Variability of low-density lipoprotein cholesterol response with different doses of atorvastatin, rosuvastatin, and simvastatin: results from VOYAGER

Karlson BW, Wiklund O, Palmer MK, et al.
Eur Heart J Cardiovasc Pharmacother 2016;published online ahead of print

Background

Recent ACC/AHA guidelines recommend the following [1]:

• all patients at high atherosclerotic cardiovascular disease (ASCVD) risk should be treated with high-intensity statins, defined as atorvastatin 40 and 80 mg and rosuvastatin 20 and 40 mg: expected LDL-C decrease 50% or more
• all patients at moderate ASCVD risk, those aged >75 years, or those with high-intensity statin-intolerance should be treated with moderate-intensity statins, such as atorvastatin 10–20 mg, rosuvastatin 5–10 mg, and simvastatin 20–40 mg: expected LDL-C decrease 30%-50%

However, individual response to statin treatment varies, and available data on LDL-C reduction with statins often compare average LDL-C reductions, providing limited information about the frequency of poor response [2,3].
In this study, the variability in LDL-C reduction following treatment with different statins at different doses was evaluated, using the VOYAGER (an indiVidual patient data meta-analysis Of statin therapY in At risk Groups: Effects of Rosuvastatin, atorvastatin and simvastatin) meta-analysis database, in which 32,258 patients were treated with atorvastatin 10–80 mg, rosuvastatin 5–40 mg or simvastatin 10–80 mg [4,5].

Main results

Percentage LDL-C reduction (standard deviation [SD]): 

• for all statins and doses: SD: 12.8% - 17.9%
• lowest mean LDL-C reduction: 28.4% (13.8) with simvastatin 10 mg
• highest mean LDL-C reduction: 55.5% (14.8) with rosuvastatin 40 mg
• with atorvastatin 10–80 mg: mean reduction: 35.7% (16.0) - 49.2% (17.3)
• with rosuvastatin 5–40 mg: mean reduction: 41.4% (12.8) - 55.5% (14.8)
• with simvastatin 10–80 mg: mean reduction: 28.4% (13.8) - 45.7% (13.1)

Non-response with atorvastatin 10 mg:

• 10.2% of patients failed to achieve a 15% reduction in LDL-C
• 27.2% failed to achieve a 30% reduction
• 85.9% failed to achieve a 50% reduction

Non-response with atorvastatin 20 mg:

• 4.3% of patients failed to achieve a 15% reduction in LDL-C
• 12.8% failed to achieve a 30% reduction
• 67.7% failed to achieve a 50% reduction

Non-response with atorvastatin 40 mg:

• 2.8% of patients failed to achieve a 15% reduction in LDL-C
• 7.6% failed to achieve a 30% reduction
• 52.6% failed to achieve a 50% reduction

Non-response with atorvastatin 80 mg:

• 4.7% of patients failed to achieve a 15% reduction in LDL-C
• 11.3% failed to achieve a 30% reduction
• 42.5% failed to achieve a 50% reduction 

When rosuvastatin was given, the proportions failing to achieve a reduction in LDL-C of 15%, 30% and 50% were, respectively 4.9%, 14.7% and 76.5%, at the 5 mg dose, 7.8%, 17.5% and 59.6% at the 10 mg dose, 4.8%, 9.4% and 42.7% at the 20 mg dose, and 2.7%, 5.3% and 26.2% at the 40 mg dose.

When simvastatin was given, the proportions failing to achieve a reduction in LDL-C of 15%, 30% and 50% were, respectively, 12.7%, 53.3% and 98.8%, at the 10 mg dose, 10.7%, 32.8% and 90.2% at the 20 mg dose, 4.4%, 17.7% and 78.6% at the 40 mg dose and 4.2%, 9.0% and 56.9% at the 80 mg dose.

The percentage of patients experiencing a suboptimal response (<30% reduction in LDL-C) ranged from 2.8% to 53.3%.

Conclusion

There is considerable individual variation in the LDL-C reduction at all doses of simvastatin, atorvastatin and rosuvastatin. This individual variability is important to consider in daily clinical practice, especially when interpreting the ACC/AHA guideline recommendations, in order to amend treatment as appropriate.

Find this article online at http://ehjcvp.oxfordjournals.org/content/early/2016/03/29/ehjcvp.pvw006.abstract?papetoc

References

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2. Weng TC, Yang YH, Lin SJ, et al. A systematic review and meta-analysis on the therapeutic equivalence of statins. J Clin Pharm Ther 2010;35:139-151
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