A VOYAGER Meta-Analysis of the Impact of Statin Therapy on Low-Density Lipoprotein Cholesterol and Triglyceride Levels in Patients with Hypertriglyceridaemia

Karlson BW, Palmer MK, Nicholls SJ, et al.
The American Journal of Cardiology 2016;published online ahead of print

Background

Elevated plasma triglyceride levels have been shown to be independent predictors of cardiovascular risk, even in patients who have achieved their LDL-C treatment goals with statin therapy [1,2]. LDL-C reduction with statins remains the primary treatment goal for these patients, although previous analyses have found no clear relationship between statin-mediated reductions in LDL-C and reductions in TG [3].
For severe hypertriglyceridemia, defined as a TG level of >885 mg/dL [>10.0 mmol/L]), which is also a risk factor for pancreatitis, clear management guidance exists, using agents that target mainly elevated TG levels [3,4]. However, it is not very clear how to treat mild to moderate hypertriglyceridemia (defined as a TG level of 177–885 mg/dL [2.0–10.0 mmol/L]) for which, according to guidelines, a TG level of <150 mg/dL (<1.7 mmol/L) is desirable [5,6].
In this analysis, LDL-C and TG reductions were evaluated in 15,800 patients with TG ≥177 mg/dL (≥2.0 mmol/L) who were receiving treatment with different statins and doses in randomised direct comparison studies. The source of patient data is the indiVidual patient meta-analysis Of statin therapY in At risk Groups: Effects of Rosuvastatin, atorvastatin and simvastatin (VOYAGER) database [7].

Main results

• Reductions in LDL-C: There was a clear relationship between increasing statin dose and reduction in LDL-C. Across all statins and doses, the mean percent reduction (±SEM) in LDL-C ranged from –26.9% (2.0%) to –55.5% (0.8%)

• the LDL-C reductions with rosuvastatin 10, 20, and 40 mg were significantly greater than those with equal or double mg doses of atorvastatin and simvastatin (P<0.05 for all comparisons)
• the LDL-C reductions in with atorvastatin 80 mg were significantly greater than those with rosuvastatin 5 and 10 mg (P<0.05)
• the LDL-C reductions with rosuvastatin 5, 10 and 20 mg were greater than those with simvastatin 20, 40 and 80 mg, respectively (P<0.05)

• Reductions in TG: There was a weaker relationship between increasing statin dose and reductions in levels of TG. Across all statins and all doses mean TG reductions (± SEM) ranged from –15.1% (3.2%) to –31.3% (1.4%)

• rosuvastatin 10 mg resulted in a significantly greater reduction in TG compared with atorvastatin 10 mg (P<0.001)
• TG reductions with rosuvastatin 20 and 40 mg were similar to those observed with equal doses of atorvastatin
• atorvastatin 80 mg resulted in significantly greater reductions in TG than rosuvastatin 10 mg (P<0.05)
• rosuvastatin 10–40 mg resulted in significantly greater TG reductions compared with equal or double doses of simvastatin (P<0.05)

• The percentages of patients achieving an on-treatment TG level of <150 mg/dL (<1.7 mmol/L) were as follows:

• for atorvastatin 10, 20, 40, and 80 mg: 30.3%, 38.5%, 44.8%, and 54.8% respectively
• for rosuvastatin 5, 10, 20, and 40 mg: 28.3%, 35.0%, 38.3%, and 48.9% respectively
• for simvastatin 10, 20, 40, and 80 mg: 22.6%, 25.4%, 25.9%, and 35.7% respectively

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Conclusion

In patients with hypertriglyceridemia, statin monotherapy resulted in TG reductions, however, a substantial number of patients did not achieve the recommended TG level of <150 mg/dL (<1.7 mmol/L). Additional TG-lowering therapy should be considered to further reduce the residual cardiovascular risk in patients with persisting high TG levels, even if LDL-C goals are met with statin therapy.

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References

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