data, pooled mean differences (MD) (with 95% confidence intervals (CI)) were calculated. We contacted trial authors to obtain missing data.

Main results: The latest search found four new trials and updated follow-up data on three trials included in the original review. Eighteen randomised control trials (19 trial arms; 56,934 participants) were included. Fourteen trials recruited patients with specific conditions (raised lipids, diabetes, hypertension, microalbuminuria). All-cause mortality was reduced by statins (OR 0.86, 95% CI 0.79 to 0.94); as was combined fatal and non-fatal CVD RR 0.75 (95% CI 0.70 to 0.81), combined fatal and non-fatal CHD events RR 0.73 (95% CI 0.67 to 0.80) and combined fatal and non-fatal stroke (RR 0.78, 95% CI 0.68 to 0.89). Reduction of revascularisation rates (RR 0.62, 95% CI 0.54 to 0.72) was also seen. Total cholesterol and LDL cholesterol were reduced in all trials but there was evidence of heterogeneity of effects. There was no evidence of any serious harm caused by statin prescription. Evidence available to date showed that primary prevention with statins is likely to be cost-effective and may improve patient quality of life. Recent findings from the Cholesterol Treatment Trialists study using individual patient data meta-analysis indicate that these benefits are similar in people at lower (< 1% per year) risk of a major cardiovascular event.

Authors' conclusions: Reductions in all-cause mortality, major vascular events and revascularisations were found with no excess of adverse events among people without evidence of CVD treated with statins.

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Conflict of interest statement

None known.

Figures

1
1

Study flow diagram for the update

2
2

Methodological quality summary: review authors' judgements about each methodological quality item for each included study.

3
3

Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.

4
4

Funnel plot of comparison: 2 Mortality and Morbidity, outcome: 2.1 Total Mortality.

1.1
1.1. Analysis

Comparison 1: Mortality and Morbidity, Outcome 1: Total Mortality

1.2
1.2. Analysis

Comparison 1: Mortality and Morbidity, Outcome 2: Total Number of CHD Events

1.3
1.3. Analysis

Comparison 1: Mortality and Morbidity, Outcome 3: Number of Fatal CHD Events

1.4
1.4. Analysis

Comparison 1: Mortality and Morbidity, Outcome 4: Number of Non‐fatal CHD Events

1.5
1.5. Analysis

Comparison 1: Mortality and Morbidity, Outcome 5: Total Number of CVD Events

1.6
1.6. Analysis

Comparison 1: Mortality and Morbidity, Outcome 6: Number of Fatal CVD Events

1.7
1.7. Analysis

Comparison 1: Mortality and Morbidity, Outcome 7: Number of Non‐fatal CVD Events

1.8
1.8. Analysis

Comparison 1: Mortality and Morbidity, Outcome 8: Total Number of Stroke Events

1.9
1.9. Analysis

Comparison 1: Mortality and Morbidity, Outcome 9: Number of Fatal Stroke Events

1.10
1.10. Analysis

Comparison 1: Mortality and Morbidity, Outcome 10: Number of Non‐fatal Stroke Events

1.11
1.11. Analysis

Comparison 1: Mortality and Morbidity, Outcome 11: Total Number of Fatal and Non‐fatal CHD, CVD and Stroke Events

1.12
1.12. Analysis

Comparison 1: Mortality and Morbidity, Outcome 12: Number of Study Participants who underwent Revascularisation

2.1
2.1. Analysis

Comparison 2: Lipids (mmol/L), Outcome 1: Total Cholesterol (mmol/L)

2.2
2.2. Analysis

Comparison 2: Lipids (mmol/L), Outcome 2: LDL Cholesterol (mmol/L)

3.1
3.1. Analysis

Comparison 3: Adverse Events, Outcome 1: Number of study participants who had adverse events

3.2
3.2. Analysis

Comparison 3: Adverse Events, Outcome 2: Number of study participants who stopped treatment due to adverse events

3.3
3.3. Analysis

Comparison 3: Adverse Events, Outcome 3: Number of study participants who were admitted to hospital

3.4
3.4. Analysis

Comparison 3: Adverse Events, Outcome 4: Number of study participants who developed cancer

3.5
3.5. Analysis

Comparison 3: Adverse Events, Outcome 5: Number of study participants who developed myalgia or muscle pain

3.6
3.6. Analysis

Comparison 3: Adverse Events, Outcome 6: Number of study participants who developed rhabdomyolysis

3.7
3.7. Analysis

Comparison 3: Adverse Events, Outcome 7: Number of study participants who developed diabetes

3.8
3.8. Analysis

Comparison 3: Adverse Events, Outcome 8: Number of study participants who developed haemorrhagic stroke

3.9
3.9. Analysis

Comparison 3: Adverse Events, Outcome 9: Number of study participants who had elevated liver enzymes

3.10
3.10. Analysis

Comparison 3: Adverse Events, Outcome 10: Number of study participants who developed renal disorder

3.11
3.11. Analysis

Comparison 3: Adverse Events, Outcome 11: Number of study participants who developed arthritis

4.1
4.1. Analysis

Comparison 4: Treatment Compliance, Outcome 1: Treatment Compliance

5.1
5.1. Analysis

Comparison 5: Sensitivity Analysis, Outcome 1: Early stopping of trials and total mortality

5.2
5.2. Analysis

Comparison 5: Sensitivity Analysis, Outcome 2: Early stopping of trials and total CHD events

5.3
5.3. Analysis

Comparison 5: Sensitivity Analysis, Outcome 3: Study Size for total Mortality

5.4
5.4. Analysis

Comparison 5: Sensitivity Analysis, Outcome 4: Study Size for total CHD events

Update of

  • Statins for the primary prevention of cardiovascular disease.

    Taylor F, Ward K, Moore TH, Burke M, Davey Smith G, Casas JP, Ebrahim S. Taylor F, et al. Cochrane Database Syst Rev. 2011 Jan 19;(1):CD004816. doi: 10.1002/14651858.CD004816.pub4. Cochrane Database Syst Rev. 2011. PMID: 21249663 Free PMC article. Updated. Review.

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References

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CERDIA 2004 {published data only}
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Derosa 2003 {published data only}
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HYRIM 2007 {published data only}
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JUPITER 2008 {published data only}
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KAPS 1995 {published data only}
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METEOR 2010 {published data only}
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MRC/BHF Heart Protection {published data only}
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PREVEND IT 2004 {published data only}
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Agewall 2006 {published data only}
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ALLHAT‐LLT 2002 {published data only}
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BCAPS 2001 {published data only}
    1. Hedblad B, Wikstand J, Janzon L, WedelH, Berglund G. Low dose metaprolol CR/XL and fluvastatin slow progression of carotid intima-media thickness: main results from the Beta-Blocker Cholesterol-Lowering Asymptomatic Plaque Study. Circulation 2001;103:1721-6. - PubMed
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Byington 1993 {published data only}
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CASHMERE 2007 {published data only}
    1. Pfizer. Carotid Atorvastatin Study in Hyperlipidemic Post-MEnopausal Women: a Randomised Evaluation of atorvastatin versus placebo (CASHMERE). Protocol A2581051. PhRMA Web Synopsis 2007.
Cassader 1993 {published data only}
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CHALLENGER {published data only}
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Chan 1996 {published data only}
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Chuengsamarn 2010 {published data only}
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CLIP 2002 {published data only}
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Cowan 2010 {published data only}
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CURVES 1998 {published data only}
    1. Jones PH, Kafonek S, Laurora I, Hunninghake DB. Comparative dose efficacy study of atorvastatin with that of lovastatin, pravastatin, simvastatin and fluvastatin in patients With hypercholesterolemia (the CURVES Study). American Journal of Cardiology 1998;81(5):582-7. - PubMed
Dangas 1999 {published data only}
    1. Dangas G, Badimon JJ, Smith DA, Unger AH, Levine D, Shao JH, et al. Pravastatin therapy in hyperlipidemia: effects on thrombus formation and the systemic hemostatic profile. Journal of the American College of Cardiology. 1999;33(5):1294-304. - PubMed
Davidson 1997 {published data only}
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Duffy 2001 {published data only}
    1. Duffy SJ, O'Brien RC, New G, Harper RW, Meredith IT. Effect of anti-oxidant treatment and cholesterol lowering on resting arterial tone, metabolic vasodilation and endothelial function in the human forearm: a randomized, placebo-controlled study. Clinical & Experimental Pharmacology & Physiology. 2001;28(5-6):409-18. - PubMed
Egashira 1994 {published data only}
    1. Egashira K, Hirooka Y, Kai H, Sugimachi M, Suzuki S, Inou T, er al. Reduction in serum cholesterol with pravastatin improves endothelium-dependent coronary vasomotion in patients with hypercholesterolemia. Circulation 1994;89:2519-24. - PubMed
Eriksson 1998 {published data only}
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EXCEL 1990 {published data only}
    1. Bradford RH, Shear CL, Chremos AN, Dujovne C, Downton M, Franklin FA, et al. Expanded Clinical Evaluation of Lovastatin (EXCEL) study results. I. Efficacy in modifying plasma lipoproteins and adverse event profile in 8245 patients with moderate hypercholesterolemia. Archives of Internal Medicine 1991;151(1):43-9. - PubMed
    1. Bradford RH, Shear CL, Chremos AN, Dujovne C, Franklin FA, Hesney M, et al. Expanded clinical evaluation of lovastatin (EXCEL) study: design and patient characteristics of a double-blind, placebo-controlled study in patients with moderate hypercholesterolemia. American Journal of Cardiology. 1990;66(8):44B-55B. - PubMed
    1. Bradford RH, Shear CL, Chremos AN, Dujovne CA, Franklin FA, Grillo RB, et al. Expanded Clinical Evaluation of Lovastatin (EXCEL) study results: two-year efficacy and safety follow-up. American Journal of Cardiology 1994;74(7):667-73. - PubMed
    1. Bradford RH, Shear CL, Chremos AN, Franklin FA, Nash DT, Hurley DP, et al. Expanded clinical evaluation of lovastatin (EXCEL) study results: III. Efficacy in modifying lipoproteins and implications for managing patients with moderate hypercholesterolemia. American Journal of Medicine 1991;91(1B):18S-24S. - PubMed
Faergeman 2009 {published data only}
    1. Faergeman O, Holme I, Fayyad R, Bhatia S, Grundy SM, Kastelein JJ, et al, Steering Committees of IDEAL and TNT Trials. Plasma triglycerides and cardiovascular events in the Treating to New Targets and Incremental Decrease in End-Points through Aggressive Lipid Lowering trials of statins in patients with coronary artery disease. American Journal of Cardiology 2009;104(4):459-63. - PubMed
FAST 2002 {published data only}
    1. Sawayama Y, Shimizu C, Maeda N, Tatsukawa M, Kinukawa N, Koyanagi S, et al. Effects of probucal and pravastatin on common carotid atherosclerosis in patients with asymptomatic hypercholesterolemia. Fukuoka atherosclerosis trial (FAST). Journal of the American College of Cardiology 2002;39(4):610-6. - PubMed
Ferrari 1993 {published data only}
    1. Ferrari P, Weidmann P, Riesen WF, Martius F, Luban S, Pasotti E, et al. Pravastatin in the treatment of primary hypercholesterolemia: a Swiss multicenter study [Pravastatin zur Behandlung der primaren Hypercholesterinamie: Schweizer Multizenter-Studie]. Schweizerische Medizinische Wochenschrift [Journal Suisse de Medecine] 1993;123(37):1736-41. - PubMed
Gentile 2000 {published data only}
    1. Gentile S, Turco S, Guarino G, Sasso CF, Amodio M, Magliano P, et al. Comparative efficacy study of atorvastatin vs. simvastatin, pravastatin, lovastatin and placebo in type 2 diabetic patients with hypercholesterolaemia. Diabetes, Obesity and Metabolism 2000;2(6):355-62. - PubMed
Glasser 1996 {published data only}
    1. Glasser SP, DiBianco R, Effron BA, Faas F, Germino FW, Shane LE, et al. The efficacy and safety of pravastatin in patients aged 60 to 85 years with low-density lipoprotein cholesterol > 160 mg/dl. The American Journal Of Cardiology 1996;77:83-5. - PubMed
Gomez‐Garcia 2007 {published data only}
    1. Gómez-García A, Martínez Torres G, Ortega-Pierres LE, Rodríguez-Ayala E, Alvarez-Aguilar C. Rosuvastatin and metformin decrease inflammation and oxidative stress in patients with hypertension and dyslipidemia [Rosuvastatina y metformina reducen la inflamacion y el estres oxidativo en pacientes con hipertension y dislipemia]. Revista Espanola de Cardiologia 2007;60(12):1242-9. - PubMed
Guisasola 2009 {published data only}
    1. Guisasola MC, Dulin E, Almendral J, Garcia-Barreno P. Reduction of heat shock protein antibody levels by statin therapy. Lipids 2009;44:317-24. - PubMed
Hokuriku NK‐104 Study 02 {published data only}
    1. Noji Y, Higashikata T, Inazu A, Nohara A, Ueda K, Miyamoto S, et al. Long-term treatment with pitavastatin (NK-104), a new HMG-CoA reducatase inhibitor, of patients with heterozygous familial hypercholesterolemia. Atherosclerosis 2002;163:157-64. - PubMed
Hongo 2010 {published data only}
    1. Hongo M, Kumazaki S, Izawa A, Kasai H, Tanita T, Yazaki Y. Rosuvastatin improves arterial stiffness in hypertensive patients with dyslipidemia. In: European Heart Journal. Conference.
Hufnagel 2000 {published data only}
    1. Hufnagel G, Vrtovsnik CMF, Queffeulou G, Kossari N, Mignon F. Effects of atorvastatin on dyslipidemia in uraemic patients on peritoneal dialysis. Nephrology Dialysis Transplantation 2000;15:684-8. - PubMed
Italian Family Physician {published data only}
    1. Cattin L, Da Col PG, Bordin P, Battello C, Petrucco A, Fonda M on behalf of the Italian Postmarketing Surveillance Simvastatin Study Group. Efficacy and safety of simvastatin in current clinical practice: The Italian Family Physician Simvastatin Study. Current Therapeutic Research 1996;57(6):418-29.
Jardine 2006 {published data only}
    1. Jardine A Holdaas H, Fellstrom B, Cole E, Nyberg G, Grönhagen-Riska C, et al, ALERT Study Investigators. Fluvastatin prevents cardiac death and myocardial infarction in renal transplant recipients: post hoc analysis of the ALERT study. American Journal of Transplantation 2006;4(6):988-95. - PubMed
JART 2011 {published data only}
    1. Hohara R, Daida H, Hata M, Kaku K, Kawamori R. Effect of intensive lipid lowering therapy with rosuvastatin of carotid intima-media thickness in Japanese patients: Justification of Atherosclorosis Regression Treatment (JART) study. Circulation 2012 (Epub 2011);76:221-9. - PubMed
JELIS 2009 {published data only}
    1. Oikawa S, Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Saito Y, et al, JELIS Investigators, Japan. Suppressive effect of EPA on the incidence of coronary events in hypercholesterolemia with impaired glucose metabolism: Sub-analysis of the Japan EPA Lipid Intervention Study (JELIS). Atherosclerosis 2009;206(2):535-9. - PubMed
J‐LIT 2007 {published data only}
    1. ShimamotoK, Kita T, Mabuchi H, Matsuzaki M, Matsuzawa Y, Nakaya N, et al, J-LIT Study Group. Effects of hypertension and type 2 diabetes mellitus on the risk of total cardiovascular events in Japanese patients with hypercholesterolemia: implications from the Japan Lipid Intervention Trial (J-LIT). Hypertension Research - Clinical & Experimental 2007;30(2):119-23. - PubMed
Jones 1991 {published data only}
    1. Jones PH, Farmer JA, Cressman MD, McKenney JM, Wright JT, Proctor JD, et al. Once-daily pravastatin in patients with primary hypercholesterolemia: a dose-response study. Clinical Cardiology 1991;14:146-51. - PubMed
Kappelle 2009 {published data only}
    1. Kappelle, PJWH, Zwang L, Huisman MV, Banga JD, Sluiter WJ, Dallinga-Thie GM, et al. Atorvastatin affects low density lipoprotein and non-high density lipoprotein cholesterol relations with apolipoprotein B in type 2 diabetes mellitus: Modification by triglycerides and cholesteryl ester transfer protein. Expert Opinion on Therapeutic Targets 2009;13(7):743-51. - PubMed
KLIS 2000 {published data only}
    1. Sasaki J, Arakawa K, KLIS group. Abstract at XIIth International Symposium on Atherosclerosis, Stockholm, Sweden, June 25-29 2000. Pravastatin use and risk of coronary events and cerebral infarction in Japanese men with hypercholesterolemia: The Kyushu Lipid Intervention Study (KLIS). Atherosclerosis 2000;151(1):37.
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Kojima 2010 {published data only}
    1. Kojima S, Sakamoto T, Ogawa H, Kitagawa A, Matsui K, Shimomura H, et al, Multicenter Study for Aggressive Lipid-lowering Strategy by HMG-CoA Reductase Inhibitors Investigators. Standard-dose statin therapy provides incremental clinical benefits in normocholesterolemic diabetic patients. Circulation Journal 2010;74(4):779-85. - PubMed
Lemaitre 2002 {published data only}
    1. Lemaitre RN, Psaty BM, Heckbert SR, Kronmal RA, Newman AB, Burke GL. Therapy with hydroxymethylglutaryl coenzyme a reductase inhibitors (statins) and associated risk of incident cardiovascular events in older adults: evidence from the Cardiovascular Health Study. Archives of Internal Medicine 2002;162(12):1395-400. - PubMed
Lin 2010 {published data only}
    1. Lin Z, Zhang Z, Zhang R, Shu P, Wu S. Effects of rosuvasatin on left ventricular cardiac function, arteriosclerotic plaque and high sensitive C-reactive protein in hyepertensive patienrs with mild LdL-C elevation. Journal of Southern Medical University (China) 2010;30:588-90. - PubMed
LIPID 2010 {published data only}
    1. Cui J, Forbes A, Kirby A, Marshner I, Simes J, Hunt D, et al. Semi-parametric risk prediction models for recurrent cardiovascular events in the LIPID study. BMC Medical Research Methodology 2010;10:27. - PMC - PubMed
Mareev 2008 {published data only}
    1. Mareev VI, Belenkov IuN, Oganov RG, Barbir-Zhagor B, Mareev Vn, Belenkov Iv. Atorvastatin in treatment of patients with coronary heart disease and dislipidemiya and high general risk: efficiency and safety estimation. Design and main results of ATLANTIKA [Russian]. Kardiologiia 2008;48:4-13. - PubMed
McDermott 2003 {published data only}
    1. McDermott MM, Guralnik JM, Greenland P, Pearce WH, Criqui MH, Liu K, et al. Statin use and leg functioning in patients with and without lower-extremity peripheral arterial disease. Circulation 2003;107:757-61. - PubMed
Mizuguchi 2008 {published data only}
    1. Mizuguchi Y, Oishi Y, Miyoshi H, Iuchi A, Nagase N, Oki T. Impact of statin therapy on left ventricular function and carotid arterial stiffness in patients with hypercholesterolemia. Circulation Journal 2008;72(4):538-44. - PubMed
Mohler 2003 {published data only}
    1. Mohler E, Hiatt W, Creager M. Cholesterol reduction with atorvastatin improves walking distance in patients with peripheral arterial disease. Circulation 2003;108:1481-6. - PubMed
Mok 2009 {published data only}
    1. Mok VCT, Lam WWM, Chen XY, Wong A, Ng PW, Tsoi TH. Statins for asymptomatic middle cerebral artery stenosis: The Regression of Cerebral Artery Stenosis study. Cerebrovascular Diseases 2009;28(1):18-25. - PubMed
Muldoon 1997 {published data only}
    1. Muldoon MF, Barger SD, Ryan CM, Flory JD, Lehoczky JP, Matthews KA, et al. Effects of lovastatin on cognitive function and psychological well-being. American Journal of Medicine 2000;108(7):538-46. - PubMed
    1. Muldoon MF, Flory JD, Marsland A, Manuck SB, Whiteside TL, Rabin B. Effects of lovastatin on the immune system. American Journal of Cardiology. 1997;80(10):1391-4. - PubMed
Nephrotic Syndrome Study {published data only}
    1. Olbricht CJ, Wanner C, Thiery J, Basten A, for the Simvastatin in Nephrotic Syndrome Study Group. Simvastatin in nephrotic syndrome. Kidney International 1999;56(Suppl. 71):S-113-6. - PubMed
Ohta 2000 {published data only}
    1. Ohta H, Masuda A, Fuyuki T, Sugimoto I, Suda Y, Makita K, et al. Usefulness of HMG-CoA reductase inhibitor in Japanese hyperlipidemic women within seven years of menopause. Hormone Research. 2000;53(3):120-4. - PubMed
Oi 1997 {published data only}
    1. Oi K, Komori H. Abstract of the 11th Internationial Symposium on Atherosclerosis Paris, 5-9 October 1997. 2.P.51 Escape phenomenon during the long-term administration of pravastatin for hyperlipidemia associated with diabetes. Atherosclerosis 1997;134(1-2):127.
Olzowy 2007 {published data only}
    1. Olzowy B, Canis M, Hempel JM. Effect of atorvastatin on progression of sensorineural hearing loss and tinnitus in the elderly: Results of a prospective, randomized, double-blind clinical trial. Otology and Neurotology 2007;28:455-8. - PubMed
Ormiston 2003 {published data only}
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Pavia 2000 {published data only}
    1. Pavia Lopez A, Zamorano J, Kim JH, Erdine S, Al Khadra A, Westergaard M, et al. Treatment strategies for cardiovascular risk factor management in patients with hypertension and additional risk factors-experiences from the usual care arm of the Crucial trial. In: Journal of Hypertension. Vol. Conference. 2010:p e276–e277.
Pitt 1999 {published data only}
    1. Pitt B, Waters D, Brown WV, Boven AJ, Schwartz L, Title LM, et al. Aggressive lipid-lowering therapy compared with angioplasty in stable coronary artery disease. New England Journal of Medicine 1999;341(2):70-6. - PubMed
POSCH 1990 {published data only}
    1. Buchwald H, Campos CT, Boen JR, Nguyen PA, Williams SE, for the POSCH Group. Disease-free intervals after partial ileal bypass in patients with coronary heart disease and hypercholesterolemia: Report from the Program on the Surgical Control of the Hyperlipidemias (POSCH). Journal of American College Cardiology 1995;26:351-7. - PubMed
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Pravastatin Multi 1993 {published data only}
    1. The Pravastatin Multinational Study Group for Cardiac Risk Patients. Effects of pravastatin in patients with serum total cholesterol levels from 5.2 to 7.8 mmol/liter (200 to 300 mg/dl) plus two additional atherosclerotic risk factors. American Journal of Cardiology. 1993;72(14):1031-7. - PubMed
PROSPER 2002 {published data only}
    1. Avorn J, Benner J, Ford I, Ganz DA, Gaw A, Glynn RJ, et al. Measuring the cost-effectiveness of lipid-lowering drugs in the elderly: the outcomes research and economic analysis components of the PROSPER trial. Controlled Clinical Trials 2002;23(6):757-73. - PubMed
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Safaei 2007 {published data only}
    1. Safaei H, Janghorbani M, Aminorroaya A, Amini M. Lovastatin effects on bone mineral density in postmenopausal women with type 2 diabetes mellitus. Acta Diabetologica 2007;44(2):76-82. - PubMed
SANDS 2008 {published data only}
    1. Howard BV, Roman MJ, Devereux RB, Fleg JL, Galloway JM, Henderson JA, et al. Effect of lower targets for blood pressure and LDL cholesterol on atherosclerosis in diabetes: The SANDS randomized trial. JAMA 2008;299(14):1678-89. - PMC - PubMed
Schmermund 2006 {published data only}
    1. Schmermund A, Achenbach S, BuddeT, Buziashvili Y, Förster A, Friedrich G, et al. Effect of intensive versus standard lipid-lowering treatment with atorvastatin on the progression of calcified coronary atherosclerosis over 12 months: A multicenter, randomized, double-blind trial. Circulation 2006;113(3):427-37. - PubMed
Sen 2000 {published data only}
    1. Sen K, Misra A, Kumar A. Double blind randomized trial of efficacy of simvastatin on retinopathy in hyperlipidemic diabetic patients. In: Journal of the Association of Physicians of India. 2000.
Sprecher 1994 {published data only}
    1. Sprecher DL, Abrams J, Allen JW, Keane WF, Chrysant SG, Ginsberg H, et al. Low-dose combined therapy with fluvastatin and cholestyramine in hyperlipidemic patients. Annals of Internal Medicine 1994;120:537-43. - PubMed
Stein 1997 {published data only}
    1. Stein E, Sprecher D, Allenby KS, Tosielle RL, Whalen E, Ripa SR, the Cerivastatin Study Group. Cerivastatin, a new potent synthetic HMG Co-A reductase inhibitor: effect of 0.2mg daily in subjects with primary hypercholesterolemia. Journal of Cardiovascular Pharmacology and Therapeutics 1997;2(1):7-16. - PubMed
Su 2000 {published data only}
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Tanaka 2001 {published data only}
    1. Akira T, Nobuhiro Y, Saito Y, Kawakami M, Ohashi Y, Akanuma Y. A double-blind trial on the effects of atorvastatin on glycemic control in Japanese diabetic patients with hypercholesterolemia. Clinica Chimica Acta 2001;312:41-47. - PubMed
Tarin 2010 {published data only}
    1. Tarin N, Tunan-Fernandez JT, Sanz P, Espana E, Turbi C, Mischke J et al. Statins reduce the incidence of cardiovascular events in postmenopausal women in secondary but not in primary prevention. A retrospective analysis of the Ruth study. In: European Heart Journal. 2010.
Teixeira 2011 {published data only}
    1. Teixeira A, Buffani A, Tavaraes A, Ribeiro A, Zanella M, Kohlmann O Jr, et al. Effects of fluvastatin on insulin resistance and cardiac morpholgy in hypertensive patients. Journal of Human Hypertension 2011;25(8):492-9. - PubMed
Tekin 2008 {published data only}
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Thomas 1993 {published data only}
    1. Thomas ME, Harris KP, Ramaswamy C, Hattersley JM, Wheeler DC, Varghese Z, et al. Simvastatin therapy for hypercholesterolemic patients with nephrotic syndrome or significant proteinuria. Kidney International. 1993;44(5):1124-9. - PubMed
Thrombosis Prevention {published data only}
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Togha 2009 {published data only}
    1. Togha M, Karvigh SA, Nabavi M, Moghadam NB, Harirchian MH, Sahraian MA, et al. Simvastatin treatment in patients with relapsing-remitting multiple sclerosis receiving interferon beta 1a: a double-blind randomized controlled trial. Multiple Sclerosis 2010;16(7):848-54. - PubMed
Tran 2007 {published data only}
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Wallace 2003 {published data only}
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Wu 2007 {published data only}
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Yu‐An 1998 {published data only}
    1. Yu-An DP, Huey-Herng SW, An HC, Pei D. Efficacy and safety of fluvastatin in patients with non-insulin-dependent diabetes mellitus and hypercholesterolemia. Atherosclerosis 1998;136:S42.
Zachoval 2000 {published data only}
    1. Zachoval R, Parhofer KG, Schwandt P, Gerbes AL. Cerivastatin and Pravastatin in the hyperlipoproteinaemia therapy in patients after liver transplantation - Results of a randomised, cross-over study. Zeitschrift fur Gastroenterologie. 2000;38:531.

References to studies awaiting assessment

Babes 2010 {published and unpublished data}
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References to other published versions of this review

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