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- Palmer, M. K., et al.
(author)
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Comparing a novel equation for calculating low-density lipoprotein cholesterol with the Friedewald equation: A VOYAGER analysis
- 2019
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In: Clinical Biochemistry. - : Elsevier BV. - 0009-9120 .- 1873-2933. ; 64, s. 24-29
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Journal article (peer-reviewed)abstract
- Treating elevated low-density lipoprotein cholesterol (LDL-C) to risk-stratified target levels is recommended in several guidelines. Thus, accurate estimation of LDL-C is required. LDL-C is typically calculated using the Friedewald equation: (total cholesterol) - (non-high-density lipoprotein cholesterol [non-HDL-C]) - (triglycerides [TGs]/5). As the equation uses a fixed value equal to 5 as a divisor for TGs, it does not account for inter-individual variability, often resulting in underestimation of risk and potentially undertreatment. It is specifically inapplicable in patients with fasting triglycerides >= 400 mg/dL. A novel method of LDL-C calculation was derived and validated by Martin et al.: (non-HDL-C) - (triglycerides/adjustable factor). This equation uses an adjustable factor, the median TG:very-low-density lipoprotein cholesterol ratio in strata defined by levels of TG and non-HDLC, as divisor for TGs, and the adjustable factor ranging from 3 to 12 has been shown to provide more accurate estimates of LDL-C compared with the Friedewald equation using a direct assay as the gold standard. We used 70,209 baseline and on-treatment lipid values from the VOYAGER meta-analysis database to determine the difference in calculated LDL-C values using the Friedewald and novel equations. In patients with TGs < 400 mg/dL, LDL-C values calculated using the novel equation were plotted against those calculated using the Friedewald equation. The novel equation generally resulted in LDL-C values greater than the Friedewald calculation, with differences increasing with decreasing LDL-C levels; 23% of individuals who reached a LDL-C target of 70 mg/dL with the Friedewald equation did not achieve this target when the novel equation was used to calculate LDL-C; these figures were 8% and 2% for < 100 mg/dL and < 130 mg/dL targets, respectively. In patients with triglycerides >= 400 mg/dL, in whom the Friedewald equation is not valid, lipid values calculated using the novel equation were compared with those obtained by beta-quantification. Values calculated with the novel equation did not appear to be closely related with those calculated by beta-quantification in these patients. In conclusion, the novel equation provides a higher estimation of exact LDL-C values than the Friedewald equation, particularly in patients with low LDL-C levels, which may result in undertreatment of some patients whose LDL-C was calculated using the Friedewald method. However, neither may be suitable for patients with TG >= 400 mg/dL.
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- Karlson, Björn W., 1953, et al.
(author)
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A VOYAGER Meta-Analysis of the Impact of Statin Therapy on Low-Density Lipoprotein Cholesterol and Triglyceride Levels in Patients With Hypertriglyceridemia
- 2016
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In: American Journal of Cardiology. - : Elsevier BV. - 0002-9149 .- 1879-1913. ; 117:9, s. 1444-1448
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Journal article (peer-reviewed)abstract
- Elevated triglyceride (TG) levels are associated with increased cardiovascular disease risk. In patients with mild-to-moderate hypertriglyceridemia, defined by the European Atherosclerosis Society Consensus Panel as a TG level of 177 to 885 mg/dl (2.0 to 10.0 mmol/L), low-density lipoprotein cholesterol (LDL-C) reduction remains the primary treatment goal. Using data from the indiVidual patient meta-analysis Of statin therapY in At risk Groups: Effects of Rosuvastatin, atorvastatin and simvastatin (VOYAGER) meta-analysis, we analyzed LDL-C and TG reductions in patients with baseline TG 2177 mg/dl (>= 2.0 mmol/L). Least squares mean percentage change from baseline in LDL-C and TG was compared using 15,800 patient exposures to rosuvastatin 5 to 40 mg, atorvastatin 10 to 80 mg, and simvastatin 10 to 80 mg in patients with baseline TG >= 177 mg/dl (>= 2.0 mmol/L). Comparisons were made using mixed-effects models with data only from studies directly comparing treatments by randomized design. Mean LDL-C reductions ranged from -26.9% to -55.5%. Rosuvastatin 10 to 40 mg resulted in significantly greater LDL-C reductions than equal or double doses of atorvastatin and simvastatin (p <0.05). Mean TG reductions ranged from -15.1% to -31.3%. Rosuvastatin 10 mg resulted in significantly greater TG reductions than atorvastatin 10 mg (p <0.05). Rosuvastatin 20 and 40 mg resulted in TG reductions similar to those with equal doses of atorvastatin. Rosuvastatin 10 to 40 mg resulted in significantly greater TG reductions than equal or double doses of simvastatin (p <0.05). In conclusion, in patients with hypertriglyceridemia, LDL-C reduction was substantial and dependent on the choice and dose of statin. TG reduction was numerically less than for LDL-C, and additional TG-lowering therapy may be considered to further reduce residual cardiovascular risk. (C) 2016 Elsevier Inc. All rights reserved.
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- Karlson, Björn W., 1953, et al.
(author)
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Effects of age, gender and statin dose on lipid levels: Results from the VOYAGER meta-analysis database
- 2017
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In: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 265, s. 54-59
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Journal article (peer-reviewed)abstract
- Background and aims The effectiveness of statins in the treatment of dyslipidaemia and reduction of cardiovascular risk is well established. However, the association of statin-mediated lipid effects with age and gender is unclear. This study aimed to determine whether age and gender are associated with statin-mediated changes in low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and non-HDL-C. Methods Individual patient data (n = 32,258) were obtained from VOYAGER. Least-squares mean percentage change from baseline in LDL-C, non-HDL-C and HDL-C with atorvastatin 10–80 mg, rosuvastatin 5–40 mg or simvastatin 10–80 mg was estimated in women aged <70 years, women aged ≥70 years, men aged <70 years and men aged ≥70 years. Results All statins and doses gave significant dose-dependent reductions in LDL-C and non-HDL-C, and increases in HDL-C, in all four patient groups. A 2.1% greater reduction in LDL-C was observed in women, compared with men (p < 0.0001). Patients aged ≥70 years experienced a 2.7% greater reduction in LDL-C compared with younger patients (p < 0.0001). Similar results were also observed for statin-mediated changes in non-HDL-C. Men experienced a significantly greater increase in HDL-C than women, and patients aged ≥70 years achieved a significantly greater increase than younger patients (both p = 0.001). Conclusions While statins improve the lipid profile in all gender and age groups analysed, the improvements are greater in women than in men and in those aged ≥70 years compared with those aged <70 years. © 2017 Elsevier B.V.
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- Karlson, Björn W., 1953, et al.
(author)
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Modeling Statin-Induced Reductions of Cardiovascular Events in Primary Prevention: A VOYAGER Meta-Analysis
- 2018
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In: Cardiology. - : S. Karger AG. - 0008-6312 .- 1421-9751. ; 140:1, s. 30-34
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Journal article (peer-reviewed)abstract
- Objective: We used individual patient data from the VOYAGER database to estimate cardiovascular (CV) risk reduction with commonly used high-intensity statins. Methods: In patients with known atherosclerotic CV disease (ASCVD) treated with high-intensity statin therapy (n = 6,735), the predicted risk reduction was estimated using the Cholesterol Treatment Trialists' Collaboration meta-analysis, which determined risk reduction per 38.7 mg/dL statin-mediated reduction in low-density lipoprotein cholesterol. Results: The greatest reductions in risk were seen in major vascular events (estimated rate ratios ranged from 0.55 with rosuvastatin [RSV] 40 mg to 0.60 with atorvastatin [ATV] 40 mg) and coronary heart disease death (estimated rate ratios ranged from 0.58 with RSV 40 mg to 0.64 with ATV 40 mg). Conclusions: Our results show that, in individuals without clinical ASCVD, statin therapy has the potential to reduce the frequency of CV events. (C) 2018 S. Karger AG, Basel
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- Karlson, Björn W., 1953, et al.
(author)
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To what extent do high-intensity statins reduce low-density lipoprotein cholesterol in each of the four statin benefit groups identified by the 2013 American College of Cardiology/American Heart Association guidelines? A VOYAGER meta-analysis
- 2015
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In: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 241:2, s. 450-454
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Journal article (peer-reviewed)abstract
- Background: The 2013 American College of Cardiology and American Heart Association (ACC/AHA) guidelines identify four patient groups who benefit from moderate-or high-intensity statin treatment; those with: 1) atherosclerotic cardiovascular disease (ASCVD); 2) low-density lipoprotein cholesterol (LDL-C) >= 190 mg/dl; 3) diabetes; or 4) a 10-year ASCVD risk >= 7.5%. High-intensity statins, anticipated to reduce LDL-C by >= 50%, were identified as rosuvastatin 20-40 mg and atorvastatin 40-80 mg. Methods and Results: Individual patient data (32,258) from the VOYAGER database of 37 studies were used to calculate least-squares mean (LSM) percentage change in LDL-C during 8496 patient exposures to rosuvastatin 20-40 mg, and atorvastatin 40-80 mg in the four patient benefit groups. LSM percentage reductions in LDL-C with rosuvastatin 20 and 40 mg were greater than with atorvastatin 40 mg, overall and in each statin benefit group, and with rosuvastatin 40 mg were greater than with atorvastatin 80 mg overall and in three of the four benefit groups (all p < 0.05). For example, in the ASCVD group, 40%, 59%, 57% and 71% of patients treated with atorvastatin 40 mg, atorvastatin 80 mg, rosuvastatin 20 mg and rosuvastatin 40 mg, respectively, had a >= 50% reduction in LDL-C. Conclusions: The choice and dose of statin have an impact both on the percentage LDL-C reduction and achievement of >= 50% reduction in LDL-C, overall and within each of the four statin benefit groups outlined by the 2013 ACC/AHA guidelines. This may be of importance for clinicians in their choice of treatment for individual patients. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
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