A 52-Week Placebo-Controlled Trial of Evolocumab in Hyperlipidemia
Open accessAbstract
BACKGROUND: Evolocumab, a monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9), significantly reduced low-density lipoprotein (LDL) cholesterol levels in phase 2 studies. We conducted a phase 3 trial to evaluate the safety and efficacy of 52 weeks of treatment with evolocumab. METHODS: We stratified patients with hyperlipidemia according to the risk categories outlined by the Adult Treatment Panel III of the National Cholesterol Education Program. On the basis of this classification, patients were started on background lipid-lowering therapy with diet alone or diet plus atorvastatin at a dose of 10 mg daily, atorvastatin at a dose of 80 mg daily, or atorvastatin at a dose of 80 mg daily plus ezetimibe at a dose of 10 mg daily, for a run-in period of 4 to 12 weeks. Patients with an LDL cholesterol level of 75 mg per deciliter (1.9 mmol per liter) or higher were then randomly assigned in a 2:1 ratio to receive either evolocumab (420 mg) or placebo every 4 weeks. The primary end point was the percent change from baseline in LDL cholesterol, as measured by means of ultracentrifugation, at week 52. RESULTS: Among the 901 patients included in the primary analysis, the overall least-squares mean (±SE) reduction in LDL cholesterol from baseline in the evolocumab group, taking into account the change in the placebo group, was 57.0±2.1% (P<0.001). The mean reduction was 55.7±4.2% among patients who underwent background therapy with diet alone, 61.6±2.6% among those who received 10 mg of atorvastatin, 56.8±5.3% among those who received 80 mg of atorvastatin, and 48.5±5.2% among those who received a combination of 80 mg of atorvastatin and 10 mg of ezetimibe (P<0.001 for all comparisons). Evolocumab treatment also significantly reduced levels of apolipoprotein B, non-high-density lipoprotein cholesterol, lipoprotein(a), and triglycerides. The most common adverse events were nasopharyngitis, upper respiratory tract infection, influenza, and back pain. CONCLUSIONS: At 52 weeks, evolocumab added to diet alone, to low-dose atorvastatin, or to high-dose atorvastatin with or without ezetimibe significantly reduced LDL cholesterol levels in patients with a range of cardiovascular risks. (Funded by Amgen; DESCARTES ClinicalTrials.gov number, NCT01516879.).
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 current trial and the FOURIER trial showed similar improvements in composite cardiovascular outcomes with PCSK9 inhibition among patients with a baseline LDL cholesterol level of 70 mg/dL or more and an average baseline LDL cholesterol level of approximately 90 mg/dL.
“The current trial and the FOURIER trial showed similar improvements in composite cardiovascular outcomes with PCSK9 inhibition among patients who had a baseline LDL cholesterol level of 70 mg or more per deciliter and whose average baseline LDL cholesterol level was approximately 90 mg per deciliter. 10”
From Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome (2018) · cites this paper as [10]
Split into 2 atoms — 0 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredTreatment with PCSK9 inhibitors reduces LDL-C by approximately -60%.
“Treatment with PCSK9 inhibitors reduces LDL-C by approximately − 60% [75–79].”
From Established and Emerging Lipid-Lowering Drugs for Primary and Secondary Cardiovascular Prevention (2023) · cites this paper as [79]
Monoclonal antibodies to PCSK9 produce substantial reductions in LDL cholesterol when administered alone or with a statin.
“These findings have led to the development of monoclonal antibodies to PCSK9 that produce substantial reductions in LDL cholesterol when administered alone or with a statin. 8-12”
From Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome (2018) · cites this paper as [10]
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
Grundy, S. M., Bilheimer, D. W., Chait, A., Clark, L. T., Denke, M. A., Havel, R. J., Hazzard, W. R., Hulley, S. B., Hunninghake, D. B., Kreisberg, R. A., et al. (1993) · JAMA · doi:10.1001/jama.269.23.3015 · Cited by 27,944 · see citing works
Detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III)
Grundy, S. M., Becker, D. M., Clark, L. T., Cooper, R., Denke, M. A., Howard, J. L., Hunninghake, D. B., Illingworth, D. R., Luepker, R. V., McBride, P. E., et al. (2002) · Civil War Book Review · Cited by 12,198 · see citing works
Stein, E. A., Gipe, D., Bergeron, J., Gaudet, D., Weiss, R., Dufour, R., Wu, R., & Pordy, R. C. (2012) · The Lancet · doi:10.1016/s0140-6736(12)60771-5 · Cited by 575 · see citing works
Self-citationMcKenney, J. M., Koren, M. J., Kereiakes, D. J., Hanotin, C., Ferrand, A.-C., & Stein, E. A. (2012) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2012.03.007 · Cited by 507 · see citing works
Self-citationRaal, F. J., Scott, R. C., Somaratne, R. M., Bridges, I. M., Li, G., Wasserman, S. M., & Stein, E. A. (2012) · Circulation · doi:10.1161/circulationaha.112.144055 · Cited by 502 · see citing works
Self-citationAtorvastatin with or without an Antibody to PCSK9 in Primary Hypercholesterolemia
Roth, E. M., McKenney, J. M., Hanotin, C., Asset, G., & Stein, E. A. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1201832 · Cited by 459 · see citing works
Self-citationLambert (2012) · doi:10.1194/jlr.r026658 · Cited by 448 · see citing works
Sullivan, D., Olsson, A. G., Scott, R., Kim, J. B., Xue, A., Gebski, V., Wasserman, S. M., & Stein, E. A. (2012) · JAMA · doi:10.1001/jama.2012.25790 · Cited by 447 · see citing works
Self-citationGiugliano, R. P., Desai, N. R., Kohli, P., Rogers, W. J., Somaratne, R. M., Huang, F., Liu, T., Mohanavelu, S., Hoffman, E. B., McDonald, S. T., et al. (2012) · The Lancet · doi:10.1016/s0140-6736(12)61770-x · Cited by 425 · see citing works
Self-citationMyers, G. L., Cooper, G. R., Winn, C., & Smith, S. J. (1989) · Clinics in Laboratory Medicine · doi:10.1016/s0272-2712(18)30645-0 · Cited by 404 · see citing works
Koren, M. J., Scott, R. C., Kim, J. B., Knüsel, B., Liu, T., Lei, L., Bolognese, M. A., & Wasserman, S. M. (2012) · The Lancet · doi:10.1016/s0140-6736(12)61771-1 · Cited by 364 · see citing works
Self-citationEffects of AMG 145 on Low-Density Lipoprotein Cholesterol Levels
Dias, C. S., Shaywitz, A. J., Wasserman, S. M., Smith, B. P., Gao, B., Stolman, D., Crispino, C., Smirnakis, K. V., Emery, M. G., Colbert, A., et al. (2012) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2012.08.986 · Cited by 230 · see citing works
Self-citationKoren, M. J., Giugliano, R. P., Raal, F. J., SULLIVAN, D. R., Bolognese, M. A., Langslet, G., Civeira, F., Somaratne, R. M., Nelson, P., Liu, T., et al. (2013) · Circulation · doi:10.1161/circulationaha.113.007012 · Cited by 216 · see citing works
Self-citationPotential of Proprotein Convertase Subtilisin/Kexin Type 9 Based Therapeutics
Stein, E. A., & Swergold, G. D. (2013) · Current Atherosclerosis Reports · doi:10.1007/s11883-013-0310-3 · Cited by 84 · see citing works
Self-citation
Flagged first, then by citations
1 of the 16 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- [1]1. Lambert G, Sjouke B, Choque B, Kas- telein JJ, Hovingh GK. The PCSK9 decade. J Lipid Res 2012;53:2515-24.
Cited by
Sorted by citations
Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease
Sabatine, M. S., Giugliano, R. P., Keech, A. C., Honarpour, N., Wiviott, S. D., Murphy, S. A., Kuder, J. F., Wang, H., Liu, T., Wasserman, S. M., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1615664 · Cited by 6,138 · see citing works
Self-citationAlirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome
Schwartz, G. G., Steg, P. G., Szarek, M., Bhatt, D. L., Bittner, V. A., Diaz, R., Edelberg, J. M., Goodman, S. G., Hanotin, C., Harrington, R. A., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1801174 · Cited by 3,634 · see citing works
Efficacy 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-citationMechanisms and regulation of cholesterol homeostasis
Luo, J., Yang, H., & Song, B.-L. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0190-7 · Cited by 1,980 · 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-citationPleiotropic Effects of Statins on the Cardiovascular System
Oesterle, A., Laufs, U., & Liao, J. K. (2017) · Circulation Research · doi:10.1161/circresaha.116.308537 · Cited by 1,247 · see citing works
Clinical Update: Cardiovascular Disease in Diabetes Mellitus
Wang, C. C. L., Hess, C. N., Hiatt, W. R., & Goldfine, A. B. (2016) · Circulation · doi:10.1161/circulationaha.116.022194 · Cited by 1,183 · see citing works
Nicholls, S. J., Puri, R., Anderson, T., Ballantyne, C. M., Cho, L., Kastelein, J. J. P., Koenig, W., Somaratne, R., Kassahun, H., Yang, J., et al. (2016) · JAMA · doi:10.1001/jama.2016.16951 · Cited by 1,178 · see citing works
Self-citationGarber, A. J., Abrahamson, M. J., Barzilay, J. I., Blonde, L., Bloomgarden, Z. T., Bush, M. A., Dagogo-Jack, S. E., DeFronzo, R. A., EINHORN, D. F., Fonseca, V. A., et al. (2016) · Endocrine Practice · doi:10.4158/ep151126.cs · Cited by 874 · 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-citationVariation in<i>PCSK9</i>and<i>HMGCR</i>and Risk of Cardiovascular Disease and Diabetes
Ference, B. A., Robinson, J. G., Brook, R. D., Catapano, A. L., Chapman, M. J., Neff, D. R., Voros, S., Giugliano, R. P., Davey Smith, G., Fazio, S., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1604304 · Cited by 743 · see citing works
Raal, 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 · see citing works
Self-citationTargeting Early Atherosclerosis: A Focus on Oxidative Stress and Inflammation
Marchio, P., Guerra‐Ojeda, S., Vila, J. M., Aldasoro, M., Víctor, V. M., & Mauricio, M. D. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/8563845 · Cited by 628 · see citing works
Garber, A. J., Handelsman, Y., Grunberger, G., Einhorn, D., Abrahamson, M. J., Barzilay, J. I., Blonde, L., Bush, M. A., DeFronzo, R. A., Garber, J. R., et al. (2020) · Endocrine Practice · doi:10.4158/cs-2019-0472 · Cited by 598 · see citing works
Kopin, L., & Lowenstein, C. J. (2017) · Annals of Internal Medicine · doi:10.7326/aitc201712050 · Cited by 589 · see citing works
Lloyd-Jones, D. M., Morris, P. B., Ballantyne, C. M., Birtcher, K. K., Covington, A. M., DePalma, S. M., Minissian, M. B., Orringer, C. E., Smith, S. C., Waring, A. A., et al. (2022) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2022.07.006 · Cited by 569 · see citing works
Self-citationBorén, J., & Williams, K. J. (2016) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000330 · Cited by 524 · see citing works
Li-ya, W., & Parhofer, K. G. (2014) · Metabolism · doi:10.1016/j.metabol.2014.08.010 · Cited by 523 · see citing works
Garber, A. J., Abrahamson, M. J., Barzilay, J. I., Blonde, L., Bloomgarden, Z. T., Bush, M. A., Dagogo-Jack, S. E., DeFronzo, R. A., EINHORN, D. F., Fonseca, V. A., et al. (2018) · Endocrine Practice · doi:10.4158/cs-2017-0153 · Cited by 499 · see citing works
Inhibition of PCSK9 potentiates immune checkpoint therapy for cancer
Liu, X., Bao, X., Hu, M., Chang, H., Jiao, M., Cheng, J., Xie, L., Huang, Q., Li, F., & Li, C.-Y. (2020) · Nature · doi:10.1038/s41586-020-2911-7 · Cited by 490 · see citing works
Garber, A. J., Abrahamson, M. J., Barzilay, J. I., Blonde, L., Bloomgarden, Z. T., Bush, M. A., Dagogo-Jack, S., DeFronzo, R. A., Einhorn, D., Fonseca, V. A., et al. (2017) · Endocrine Practice · doi:10.4158/ep161682.cs · Cited by 435 · 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 · see citing works
Cannon, C. P., Cariou, B., Blom, D. J., McKenney, J. M., Lorenzato, C., Pordy, R. C., Chaudhari, U., & Colhoun, H. M. (2015) · European Heart Journal · doi:10.1093/eurheartj/ehv028 · Cited by 401 · see citing works
Self-citationLloyd‐Jones, D. M., Morris, P. B., Ballantyne, C. M., Birtcher, K. K., Daly, D. D., DePalma, S. M., Minissian, M., Orringer, C. E., & Smith, S. C. (2017) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2017.07.745 · Cited by 383 · see citing works
Self-citationKazi, D. S., Moran, A. E., Coxson, P. G., Penko, J., Ollendorf, D. A., Pearson, S. D., Tice, J. A., Guzman, D., & Bibbins-Domingo, K. (2016) · JAMA · doi:10.1001/jama.2016.11004 · Cited by 382 · see citing works
PCSK9 and LDLR degradation: regulatory mechanisms in circulation and in cells
Lagace, T. A. (2014) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000114 · Cited by 372 · see citing works
Kereiakes, D. J., Robinson, J. G., Cannon, C. P., Lorenzato, C., Pordy, R., Chaudhari, U., & Colhoun, H. M. (2015) · American Heart Journal · doi:10.1016/j.ahj.2015.03.004 · Cited by 349 · see citing works
Ray, K. K., Troquay, R. P. T., Visseren, F. L. J., Leiter, L. A., Scott Wright, R., Vikarunnessa, S., Talloczy, Z., Zang, X., Maheux, P., Lesogor, A., et al. (2023) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(22)00353-9 · Cited by 328 · see citing works
PCSK9 inhibitors: A new era of lipid lowering therapy
Chaudhary, R., Garg, J., Shah, N., & Sumner, A. (2017) · World Journal of Cardiology · doi:10.4330/wjc.v9.i2.76 · Cited by 299 · see citing works
Garber, A. J., Abrahamson, M. J., Barzilay, J. I., Blonde, L., Bloomgarden, Z. T., Bush, M. A., Dagogo-Jack, S., DeFronzo, R. A., Einhorn, D., Fonseca, V. A., et al. (2019) · Endocrine Practice · doi:10.4158/cs-2018-0535 · Cited by 297 · see citing works
Lipid management in patients with chronic kidney disease
Ferro, C. J., Mark, P. B., Kanbay, M., Sarafidis, P. A., Heine, G. H., Rossignol, P., Massy, Z. A., Mallamaci, F., Valdivielso, J. M., Małyszko, J., et al. (2018) · Nature Reviews Nephrology · doi:10.1038/s41581-018-0072-9 · Cited by 275 · see citing works
LDL cholesterol: controversies and future therapeutic directions
Ridker, P. M. (2014) · The Lancet · doi:10.1016/s0140-6736(14)61009-6 · Cited by 274 · see citing works
The 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
Safety and efficacy of anti-PCSK9 antibodies: a meta-analysis of 25 randomized, controlled trials
Zhang, X.-L., Zhu, Q.-Q., Zhu, L., Chen, J.-Z., Chen, Q.-H., Li, G.-N., Xie, J., Kang, L.-N., & Xu, B. (2015) · BMC Medicine · doi:10.1186/s12916-015-0358-8 · Cited by 260 · see citing works
Cho, J. H., & Feldman, M. A. (2015) · Nature Medicine · doi:10.1038/nm.3897 · Cited by 259 · see citing works
Lipinski, M. J., Benedetto, U., Escarcega, R. O., Biondi-Zoccai, G., Lhermusier, T., Baker, N. C., Torguson, R., Brewer, H. B., & Waksman, R. (2016) · European Heart Journal · doi:10.1093/eurheartj/ehv563 · Cited by 256 · see citing works
Roth, E. M., Taskinen, M., Ginsberg, H. N., Kastelein, J. J. P., Colhoun, H. M., Robinson, J. G., Merlet, L., Pordy, R. C., & Baccara‐Dinet, M. T. (2014) · International Journal of Cardiology · doi:10.1016/j.ijcard.2014.06.049 · Cited by 247 · see citing works
Self-citationCholesterol crystal induced arterial inflammation and destabilization of atherosclerotic plaque
Janoudi, A., Shamoun, F. E., Kalavakunta, J. K., & Abela, G. S. (2015) · European Heart Journal · doi:10.1093/eurheartj/ehv653 · Cited by 242 · see citing works
Lipid lowering with PCSK9 inhibitors
Dadu, R. T., & Ballantyne, C. M. (2014) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2014.84 · Cited by 232 · see citing works
Self-citationPhase 2b Randomized Trial of the Oral PCSK9 Inhibitor MK-0616
Ballantyne, C. M., Banka, P., Méndez, G., Garcia, R., Rosenstock, J., Rodgers, A., Mendizabal, G., Mitchel, Y., & Catapano, A. L. (2023) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2023.02.018 · Cited by 231 · see citing works
Self-citationBays, H. E., Gaudet, D., Weiss, R., Ruiz, J. L., Watts, G. F., Gouni‐Berthold, I., Robinson, J. G., Zhao, J. M., Hanotin, C., & Donahue, S. (2015) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2015-1520 · Cited by 219 · see citing works
Karatasakis, A., Danek, B. A., Karacsonyi, J., Rangan, B. V., Roesle, M. K., Knickelbine, T., Miedema, M. D., Khalili, H., Ahmad, Z., Abdullah, S., et al. (2017) · Journal of the American Heart Association · doi:10.1161/jaha.117.006910 · Cited by 215 · see citing works
PCSK9 monoclonal antibodies for the primary and secondary prevention of cardiovascular disease
Schmidt, A. F., Pearce, L. S., Wilkins, J. T., Overington, J. P., Hingorani, A. D., & Casas, J. P. (2017) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd011748.pub2 · Cited by 202 · see citing works
Cardiovascular Drug Development
Fordyce, C. B., Roe, M. T., Ahmad, T., Libby, P., Borer, J. S., Hiatt, W. R., Bristow, M. R., Packer, M., Wasserman, S. M., Braunstein, N., et al. (2015) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2015.03.016 · Cited by 202 · see citing works
Self-citationAre PCSK9 Inhibitors the Next Breakthrough in the Cardiovascular Field?
Giugliano, R. P., & Sabatine, M. S. (2015) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2015.05.001 · Cited by 197 · see citing works
Proprotein Convertase Subtilisin/Kexin Type 9 Inhibition
Bergeron, N., Phan, B. A. P., Ding, Y., Fong, A., & Krauss, R. M. (2015) · Circulation · doi:10.1161/circulationaha.115.016080 · Cited by 186 · see citing works
Triglycerides and Triglyceride-Rich Lipoproteins in the Causal Pathway of Cardiovascular Disease
Budoff, M. J. (2016) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2016.04.004 · Cited by 186 · see citing works
Lipid Metabolism, Disorders and Therapeutic Drugs - Review
Vijayakumar, N., & Kim, S. (2021) · Biomolecules & Therapeutics · doi:10.4062/biomolther.2021.122 · Cited by 183 · see citing works
Sabatine, M. S., Giugliano, R. P., Keech, A., Honarpour, N., Wang, H., Liu, T., Wasserman, S. M., Scott, R., Sever, P. S., & Pedersen, T. R. (2016) · American Heart Journal · doi:10.1016/j.ahj.2015.11.015 · Cited by 176 · see citing works
Self-citationColhoun, H. M., Ginsberg, H. N., Robinson, J. G., Leiter, L. A., Müller-Wieland, D., Henry, R. R., Cariou, B., Baccara-Dinet, M. T., Pordy, R., Merlet, L., et al. (2016) · European Heart Journal · doi:10.1093/eurheartj/ehw292 · Cited by 172 · see citing works
Ballantyne, C. M., Neutel, J., Cropp, A., Duggan, W. T., Wang, E. Q., Plowchalk, D. R., Sweeney, K., Kaila, N., Vincent, J., & Bays, H. E. (2015) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2015.02.006 · Cited by 170 · see citing works
Self-citationArvanitis, M., & Lowenstein, C. J. (2023) · Annals of Internal Medicine · doi:10.7326/aitc202306200 · Cited by 168 · see citing works
Recent advances in pharmacotherapy for hypertriglyceridemia
Sahebkar, A., Chew, G. T., & Watts, G. F. (2014) · Progress in Lipid Research · doi:10.1016/j.plipres.2014.07.002 · Cited by 166 · see citing works
Creager, M. A., Matsushita, K., Arya, S., Beckman, J. A., Duval, S., Goodney, P. P., Gutierrez, J. A. T., Kaufman, J. A., Joynt Maddox, K. E., Pollak, A. W., et al. (2021) · Circulation · doi:10.1161/cir.0000000000000967 · Cited by 164 · see citing works
Targeting inflammation to reduce cardiovascular disease risk: A realistic clinical prospect?
Welsh, P., Grassia, G., Botha, S., Sattar, N., & Maffia, P. (2017) · British Journal of Pharmacology · doi:10.1111/bph.13818 · Cited by 164 · see citing works
Yuan, J., Cai, T., Zheng, X., Ren, Y., Qi, J., Lü, X., Chen, H., Lin, H., Chen, Z., Liu, M., et al. (2021) · Protein & Cell · doi:10.1007/s13238-021-00821-2 · Cited by 160 · see citing works
The genetics and screening of familial hypercholesterolaemia
Henderson, R., O’Kane, M., McGilligan, V., & Watterson, S. (2016) · Journal of Biomedical Science · doi:10.1186/s12929-016-0256-1 · Cited by 156 · see citing works
Fonarow, G. C., KEECH, A. C., Pedersen, T. R., Giugliano, R. P., Sever, P. S., Lindgren, P., van Hout, B., Villa, G., Qian, Y., Somaratne, R. M., et al. (2017) · JAMA Cardiology · doi:10.1001/jamacardio.2017.2762 · Cited by 153 · see citing works
Khan, S. U., Yedlapati, S. H., Lone, A. N., Hao, Q., Guyatt, G., Delvaux, N., Bekkering, G. E. (., Vandvik, P. O., Riaz, I. B., Li, S., et al. (2022) · BMJ · doi:10.1136/bmj-2021-069116 · Cited by 151 · see citing works
Boyd, J. H., Fjell, C. D., Russell, J. A., Sirounis, D., Cirstea, M. S., & Walley, K. R. (2016) · Journal of Innate Immunity · doi:10.1159/000442976 · Cited by 151 · see citing works
Effect of Alirocumab on Mortality After Acute Coronary Syndromes
Steg, P. G., Szarek, M. J., Bhatt, D. L., Bittner, V., Brégeault, M.-F., Dalby, A. J., Díaz, R., Edelberg, J. M., Goodman, S. G., Hanotin, C., et al. (2019) · Circulation · doi:10.1161/circulationaha.118.038840 · Cited by 149 · see citing works
Long-Term Efficacy and Safety of Evolocumab in Patients With Hypercholesterolemia
Koren, M. J., Sabatine, M. S., Giugliano, R. P., Langslet, G., Wiviott, S. D., Ruzza, A., Ma, Y., Hamer, A. W., Wasserman, S. M., & Raal, F. J. (2019) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2019.08.1024 · Cited by 148 · see citing works
Self-citationAdipokines at the crossroad between obesity and cardiovascular disease
Morel, S., Kwak, B. R., Rohner‐Jeanrenaud, F., Steffens, S., & Molica, F. (2014) · Thrombosis and Haemostasis · doi:10.1160/th14-06-0513 · Cited by 146 · see citing works
Effect of Evolocumab on Coronary Plaque Composition
Nicholls, S. J., Puri, R., Anderson, T. J., Ballantyne, C. M., Cho, L., Kastelein, J. J. P., Köenig, W., Somaratne, R. M., Kassahun, H., Yang, J., et al. (2018) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2018.06.078 · Cited by 145 · see citing works
Self-citationSattar, N. A., Preiss, D., Robinson, J. G., Djedjos, C. S., Elliott, M., Somaratne, R. M., Wasserman, S. M., & Raal, F. J. (2016) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(16)00003-6 · Cited by 143 · see citing works
Self-citationNorata, G. D., Tavori, H., Pirillo, A., Fazio, S., & Catapano, A. L. (2016) · Cardiovascular Research · doi:10.1093/cvr/cvw194 · Cited by 142 · see citing works
Molecular and cellular function of the proprotein convertase subtilisin/kexin type 9 (PCSK9)
Schulz, R., Schlüter, K.-D., & Laufs, U. (2015) · Basic Research in Cardiology · doi:10.1007/s00395-015-0463-z · Cited by 137 · see citing works
Clinical Pharmacokinetics and Pharmacodynamics of Evolocumab, a PCSK9 Inhibitor
Kasichayanula, S., Grover, A., Emery, M. G., Gibbs, M. A., Somaratne, R., Wasserman, S. M., & Gibbs, J. P. (2018) · Clinical Pharmacokinetics · doi:10.1007/s40262-017-0620-7 · Cited by 135 · see citing works
Self-citationDyslipidemia in Patients with Chronic Kidney Disease: An Updated Overview
Suh, S. H., & Kim, S. W. (2023) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2023.0067 · Cited by 132 · see citing works
Lipid lowering therapy and circulating PCSK9 concentration
Nozue, T. (2017) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.rv17012 · Cited by 127 · see citing works
The evolution of domain arrangements in proteins and interaction networks
Bornberg‐Bauer, E., Beaussart, F., Kummerfeld, S., Teichmann, S. A., & Weiner, J. M. (2005) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-004-4416-1 · Cited by 124 · see citing works
PCSK9 monoclonal antibodies for the primary and secondary prevention of cardiovascular disease
Schmidt, A. F., Carter, J.-P. L., Pearce, L. S., Wilkins, J. T., Overington, J. P., Hingorani, A. D., & Casas, J. (2020) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd011748.pub3 · Cited by 123 · see citing works
de Carvalho, L. S. F., Campos, A. M., & Sposito, A. C. (2018) · Diabetes Care · doi:10.2337/dc17-1464 · Cited by 121 · see citing works
A radioimmunoassay for bradykinin in plasma and synovial fluid.
Talamo, R. C., Haber, E., & Austen, K. F. (1969) · PubMed · Cited by 120 · see citing works
Sahebkar, A., Di Giosia, P., Stamerra, C. A., Grassi, D., Pedone, C., Ferretti, G., Bacchetti, T., Ferri, C., & Giorgini, P. (2016) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.12905 · Cited by 116 · see citing works
Kiyosue, A., Honarpour, N., Kurtz, C., Xue, A., Wasserman, S. M., & Hirayama, A. (2016) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2015.10.021 · Cited by 114 · see citing works
Self-citationTavori, H., Giunzioni, I., Predazzi, I. M., Plubell, D. L., Shivinsky, A., Miles, J., DeVay, R. M., Hong, L., Rashid, S., Linton, M. F., et al. (2016) · Cardiovascular Research · doi:10.1093/cvr/cvw053 · Cited by 114 · see citing works
PCSK9 (Proprotein convertase subtilisin/kexin type 9) inhibitors: past, present, and the future
Shimada, Y. J., & Cannon, C. P. (2015) · European Heart Journal · doi:10.1093/eurheartj/ehv174 · Cited by 111 · see citing works
Postprandial hyperglycemia and postprandial hypertriglyceridemia in type 2 diabetes
Hiyoshi, T., Fujiwara, M., & Zemin, Y. (2018) · Journal of Biomedical Research · doi:10.7555/jbr.31.20160164 · Cited by 110 · see citing works
Ezetimibe for the prevention of cardiovascular disease and all-cause mortality events
Zhan, S., Tang, M., Liu, F., Xia, P., Shu, M., & Wu, X. (2018) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd012502.pub2 · Cited by 109 · see citing works
Established and Emerging Lipid-Lowering Drugs for Primary and Secondary Cardiovascular Prevention
Michaeli, D. T., Michaeli, J. C., Albers, S., Boch, T., & Michaeli, T. (2023) · American Journal of Cardiovascular Drugs · doi:10.1007/s40256-023-00594-5 · Cited by 109 · see citing works
PCSK9 Inhibition: From Current Advances to Evolving Future
Liu, C., Chen, J., Chen, H., Zhang, T., He, D., Luo, Q., Chi, J., Hong, Z., Liao, Y., Zhang, S., et al. (2022) · Cells · doi:10.3390/cells11192972 · Cited by 106 · see citing works
A systematic review of PCSK9 inhibitors alirocumab and evolocumab
McDonagh, M., Peterson, K., Holzhammer, B., & Fazio, S. (2016) · Journal of Managed Care & Specialty Pharmacy · doi:10.18553/jmcp.2016.22.6.641 · Cited by 103 · see citing works
Abifadel, M., Elbitar, S., Khoury, P. E., Ghaleb, Y., Chemaly, M., Moussalli, M.-L., Rabès, J., Varret, M., & Boileau, C. (2014) · Current Atherosclerosis Reports · doi:10.1007/s11883-014-0439-8 · Cited by 102 · see citing works
A Comprehensive Review of PCSK9 Inhibitors
Coppinger, C., Movahed, M. R., Azemawah, V., Peyton, L., Gregory, J., & Hashemzadeh, M. (2022) · Journal of Cardiovascular Pharmacology and Therapeutics · doi:10.1177/10742484221100107 · Cited by 99 · see citing works
PCSK9 Inhibitors: Mechanism of Action, Efficacy, and Safety
Roth, E. M., & Davidson, M. H. (2018) · Reviews in Cardiovascular Medicine · doi:10.3909/ricm19s1s0002 · Cited by 98 · see citing works
Self-citationSahebkar, A., Simental‐Mendía, L. E., Guerrero‐Romero, F., Golledge, J., & Watts, G. F. (2015) · Diabetes Obesity and Metabolism · doi:10.1111/dom.12536 · Cited by 96 · see citing works
Lipids, blood pressure and kidney update 2014
Banach, M., Aronow, W. S., Șerban, M.-C., Sahabkar, A., Rysz, J., Voroneanu, L. E., & Covic, A. C. (2015) · Pharmacological Research · doi:10.1016/j.phrs.2015.03.009 · Cited by 92 · see citing works
Toth, P. P., Worthy, G., Gandra, S. R., Sattar, N. A., Bray, S. L., Cheng, L., Bridges, I. M., Worth, G. M., Dent, R. E., Forbes, C. A., et al. (2017) · Journal of the American Heart Association · doi:10.1161/jaha.116.005367 · Cited by 92 · see citing works
Self-citationManagement of residual risk after statin therapy
Reith, C. A., & Armitage, J. (2015) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2015.12.018 · Cited by 91 · see citing works
PCSK9 Inhibition: Insights From Clinical Trials and Future Prospects
Katzmann, J. L., Gouni‐Berthold, I., & Laufs, U. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.595819 · Cited by 89 · see citing works
PCSK9 inhibitors for treating hypercholesterolemia
Pasta, A., Cremonini, A. L., Pisciotta, L., Buscaglia, A., Porto, I., Barra, F., Ferrero, S., Brunelli, C., & Rosa, G. M. (2020) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2019.1702970 · Cited by 87 · see citing works
Tavori, H., Rashid, S., & Fazio, S. (2015) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2014.12.017 · Cited by 86 · see citing works
PCSK9 and Atherosclerosis - Lipids and Beyond
Shapiro, M. D., & Fazio, S. (2017) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.rv17003 · Cited by 85 · see citing works
Handelsman, Y., & Lepor, N. E. (2018) · Journal of the American Heart Association · doi:10.1161/jaha.118.008953 · Cited by 85 · see citing works
Effects of Evolocumab on Vitamin E and Steroid Hormone Levels
Blom, D. J., Djedjos, C. S., Monsalvo, M. L., Bridges, I. M., Wasserman, S. M., Scott, R. C., & Roth, E. M. (2015) · Circulation Research · doi:10.1161/circresaha.115.307071 · Cited by 84 · see citing works
Self-citationPCSK9 Inhibitors: Mechanisms of Action, Metabolic Effects, and Clinical Outcomes
Hess, C. N., Wang, C. C. L., & Hiatt, W. R. (2017) · Annual Review of Medicine · doi:10.1146/annurev-med-042716-091351 · Cited by 84 · see citing works
Lipoprotein(a): a genetic marker for cardiovascular disease and target for emerging therapies
Cesaro, A., Schiavo, A., Moscarella, E., Coletta, S., Conte, M., Gragnano, F., Fimiani, F., Monda, E., Caiazza, M., Limongelli, G., et al. (2020) · Journal of Cardiovascular Medicine · doi:10.2459/jcm.0000000000001077 · Cited by 84 · see citing works
The Treatment of Disorders of Lipid Metabolism
Parhofer, K. G. (2016) · Deutsches Ärzteblatt international · doi:10.3238/arztebl.2016.0261 · Cited by 84 · see citing works
Zhu, Y. M., Anderson, T. J., Sikdar, K. C., Fung, M., McQueen, M., Lonn, E., & Verma, S. (2015) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.115.306172 · Cited by 82 · see citing works
- Authors
- 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., Monsalvo, M. L., Tsirtsonis, K., Kim, J. B., Scott, R., Wasserman, S. M., & Stein, E. A.
- Affiliations
- University of Cape Town (ZA)
- National Institutes of Health (US)
- Midwest Institute for Clinical Research (US)
- Stellenbosch University (ZA)
- Sterling Research Group (US)
- Jacksonville Center for Clinical Research (US)
- Houston Methodist (US)
- Amgen (United States) (US)
- Amgen (United Kingdom) (GB)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2014-05-08
- Volume
- 370
- Issue
- 19
- Pages
- 1809-1819
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2155259933
- Semantic Scholar
- 8d480541d9ba40d0cf45fea465f3b42bfc2b2f19
- Cited by
- 720
- References
- 16
- Citations by year
- 2026: 25 · 2025: 35 · 2024: 44 · 2023: 44 · 2022: 26 · 2021: 33 · 2020: 46 · 2019: 49 · 2018: 62 · 2017: 92 · 2016: 110 · 2015: 103 · 2014: 48
- FWCI
- 116.60
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Open University of Cape Town (University of Cape Town) (submittedVersion)
- Funders
- Amgen
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- evolocumab, PCSK9 inhibition, hyperlipidemia, LDL cholesterol lowering, monoclonal antibodies, atorvastatin, ezetimibe, apolipoprotein B, lipoprotein(a), triglycerides, non-HDL cholesterol, treatment safety
- MeSH terms
- Atorvastatin, Ezetimibe, Proprotein Convertase 9, Adult, Aged, Antibodies, Monoclonal, Azetidines, Combined Modality Therapy, Double-Blind Method, Female, Heptanoic Acids, Humans, Hyperlipidemias, Cholesterol, LDL, Male, Middle Aged, Pyrroles, Serine Endopeptidases, Least-Squares Analysis, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Proprotein Convertases, Antibodies, Monoclonal, Humanized
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
