Cited by 558Lipoproteins and Cardiovascular HealthAcute Myocardial Infarction ResearchCancer, Lipids, and Metabolism

The DOI matches its Crossref record; 37 of the 38 references it cites were found in a registry or an index.

Intensive lowering of LDL cholesterol with 80 mg versus 20 mg simvastatin daily in 12 064 survivors of myocardial infarction: a double-blind randomised trial

Open access

Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH) Collaborative Group·2010·The Lancet

DOI 10.1016/s0140-6736(10)60310-8PMC PMC2988223

Open this paper in CoChat — free account Open PDF

Abstract

Background Lowering of LDL cholesterol reduces major vascular events, but whether more intensive therapy safely produces extra benefits is uncertain. We aimed to establish efficacy and safety of more intensive statin treatment in patients at high cardiovascular risk.Methods We undertook a double-blind randomised trial in 12,064 men and women aged 18-80 years with a history of myocardial infarction. Participants were either currently on or had clear indication for statin therapy, and had a total cholesterol concentration of at least 3·5 mmol/L if already on a statin or 4·5 mmol/L if not. Randomisation to either 80 mg or 20 mg simvastatin daily was done centrally using a minimisation algorithm. Participants were assessed at 2, 4, 8, and 12 months after randomisation and then every 6 months until final follow-up. The primary endpoint was major vascular events, defined as coronary death, myocardial infarction, stroke, or arterial revascularisation. Analysis was by intention to treat. This study is registered, number ISRCTN74348595.Findings 6031 participants were allocated 80 mg simvastatin daily, and 6033 allocated 20 mg simvastatin daily. During a mean follow-up of 6·7 (SD 1·5) years, allocation to 80 mg simvastatin produced an average 0·35 (SE 0·01) mmol/L greater reduction in LDL cholesterol compared with allocation to 20 mg. Major vascular events occurred in 1477 (24·5%) participants allocated 80 mg simvastatin versus 1553 (25·7%) of those allocated 20 mg, corresponding to a 6% proportional reduction (risk ratio 0·94, 95% CI 0·88-1·01; p=0·10). There were no apparent differences in numbers of haemorrhagic strokes (24 [0·4%] vs 25 [0·4%]) or deaths attributed to vascular (565 [9·4%] vs 572 [9·5%]) or non-vascular (399 [6·6%] vs 398 [6·6%]) causes. Compared with two (0·03%) cases of myopathy in patients taking 20 mg simvastatin daily, there were 53 (0·9%) cases in the 80 mg group.Interpretation The 6% (SE 3·5%) reduction in major vascular events with a further 0·35 mmol/L reduction in LDL cholesterol in our trial is consistent with previous trials. Myopathy was increased with 80 mg simvastatin daily, but intensive lowering of LDL cholesterol can be achieved safely with other regimens.Funding Merck; The Clinical Trial Service Unit also receives funding from the UK Medical Research Council and the British Heart Foundation.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1016/s0140-6736(10)60310-8

Cites

37 of 37 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S)
OLSSON, A. G., McMurray, J. J. V., Thorgeirsson, G., Spaulding, C. M., Slattery, J., Pyörälà, K., Færgeman, O., Wright, R. S., Berg, K. M., Wilhelmsen, L., et al. (1994) · The Lancet · Cited by 8,467
Design and analysis of randomized clinical trials requiring prolonged observation of each patient. II. Analysis and examples
Peto, R., Pike, M. C., Armitage, P., Breslow, N. E., Cox, D. R., Howard, S. V., Mantel, N., McPherson, K., Peto, J., & Smith, P. G. (1977) · British Journal of Cancer · doi:10.1038/bjc.1977.1 · Cited by 8,285
The Effect of Pravastatin on Coronary Events after Myocardial Infarction in Patients with Average Cholesterol Levels
Sacks, F. M., Pfeffer, M. A., Moye, L. A., Rouleau, J. L., Rutherford, J. D., Cole, T. G., Brown, L., Warnica, J. W., Arnold, J. M. O., Wun, C.-C., et al. (1996) · New England Journal of Medicine · doi:10.1056/nejm199610033351401 · Cited by 7,439
MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20 536 high-risk individuals: a randomised placebocontrolled trial
(2002) · The Lancet · doi:10.1016/s0140-6736(02)09327-3 · Cited by 6,992
Implications of Recent Clinical Trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines
Grundy, S. M., Cleeman, J. I., Merz, C. N. B., Brewer, H. B., Clark, L. T., Hunninghake, D. B., Pasternak, R. C., Smith, S. C., & Stone, N. J. (2004) · Circulation · doi:10.1161/01.cir.0000133317.49796.0e · Cited by 6,902
Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90 056 participants in 14 randomised trials of statins
(2005) · The Lancet · doi:10.1016/s0140-6736(05)67394-1 · Cited by 6,848
Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170 000 participants in 26 randomised trials
Cholesterol Treatment Trialists' (CTT) Collaboration (2010) · The Lancet · doi:10.1016/s0140-6736(10)61350-5 · Cited by 6,550
Intensive versus Moderate Lipid Lowering with Statins after Acute Coronary Syndromes
Cannon, C. P., Braunwald, E., McCabe, C. H., Rader, D. J., Rouleau, J. L., Belder, R., Joyal, S. V., Hill, K. A., Pfeffer, M. A., & Skene, A. M. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa040583 · Cited by 4,938
Diabetes, Other Risk Factors, and 12-Yr Cardiovascular Mortality for Men Screened in the Multiple Risk Factor Intervention Trial
Stamler, J., Vaccaro, O., Neaton, J. D., Wentworth, D., & The Multiple Risk Factor Intervention Trial Research Group (1993) · Diabetes Care · doi:10.2337/diacare.16.2.434 · Cited by 4,063
Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S)
SCANDINAVIANSIMVASTATINSURVIVAL (1994) · The Lancet · doi:10.1016/s0140-6736(94)90566-5 · Cited by 3,638

Show all 38 references

Sorted by citations

Items 301–400 of 557

Statins and Diabetes
Maki, K. C., Dicklin, M. R., & Baum, S. J. (2016) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2015.09.006 · Cited by 12
The Complex Nature of Knowledge
Sturmberg, J. P., & Miles, A. (2012) · Springer eBooks · doi:10.1007/978-1-4614-4998-0_4 · Cited by 12
Statins in Secondary Prevention
Stone, N. J. (2017) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2017.04.018 · Cited by 12
The Risk-Benefit Paradigm vs the Causal Exposure Paradigm: LDL as a primary cause of vascular disease
Toth, P. P., Thanassoulis, G., Williams, K., Furberg, C. D., & Sniderman, A. D. (2014) · Journal of clinical lipidology · doi:10.1016/j.jacl.2014.08.004 · Cited by 11
Emerging innovative therapeutic approaches targeting PCSK9 to lower lipids
Shantha, G., & Robinson, J. G. (2015) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.281 · Cited by 11
Break the fast? Update on patient preparation for cholesterol testing.
Naugler, C. T., & Sidhu, D. (2014) · PubMed Central · Cited by 11
Statins: the Panacea of Cirrhosis?
Cabrera, L., & Abraldeṣ, J. G. (2016) · Current Hepatology Reports · doi:10.1007/s11901-016-0287-9 · Cited by 11
National Assessment of Statin Therapy in Patients Hospitalized with Acute Myocardial Infarction: Insight from China PEACE-Retrospective AMI Study, 2001, 2006, 2011
Zhang, L., Li, J., Li, X., Nasir, K., Zhang, H., Wu, Y., Hu, S., Wang, Q., Downing, N. S., Desai, N. R., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0150806 · Cited by 11
Statins and the cholesterol mortality paradox
Nunes, J. P. L. (2016) · Scottish Medical Journal · doi:10.1177/0036933016681913 · Cited by 11
“More worrying might be elevations in alanine aminotransferase levels(8,9,11) and myopathy.(10) Highdose simvastatin (80mg) is not currently recommended owing to the occurrence of myopathy.”
Background
Relative Effect of Current Intensive Lipid-Lowering Drugs on Cardiovascular Outcomes in Secondary Prevention ― A Meta-Analysis of 12 Randomized Trials ―
Wang, S., Xiu, J., Liao, W., Liao, Y., & Bin, J. (2019) · Circulation Journal · doi:10.1253/circj.cj-18-1321 · Cited by 11
Time‐Dependent Cardiovascular Treatment Benefit Model for Lipid‐Lowering Therapies
Khan, I., Peterson, E. D., Cannon, C. P., Sedita, L. E., Edelberg, J. M., & Ray, K. K. (2020) · Journal of the American Heart Association · doi:10.1161/jaha.120.016506 · Cited by 10
Reduced exposure variability of the CYP3A substrate simvastatin by dose individualization to CYP3A activity
Stoll, F., Burhenne, J., Lausecker, B., Weiß, J., Thomsen, T., Haefeli, W. E., & Mikus, G. (2013) · The Journal of Clinical Pharmacology · doi:10.1002/jcph.161 · Cited by 11
“Awell‐knownCYP3Asubstrate sharing thesecharacteristics is simvastatin; interindividual variability of pharmacokinetics is large and varies approximately 50‐fold, and LDL‐cholesterol lowering effects are dose‐dependent(10,15) as are adverse events.(11,16) Moreover, impaired elimination may lead to accumulation and inde…”
Background
Chronic exposure to environmental contaminant nonylphenol exacerbates adenine-induced chronic renal insufficiency: Role of signaling pathways and therapeutic impact of rosuvastatin
Yen, C., Lin, K., Leu, S., Sun, C., Chang, L., Chai, H., Chung, S., Chang, H., Ko, S., Chen, Y.-T., et al. (2012) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2012.03.009 · Cited by 11
Statin-ezetimibe versus statin lipid-lowering therapy in patients with acute coronary syndromes undergoing percutaneous coronary intervention
Dai, Y., Zhang, H., Zhang, X.-G., Guan, Q., Gao, Y. J., Li, Y., Zhang, Y., Jia, D., Sun, Y., Qi, G., et al. (2017) · Journal of Thoracic Disease · doi:10.21037/jtd.2017.05.46 · Cited by 12
“This finding was not consistent with the previous studies (30).”
Result
Cardiovascular Pharmacogenetics: From Discovery of Genetic Association to Clinical Adoption of Derived Test
Delabays, B., Trajanoska, K., Walonoski, J., & Mooser, V. (2024) · Pharmacological Reviews · doi:10.1124/pharmrev.123.000750 · Cited by 12
Guía de práctica clínica para la prevención, detección temprana, diagnóstico, tratamiento y seguimiento de las dislipidemias: tratamiento farmacológico con estatinas
Múñoz, Ó., Peña, Á. A. G., Fernández, D., Higuera, A. M., Ruiz, Á. J., Aschner, P. J., Toro, J. M., Arteaga, J. M., Merchán, A., Vallejo, G. S., et al. (2015) · Revista Colombiana de Cardiología · doi:10.1016/j.rccar.2015.02.001 · Cited by 10
Effect of Intensive and Standard Lipid-Lowering Therapy on the Progression of Stroke in Patients With Coronary Artery Syndromes: A Meta-Analysis of Randomized Controlled Trials
Xie, C., Zhu, M., Hu, Y., & Wang, K. (2019) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0000000000000784 · Cited by 10
Associations between statins and adverse events in secondary prevention of cardiovascular disease: Pairwise, network, and dose-response meta-analyses of 47 randomized controlled trials
Wang, X., Li, J., Wang, T., Zhang, Z., Li, Q., Ma, D., Chen, Z., Ju, J., Xu, H., & Chen, K. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.929020 · Cited by 12
Impact of statin adherence and interruption within 6 months after ST-segment elevation myocardial infarction (STEMI): Results from the real-world regional registry FAST-STEMI
Giacobbe, F., Giannino, G., Annone, U., Morena, A., Vita, U. D., Carmagnola, L., Nebiolo, M., Rollo, C., Ravetti, E., Troncone, M., et al. (2024) · International Journal of Cardiology · doi:10.1016/j.ijcard.2024.131933 · Cited by 10
Simultaneous quantification of simvastatin and simvastatin hydroxy acid in blood serum at physiological pH by ultrahigh performance liquid chromatography–tandem mass spectrometry (UHPLC/MS/MS)
Bews, H. J., Carlson, J. C., Jha, A., Basu, S., Halayko, A. J., & Wong, C. S. (2014) · Journal of Chromatography B · doi:10.1016/j.jchromb.2013.12.030 · Cited by 10
Lipid management in 13,000 high risk cardiovascular patients treated under daily practice conditions: LIMA Registry
Pittrow, D. B., Schaefer, Gitt, Weizel, Jannowitz, Karmann, Bestehorn, K. P., & Sonntag (2013) · Vascular Health and Risk Management · doi:10.2147/vhrm.s37143 · Cited by 10
Initiation of Statin Therapy: Are There Age Limits?
Desai, D. A., Zakaria, S., & Ouyang, P. (2011) · Current Atherosclerosis Reports · doi:10.1007/s11883-011-0220-1 · Cited by 11
Risk of new-onset diabetes mellitus during treatment with low-dose statins in Japan: A retrospective cohort study
Kato, S., & Miura, M. (2018) · Journal of Clinical Pharmacy and Therapeutics · doi:10.1111/jcpt.12675 · Cited by 10
Progression of Precision Statin Prescribing for Reduction of Statin-Associated Muscle Symptoms
Petry, N., Baye, J. F., Frear, S., Jacobsen, K., Massmann, A., Schultz, A., Heukelom, J. V., & Christensen, K. D. (2022) · Pharmacogenomics · doi:10.2217/pgs-2022-0055 · Cited by 10
Addition of Simvastatin to Carvedilol and Endoscopic Variceal Ligation improves rebleeding and survival in patients with Child-Pugh A and B class but not in Child Pugh C class
Jha, S., Saharawat, K., Keshari, R., Jha, P., Purkayastha, S., & Ranjan, R. (2019) · Annals of Clinical Gastroenterology and Hepatology · doi:10.29328/journal.acgh.1001010 · Cited by 9
“Rhabdomyolysis has been particularly associated with higher doses of simvastatin (80mg) [22].”
Background
Statin therapy for preventing cardiovascular diseases in patients treated with tacrolimus after kidney transplantation
Han, N., Han, S. H., Song, Y.-K., Kim, M. G., Kim, Y. S., Kim, I., & Oh, J. M. (2017) · Therapeutics and Clinical Risk Management · doi:10.2147/tcrm.s147327 · Cited by 9
Guanmaitong Granule Attenuates Atherosclerosis by Inhibiting Inflammatory Immune Response in ApoE−/− Mice Fed High-Fat Diet
Yang, M., Jiao, H., Li, Y., Zhang, L., Zhang, J., Zhong, X., & Xue, Y. (2022) · Drug Design Development and Therapy · doi:10.2147/dddt.s372143 · Cited by 9
Strategies for Improving Enrollment of Diverse Populations with a Focus on Lipid-Lowering Clinical Trials
Ogungbe, O., Grant, J. K., Ayoola, A., Bansah, E. C., Miller, H., Plante, T. B., Sheikhattari, P., Commodore-Mensah, Y. Y., Turkson‐Ocran, R., Juraschek, S. P., et al. (2023) · Current Cardiology Reports · doi:10.1007/s11886-023-01942-2 · Cited by 9
From a fish tank injury to hospital haemodialysis: the serious consequences of drug interactions
Hill, F. J., McCloskey, S., & Sheerin, N. (2015) · BMJ Case Reports · doi:10.1136/bcr-2015-209961 · Cited by 9
Simvastatin dose and risk of rhabdomyolysis: Nested case–control study based on national health and drug dispensing data
Parkin, L., Paul, C., & Herbison, P. (2014) · International Journal of Cardiology · doi:10.1016/j.ijcard.2014.03.150 · Cited by 9
Safety and Efficacy of Colesevelam HCl in the Treatment of Elderly Patients
Gavin, J. R., Jones, M. R., Ford, D. M., & Truitt, K. E. (2014) · Drugs & Aging · doi:10.1007/s40266-014-0174-4 · Cited by 9
The effect of HMG-CoA reductase inhibitors on thrombolysis-induced haemorrhagic transformation
Wu, Y., Lu, D., & Xu, A. (2019) · Journal of Clinical Neuroscience · doi:10.1016/j.jocn.2019.08.074 · Cited by 9
Persistent Use of Against‐Label Statin‐Fibrate Combinations from 2003–2009 Despite United States Food and Drug Administration Dose Restrictions
Alford, J. C., Saseen, J. J., Allen, R. R., & Nair, K. V. (2012) · Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy · doi:10.1002/j.1875-9114.2011.01090.x · Cited by 9
“These data are timely considering results of the Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH) collaborative group trial.(46) The SEARCH trial reported increased myopathy with higher doses of simvastatin.”
Result
LDL cholesterol targets – how low to go?
Bulbulia, R. A., & Armitage, J. (2012) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e3283556c1b · Cited by 9
“Unau 0957-9672 2012 Wolters Kluwer Health | Lippincott Williams & Wilk patients per annum), but this risk is increased 10-fold with 80 mg simvastatin daily to 1 per 1000 patients per year [9].”
Background
Efficacy of low- and moderate-intensity statins for achieving low- density lipoprotein cholesterol targets in Thai type 2 diabetic patients
Thongtang, N., Sitthananun, C., Sriussadaporn, S., & Nitiyanant, W. (2017) · Journal of Diabetes & Metabolic Disorders · doi:10.1186/s40200-017-0290-x · Cited by 9
Statins in Asthma: A Closer Look into the Pharmacological Mechanism of Action
Al‐Sawalha, N. A., & Knoll, B. J. (2016) · Pharmacology · doi:10.1159/000449062 · Cited by 9
Should an LDL-Cholesterol Target–Based Approach Be Readopted?
White, C. M., Weeda, E. R., & Nguyen, E. (2017) · Annals of Pharmacotherapy · doi:10.1177/1060028017722009 · Cited by 8
Gemcabene, a First-in-Class Hypolipidemic Small Molecule in Clinical Development, Attenuates Osteoarthritis and Pain in Animal Models of Arthritis and Pain
Srivastava, R. A. K., Cornicelli, J. A., Markham, B. E., & Bisgaier, C. L. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.00471 · Cited by 8
“…disease (CVD) Frontiers in Pharmacology | www.frontiersin.org 9 May 2018 | Volume 9 | Article 471 attenuation compared to agents with only antihyperlipidemic properties (Srivastava et al., 2006; Armitage et al., 2010; Ballantyne et al., 2013; Pinkosky et al., 2013; Song and FitzGerald, 2013).”
Background
Sex/Gender Disparities in Randomized Controlled Trials of Statins: The Impact of Awareness Efforts
Farahani, P. (2014) · Clinical and investigative medicine · doi:10.25011/cim.v37i3.21383 · Cited by 8
Guía de práctica clínica para la prevención, detección temprana, diagnóstico, tratamiento y seguimiento de las dislipidemias: evaluación del riesgo cardiovascular
Múñoz, Ó., Peña, Á. A. G., Fernández-Ávila, D. G., Higuera, A. M., Ruiz, Á. J., Aschner, P. J., Toro, J. M., Arteaga, J. M., Merchán, A., Sánchez, G., et al. (2015) · Revista Colombiana de Cardiología · doi:10.1016/j.rccar.2015.04.009 · Cited by 12
Reaching LDL-c targets in high-risk patients requires high-efficacy cholesterol-lowering drugs in more than 50% of cases. The results of the CHECK study
Poli, A., Casula, M., Tragni, E., Brignoli, O., Filippi, A., Cricelli, C. A., & Catapano, A. L. (2011) · Pharmacological Research · doi:10.1016/j.phrs.2011.06.017 · Cited by 8
Statins: Definitive Translational Research
Grundy, S. M. (2014) · Molecular Medicine · doi:10.2119/molmed.2014.00194 · Cited by 8
Evolocumab for the treatment of hypercholesterolemia
Tomlinson, B., Hu, M., Zhang, Y., Chan, P., & Liu, Z.-M. (2017) · Expert Opinion on Biological Therapy · doi:10.1080/14712598.2017.1365134 · Cited by 8
“Other individual clinical trials of more versus less intensive statin treatments, such as Treating to New Targets (TNT) [72], Incremental Decrease in End Points Through Aggressive Lipid Lowering (IDEAL) [73], or Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH) [74], or the a…”
Background
Robust Performance of Potentially Functional SNPs in Machine Learning Models for the Prediction of Atorvastatin-Induced Myalgia
Ooi, B. N. S., Raechell, R., Ying, A. F., Koh, Y. Z., Jin, Y., Yee, S. W. L., Lee, J. H. S., Chong, S. S., Tan, J. W. C., Liu, J., et al. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.605764 · Cited by 8
Commentary: Should Pharmacogenomic Evidence Be Considered in Clinical Decision Making? Focus on Select Cardiovascular Drugs
Bottorff, M. B., Bright, D. R., & Kisor, D. F. (2017) · Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy · doi:10.1002/phar.1979 · Cited by 8
Trends in statin therapy initiation during the period 2000–2010 in Israel
Shalev, V., Weil, C., Raz, R., Goldshtein, I., Weitzman, D., & Chodick, G. (2014) · European Journal of Clinical Pharmacology · doi:10.1007/s00228-013-1637-y · Cited by 7
Clinical characteristics and lipid lowering treatment of patients initiated on proprotein convertase subtilisin-kexin type 9 inhibitors: a nationwide cohort study
Jensen, J. S., Weeke, P. E., Bang, L. E., Høfsten, D. E., Ripa, M. S., Schjerning, A.-M., Theilade, J., Køber, L., Gislason, G., & Pallisgaard, J. L. (2019) · BMJ Open · doi:10.1136/bmjopen-2018-022702 · Cited by 7
High-intensity lipid-lowering regimens in patients with stable coronary artery disease: the intriguing question of all-cause mortality
Danchin, N., & Simon, T. (2019) · European Heart Journal - Cardiovascular Pharmacotherapy · doi:10.1093/ehjcvp/pvz049 · Cited by 7
In-hospital statin initiation characteristics and one-year statin adherence rates in patients hospitalised for acute coronary syndrome
Şimşek, B., Çınar, T., Tanık, V. O., İnan, D., Avcı, İ. İ., Zeren, G., Tekkeşin, A. İ., Karabay, C. Y., Güngör, B., & Tokgözoğlu, L. S. (2020) · Acta cardiologica. Supplementum · doi:10.1080/00015385.2020.1794162 · Cited by 7
How to Use Statins in Secondary Prevention of Atherosclerotic Diseases: from the Beneficial Early Initiation to the Potentially Unfavorable Discontinuation
Kadoglou, N. P. E., & Stasinopoulou, M. (2021) · Cardiovascular Drugs and Therapy · doi:10.1007/s10557-021-07233-8 · Cited by 10
Harmonisation of large-scale, heterogeneous individual participant adverse event data from randomised trials of statin therapy
Cholesterol Treatment Trialists’ Collaboration (2022) · Clinical Trials · doi:10.1177/17407745221105509 · Cited by 7
Breaking down statin myopathy: understanding the self-limited and autoimmune subtypes
Wright, J., & Christopher‐Stine, L. (2024) · Rheumatology · doi:10.1093/rheumatology/keae284 · Cited by 7
Significance of LDL-C lowering therapy in diabetic patients
Martinez-Hervas, M. S., Carmena, M. R., & Ascaso, M. J. F. (2011) · Clinical Lipidology · doi:10.2217/clp.11.28 · Cited by 7
Pharmacokinetic interactions between simvastatin and setipiprant, a CRTH2 antagonist
Géhin, M., Sidharta, P. N., Gnerre, C., Treiber, A., Halabi, A., & Dingemanse, J. (2014) · European Journal of Clinical Pharmacology · doi:10.1007/s00228-014-1767-x · Cited by 7
Beneficio clínico de las estatinas: ¿hemos cubierto todo el espectro?
Badimón, L., & Vilahur, G. (2011) · Revista Española de Cardiología Suplementos · doi:10.1016/s1131-3587(11)12002-6 · Cited by 7
Statins and beyond: Concurrent strategies for prevention of cardiovascular disease in patients with type 2 diabetes
Standl, E. (2012) · Diabetes and Vascular Disease Research · doi:10.1177/1479164112448876 · Cited by 7
Prevalence of high-risk cardiovascular patients with therapy-resistant hypercholesterolemia
Kostev, K., Parhofer, K. G., & Dippel, F. W. (2016) · Cardiovascular Endocrinology · doi:10.1097/xce.0000000000000098 · Cited by 7
Should anyone still be taking simvastatin 80 mg?
Tayal, U., & Carroll, R. (2013) · BMJ Case Reports · doi:10.1136/bcr-2013-200415 · Cited by 6
Application potential of senolytics in clinical treatment
Li, T., Li, S., Ma, K., & Kong, J. (2023) · Biogerontology · doi:10.1007/s10522-023-10084-5 · Cited by 6
“However, a further increase in the dose of statins also indicates a high incidence of side effects (myopathy and new-onset diabetes) (Armitage et al. 2010; Preiss et al. 2011).”
Reinitiation of Statins After Statin-Associated Musculoskeletal Symptoms
Brito, J. P., & Montori, V. M. (2013) · Circulation Cardiovascular Quality and Outcomes · doi:10.1161/circoutcomes.111.000039 · Cited by 6
“4–157) in the 12 064-patient SEARCH (Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine) trial.(19) After evaluating these data, the US Food and Drug Administration limited the use of simvastatin (80 mg) because of increased risk of muscle damage.”
Background
The Year in Non–ST-Segment Elevation Acute Coronary Syndrome
Giugliano, R. P., & Braunwald, E. (2011) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2011.08.042 · Cited by 6
Society Guidelines 2012 Update of the Canadian Cardiovascular Society Guidelines for the Diagnosis and Treatment of Dyslipidemia for the Prevention of Cardiovascular Disease in the Adult
Anderson, T. J., Grégoire, J., Hegele, R. A., Couture, P., McPherson, R., Francis, G. A., Poirier, P., Lau, D. C. W., Grover, S. A., Carpentier, A. C., et al. (2013) · Cited by 6
Lipids: a personal view of the past decade
Katsiki, N., & Mikhailidis, D. P. (2018) · HORMONES · doi:10.1007/s42000-018-0058-9 · Cited by 6
Advances in the management of statin myopathy
Gallo, A., Perregaux, J., & Bruckert, É. (2020) · Current Opinion in Endocrinology Diabetes and Obesity · doi:10.1097/med.0000000000000595 · Cited by 6
Successful re-challenge of daptomycin therapy after initial rhabdomyolysis with co-administration of simvastatin
Bland, C. M., Bookstaver, P. B., & Thomas, S. (2011) · International Journal of Antimicrobial Agents · doi:10.1016/j.ijantimicag.2011.08.003 · Cited by 6
Analysis of secondary care data to evaluate the clinical relevance of the drug-drug interaction between amlodipine and simvastatin
Fuhrmann, S., Koppen, A., Seeling, A., Knoth, H., & Schröder, J. (2019) · Zeitschrift für Evidenz Fortbildung und Qualität im Gesundheitswesen · doi:10.1016/j.zefq.2019.06.003 · Cited by 6
Complications of Pediatric Renal Transplantation
Dharnidharka, V. R., & Araya, C. E. (2015) · Springer eBooks · doi:10.1007/978-3-662-43596-0_67 · Cited by 6
Lipid‐Lowering Effect and Safety of Ezetimibe and Atorvastatin 5 mg in Patients With Primary Hypercholesterolemia or Mixed Dyslipidemia: A Randomized, Double‐Blind, Parallel, Multicenter, Phase 3 Clinical Trial
Ki, Y., Kim, W., Lee, K. H., Han, S. J., Kim, Y., Doh, J., Kim, T. N., Chung, C. H., Kim, D. Y., Cho, J., et al. (2025) · Clinical Cardiology · doi:10.1002/clc.70138 · Cited by 5
Effect of moderate-intensity statin on carotid intraplaque neovascularization of coronary artery disease: a retrospective cohort study
Han, Y., Ren, L., Fei, X., Wang, J., Chen, T., Guo, J., & Wang, Q. (2024) · Quantitative Imaging in Medicine and Surgery · doi:10.21037/qims-23-1104 · Cited by 5
“Many clinical studies have shown that the LDL-C-lowering effect of high-intensity statin is more prominent than that of low-and moderate-intensity statin therapy (2,4,5,25).”
A Meta‐Analysis of the Incidence of Adverse Reactions of Statins in Various Diseases
Li, W., Wang, D., Lin, C., Cai, T., Zhao, M., Liang, L., Zhao, X., He, X., Liang, X., & Zheng, J. (2025) · Cardiovascular Therapeutics · doi:10.1155/cdr/6684099 · Cited by 8
“Double-blind methods were employed in 28 studies [12 – 14, 17 – 20, 22 – 24, 27, 28, 30, 34 – 36, 38 – 41, 43 – 46, 49 – 52], and two studies mentioned outcome concealment [19, 21].”
Consensus statement on the management of dyslipidaemias in adults
Béliard, S., Bonnet, F., Bouhanick, B., Bruckert, É., Cariou, B., Charrière, S., Durlach, V., Moulin, P., Valéro, R., & Vergès, B. L. (2017) · Annales d Endocrinologie · doi:10.1016/j.ando.2016.11.001 · Cited by 5
Prebiotic‐Based Nanoamorphous Atorvastatin Attenuates Nonalcoholic Fatty Liver Disease by Retrieving Gut and Liver Health
Cui, J., Li, R., Ma, X., Yu, H., Luo, Z., Du, P., Ren, L., Ding, X., Guo, X., Zheng, W., et al. (2023) · Small Structures · doi:10.1002/sstr.202200312 · Cited by 5
Implications of high-dose statin link with incident diabetes
Davidson, M. H. (2011) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2011.118 · Cited by 5
Sigmoidal Maximal Effect Modeling of Low‐Density Lipoprotein Cholesterol Concentration and Annual Incidence of Coronary Heart Disease Events in Secondary Prevention Trials
Charland, S. L., & Stanek, E. J. (2013) · Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy · doi:10.1002/phar.1368 · Cited by 5
Intensifying statin therapy to maximize cardiovascular risk reduction: is 50 the new 70? Goals are getting old
Ramjee, V., & Jacobson, T. A. (2011) · Clinical Lipidology · doi:10.2217/clp.11.4 · Cited by 5
LIPID‐LOWERING THERAPY IN CHRONIC KIDNEY DISEASE: IS THERE A ROLE FOR EZETIMIBE?
Green, D., Panayotova, R., Ritchie, J. P., O’Riordan, E., & McDonald, J. (2012) · Journal of Renal Care · doi:10.1111/j.1755-6686.2012.00309.x · Cited by 5
Lipid management: maximising reduction of cardiac risk
Webb, J., Gonna, H., & Ray, K. K. (2013) · Clinical Medicine · doi:10.7861/clinmedicine.13-6-618 · Cited by 5
Evaluating quality and its determinants in lipid control for secondary prevention of heart disease and stroke in primary care: a study in an inner London Borough
Dodhia, H., Kun, L., Ellis, H. L., Crompton, J., Wierzbicki, A. S., Williams, H., Hodgkinson, A., & Balazs, J. (2015) · BMJ Open · doi:10.1136/bmjopen-2015-008678 · Cited by 5
Statin prescription strategies and atherogenic cholesterol goals attainment in Lebanese coronary artery disease patients
Soubra, L., Domiati, S. A., & Fattouh, Y. (2017) · International Journal of Clinical Pharmacy · doi:10.1007/s11096-017-0483-x · Cited by 5
The Impact of US FDA and Health Canada Warnings Related to the Safety of High-dose Simvastatin
Anand, K., SKETRIS, I. S., Zhang, Y., Levy, A. R., & Gamble, J. (2017) · Drugs - Real World Outcomes · doi:10.1007/s40801-017-0116-7 · Cited by 5
Management of Dyslipidemia
Toth, P. P. (2010) · Humana Press eBooks · doi:10.1007/978-1-60327-963-5_3 · Cited by 5
Lipid-modifying and antiatherosclerotic drugs
Gotto, A. M., & Opie, L. H. (2013) · Elsevier eBooks · doi:10.1016/b978-1-4557-3322-4.00019-3 · Cited by 5
NEONATAL LIPID LEVELS - CAN THEY BE A BENCHMARK FOR LIPID LOWERING IN ADULTS?
Nil, S. M., & Murthy, K. V. (2014) · Asian Journal of Pharmaceutical and Clinical Research · Cited by 5
The Influence of Statins on Glucose Tolerance and Incipient Diabetes
O’Keefe, J. H., DiNicolantonio, J. J., Lavie, C. J., & Bell, D. S. H. (2014) · US Endocrinology · doi:10.17925/use.2014.10.01.68 · Cited by 5
Effect of simvastatin–amiodarone drug interaction alert on appropriate prescribing
Prom, R., Umscheid, C. A., Kasbekar, N., & Spinler, S. A. (2013) · American Journal of Health-System Pharmacy · doi:10.2146/ajhp120553 · Cited by 5
Pitavastatin: an overview of the LIVES study
Kastelein, J. J. P., & Braamskamp, M. J. A. M. (2012) · Clinical Lipidology · doi:10.2217/clp.12.24 · Cited by 5
Lipid lowering in patients with chronic kidney disease: a SHARP turn in the wrong direction?
Berthold, H. K., Krone, W., Erdmann, E., & Gouni‐Berthold, I. (2011) · European Journal of Cardiovascular Prevention & Rehabilitation · doi:10.1177/1741826711423116 · Cited by 5
Statin‐Related Myopathy and Rhabdomyolysis
Newman, C. B., & Tobert, J. A. (2018) · Wiley eBooks · doi:10.1002/9781119374800.ch45 · Cited by 5
All at sea: new lipid-lowering drug trials continue to disappoint
Wierzbicki, A. S. (2013) · International Journal of Clinical Practice · doi:10.1111/ijcp.12126 · Cited by 4
Agreement Between Mega-Trials and Smaller Trials
Kastrati, L., Raeisi‐Dehkordi, H., Llanaj, E., Quezada‐Pinedo, H. G., Khatami, F., Ahanchi, N. S., Llane, A., Meçani, R., Muka, T., & Ioannidis, J. P. A. (2024) · JAMA Network Open · doi:10.1001/jamanetworkopen.2024.32296 · Cited by 5
Eficacia bioquímica y beneficio clínico de la doble inhibición con ezetimiba y simvastatina
Padial, L. R., & Soriano, F. R. (2012) · Revista Española de Cardiología Suplementos · doi:10.1016/s1131-3587(12)70033-x · Cited by 4
New cholesterol guidelines and the secondary prevention of cardiovascular disease — A commentary on epistemic aspects
Nunes, J. P. L. (2014) · Preventive Medicine · doi:10.1016/j.ypmed.2014.06.035 · Cited by 4
Is combination therapy an effective way of reaching lipid goals in Type 2 diabetes mellitus?
Handelsman, Y., Fonseca, V. A., & Rosenstock, J. (2011) · Expert Review of Clinical Pharmacology · doi:10.1586/ecp.11.73 · Cited by 4
Changes in serum cholesterol levels determine future risk of cardiovascular events in patients with acute coronary syndrome in the Japanese Coronary Artery Disease (JCAD) Study
Fukuda, S., Shimada, K., Fujita, M., Yoshiyama, M., Yoshikawa, J., Kohro, T., Hayashi, D., Yamazaki, T., & Nagai, R. (2013) · Journal of Cardiology · doi:10.1016/j.jjcc.2013.02.006 · Cited by 4
“Cholesterol-lowering therapy using statins offers clinical benefits for primary [4,5] and secondary prevention [3,6] of CV events in patients with hypercholesterolemia.”
BackgroundResult
Effects of simvastatin on lipid profile and nerve conduction velocity in obese Sprague Dawley rats.
Jabeen, A., Khan, U. A., & Lodhi, G. M. (2011) · PubMed · Cited by 4
Lipid and other management to improve arterial disease and survival in end stage renal disease
Dimmitt, S. B., & Martin, J. H. (2017) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2017.1285905 · Cited by 4
Disorders of Lipid Metabolism
Semenkovich, C. F. (2012) · Elsevier eBooks · doi:10.1016/b978-1-4377-1604-7.00213-x · Cited by 7
Effect of atorvastatin on skeletal muscles of patients with knee osteoarthritis: Post-hoc analysis of a randomised controlled trial
Lim, Y. Z., Cicuttini, F., Wluka, A. E., Jones, G., Hill, C. L., Forbes, A. B., Tonkin, A. M., Berezovskaya, S., Tan, L., Ding, C., et al. (2022) · Frontiers in Medicine · doi:10.3389/fmed.2022.939800 · Cited by 4
Glycemic effects of simvastatin: Where do we stand?
Razali, N. R., Huri, H. Z., Ibrahim, L., Vethakkan, S. R., & Abdullah, B. M. (2018) · Brazilian Journal of Pharmaceutical Sciences · doi:10.1590/s2175-97902018000117192 · Cited by 5
Statins Alone or in Combination with Ezetimibe or PCSK9 Inhibitors in Atherosclerotic Cardiovascular Disease Protection
Vavlukis, M., & Vavlukis, A. (2019) · IntechOpen eBooks · doi:10.5772/intechopen.82520 · Cited by 4

Authors: Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH) Collaborative Group
Corresponding author: Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH) Collaborative Group
Venue: The Lancet
Publisher: Elsevier BV
Published: 2010-11
Volume: 376
Issue: 9753
Pages: 1658-1669
ISSN: 0099-5355 (ISSN-L)
0140-6736
DOI: 10.1016/s0140-6736(10)60310-8
PMC: PMC2988223
OpenAlex: W1523152575
Cited by: 558
References: 38
Citations by year: 2026: 6 · 2025: 10 · 2024: 20 · 2023: 23 · 2022: 28 · 2021: 22 · 2020: 29 · 2019: 31 · 2018: 33 · 2017: 35 · 2016: 40 · 2015: 47 · 2014: 52 · 2013: 50 · 2012: 68
FWCI: 61.00
Type: journal article
Language: en
Update notices: erratum (2011-01-08)
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: The Lancet (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
ePrints Soton (University of Southampton) (submittedVersion)
ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
Funders: British Heart Foundation (PG/12/32/29544)
University of Southampton
University of Oxford
Medical Research Council (MC_EX_G0801669)
Topics: Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Acute Myocardial Infarction Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
Keywords: simvastatin, LDL cholesterol lowering, high-intensity statin therapy, myocardial infarction survivors, major vascular events, coronary artery disease, stroke, cardiovascular mortality, statin safety, lipid-lowering therapy, high cardiovascular risk patients, dose comparison, hemorrhagic stroke, coronary death, myocardial infarction recurrence, secondary prevention
MeSH terms: Adult, Aged, Aged, 80 and over, Anticholesteremic Agents, Double-Blind Method, Female, Humans, Hypercholesterolemia, Cholesterol, HDL, Cholesterol, LDL, Male, Middle Aged, Myocardial Infarction, Triglycerides, Simvastatin, Young Adult

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Intensive lowering of LDL cholesterol with 80 mg versus 20 mg simvastatin daily in 12 064 survivors of myocardial infarction: a double-blind randomised trial

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks