Nonstatin Low-Density Lipoprotein–Lowering Therapy and Cardiovascular Risk Reduction—Statement From ATVB Council
Open accessAbstract
Pharmacological reduction of low-density lipoprotein (LDL) cholesterol using statin drugs is foundational therapy to reduce cardiovascular disease (CVD) risk. Here, we consider the place of nonstatin therapies that also reduce LDL cholesterol in prevention of CVD. Among conventional nonstatins, placebo-controlled randomized clinical trials showed that bile acid sequestrants, niacin, and fibrates given as monotherapy each reduce CVD end points. From trials in which patients’ LDL cholesterol was already well controlled on a statin, adding ezetimibe incrementally reduced CVD end points, whereas adding a fibrate or niacin showed no incremental benefit. Among emerging nonstatins, monoclonal antibodies against proprotein convertase subtilisin kexin type 9 added to a statin and given for ≤78 weeks showed preliminary evidence of reductions in CVD outcomes. Although these promising early findings contributed to the recent approval of these agents in Europe and in North America, much larger and longer duration outcomes studies are ongoing for definitive proof of CVD benefits. Other nonstatin agents recently approved in the United States include lomitapide and mipomersen, which both act via distinctive LDL receptor independent mechanisms to substantially reduce LDL cholesterol in homozygous familial hypercholesterolemia. We also address some unanswered questions, including measuring alternative biochemical variables to LDL cholesterol, evidence for treating children with monitoring of subclinical atherosclerosis, and potential risks of extremely low LDL cholesterol. As evidence for benefit in CVD prevention accumulates, we anticipate that clinical practice will shift toward more assertive LDL-lowering treatment, using both statins and nonstatins initiated earlier in appropriately selected patients.
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
Cites
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?
The clinical benefit of the previously recommended use of nonstatin therapies to lower LDL-C is less definitive.
“the clinical benefit of the previously recommended use of nonstatin therapies to lower LDL-C is less definitive.7”
From Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions: A Systematic Review and Meta-analysis (2016) · cites this paper as [7]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Prediction of coronary heart disease using risk factor categories
Wilson, P. W. F., D’Agostino, R. B., Levy, D., Belanger, A. M., Silbershatz, H., & Kannel, W. B. (1998) · Circulation · doi:10.1161/01.cir.97.18.1837 · Cited by 9,581 · see citing works
Prevention of Coronary Heart Disease with Pravastatin in Men with Hypercholesterolemia
Shepherd, J., Cobbe, S. M., Ford, I., Isles, C. G., Lorimer, A. R., Macfarlane, P. W., McKillop, J. H., & Packard, C. J. (1995) · New England Journal of Medicine · doi:10.1056/nejm199511163332001 · Cited by 7,449 · see citing works
Rosuvastatin to Prevent Vascular Events in Men and Women with Elevated C-Reactive Protein
Ridker, P. M., Danielson, E., Fonseca, F. A. H., Genest, J., Gotto, A. M., Kastelein, J. J. P., Koenig, W., Libby, P., Lorenzatti, A. J., MacFadyen, J. G., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0807646 · Cited by 6,674 · cited 1× · see citing works
“Stronger statins, such as rosuvastatin, lower risk by 45%.(36) The Lipid Research Clinics (LRC)(30,37) and Cholesterol Treatment Trialists Collaboration (CTTC) each concurred that lower is better, whether achieved with a statin or nonstatin mechanism.”
BackgroundCholesterol Treatment Trialists' (CTT) Collaboration (2010) · The Lancet · doi:10.1016/s0140-6736(10)61350-5 · Cited by 6,550 · see citing works
2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk
Goff, D. C., Lloyd-Jones, D. M., Bennett, G., Coady, S., D’Agostino, R. B., Gibbons, R., Greenland, P., Lackland, D. T., Levy, D., O’Donnell, C. J., et al. (2014) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2013.11.005 · Cited by 4,945 · see citing works
Self-citationSpence, J. (2013) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.718113553.793483968 · Cited by 4,644 · see citing works
Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes
Cannon, C. P., Blazing, M. A., Giugliano, R. P., McCagg, A., White, J. A., Theroux, P., Darius, H., Lewis, B. S., Ophuis, T. O., Jukema, J. W., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1410489 · Cited by 4,487 · see citing works
Berenson, G. S., Srinivasan, S. R., Bao, W., Newman, W. P., Tracy, R. E., & Wattigney, W. A. (1998) · New England Journal of Medicine · doi:10.1056/nejm199806043382302 · Cited by 4,032 · see citing works
Helsinki Heart Study: Primary-Prevention Trial with Gemfibrozil in Middle-Aged Men with Dyslipidemia
Frick, M. H., Elo, O., Haapa, K., Heinonen, O. P., Heinsalmi, P., Helo, P., Huttunen, J. K., Kaitaniemi, P., Koskinen, P., Manninen, V., et al. (1987) · New England Journal of Medicine · doi:10.1056/nejm198711123172001 · Cited by 3,881 · see citing works
Colhoun, H. M., Betteridge, D. J., Durrington, P. N., Hitman, G. A., W Neil, H. A., Livingstone, S. J., Thomason, M. J., Mackness, M. I., Charlton-Menys, V., & Fuller, J. H. (2004) · The Lancet · doi:10.1016/s0140-6736(04)16895-5 · Cited by 3,755 · see citing works
Goff, D. C., Lloyd-Jones, D. M., Bennett, G., Coady, S., D’Agostino, R. B., Gibbons, R., Greenland, P., Lackland, D. T., Levy, D., O’Donnell, C. J., et al. (2014) · Circulation · doi:10.1161/01.cir.0000437741.48606.98 · Cited by 3,697 · see citing works
Self-citationSCANDINAVIANSIMVASTATINSURVIVAL (1994) · The Lancet · doi:10.1016/s0140-6736(94)90566-5 · Cited by 3,638 · see citing works
ESC/EAS Guidelines for the management of dyslipidaemias
Reiner, Ž., Catapano, A. L., De Backer, G., Graham, I., Taskinen, M.-R., Wiklund, O., Agewall, S., Alegria, E., Chapman, M. J., Durrington, P., et al. (2011) · European Heart Journal · doi:10.1093/eurheartj/ehr158 · Cited by 3,549 · see citing works
Rubins, H. B., Robins, S. J., Collins, D., Fye, C. L., Anderson, J. W., Elam, M. B., Faas, F. H., Linares, E., Schaefer, E. J., Schectman, G., et al. (1999) · New England Journal of Medicine · doi:10.1056/nejm199908053410604 · Cited by 3,439 · see citing works
Sequence Variations in <i>PCSK9,</i> Low LDL, and Protection against Coronary Heart Disease
Cohen, J. C., Boerwinkle, E., Mosley, T. H., & Hobbs, H. H. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa054013 · Cited by 3,181 · cited 1× · see citing works
“Gain-of-function mutations in the PCSK9 gene cause autosomal-dominant hypercholesterolemia,(73) whereas loss-of-function mutations are associated with lower LDL cholesterol and reduced CVD risk.(21,74) Monoclonal antibodies (mAbs) against PCSK9 were recently approved in Europe and in North America.”
BackgroundEffects of torcetrapib in patients at high risk for coronary events
Barter, P. J., Caulfield, M., Eriksson, M., Grundy, S. M., Kastelein, J. J. P., Komajda, M., Lopez-Sendon, J., Mosca, L., Tardif, J.-C., Waters, D. D., et al. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa0706628 · Cited by 3,139 · cited 1× · see citing works
“Thus, CETP has received considerable attention as a drug target, although 2 CETP inhibitors have failed in large CVD outcome trial.(103,104) Torcetrapib-treated individuals experienced increased CV events and mortality despite substantial reductions in LDL cholesterol,(103) putatively because of off-target increases i…”
BackgroundMutations in PCSK9 cause autosomal dominant hypercholesterolemia
Abifadel, M., Varret, M., Rabès, J.-P., Allard, D., Ouguerram, K., Devillers, M., Cruaud, C., Benjannet, S., Wickham, L., Erlich, D., et al. (2003) · Nature Genetics · doi:10.1038/ng1161 · Cited by 2,985 · see citing works
Niacin in Patients with Low HDL Cholesterol Levels Receiving Intensive Statin Therapy
The AIM-HIGH Investigators (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1107579 · Cited by 2,911 · see citing works
Effects of Combination Lipid Therapy in Type 2 Diabetes Mellitus
(2010) · New England Journal of Medicine · doi:10.1056/nejmoa1001282 · Cited by 2,837 · see citing works
Self-citationCollaborators, C. T. T. (. (2012) · The Lancet · doi:10.1016/s0140-6736(12)60367-5 · Cited by 2,833 · cited 1× · see citing works
“The Lipid Research Clinics (LRC)(30,37) and Cholesterol Treatment Trialists Collaboration (CTTC) each concurred that lower is better, whether achieved with a statin or nonstatin mechanism.(2,38)”
BackgroundGersh, B. (2011) · Yearbook of Medicine · doi:10.1016/s0084-3873(11)00278-1 · Cited by 2,768 · see citing works
Nordestgaard, B. G., Chapman, M. J., Humphries, S. E., Ginsberg, H. N., Masana, L., Descamps, O. S., Wiklund, O., Hegele, R. A., Raal, F. J., Defesche, J. C., et al. (2013) · European Heart Journal · doi:10.1093/eurheartj/eht273 · Cited by 2,761 · see citing works
Self-citationMajor lipids, apolipoproteins, and risk of vascular disease
The Emerging Risk Factors Collaboration* (2009) · JAMA · doi:10.1001/jama.2009.1619 · Cited by 2,731 · see citing works
Niacin in Patients with Low HDL Cholesterol Levels Receiving Intensive Statin Therapy
Toth, P. P. (2012) · doi:10.1016/s0084-3873(12)00317-3 · Cited by 2,556 · cited 2×
“the Incidence of Vascular Events (HPS2-THRIVE) showed no reductions in CVD events or mortality when niacin was added to statin therapy in patients with pre-existing CVD and well-controlled LDL cholesterol.(28,52) These results undermined the hypothesis that HDL directly protects from atherosclerosis,(53) and when cons…”
BackgroundStatins and risk of incident diabetes: A collaborative meta-analysis of randomised statin trials
Sattar, N., Preiss, D., Murray, H. M., Welsh, P., Buckley, B. M., de Craen, A. J., Seshasai, S. R. K., McMurray, J. J., Freeman, D. J., Jukema, J. W., et al. (2010) · The Lancet · doi:10.1016/s0140-6736(09)61965-6 · Cited by 2,436 · cited 1× · see citing works
“treated to cause 1 new case of type 2 diabetes mellitus, emphasizing risk-benefit considerations of statin therapy.(150,151) To date,”
BackgroundEfficacy and Safety of Alirocumab in Reducing Lipids and Cardiovascular Events
Robinson, J. G., Farnier, M., Krempf, M., Bergeron, J., Luc, G., Averna, M., Stroes, E. S., Langslet, G., Raal, F. J., El Shahawy, M., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1501031 · Cited by 2,296 · see citing works
Self-citationAtherosclerosis: current pathogenesis and therapeutic options
Weber, C., & Noels, H. (2011) · Nature Medicine · doi:10.1038/nm.2538 · Cited by 2,203 · cited 1× · see citing works
“Even as new proinflammatory and anti-inflammatory pathways are being discovered, the foundational role of LDL in atherogenesis remains axiomatic.(12)”
BackgroundKavey, R., Simons-Morton, D., & de Jesus, J. D. (2011) · Pediatrics · doi:10.1542/peds.2009-2107c · Cited by 2,131 · see citing works
Collaborators, C. T. T. (. (2008) · The Lancet · doi:10.1016/s0140-6736(08)60104-x · Cited by 2,081 · see citing works
Effects of dalcetrapib in patients with a recent acute coronary syndrome
Schwartz, G. G., Olsson, A. G., Abt, M., Ballantyne, C. M., Barter, P. J., Brumm, J., Chaitman, B. R., Holme, I. M., Kallend, D., Leiter, L. A., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1206797 · Cited by 2,022 · cited 2× · see citing works
“An outcomes trial using dalcetrapib, an agent with modest HDL-raising effects and essentially no effect on LDL cholesterol, was stopped for futility.(104) Two other compounds, anacetrapib and evacetrapib, remain under active investigation; both have substantial”
BackgroundMethodFat Transport in Lipoproteins — An Integrated Approach to Mechanisms and Disorders
Fredrickson, D. S., Levy, R. I., & Lees, R. S. (1967) · New England Journal of Medicine · doi:10.1056/nejm196701052760107 · Cited by 1,911 · cited 1× · see citing works
“related to the total number of apoB-containing particles rather than LDL cholesterol concentration.(111) One apoB molecule is”
BackgroundFifteen year mortality in Coronary Drug Project patients: long-term benefit with niacin
Canner, P. L., Berge, K. G., Wenger, N. K., Stamler, J., Friedman, L., Prineas, R. J., & Friedewald, W. (1986) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(86)80293-5 · Cited by 1,824 · cited 1× · see citing works
“As monotherapy, niacin administered to hypercholesterolemic men reduced the risk of recurrent myocardial infarction in the Coronary Drug Project(50) and also reduced total mortality in a 15-year follow-up.(26) Decreased atherosclerosis progression has also been observed in imaging studies of niacin’s effects.”
BackgroundClofibrate and Niacin in Coronary Heart Disease
Stamler, J. (1975) · JAMA · doi:10.1001/jama.1975.03240160024021 · Cited by 1,750 · see citing works
Raitakari, O. T., Juonala, M., Kähönen, M., Taittonen, L., Laitinen, T., Mäki-Torkko, N., Järvisalo, M. J., Uhari, M., Jokinen, E., Rönnemaa, T., et al. (2003) · JAMA · doi:10.1001/jama.290.17.2277 · Cited by 1,732 · see citing works
Atherosclerosis: Basic Mechanisms
Berliner, J. A., Navab, M., Fogelman, A. M., Frank, J. S., Demer, L. L., Edwards, P. A., Watson, A. D., & Lusis, A. J. (1995) · Circulation · doi:10.1161/01.cir.91.9.2488 · Cited by 1,726 · see citing works
Effects of extended-release niacin with laropiprant in high-risk patients
The HPS2-THRIVE Collaborative Group (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1300955 · Cited by 1,668 · see citing works
Tuomilehto, J., Vidgrén, G., Toivanen, L., Tuomilehto-Wolf, E., Kohtamäki, K., Stengård, J., Zimmet, P., Mackay, I., Rowley, M., & Koskela, P. (1994) · The Lancet · doi:10.1016/s0140-6736(94)92521-6 · Cited by 1,658 · see citing works
HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events
Barter, P., Gotto, A. M., LaRosa, J. C., Maroni, J., Szarek, M., Grundy, S. M., Kastelein, J. J. P., Bittner, V., & Fruchart, J.-C. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa064278 · Cited by 1,610 · see citing works
Efficacy and Safety of Evolocumab in Reducing Lipids and Cardiovascular Events
Sabatine, M. S., Giugliano, R. P., Wiviott, S. D., Raal, F. J., Blom, D. J., Robinson, J., Ballantyne, C. M., Somaratne, R., Legg, J., Wasserman, S. M., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1500858 · Cited by 1,509 · see citing works
Self-citationToth, P. (2012) · Yearbook of Endocrinology · doi:10.1016/j.yend.2012.05.035 · Cited by 1,362 · cited 1× · see citing works
“reduced CVD events in patients with renal impairment.(40) In”
Fleisher, L. A., Fleischmann, K. E., Auerbach, A. D., Barnason, S. A., Beckman, J. A., Bozkurt, B., Dávila‐Román, V. G., Gerhard‐Herman, M. D., Holly, T. A., Kane, G. C., et al. (2014) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2014.07.944 · Cited by 1,323 · cited 3× · see citing works
“2013 AHA/ACC guidelines eliminated lipid targets, instead advising treatment decisions based on CVD risk.(97) Other juris-”
BackgroundMethodInfluentialStamler, J. (1986) · JAMA · doi:10.1001/jama.1986.03380200061022 · Cited by 1,318 · see citing works
Chapman, M. J., Ginsberg, H. N., Amarenco, P., Andreotti, F., Borén, J., Catapano, A. L., Descamps, O. S., Fisher, E., Kovanen, P. T., Kuivenhoven, J. A., et al. (2011) · European Heart Journal · doi:10.1093/eurheartj/ehr112 · Cited by 1,227 · see citing works
Self-citationCriteria for Evaluation of Novel Markers of Cardiovascular Risk
Hlatky, M., Greenland, P., Arnett, D., Ballantyne, C., Criqui, M., Elkind, M., Go, A., Harrell, F. E. J., Hong, Y.-L., Howard, B., et al. (2009) · Circulation · doi:10.1161/circulationaha.109.192278 · Cited by 1,153 · see citing works
Cuchel, M., Bruckert, E., Ginsberg, H. N., Raal, F. J., Santos, R. D., Hegele, R. A., Kuivenhoven, J. A., Nordestgaard, B. G., Descamps, O. S., Steinhagen-Thiessen, E., et al. (2014) · European Heart Journal · doi:10.1093/eurheartj/ehu274 · Cited by 1,057 · see citing works
Self-citationBuchwald, H., Varco, R. L., Matts, J. P., Long, J. M., Fitch, L. L., Campbell, G. S., Pearce, M. B., Yellin, A. E., Edmiston, W. A., Smink, R. D., et al. (1990) · New England Journal of Medicine · doi:10.1056/nejm199010043231404 · Cited by 1,001 · see citing works
Effects of fibrates on cardiovascular outcomes: a systematic review and meta-analysis
Jun, M., Foote, C., Lv, J., Neal, B., Patel, A., Nicholls, S. J., Grobbee, D. E., Cass, A., Chalmers, J., & Perkovic, V. (2010) · The Lancet · doi:10.1016/s0140-6736(10)60656-3 · Cited by 933 · cited 1× · see citing works
“in subjects with high triglyceride with or without low HDL cholesterol.(68)”
Raal, F. J., Santos, R. D., Blom, D. J., Marais, A. D., Charng, M., Cromwell, W. C., Lachmann, R., Gaudet, D., Tan, J. L., Chasan-Taber, S., et al. (2010) · The Lancet · doi:10.1016/s0140-6736(10)60284-x · Cited by 921 · cited 1× · see citing works
“Because mipomersen does not require functional LDL receptors, equivalent responsiveness is seen in LDL receptor negative homozygous FH patients.(83) Side effects include injection site reactions and influenza-like symptoms; discontinuation rates in RCTs have been high.”
BackgroundSelf-citationWiegman, A., Gidding, S. S., Watts, G. F., Chapman, M. J., Ginsberg, H. N., Cuchel, M., Ose, L., Averna, M., Boileau, C., Borén, J., et al. (2015) · European Heart Journal · doi:10.1093/eurheartj/ehv157 · Cited by 891 · see citing works
Self-citationMcQueen, M. J., Hawken, S., Wang, X., Ounpuu, S., Sniderman, A., Probstfield, J., Steyn, K., Sanderson, J. E., Hasani, M., Volkova, E., et al. (2008) · The Lancet · doi:10.1016/s0140-6736(08)61076-4 · Cited by 864 · see citing works
Ridker, P., Rifai, N., Cook, N., Bradwin, G., & Buring, J. (2005) · Journal of the American Medical Association (JAMA) · doi:10.1016/j.accreview.2005.09.030 · Cited by 832 · cited 2× · see citing works
“to LDL cholesterol in CHD prediction was shown in the Health Professionals Follow-up Study,(115) the Framingham Heart Study(116) and Framingham Offspring Study,(117) and the Women’s Health Study.(118) Non-HDL cholesterol and apoB”
MethodRidker, P. M., Pradhan, A., MacFadyen, J. G., Libby, P., & Glynn, R. J. (2012) · The Lancet · doi:10.1016/s0140-6736(12)61190-8 · Cited by 816 · see citing works
Boekholdt, S. M., Arsenault, B. J., Mora, S., Pedersen, T. R., LaRosa, J. C., Nestel, P. J., Simes, R. J., Durrington, P., Hitman, G. A., Welch, K. M. A., et al. (2012) · JAMA · doi:10.1001/jama.2012.366 · Cited by 795 · see citing works
Report, S., & Daniels, S. (2014) · Pediatric Clinical Practice Guidelines & Policies · doi:10.1542/9781581108613-part06-expert · Cited by 784 · see citing works
Raal, F. J., Stein, E. A., Dufour, R., Turner, T., Civeira, F., Burgess, L., Langslet, G., Scott, R., Olsson, A. G., Sullivan, D., et al. (2015) · The Lancet · doi:10.1016/s0140-6736(14)61399-4 · Cited by 756 · see citing works
Self-citationSafety of anacetrapib in patients with or at high risk for coronary heart disease
Cannon, C. P., Shah, S., Dansky, H. M., Davidson, M., Brinton, E. A., Gotto, A. M., Stepanavage, M., Liu, S. X., Gibbons, P., Ashraf, T. B., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1009744 · Cited by 749 · see citing works
Cuchel, M., Meagher, E. A., du Toit Theron, H., Blom, D. J., Marais, A. D., Hegele, R. A., Averna, M. R., Sirtori, C. R., Shah, P. K., Gaudet, D., et al. (2013) · The Lancet · doi:10.1016/s0140-6736(12)61731-0 · Cited by 744 · see citing works
Self-citationRaal, F. J., Honarpour, N., Blom, D. J., Hovingh, G. K., Xu, F., Scott, R. C., Wasserman, S. M., & Stein, E. A. (2014) · The Lancet · doi:10.1016/s0140-6736(14)61374-x · Cited by 733 · cited 1× · see citing works
“In patients with homozygous FH on maximal lipid-lowering therapy, evolocumab 420 mg every 4 weeks reduced LDL cholesterol by ≈30%, with efficacy related to the degree of residual LDL receptor activity.(82) In addition to robust LDL cholesterol lowering, evolocumab and alirocumab improve other lipid parameters, for exa…”
BackgroundSelf-citationA 52-Week Placebo-Controlled Trial of Evolocumab in Hyperlipidemia
Blom, D. J., Hala, T., Bolognese, M., Lillestol, M. J., Toth, P. D., Burgess, L., Ceska, R., Roth, E., Koren, M. J., Ballantyne, C. M., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1316222 · Cited by 720 · cited 3× · see citing works
“Efficacy appears similar across most patient subgroups, including heterozygous FH patients.(78,79) PCSK9 mAbs allowed a substantial proportion of FH patients to achieve LDL cholesterol <1.”
BackgroundReduction in saturated fat intake for cardiovascular disease
Hooper, L., Martin, N., Abdelhamid, A., & Davey Smith, G. (2015) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd011737 · Cited by 704 · see citing works
Mahoney, L., Burns, T., Stanford, W., Thompson, B., Witt, J., Rost, C. A., & Lauer, R. (1996) · Journal of the American College of Cardiology · doi:10.1016/0735-1097(95)00461-0 · Cited by 693 · see citing works
Swerdlow, D. I., Preiss, D., Kuchenbaecker, K. B., Holmes, M. V., Engmann, J. E. L., Shah, T., Sofat, R., Stender, S., Johnson, P. C. D., Scott, R. A., et al. (2015) · The Lancet · doi:10.1016/s0140-6736(14)61183-1 · Cited by 680 · see citing works
Self-citationSniderman, A. D., Williams, K., Contois, J. H., Monroe, H. M., McQueen, M. J., de Graaf, J., & Furberg, C. D. (2011) · Circulation: Cardiovascular Quality and Outcomes · doi:10.1161/circoutcomes.110.959247 · Cited by 659 · see citing works
Extended-Release Niacin or Ezetimibe and Carotid Intima–Media Thickness
Taylor, A. J., Villines, T. C., Stanek, E. J., Devine, P. J., Griffen, L., Miller, M. J., Weissman, N. J., & Turco, M. A. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0907569 · Cited by 643 · cited 1× · see citing works
“Decreased atherosclerosis progression has also been observed in imaging studies of niacin’s effects.(51)”
BackgroundIngelsson, E., Schaefer, E. J., Contois, J. H., McNamara, J. R., Sullivan, L., Keyes, M. J., Pencina, M. J., Schoonmaker, C., Wilson, P. W. F., D’Agostino, R. B., et al. (2007) · JAMA · doi:10.1001/jama.298.7.776 · Cited by 608 · see citing works
Very Low Levels of Atherogenic Lipoproteins and the Risk for Cardiovascular Events
Boekholdt, S. M., Hovingh, G. K., Mora, S., Arsenault, B. J., Amarenco, P., Pedersen, T. R., LaRosa, J. C., Waters, D. D., DeMicco, D. A., Simes, R. J., et al. (2014) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2014.02.615 · Cited by 581 · cited 1× · see citing works
“39 mmol/L (15 mg/dL).(156,157) This suggests that combinations of maximally tolerated statins, ezetimibe, and new drugs, such as PCSK9 or CETP inhibitors, to dramat-”
BackgroundInhibition of microsomal triglyceride transfer protein in familial hypercholesterolemia
Cuchel, M., Bloedon, L. T., Szapary, P. O., Kolansky, D. M., Wolfe, M. L., Sarkis, A., Millar, J. S., Ikewaki, K., Siegelman, E. S., Gregg, R. E., et al. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa061189 · Cited by 580 · cited 5× · see citing works
“Thus, lomitapide, an oral microsomal triglyceride transfer protein inhibitor, reduces LDL cholesterol by 35 to 50% in subjects with homozygous FH.(84,85) Lomitapide has Food and Drug Administration (FDA) and European Medicines Agency (EMA) approval for the treatment of homozygous FH as an adjunct to diet and drug ther…”
BackgroundInfluentialSelf-citationMcgill, H., Mcmahan, C., & Gidding, S. (2008) · Circulation · doi:10.1161/circulationaha.107.717033 · Cited by 575 · see citing works
Self-citationPischon, T., Girman, C., Sacks, F., Rifai, N., Stampfer, M., & Rimm, E. (2005) · Circulation · doi:10.1161/circulationaha.104532499 · Cited by 564
Anti-PCSK9 Antibody Effectively Lowers Cholesterol in Patients With Statin Intolerance
Stroes, E., Colquhoun, D., Sullivan, D., Civeira, F., Rosenson, R. S., Watts, G. F., Bruckert, E., Cho, L., Dent, R., Knusel, B., et al. (2014) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2014.03.019 · Cited by 526 · see citing works
Mendelian Randomization: New Applications in the Coming Age of Hypothesis-Free Causality
Evans, D. M., & Smith, G. D. (2015) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-090314-050016 · Cited by 524 · cited 1× · see citing works
“Within the Mendelian randomization framework, if a biomarker is causally associated with a disease, its genetic determinants are also associated with disease risk.(20) Mendelian randomization avoids confounding and reverse causation(20) and assumes that the culprit genetic variants influence only the biomarker of inte…”
BackgroundRobinson, J. G., Nedergaard, B. S., Rogers, W. J., Fialkow, J., Neutel, J. M., Ramstad, D., Somaratne, R., Legg, J. C., Nelson, P., Scott, R., et al. (2014) · JAMA · doi:10.1001/jama.2014.4030 · Cited by 496 · see citing works
Self-citationGagné, C., Gaudet, D., & Bruckert, É. (2002) · Circulation · doi:10.1161/01.cir.0000018744.58460.62 · Cited by 480 · see citing works
Lipids, apolipoproteins, and their ratios in relation to cardiovascular events with statin treatment
Kastelein, J. J. P., van der Steeg, W. A., Holme, I., Gaffney, M., Cater, N. B., Barter, P., Deedwania, P., Olsson, A. G., Boekholdt, S. M., Demicco, D. A., et al. (2008) · Circulation · doi:10.1161/circulationaha.107.713438 · Cited by 478 · see citing works
Barter, P. J., Ballantyne, C. M., Carmena, R., Cabezas, M. C., Chapman, M. J., Couture, P., Graaf, J. D., Durrington, P. N., Færgeman, O., Frohlich, J., et al. (2006) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2006.01616.x · Cited by 463 · cited 1× · see citing works
“directly measure circulating atherogenic lipoproteins than LDL cholesterol.(110,113) ApoB has analytic and biological sta-”
BackgroundTsujita, K., Sugiyama, S., Sumida, H., Shimomura, H., Yamashita, T., Yamanaga, K., Komura, N., Sakamoto, K., Oka, H., Nakao, K., et al. (2015) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2015.05.065 · Cited by 459 · cited 1× · see citing works
“regression of coronary artery plaque volume than atorvastatin alone.(41) Collectively, these results support LDL cholesterol”
ResultCARLSON, L. A., HAMSTEN, A., & ASPLUND, A. (1989) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.1989.tb01393.x · Cited by 443 · cited 1× · see citing works
“At high doses, niacin also lowers Lp(a) by ≈30%.(49) As monotherapy, niacin administered to hypercholesterolemic men reduced the risk of recurrent myocardial infarction in the Coronary Drug Project(50) and also reduced total mortality in a 15-year follow-up.”
BackgroundInactivating Mutations in <i>NPC1L1</i> and Protection from Coronary Heart Disease
The Myocardial Infarction Genetics Consortium Investigators (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1405386 · Cited by 419 · see citing works
Nicholls, S. J., Brewer, H. B., Kastelein, J. J. P., Krueger, K. A., Wang, M.-D., Shao, M., Hu, B., McErlean, E., & Nissen, S. E. (2011) · JAMA · doi:10.1001/jama.2011.1649 · Cited by 410 · see citing works
Pleiotropic Effects of Statins: Benefit Beyond Cholesterol Reduction?
Robinson, J. G., Smith, B., Maheshwari, N., & Schrott, H. G. (2005) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2005.05.085 · Cited by 407 · cited 2× · see citing works
“detrimental effects.(4) With the recent approval of inhibitors of proprotein convertase subtilisin kexin 9 (PCSK9), a review of all nonstatin LDL cholesterol–lowering therapies was timely.”
BackgroundSelf-citationFerence, B. A., Majeed, F., Penumetcha, R., Flack, J. M., & Brook, R. D. (2015) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2015.02.020 · Cited by 407 · see citing works
Navarese, E. P., Kołodziejczak, M. M., Schulze, V., Gurbel, P. A., Tantry, U. S., Lin, Y., Brockmeyer, M., Kandzari, D. E., Umińska, J. M., D’Agostino, R. B., et al. (2015) · Annals of Internal Medicine · doi:10.7326/m14-2957 · Cited by 404 · cited 1× · see citing works
“A meta-analysis of phase 2 and 3 trials found reduced total mortality with alirocumab and evolocumab, in trials ranging from 12 to 78 weeks.(92) Four large, ongoing trials of CVD events and safety are evaluating alirocumab, evolocumab, and bococizumab in high risk patient populations.”
MethodDeedwania, P., Barter, P., Carmena, R., Fruchart, J.-C., Grundy, S. M., Haffner, S., Kastelein, J. J., LaRosa, J. C., Schachner, H., Shepherd, J., et al. (2006) · The Lancet · doi:10.1016/s0140-6736(06)69292-1 · Cited by 387 · see citing works
Association Between Familial Hypercholesterolemia and Prevalence of Type 2 Diabetes Mellitus
Besseling, J., Kastelein, J. J. P., Defesche, J. C., Hutten, B. A., & Hovingh, G. K. (2015) · JAMA · doi:10.1001/jama.2015.1206 · Cited by 387 · see citing works
Drug treatment of lipid disorders.
Broeders, N., Knoop, C., & Abramowicz, D. (1999) · New England Journal of Medicine · doi:10.1056/nejm199912233412617 · Cited by 385 · cited 1× · see citing works
“5 g colesevelam, LDL cholesterol is reduced 18% to 25%.(44) Bile acid sequestrants also”
BackgroundCastelli, W., & Anderson, K. (1986) · The American Journal of Medicine · doi:10.1016/0002-9343(86)90157-9 · Cited by 374 · see citing works
Heart Protection Study Collaborative Group (2011) · The Lancet · doi:10.1016/s0140-6736(11)61125-2 · Cited by 373 · see citing works
Robinson, J. G., Wang, S., Smith, B. J., & Jacobson, T. A. (2009) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2008.10.024 · Cited by 368 · see citing works
Self-citationRaal, F. J., Pilcher, G. J., Panz, V. R., van Deventer, H. E., Brice, B. C., Blom, D. J., & Marais, A. D. (2011) · Circulation · doi:10.1161/circulationaha.111.042523 · Cited by 366 · cited 1× · see citing works
“events in childhood; LDL cholesterol reduction is greater with the addition of ezetimibe or colesevelam.(71,72,134,135) Clinical tri-”
BackgroundSelf-citationPredictors of New-Onset Diabetes in Patients Treated With Atorvastatin
Waters, D. D., Ho, J. E., DeMicco, D. A., Breazna, A., Arsenault, B. J., Wun, C.-C., Kastelein, J. J., Colhoun, H., & Barter, P. (2011) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2010.10.047 · Cited by 333 · cited 1× · see citing works
“with 9% higher type 2 diabetes mellitus risk over 4 years, with greater risk associated with intensive statin therapy(151) and preexisting risk factors for diabetes mellitus.(152) No compelling”
BackgroundGinsberg, H. N., & MacCallum, P. R. (2009) · Journal of the CardioMetabolic Syndrome · doi:10.1111/j.1559-4572.2008.00044.x · Cited by 331 · cited 1× · see citing works
“type 2 diabetes mellitus, are at higher risk for CVD events and mortality.(55,56) Lowering LDL cholesterol with statins in”
BackgroundSelf-citationPCSK9R46L, Low-Density Lipoprotein Cholesterol Levels, and Risk of Ischemic Heart Disease
Benn, M., Nordestgaard, B. G., Grande, P., Schnohr, P., & Tybjærg-Hansen, A. (2010) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2010.02.044 · Cited by 316 · cited 1× · see citing works
“Gain-of-function mutations in the PCSK9 gene cause autosomal-dominant hypercholesterolemia,(73) whereas loss-of-function mutations are associated with lower LDL cholesterol and reduced CVD risk.(21,74) Monoclonal antibodies (mAbs) against PCSK9 were recently approved in Europe and in North America.”
BackgroundUrban, D., Pöss, J., Böhm, M., & Laufs, U. (2013) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2013.07.056 · Cited by 287 · cited 2× · see citing works
“Gain-of-function mutations in the PCSK9 gene cause autosomal-dominant hypercholesterolemia,73 whereas loss-of-function mutations are associated with lower LDL cholesterol and reduced CVD risk.21,74 Monoclonal antibodies (mAbs) against PCSK9 were recently approved in Europe and in North America.75 Alirocumab and evoloc…”
BackgroundLiu, J., Sempos, C. T., Donahue, R. P., Dorn, J., Trevisan, M., & Grundy, S. M. (2006) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2006.06.032 · Cited by 277 · see citing works
Krishna, R., Anderson, M. S., Bergman, A. J., Jin, B., Fallon, M. S., Côté, J., Rosko, K., Chavez-Eng, C. M., Lutz, R., Bloomfield, D. M., et al. (2007) · The Lancet · doi:10.1016/s0140-6736(07)61813-3 · Cited by 275 · cited 1× · see citing works
“HDL-raising and LDL-lowering effects(86,87) without apparent off-target effects.(105) Ongoing RCTs will determine whether additional beneficial effects of CETP inhibition translate into improved outcomes.”
BackgroundRader, D. J., & Kastelein, J. J. P. (2014) · Circulation · doi:10.1161/circulationaha.113.001292 · Cited by 264 · cited 5× · see citing works
“Thus, lomitapide, an oral microsomal triglyceride transfer protein inhibitor, reduces LDL cholesterol by 35 to 50% in subjects with homozygous FH.84,85 Lomitapide has Food and Drug Administration (FDA) and European Medicines Agency (EMA) approval for the treatment of homozygous FH as an adjunct to diet and drug therap…”
BackgroundInfluentialSelf-citationMetabolic Syndrome and Risk of Acute Myocardial Infarction
Mente, A., Yusuf, S., Islam, S., McQueen, M., Tanomsup, S., Onen, C. L., Rangarajan, S., Gerstein, H. C., & Anand, S. S. (2010) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2009.12.053 · Cited by 261 · cited 1× · see citing works
“type 2 diabetes mellitus, are at higher risk for CVD events and mortality.(55,56) Lowering LDL cholesterol with statins in”
BackgroundLow-density lipoprotein-independent effects of statins
Davignon, J., & Laaksonen, R. (1999) · Current Opinion in Lipidology · doi:10.1097/00041433-199912000-00010 · Cited by 244 · cited 2× · see citing works
“Elevated LDL cholesterol per se influences these processes adversely; it remains controversial whether proposed LDL-independent effects of statins could result from putative pleiotropic direct effects of statin molecules and their metabolites on non-LDL–related pathways or simply from their LDL-lowering effects.(3,4)…”
BackgroundMicrosomal triglyceride transfer protein.
Wetterau, J., Lin, M., & Jamil, H. (1997) · Biochimica et Biophysica Acta · doi:10.1016/s0005-2760(96)00168-3 · Cited by 223 · cited 1× · see citing works
“Lomitapide Microsomal triglyceride transfer protein is essential for assembly and secretion of hepatic and intestinal lipoproteins.(101) Microsomal triglyceride transfer protein facilitates the incorporation of cholesteryl ester and triglyceride into very lowdensity lipoprotein (VLDL) in hepatocytes and chylomicrons i…”
BackgroundStatin treatment and new-onset diabetes: A review of proposed mechanisms
Brault, M., Ray, J., Sandoval, Y.-H. G., Mantzoros, C. S., & Daskalopoulou, S. S. (2014) · Metabolism · doi:10.1016/j.metabol.2014.02.014 · Cited by 218 · see citing works
Knapp, H., Schrott, H., Ma, P., Knopp, R. H., Chin, B., Gaziano, J., Donovan, J. M., Burke, S., & Davidson, M. H. (2001) · American Journal of Medicine · doi:10.1016/s0002-9343(01)00638-6 · Cited by 201 · cited 1× · see citing works
“augment the LDL-lowering effects of other drugs, notably statins.(45) Colesevelam improves glycemic control modestly in patients with type 2 diabetes mellitus.”
BackgroundSacks, F., Tonkin, A., Craven, T., Pfeffer, M., Shepherd, J., Keech, A., Furberg, C., & Braunwald, E. (2002) · Circulation · doi:10.1161/01.cir.0000012918.84068.43 · Cited by 198 · see citing works
ESC/EAS Guidelines for the management of dyslipidaemias
Catapano, A. L., Reiner, Ž., De Backer, G., Graham, I., Taskinen, M.-R., Wiklund, O., Agewall, S., Alegria, E., Chapman, M. J., Durrington, P., et al. (2011) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2011.06.012 · Cited by 192 · see citing works
Rapid regression of atherosclerosis: insights from the clinical and experimental literature
Williams, K. J., Feig, J. E., & Fisher, E. A. A. (2008) · Nature Clinical Practice Cardiovascular Medicine · doi:10.1038/ncpcardio1086 · Cited by 188 · cited 1× · see citing works
“early in the course of atherosclerosis can completely regress atherosclerosis and normalize arterial function.(160) Together, these”
BackgroundBallantyne, C. M., Davidson, M. H., MacDougall, D. E., Bays, H. E., DiCarlo, L. A., Rosenberg, N. L., Margulies, J., & Newton, R. S. (2013) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2013.05.050 · Cited by 175 · see citing works
Use of atorvastatin in systemic lupus erythematosus in children and adolescents
Schanberg, L. E., Sandborg, C. I., Barnhart, H. X., Ardoin, S. P., Yow, E. S., Evans, G. W., Mieszkalski, K. L., Ilowite, N. T., Eberhard, A., Imundo, L. F., et al. (2011) · Arthritis & Rheumatism · doi:10.1002/art.30645 · Cited by 170 · see citing works
Gutierrez, M. J., Rosenberg, N. L., MacDougall, D. E., Hanselman, J. C., Margulies, J. R., Strange, P., Milad, M. A., McBride, S. J., & Newton, R. S. (2014) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.113.302677 · Cited by 170 · see citing works
The Anatomy of a Clinical Trial
Shepherd, J., & Gaw, A. (2002) · Medical Principles and Practice · doi:10.1159/000066408 · Cited by 159 · cited 1× · see citing works
“First, long-term follow-up of statin trials demonstrates persistently reduced CVD risk in statin-treated patients from the trial over the next decade or 2.(158,159) Long-term follow-up of the ongoing CVD outcomes trials of new agents will also help characterize the legacy effect of plaque stabilization and regression…”
BackgroundUse of ETC-1002 to treat hypercholesterolemia in patients with statin intolerance
Thompson, P. D., Rubino, J., Janik, M. J., MacDougall, D. E., McBride, S. J., Margulies, J. R., & Newton, R. S. (2015) · Journal of clinical lipidology · doi:10.1016/j.jacl.2015.03.003 · Cited by 158 · cited 1× · see citing works
“Bempedoic Acid Bempedoic acid (previously known as ETC-1002) is a small molecule inhibitor of ATP citrate lyase, a cytoplasmic enzyme that generates acetyl coenzyme A for de novo synthesis of fatty acids and cholesterol.(88) Phase 2 trials in patients with hypercholesterolemia(108) and type 2 diabetes mellitus(109) sh…”
BackgroundFaergeman, O., Holme, I., Fayyad, R., Bhatia, S., Grundy, S. M., Kastelein, J. J. P., LaRosa, J. C., Larsen, M. L., Lindahl, C., Olsson, A. G., et al. (2009) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2009.04.008 · Cited by 154 · see citing works
Catapano, A. L., & Papadopoulos, N. J. (2013) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2013.01.044 · Cited by 154 · see citing works
A gift from nature: the birth of the statins
Endo, A. (2008) · Nature Medicine · doi:10.1038/nm1008-1050 · Cited by 152 · cited 2× · see citing works
“Akira Endo’s painstaking pharmacological screening of compounds that interfered with cholesterol biosynthesis led to isolation of compactin in 1973 from the rice mold Penicillium citrinum Pen-51.(1) Compactin’s descendants—lovastatin, simvastatin, pravastatin, fluvastatin, atorvastatin, rosuvastatin, and pitavastatin—…”
BackgroundMychaleckyj, J. C., Craven, T., Nayak, U., Buse, J., Crouse, J. R., Elam, M., Kirchner, K., Lorber, D., Marcovina, S., Sivitz, W., et al. (2012) · Diabetes Care · doi:10.2337/dc11-1811 · Cited by 149 · cited 1× · see citing works
“on fenofibrate returned to baseline levels with cessation of treatment.(69) There is no evidence supporting the use of fenofibrate in nondyslipidemic people and in women without dyslipidemia, fenofibrate may increase risk of CVD”
BackgroundSelf-citationGuideline-Based Statin Eligibility, Coronary Artery Calcification, and Cardiovascular Events
Pursnani, A. K., Massaro, J. M., D’Agostino, R. B., O’Donnell, C. J., & Hoffmann, U. (2015) · JAMA · doi:10.1001/jama.2015.7515 · Cited by 144 · see citing works
van der Graaf, A., Cuffie-Jackson, C., Vissers, M., Trip, M., Gagné, C., Shi, G., Veltri, E., Avis, H., & Kastelein, J. (2008) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2008.09.002 · Cited by 134 · cited 2× · see citing works
“In adolescents, in combination with simvastatin, ezetimibe lowered LDL cholesterol by an additional 10% to 15%.(71) Although colesevelam modestly lowered LDL cholesterol (6%–12%) irrespective of background statin use, children on statins at trial entry sometimes discontinued this treatment during the open label phase,…”
BackgroundColesevelam lowers glucose and lipid levels in type 2 diabetes: The clinical evidence
Fonseca, V. A., Handelsman, Y., & Staels, B. (2010) · Diabetes, Obesity and Metabolism · doi:10.1111/j.1463-1326.2009.01181.x · Cited by 130 · cited 1× · see citing works
“Colesevelam improves glycemic control modestly in patients with type 2 diabetes mellitus.(46) Gastrointestinal”
BackgroundSevere Hypertriglyceridemia With Pancreatitis
Sacks, F. M., Stanesa, M., & Hegele, R. A. (2013) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2013.13309 · Cited by 119 · cited 1× · see citing works
“Lomitapide has Food and Drug Administration (FDA) and European Medicines Agency (EMA) approval for the treatment of homozygous FH as an adjunct to diet and drug therapy, with concerns over long-term effects, that is, elevated liver enzymes and hepatic steatosis.(102)”
BackgroundSelf-citationPrimary Sjögren's syndrome in men. Clinical, serologic, and immunogenetic features.
Molina, R., Provost, T., Arnett, F., Bias, W., Hochberg, M., Wilson, R. W., & Alexander, E. (1986) · American Journal of Medicine · doi:10.1016/0002-9343(86)90044-6 · Cited by 116 · see citing works
van Wijk, D. F., Sjouke, B., Figueroa, A. L., Emami, H., van der Valk, F. M., MacNabb, M. H., Hemphill, L., Schulte, D. M., Koopman, M. G., Lobatto, M. E., et al. (2014) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2014.01.088 · Cited by 105 · see citing works
Gidding, S. S. (2006) · Archives of Internal Medicine · doi:10.1001/archinte.166.21.2341 · Cited by 97 · cited 1× · see citing works
“39 mmol/L (10–15 mg/dL) increase of non–high-density lipoprotein (HDL) cholesterol is associated with an additional year of vascular aging.(14,15) Thus, a 15-year-old with heterozygous familial hypercholesterolemia (FH) has essentially the same amount of atherosclerosis as a 20- to 35-year-old with an average lipid pr…”
BackgroundSelf-citationToth, P. P. (2012) · Yearbook of Medicine · doi:10.1016/s0084-3873(12)00318-5 · Cited by 96 · cited 1× · see citing works
“treated to cause 1 new case of type 2 diabetes mellitus, emphasizing risk-benefit considerations of statin therapy.(150,151) To date,”
BackgroundCharlton-Menys, V., Betteridge, D. J., Colhoun, H., Fuller, J., France, M., Hitman, G. A., Livingstone, S. J., Neil, H. A. W., Newman, C. B., Szarek, M., et al. (2009) · Clinical Chemistry · doi:10.1373/clinchem.2008.111401 · Cited by 94 · cited 1× · see citing works
“Study (CARDS) trial, both apoB and non-HDL cholesterol predicted CHD better than LDL cholesterol.(121) Meta-analyses”
MethodCuring atherosclerosis should be the next major cardiovascular prevention goal
Robinson, J. G., & Gidding, S. S. (2014) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2014.04.009 · Cited by 87 · see citing works
Self-citationMiname, M. H., Ribeiro, M. S., Filho, J. P., Ávila, L. F., Bortolotto, L. A., Martinez, L. R. C., Rochitte, C. E., & Santos, R. D. (2010) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2010.10.001 · Cited by 85 · see citing works
Cefalu, A. B., Pirruccello, J. P., Noto, D., Gabriel, S., Valenti, V., Gupta, N., Spina, R., Tarugi, P., Kathiresan, S., & Averna, M. R. (2013) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.112.301101 · Cited by 83 · see citing works
Prevalence of ANGPTL3 and APOB Gene Mutations in Subjects With Combined Hypolipidemia
Noto, D., Cefalu, A. B., Valenti, V., Fayer, F., Pinotti, E., Ditta, M., Spina, R., Vigna, G. B., Yue, P., Kathiresan, S., et al. (2012) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.111.238766 · Cited by 82 · cited 1× · see citing works
“patients with ANGPTL3 mutations with similarly low LDL cholesterol levels.(146) In the Open-Label Study of Long-Term Evaluation Against LDL Cholesterol (OSLER) study, among those on evolocumab, 3 patients (1%) reported amnesia and 5 (1%) reported either memory or mental impairment”
BackgroundKusters, D. M., Caceres, M., Mauricio Coll, B., Cuffie, C. A., Gagné, C., Jacobson, M. S., Kwiterovich, P. O., Lee, R., Lowe, R. S., Massaad, R., et al. (2015) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2015.02.043 · Cited by 82 · cited 1× · see citing works
“Limited RCT data support ezetimibe use in children and adolescents.(70) As monotherapy, after 12 weeks of treatment, ezetimibe lowered LDL cholesterol by 27% in 6- to 10-year-old children with FH.”
BackgroundThe Lipid Research Clinics Coronary Primary Prevention Trial
Rifkind, B. M. (2012) · Drugs · doi:10.2165/00003495-198600311-00010 · Cited by 81 · see citing works
Stein, E. A., Marais, A. D., Szamosi, T., Raal, F. J., Schurr, D., Urbina, E. M., Hopkins, P. N., Karki, S., Xu, J., Misir, S., et al. (2009) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2009.08.037 · Cited by 78 · cited 2× · see citing works
“events in childhood; LDL cholesterol reduction is greater with the addition of ezetimibe or colesevelam.(71,72,134,135) Clinical tri-”
BackgroundSelf-citationPletcher, M., Sibley, C., Pignone, M., Vittinghoff, E., & Greenland, P. (2013) · Circulation · doi:10.1161/circulationaha.113.002598 · Cited by 78 · see citing works
Long-term follow-up of children with familial hypercholesterolaemia treated with cholestyramine.
West, R., Lloyd, J., & Leonard, J. (1980) · The Lancet · doi:10.1016/s0140-6736(80)92044-9 · Cited by 78 · cited 1× · see citing works
“side effects and drug interactions (perhaps somewhat lower with colesevelam) limit the use of these agents.(47) In the LRC”
Major Lipids, Apolipoproteins, and Risk of Vascular Disease
Moneta, G. L. (2010) · Yearbook of Vascular Surgery · doi:10.1016/s0749-4041(10)79320-9 · Cited by 77 · see citing works
Discordance analysis and the Gordian Knot of LDL and non-HDL cholesterol versus apoB
Sniderman, A. D., Lamarche, B., Contois, J. H., & Graaf, J. D. (2014) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000127 · Cited by 76 · cited 3× · see citing works
“determination is affected when LDL levels are low or triglycerides are high.(110) Thus, pursuit of alternatives to LDL”
BackgroundMipomersen and other therapies for the treatment of severe familial hypercholesterolemia
Burnett, J., Bell, D. A., Hooper, & Watts, G. F. (2012) · Vascular Health and Risk Management · doi:10.2147/vhrm.s28581 · Cited by 66 · cited 1× · see citing works
“ApoB Antisense Therapy Mipomersen is a second generation antisense oligonucleotide that concentrates in the liver and specifically binds to human apoB mRNA.(98) The bound mRNA is degraded by hepatic RNAse, preventing the translation of apoB and synthesis of apoB-containing lipoproteins.”
BackgroundSwiger, K. J., & Martin, S. S. (2015) · Drug Safety · doi:10.1007/s40264-015-0296-6 · Cited by 65 · cited 4× · see citing works
“The FDA issued a directive for neurocognitive assessment in ongoing PCSK9 mAb RCTs.(147)”
BackgroundInfluentialLong‐term effects of LDL apheresis in patients with severe hypercholesterolemia
Sachais, B., Katz, J., Ross, J. L., & Rader, D. J. (2005) · Journal of clinical apheresis · doi:10.1002/jca.20036 · Cited by 62 · see citing works
Self-citationLate-Breaking Clinical Trial Abstracts
Wilkins, L. (2002) · Circulation · doi:10.1161/01.cir.0000457464.79076.2c · Cited by 58 · see citing works
Everett, B., Mora, S., Glynn, R., Macfadyen, J. G., & Ridker, P. (2014) · American Journal of Cardiology · doi:10.1016/j.amjcard.2014.08.041 · Cited by 57 · cited 1× · see citing works
“diabetes mellitus, hematuria, hepatobiliary disorders, and insomnia.(148) Long-term follow-up is needed to better define”
BackgroundNiacin and HDL Cholesterol — Time to Face Facts
Lloyd‐Jones, D. M. (2014) · New England Journal of Medicine · doi:10.1056/nejme1406410 · Cited by 48 · see citing works
Niacin: another look at an underutilized lipid-lowering medication
Creider, J. C., Hegele, R. A., & JOY, T. R. (2012) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2012.22 · Cited by 47 · cited 1× · see citing works
“incompletely defined mechanisms, lower LDL cholesterol and triglyceride by ≈25% and ≈50%, respectively, and raise HDL cholesterol by ≈30%.(48) At high doses, niacin also lowers Lp(a) by ≈30%.”
BackgroundSelf-citationThe coronary drug project--findings with regard to estrogen, dextrothyroxine, clofibrate and niacin.
Stamler, J. (1977) · Advances in Experimental Medicine and Biology · doi:10.1007/978-1-4613-4220-5_6 · Cited by 46 · cited 1× · see citing works
“Of the latter, estrogen and dextrothyroxine had undesirable physiological effects and failed to reduce CVD despite cholesterol reduction.(24) Fibrates and niacin have shown some benefit when used as monotherapy,(25,26) but no incremental protection when added to a statin in patients who had achieved low LDL cholestero…”
BackgroundPuri, R., Nissen, S. E., Shao, M., Uno, K., Kataoka, Y., Kapadia, S. R., Tuzcu, E. M., & Nicholls, S. J. (2014) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2014.08.009 · Cited by 43 · cited 1× · see citing works
“39 mmol/L (15 mg/dL).(156,157) This suggests that combinations of maximally tolerated statins, ezetimibe, and new drugs, such as PCSK9 or CETP inhibitors, to dramat-”
BackgroundNew Therapies for Reducing Low-Density Lipoprotein Cholesterol
Stein, E. A., & Raal, F. J. (2014) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2014.08.008 · Cited by 42 · cited 1× · see citing works
“Mipomersen 200 mg administered subcutaneously once weekly reduces LDL cholesterol, apoB and Lp(a) by ≈30%.(99) Because mipomersen does not require functional LDL receptors, equivalent responsiveness is seen in LDL receptor negative homozygous FH patients.”
BackgroundSelf-citationBonnefont‐Rousselot, D., Condat, B., Sassolas, A., Chebel, S., Bittar, R., Federspiel, M.-C., Cazals-Hatem, D. L., & Bruckert, É. (2008) · European Journal of Gastroenterology & Hepatology · doi:10.1097/meg.0b013e3282ffd9f8 · Cited by 40 · see citing works
Lonardo, A., Tarugi, P., Ballarini, G., & Bagni, A. (1998) · Digestive Diseases and Sciences · doi:10.1023/a:1026646618643 · Cited by 40 · see citing works
Canas, J., Ross, J., Taboada, M., Sikes, K. M., Damaso, L., Hossain, J., Caulfield, M., Gidding, S., & Mauras, N. (2015) · Pediatric Diabetes · doi:10.1111/pedi.12245 · Cited by 37 · see citing works
Self-citationDuan, C., Du, Z., Wang, Y., & Jia, L. (2014) · World Journal of Pediatrics · doi:10.1007/s12519-014-0498-5 · Cited by 37 · see citing works
Corte, C. D., Fintini, D., Giordano, U., Cappa, M., Brufani, C., Majo, F., Mennini, C., & Nobili, V. (2012) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2012.04498.x · Cited by 30 · see citing works
Niacin at 56 Years of Age — Time for an Early Retirement?
Giugliano, R. P. (2011) · New England Journal of Medicine · doi:10.1056/nejme1112346 · Cited by 22 · see citing works
Gut-acting drugs for lowering cholesterol
Black, D. (2002) · Current Atherosclerosis Reports · doi:10.1007/s11883-002-0065-8 · Cited by 18 · cited 1×
“Increased 7-α-hydoxylase activity raises triglyceride.(43) At daily doses of 24 g chole-”
BackgroundMcPherson, R., & Hegele, R. A. (2014) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.114.305012 · Cited by 15 · cited 1× · see citing works
“Convincing evidence of reduced CVD events with ezetimibe has been slow to emerge.(39) In 2011, the Study of Heart and Renal Protection (SHARP) showed ezetimibe plus simvastatin versus double placebo”
BackgroundSelf-citationStatin-induced coronary artery disease regression rates differ in men and women
Puri, R., Nissen, S. E., & Nicholls, S. J. (2015) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000195 · Cited by 12 · see citing works
Li, S., Chen, W., Srinivasan, S. R., Bond, M. G., Tang, R., Urbina, E. M., & Berenson, G. S. (2003) · JAMA · doi:10.1001/jama.290.17.2271 · Cited by 8 · see citing works
Flagged first, then by citations
24 of the 181 references couldn’t be matched to a known paper.
Research works printed but not linked: 8
- [9]Law MR Wald NJ An ecological study of serum cholesterol and ischaemic heart disease between 1950 and 1990 Eur J Clin Nutr 1994 48 305 25 8055847
- [11]Lusis AJ Atherosclerosis Nature 2000 407 233 41 11001066 PMC2826222
- [39]McPherson R Hegele RA Ezetimibe: rescued by randomization (clinical and Mendelian) Arterioscler Thromb Vasc Biol 2015 35 e13 5 25550209
- [42]Grundy SM Ahrens EH Salen G Interruption of the enterohepatic circulation of bile acids in man: comparative effects of cholestyramine and ileal exclusion on cholesterol metabolism J Lab Clin Med 1971 178 94 121 5569253
- [65]Primary prevention of ischaemic heart disease: WHO coordinated cooperative trial. A summary report Bull World Health Organ 1979 57 801 5 317255 PMC2395864
- [112]Havel RJ Kane JP Introduction: structure and metabolism of plasma lipoproteins Scriver CR Beaudet AL Sly WS Valle D The Metabolic and Molecular Bases of Inherited Disease 7 New York, NY McGraw-Hill 1995 1841 51
- [126]Anderson TJ Grégoire J Hegele RA Update of the Canadian Cardiovascular Society guidelines for the diagnosis and treatment of dyslipidemia for the prevention of cardiovascular disease in the adult Can J Cardiol 2013 29 151 67 23351925
- [142]Tarugi P Lonardo A Heterozygous familial hypobetalipoproteinemia associated with fatty liver Am J Gastroenterol 1997 92 1400 1402 9260828
Cited by
Sorted by citations
Silverman, M. G., Ference, B. A., Im, K., Wiviott, S. D., Giugliano, R. P., Grundy, S. M., Braunwald, E., & Sabatine, M. S. (2016) · JAMA · doi:10.1001/jama.2016.13985 · Cited by 1,483 · see citing works
Anderson, T. J., Grégoire, J., Pearson, G. J., Barry, A. R., Couture, P., Dawes, M., Francis, G. A., Genest, J., Grover, S., Gupta, M., et al. (2016) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2016.07.510 · Cited by 1,173 · see citing works
“Results of a meta-analysis suggest a nominal benefit in the subgroup of patients with high triglyceride/low HDL-C levels at baseline (heterogeneous populations from 5 trials).(97) Because of the safety profile of fenofibrate, clinicians might consider fenofibrate for high-risk patients with residual high triglyceride/…”
BackgroundSelf-citationBorén, J., & Williams, K. J. (2016) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000330 · Cited by 524 · see citing works
Sphingolipids and phospholipids in insulin resistance and related metabolic disorders
Meikle, P. J., & Summers, S. A. (2016) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2016.169 · Cited by 426 · see citing works
“The fourth enzyme in the biosynthetic pathway that produces ceramides is sphingolipid δ(4)-desaturase (also known as dihydroceramide desaturase), and pharmacological inhibition or genetic inactivation of the most abundant isoform (DES1) are also insulin sensitizing69,139.”
BackgroundInfluentialFamilial hypercholesterolaemia
Defesche, J. C., Gidding, S. S., Harada‐Shiba, M., Hegele, R. A., Santos, R. D., & Wierzbicki, A. S. (2017) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2017.93 · Cited by 538 · see citing works
Self-citationThe Evolving Future of PCSK9 Inhibitors
Rosenson, R. S., Hegele, R. A., Fazio, S., & Cannon, C. P. (2018) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2018.04.054 · Cited by 264 · see citing works
“This has recently been readopted in the 2017 ACC Consensus Pathway for use of nonstatin agents (89,90).”
MethodSelf-citationMancini, G. B. J., Baker, S. K., Bergeron, J., FITCHETT, D. H., Frohlich, J. J., Genest, J. J., Gupta, M., Hegele, R. A., Ng, D. S., Pearson, G. J., et al. (2016) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2016.01.003 · Cited by 253 · see citing works
Self-citationFrom Lipids to Inflammation: New Approaches to Reducing Atherosclerotic Risk
Shapiro, M. D., & Fazio, S. (2016) · Circulation Research · doi:10.1161/circresaha.115.306471 · Cited by 217 · see citing works
“Ezetimibe There are numerous nonstatin LDL-C–lowering therapies that are considered in light of their ability to mitigate ASCVD risk in this review.(23) Ezetimibe inhibits cholesterol absorption at the jejunal brush border by binding to the Niemann-Pick C1-like-1 receptor, resulting in moderate reduction in LDL-C (16%…”
BackgroundATP-citrate lyase (ACLY) in lipid metabolism and atherosclerosis: An updated review
Feng, X., Zhang, L., Xu, S., & Shen, A.-Z. (2019) · Progress in Lipid Research · doi:10.1016/j.plipres.2019.101006 · Cited by 233 · see citing works
Daugherty, A., Tall, A. R., Daemen, M. J. A. P., Falk, E., Fisher, E. A. A., García‐Cardeña, G., Lusis, A. J., Owens, A. P., Rosenfeld, M. E., & Virmani, R. (2017) · Circulation Research · doi:10.1161/res.0000000000000169 · Cited by 182 · see citing works
“A large number of animal studies have contributed to the notion that lowering plasma cholesterol concentrations is an effective mode of reducing atherosclerosis,(10) which has led to therapeutic approaches for reducing plasma cholesterol concentration to effectively reduce atherosclerosis-related diseases in humans.(1…”
BackgroundPolygenic Versus Monogenic Causes of Hypercholesterolemia Ascertained Clinically
Wang, J., Dron, J. S., Ban, M. R., Robinson, J. F., McIntyre, A. D., Alazzam, M., Zhao, P., Dilliott, A. A., Cao, H., Huff, M. W., et al. (2016) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.116.308027 · Cited by 210 · see citing works
Self-citationLipid-Lowering Agents: Targets Beyond PCSK9
Hegele, R. A., & Tsimikas, S. (2019) · Circulation Research · doi:10.1161/circresaha.118.313171 · Cited by 171 · see citing works
Self-citationDron, J. S., Lazarte, J., & Hegele, R. A. (2018) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.118.311581 · Cited by 4 · see citing works
Self-citationCan LDL cholesterol be too low? Possible risks of extremely low levels
OLSSON, A. G., Angelin, B., Assmann, G., Binder, C. J., Björkhem, I., Cedazo-Mı́nguez, Á., Cohen, J. C., von Eckardstein, A., Farinaro, E., Müller‐Wieland, D., et al. (2017) · Journal of Internal Medicine · doi:10.1111/joim.12614 · Cited by 99 · see citing works
Cognition in major depressive disorder: a ‘Systemically Important Functional Index’ (SIFI)
McIntyre, R. S., & Lee, Y. (2016) · Current Opinion in Psychiatry · doi:10.1097/yco.0000000000000221 · Cited by 85 · see citing works
“LDL), despite the fact that their efficacy on total cholesterol measures may not be dissimilar [16].”
BackgroundDubland, J. A., & Francis, G. (2016) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000279 · Cited by 84 · see citing works
Liu, C., Schönke, M., Zhou, E., Li, Z., Kooijman, S., Boon, M. R., Larsson, M., Wallenius, K., Dekker, N., Barlind, L., et al. (2021) · Cardiovascular Research · doi:10.1093/cvr/cvab076 · Cited by 81 · see citing works
“The attenuation of hypercholesterolaemia potently reduces morbidity and mortality of atherosclerotic cardiovascular diseases as consistently observed in extensive clinical studies.(2) However, many at-risk patients either fail to reach their target cholesterol levels with current therapeutics such as statins or are in…”
BackgroundKusters, D. M., Caceres, M., Mauricio Coll, B., Cuffie, C. A., Gagné, C., Jacobson, M. S., Kwiterovich, P. O., Lee, R., Lowe, R. S., Massaad, R., et al. (2015) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2015.02.043 · Cited by 82 · see citing works
Mancini, G. B. J., Hegele, R. A., & Leiter, L. A. (2018) · Canadian Journal of Diabetes · doi:10.1016/j.jcjd.2017.10.019 · Cited by 70 · see citing works
Self-citationCystathionine γ-lyase protects vascular endothelium: a role for inhibition of histone deacetylase 6.
Leucker, T., Nomura, Y., Kim, J. H., Bhatta, A., Wang, V., Wecker, A., Jandu, S., Santhanam, L., Berkowitz, D., Romer, L., et al. (2017) · American Journal of Physiology. Heart and Circulatory Physiology · doi:10.1152/ajpheart.00724.2016 · Cited by 60 · see citing works
Daugherty, A., Tall, A. R., Daemen, M. J. A. P., Falk, E., Fisher, E. A. A., García‐Cardeña, G., Lusis, A. J., Owens, A. P., Rosenfeld, M. E., & Virmani, R. (2017) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atv.0000000000000062 · Cited by 316 · see citing works
Familial Hypercholesterolemia: New Horizons for Diagnosis and Effective Management
Mytilinaiou, M. G., Kyrou, I., Khan, M., Grammatopoulos, D. K., & Randeva, H. S. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.00707 · Cited by 59 · see citing works
“, 2015); however, it has not been approved for use in Europe yet (Gaudet and Brisson, 2015; Hartgers et al., 2015; Hegele et al., 2015).”
BackgroundShear stress, arterial identity and atherosclerosis
Jones, E. A. V., & Lehoux, S. (2015) · Thrombosis and Haemostasis · doi:10.1160/th15-10-0791 · Cited by 56 · see citing works
“On the other hand, both preclinical and clinical research has provided multiple lines of evidence that inflammation and immune responses are integral components of the pathogenesis of atherosclerosis (8, 9).”
BackgroundJiang, Y., Du, H., Liu, X., Fu, X., Li, X., & Cao, Q. (2019) · Journal of drug targeting · doi:10.1080/1061186x.2019.1616296 · Cited by 56 · see citing works
“The previous reports have revealed that dyslipidaemia manifesting as elevated plasma low-density lipoprotein cholesterol (LDLC) levels is the central element of atherosclerotic lesions [6].”
BackgroundBurke, A. C., Telford, D. E., Sutherland, B. G., Edwards, J. Y., Sawyez, C. G., Barrett, P. H. R., Newton, R. S., Pickering, J. G., & Huff, M. W. (2018) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.117.310676 · Cited by 46 · see citing works
Progress in the care of common inherited atherogenic disorders of apolipoprotein B metabolism
Ellis, K. L., Hooper, A. J., Burnett, J. R., & Watts, G. F. (2016) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2016.69 · Cited by 33 · see citing works
Lipoprotein(a) in clinical practice: New perspectives from basic and translational science
Scipione, C. A., Koschinsky, M. L., & Boffa, M. B. (2017) · Critical Reviews in Clinical Laboratory Sciences · doi:10.1080/10408363.2017.1415866 · Cited by 33 · see citing works
Pharmacogenetics of Lipid-Lowering Agents: Precision or Indecision Medicine?
Alfonsi, J., Hegele, R. A., & Gryn, S. E. (2016) · Current Atherosclerosis Reports · doi:10.1007/s11883-016-0573-6 · Cited by 35 · see citing works
Self-citationLangsted, A., & Nordestgaard, B. G. (2020) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000681 · Cited by 33 · see citing works
Lipid‐based gene delivery to macrophage mitochondria for atherosclerosis therapy
Zakirov, F., Zhang, D., Grechko, A. V., Wu, W., Poznyak, A. V., & Orekhov, A. N. (2020) · Pharmacology Research & Perspectives · doi:10.1002/prp2.584 · Cited by 24 · see citing works
Raatz, S. K., Johnson, L. K., Rosenberger, T. A., & Picklo, M. J. (2016) · Nutrition Research · doi:10.1016/j.nutres.2016.06.011 · Cited by 21 · see citing works
Tardif, I., Auclair, A., Piché, M., Biertho, L. D., Marceau, S., Hould, F., Biron, S., Lebel, S., Lescelleur, O., & Poirier, P. (2020) · Obesity Surgery · doi:10.1007/s11695-020-04647-5 · Cited by 22 · see citing works
Personalizing Treatment: Between Primary and Secondary Prevention.
Blaha, M. (2016) · American Journal of Cardiology · doi:10.1016/j.amjcard.2016.05.026 · Cited by 18 · see citing works
Williams, K. J., Tabas, I. A., & Fisher, E. A. A. (2015) · Circulation Research · doi:10.1161/circresaha.115.307609 · Cited by 17 · see citing works
Liu, C., Zhuang, L., Song, Z., Fan, X., Shao, H., Schönke, M., Boon, M. R., Rensen, P. C. N., & Wang, Y. (2022) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2022.10.009 · Cited by 17 · see citing works
Tandirerung, F. J. (2022) · Current Cardiology Reports · doi:10.1007/s11886-022-01783-5 · Cited by 17 · see citing works
Keyes, E., Grinnell, M., Jacoby, D. S., Vazquez, T., Diaz, D., Werth, V. P., & Williams, K. J. (2021) · International Journal of Women’s Dermatology · doi:10.1016/j.ijwd.2021.08.015 · Cited by 21 · see citing works
Li, R.-J., Zhou, Y.-L., Liu, W., Li, Y., Qin, Y., Yu, L.-L., Chen, Y., & Xu, Y.-J. (2020) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2020.111195 · Cited by 14 · see citing works
2019 George Lyman Duff Memorial Lecture
Hegele, R., & Dron, J. (2020) · Arteriosclerosis, Thrombosis and Vascular Biology · doi:10.1161/atvbaha.120.313065 · Cited by 14 · see citing works
Self-citationUnexplained reciprocal regulation of diabetes and lipoproteins
Higuchi, S., Izquierdo, M. C., & Haeusler, R. A. (2018) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000521 · Cited by 21 · see citing works
Dyslipidaemia in the elderly: to treat or not to treat?
Katsiki, N., Kolovou, G. D., Pérez‐Martínez, P., & Mikhailidis, D. P. (2018) · Expert Review of Clinical Pharmacology · doi:10.1080/17512433.2018.1425138 · Cited by 14 · see citing works
Clinoptilolite for Treatment of Dyslipidemia: Preliminary Efficacy Study
Cutovic, M. R., Lazovic, M. P., Vuković-Dejanović, V., Nikolić, D., Petronić, I., & Ćirović, D. (2017) · The Journal of Alternative and Complementary Medicine · doi:10.1089/acm.2016.0414 · Cited by 15 · see citing works
“Fibrates (peroxisome proliferatoractivated receptor agonists) have proved successful when used alone,(10) but provide no incremental benefit if LDLc is already controlled by statins.(11) Bile acid sequestrants (e.”
Abushanab, D., Al‐Badriyeh, D., Marquina, C., Bailey, C., Jaam, M. J., Liew, D., & Ademi, Z. (2022) · Current Problems in Cardiology · doi:10.1016/j.cpcardiol.2022.101211 · Cited by 15 · see citing works
Advanced in Molecular Mechanisms of Atherosclerosis: From Lipids to Inflammation
Meiliana, A., Dewi, N. M., & Wijaya, A. (2018) · The Indonesian Biomedical Journal · doi:10.18585/inabj.v10i2.479 · Cited by 9 · see citing works
“Today, it is no longer a hypothesis, but an established fact, that increased plasma concentrations of cholesterolrich apolipoprotein-B (apoB)-containing lipoproteins are causatively linked to atherosclerotic CVD and that lowering low-density lipoprotein (LDL) concentrations with statins and non-statins reduces atheros…”
BackgroundNew oral agents for treating dyslipidemia
Gryn, S. E., & Hegele, R. A. (2016) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000354 · Cited by 9 · see citing works
Self-citationClemens, K. K., Shariff, S. Z., McArthur, E., & Hegele, R. A. (2018) · Lipids in Health and Disease · doi:10.1186/s12944-017-0649-5 · Cited by 9 · see citing works
“Although recent clinical trial evidence supports the selective use of non-statin agents for cardiovascular risk reduction [7], this has not always been the case in practice, particularly for ezetimibe.”
Self-citationSchettler, V. J. J., Ringel, J., Jacob, S., Julius, U., Klingel, R., Heigl, F., Roeseler, E., & Grützmacher, P. (2017) · Atherosclerosis Supplements · doi:10.1016/j.atherosclerosissup.2017.05.005 · Cited by 7 · see citing works
Improving the Monitoring and Care of Patients With Familial Hypercholesterolemia.
Hegele, R. (2016) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2016.01.041 · Cited by 9 · see citing works
“Because ezetimibe further reduces LDL cholesterol (11), it follows that patients taking a statin plus ezetimibe were more likely to reach their goal.”
BackgroundSelf-citationRSSDI consensus recommendations for dyslipidemia management in diabetes mellitus
Saboo, B., Agarwal, S., Makkar, B. M., Chawla, R., Ghosh, S. K., Viswanathan, V., Gupta, S., Kumar, C. V., Maheshwari, A., Sreenivasamurthy, L., et al. (2022) · International Journal of Diabetes in Developing Countries · doi:10.1007/s13410-022-01063-6 · Cited by 8 · see citing works
Lachaine, J., Charron, J.-N., Gregoire, J. C., Hegele, R. A., & Leiter, L. A. (2023) · ClinicoEconomics and Outcomes Research · doi:10.2147/ceor.s377935 · Cited by 7 · see citing works
Self-citationLipid Management Guidelines from the Departments of Veteran Affairs and Defense: A Critique
Bennet, C. S., Dahagam, C., Virani, S. S., Martin, S. S., Blumenthal, R. S., Michos, E. D., & McEvoy, J. W. (2016) · The American Journal of Medicine · doi:10.1016/j.amjmed.2016.04.012 · Cited by 7 · see citing works
Drug treatment of dyslipidemia
Kim, S. (2016) · Journal of Korean Medical Association · doi:10.5124/jkma.2016.59.5.366 · Cited by 7 · see citing works
Azemi, N. A., Azemi, A. K., Abu-Bakar, L., Sevakumaran, V., Muhammad, T. S. T., & Ismail, N. (2022) · Marine Drugs · doi:10.3390/md20120762 · Cited by 5 · see citing works
Getting Real With PCSK9 Inhibitors in Familial Hypercholesterolemia.
Baass, A., & Hegele, R. (2018) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2018.05.006 · Cited by 4 · see citing works
“Since the late 1990's, statin drugs have been the cornerstone of treatment for heterozygous FH patients, in conjunction with diet and oral non-statins like ezetimibe (3,8,9).”
BackgroundSelf-citationGomes, L. L. A., Faden, D. F., Xie, L., Chambers, S., Stone, C. J., Werth, V. P., & Williams, K. J. (2025) · Lupus Science & Medicine · doi:10.1136/lupus-2024-001160 · Cited by 3 · see citing works
Ec, M. (2017) · doi:10.16966/2379-769x.132 · Cited by 3
“Justified by the lack of definitive cardiovascular outcomes results with PCSK9 inhibitors and the intrinsic differences among health care systems, the European recommendations appear to be more conservative than other recent American recommendations [44,45].”
BackgroundYu, X., Zhao, X.-D., Bao, R.-Q., Yu, J.-Y., Zhang, G.-X., & Chen, J.-W. (2016) · Evidence-Based Complementary and Alternative Medicine · doi:10.1155/2016/9238512 · Cited by 2
New Trends Approved in Management of Dyslipidaemia
Aboshahba, A. (2019) · Journal of Cardiology & Cardiovascular Therapy · doi:10.19080/jocct.2019.14.555894 · Cited by 1 · see citing works
HDL therapies — past, present and future
Barbaras, R. (2015) · JOURNAL OF MEDICINES DEVELOPMENT SCIENCES · doi:10.18063/jmds.2015.02.005
“There is a still a significant unmet medical need for addressing the remaining two-thirds of CVD risk([11]).”
BackgroundDubland, J. A. (2018) · doi:10.14288/1.0368978
“3 Importance of SMCs in atherosclerotic foam cell formation Cholesterol deposition from atherogenic lipoproteins in the artery wall is the principal driver of atherosclerotic plaque formation and the associated inflammation in coronary heart disease, and its removal is the primary predictor of lesion regression and cl…”
Background
- Authors
- Hegele, R. A., Gidding, S. S., Ginsberg, H. N., McPherson, R., Raal, F. J., Rader, D. J., Robinson, J. G., & Welty, F. K.
- Affiliations
- Western University (CA)
- ORCID
- Venue
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Published
- 2015-11
- Volume
- 35
- Issue
- 11
- Pages
- 2269-2280
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- PMC
- PMC4758700
- OpenAlex
- W2118882750
- Cited by
- 63
- References
- 181
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 1 · 2022: 5 · 2021: 2 · 2020: 5 · 2019: 3 · 2018: 9 · 2017: 11 · 2016: 20 · 2015: 4
- FWCI
- 2.81
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5p50hl083813-05)
- Canadian Institutes of Health Research (79523_1, MOP13430)
- National Heart, Lung, and Blood Institute (R01HL117933, P50-HL083813, R01HL089945)
- National Institute of Dental and Craniofacial Research (R01DE018184)
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Keywords
- LDL cholesterol, cardiovascular risk reduction, cardiovascular disease prevention, bile acid sequestrants, nicotinic acid, fibrates, ezetimibe, PCSK9 inhibitors, lomitapide, mipomersen, homozygous familial hypercholesterolemia, statin therapy
- MeSH terms
- Anticholesteremic Agents, Cardiovascular Diseases, Humans, Hypercholesterolemia, Cholesterol, LDL, Risk Factors, Biomarkers, Down-Regulation, Treatment Outcome, Practice Guidelines as Topic
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
