Physicians' Academy for Cardiovascular Education

Considerable individual variability in response to statin treatment

Karlson BW, et al. Eur Heart J Cardiovasc Pharmacother 2016


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

1. Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014;63:2889-2934
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
3. Boekholdt SM, Hovingh GK, Mora S, et al. Very low levels of atherogenic lipoproteins and the risk for cardiovascular events: a meta-analysis of statin trials. J Am Coll Cardiol 2014;64:485-494
4. Nicholls SJ, Brandrup-Wognsen G, Palmer M, et al. Meta-analysis of comparative efficacy of increasing dose of Atorvastatin versus Rosuvastatin versus Simvastatin on lowering levels of atherogenic lipids (from VOYAGER). Am J Cardiol 2010;105:69-76.
5. Karlson BW, Palmer MK, Nicholls SJ, et al. 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. Atherosclerosis 2015;241:450-454