Preventive Cardiology
A VOYAGER Meta-Analysis of the Impact of Statin Therapy on Low-Density Lipoprotein Cholesterol and Triglyceride Levels in Patients With Hypertriglyceridemia

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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 ≥177 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.

Section snippets

Methods

Data for this analysis were obtained from the VOYAGER database. Detailed patient demographics and methods from the VOYAGER meta-analysis have been reported previously.10 In brief, VOYAGER comprises results from 32,258 patients in 37 randomized, fixed-dose trials directly comparing (by randomized design) the changes in lipid levels observed during treatment with rosuvastatin, atorvastatin, and simvastatin. The present analysis includes the results of 15,800 patients with baseline TG levels of

Results

Baseline patient demographic data are presented in Table 1. A clear relationship between increasing statin dose and reduction in LDL-C was observed (Figure 1). Across all statins and doses, the mean percent reduction (±SEM) in LDL-C ranged from −26.9% (2.0%) to −55.5% (0.8%; Figure 1). The differences in LSM percent change in LDL-C between rosuvastatin and equal or higher milligram doses of atorvastatin and simvastatin are shown in Figure 2. The reductions in LDL-C observed with rosuvastatin

Discussion

It is well known that residual cardiovascular risk often persists despite the use of high-intensity statin therapy to reduce LDL-C.11, 12, 13 A component of this residual risk may relate to the persistence of elevated TG or non–high-density lipoprotein cholesterol (non–HDL-C) levels. Elevated TG levels have been shown to be independently associated with an increased incidence of cardiovascular events, even in patients who have achieved LDL-C treatment goals with statin therapy,5, 14 and TG-rich

Disclosures

Dr. Karlson is an employee of AstraZeneca; Dr. Palmer has received fees for statistical analysis from AstraZeneca; Dr. Nicholls has received research support from AstraZeneca; Dr. Lundman has received speaker fees from AstraZeneca; and Dr. Barter has received research support and speaker fees from AstraZeneca.

References (27)

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This study was funded by AstraZeneca. Editorial support was provided by Alex Mellors, Prime Medica, Knutsford, Cheshire, UK, funded by AstraZeneca. Statistical analyses were funded by AstraZeneca and performed by Michael. K. Palmer, a former employee of AstraZeneca.

See page 1447 for disclosure information.

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