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Expert Review of Clinical Pharmacology Volume 11, 2018 - Issue 10
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Perspective

LDL-C does not cause cardiovascular disease: a comprehensive review of the current literature

Uffe RavnskovIndependent investigator, Lund, SwedenCorrespondence[email protected]
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Michel de LorgerilLaboratoire Coeur et Nutrition, TIMC-IMAG, School of Medicine, University of Grenoble-Alpes, Grenoble, FranceView further author information
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David M DiamondDepartment of Molecular Pharmacology and Physiology, Center for Preclinical and Clinical Research on PTSD, University of South Florida, Tampa, FL, USA;Department of Psychology, Center for Preclinical and Clinical Research on PTSD, University of South Florida, Tampa, FL, USAView further author information
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Rokuro HamaJapan Institute of Pharmacovigilance, Osaka, JapanView further author information
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Tomohito HamazakiDepartment of Internal Medicine, Toyama Jonan Onsen Daini Hospital, University of Toyama, Toyama, JapanView further author information
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Björn HammarskjöldStrömstad Academy, Strömstad, SwedenView further author information
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Niamh HynesWestern Vascular Institute, University Hospital Galway & Galway Clinic, National University of Ireland & Royal college of Surgeons of Ireland affiliated Hospital, Galway, IrelandView further author information
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Malcolm KendrickEast Cheshire Trust, Macclesfield District General Hospital, Macclesfield, UKView further author information
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Peter H LangsjoenPrivate Practice in Cardiology, Tyler, Texas, USAView further author information
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Luca MascitelliMedical Service, Comando Brigata Alpina “Julia”/Multinational Land Force, Udine, ItalyView further author information
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Kilmer S McCullyPathology and Laboratory Medicine Service, VA Boston Healthcare System West Roxbury, Harvard Medical School, Boston, MA, USAView further author information
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Harumi OkuyamaFaculty of Pharmaceutical Science, Nagoya City University, Mizuhoku, Nagoya, JapanORCID Iconhttps://orcid.org/0000-0003-3332-4565View further author information
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Paul J RoschNew York Medical College, The American Institute of Stress, New York, NY, USAView further author information
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Tore ScherstenWallenberg Laboratory for Cardiovascluar and Metabolic Research, Sahlgren’s Academy, University of Gothenburg, Gothenburg, Sweden;Department of Metabolism, Columbia University, New York, NY, USAView further author information
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Sherif SultanWestern Vascular Institute, University Hospital Galway & Galway Clinic, National University of Ireland & Royal college of Surgeons of Ireland affiliated Hospital, Galway, IrelandView further author information
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Ralf SundbergIndependent Researcher, Lidingö, SwedenView further author information
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Pages 959-970 | Received 11 Jan 2018, Accepted 31 Aug 2018, Published online: 11 Oct 2018

Figures & data

Table 1. Mortality in the statin trials included in the meta-analysis by Silverman et al. [Citation2] and in 11 statin trials they have ignored and where the authors have reported coronary and/or total mortality. The figures for LDL-C lowering are the approximate mean differences between the treatment group and the control group. Among the ignored trials only the EXCEL trials [Citation60,Citation61] were primary preventive.

Figure 1. The association between degree of LDL-C lowering and the absolute risk reduction of CHD mortality (%/year) in 21 statin trials, where CHD mortality was recorded and which were included in the study by Silverman et al. and in 8 ignored statin trials. ARR is associated with degree of LDL-C lowering in the included trials (y = 0.16x − 0.018) but inversely associated in the ignored trials (y = 0.08x + 0.062).

Squares: included trials; triangles: ignored trials.

Figure 1. The association between degree of LDL-C lowering and the absolute risk reduction of CHD mortality (%/year) in 21 statin trials, where CHD mortality was recorded and which were included in the study by Silverman et al. and in 8 ignored statin trials. ARR is associated with degree of LDL-C lowering in the included trials (y = 0.16x − 0.018) but inversely associated in the ignored trials (y = 0.08x + 0.062).Squares: included trials; triangles: ignored trials.

Figure 2. The association between degree of LDL-C lowering and the absolute risk reduction of total mortality (%/year) in 26 statin trials, where total mortality was recorded and which were included in the study by Silverman et al. and in 11 ignored trials. ARR is weakly associated with degree of LDL-C lowering in the included trials (y = 0.28x + 0.06) but inversely associated in the excluded trials (y = −0.49x − 0.81). Symbols: see .

Figure 2. The association between degree of LDL-C lowering and the absolute risk reduction of total mortality (%/year) in 26 statin trials, where total mortality was recorded and which were included in the study by Silverman et al. and in 11 ignored trials. ARR is weakly associated with degree of LDL-C lowering in the included trials (y = 0.28x + 0.06) but inversely associated in the excluded trials (y = −0.49x − 0.81). Symbols: see Figure 1.

Figure 3. The association between the absolute 5-year risk reduction (ARR) and the degree of LDL-C lowering in 12 trials included in Table 4A in the article by Ference et al. (r = 2.59) and from 21 trials they have ignored or excluded (r = −0.1).

White symbols: trials included in the analysis by Ference et al.; black symbols: excluded or ignored trials; squares: primary-preventive trials; round symbols: secondary-preventive trials; stippled line: regression line for the included trials; full line: regression line for all trials.

Figure 3. The association between the absolute 5-year risk reduction (ARR) and the degree of LDL-C lowering in 12 trials included in Table 4A in the article by Ference et al. (r = 2.59) and from 21 trials they have ignored or excluded (r = −0.1).White symbols: trials included in the analysis by Ference et al.; black symbols: excluded or ignored trials; squares: primary-preventive trials; round symbols: secondary-preventive trials; stippled line: regression line for the included trials; full line: regression line for all trials.

Figure 4. The association between the absolute risk reduction of CHD mortality in 21 statin trials included in the study by Silverman et al. and in 7 ignored trials and the year where the trial protocols were published. The vertical line indicates the year where the new trial regulations were introduced. Symbols: see .

Figure 4. The association between the absolute risk reduction of CHD mortality in 21 statin trials included in the study by Silverman et al. and in 7 ignored trials and the year where the trial protocols were published. The vertical line indicates the year where the new trial regulations were introduced. Symbols: see Figure 1.

Figure 5. The association between the absolute risk reduction of total mortality in 26 statin trials included in the study by Silverman et al. and in 11 ignored trials and the year where the trial protocols were published. The vertical line indicates the year where the new trial regulations were introduced. Symbols: see .

Figure 5. The association between the absolute risk reduction of total mortality in 26 statin trials included in the study by Silverman et al. and in 11 ignored trials and the year where the trial protocols were published. The vertical line indicates the year where the new trial regulations were introduced. Symbols: see Figure 1.
 

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