Physicians' Academy for Cardiovascular Education

Higher dose of statin increases chances of reaching LDL-C guidelines

Literature - Karlson BW, Nicholls SJ, Lundman P, et al - Atherosclerosis. 2013 Mar 4. doi:10.1016/j.atherosclerosis.2013.02.027.


Achievement of 2011 European low-density lipoprotein cholesterol (LDL-C) goals of either <70 mg/dl or ≥50% reduction in high-risk patients: Results from VOYAGER.


Karlson BW, Nicholls SJ, Lundman P, et al
Atherosclerosis. 2013 Mar 4. doi:10.1016/j.atherosclerosis.2013.02.027.


Background

It is well established that the risk of cardiovascular (CV) events decreases with lower LDL-C levels [1-3]. Based on these observations, guidelines recommending treatment strategies and goals have been established. The 2011 EAS/ESC joint guidelines [4] emphasise that LDL-C is still the most important target for treatment. Furthermore, the guidelines emphasise the importance of evaluating the total CV risk for every individual as part of a treatment decision.
The EAS/ESC joint guidelines recommend an LDL-C treatment target of <70 mg/dl (~1.8 mmol/l) or at least a 50% reduction from baseline in LDL-C for patients at very high CV risk.
This paper reports the analysis of the percentage of patients in the VOYAGER (an individual patient data meta-analsysis Of statin therapy in At risk Groups: Effects of rosuvastatin, atorvastatin and simvastatin) database [5]who achieved the 2011 European LDL-C goal for very high-risk patients. The patients from the VOYAGER database included in this analysis were 20 539 high-risk individuals from 31 fixed-dose, randomised clinical trials that compare at least 4 weeks of 10-40 mg rosuvastatin with either atorvastatin 10-80 mg or simvastatin 10-80 mg.


Main results

  • The percentage of high-risk patients that achieved the 2011 European LDL-C goals for very high-risk patients increased with milligram dose, ranging from 43.8% to 79.0% for rosuvastatin, from 16.1% to 65.2% with atorvastatin and from 0 to 39.7% with simvastatin treatment.
  • A similar pattern was seen for percentages of patients achieving the 2011 European LDL-C goal for high-risk patients (<97 mg/dl {2.5 mmol/l]), except for the group treated with simvastatin 80 mg, in which mean baseline LDL-C was abnormally high.
  • Obtaining a >50% reduction in LDL-C occurred more often than achieving LDL-C levels <70 mg/dL.



Conclusion

These data indicate that the choice of statin and dose determine whether the 2011 European goals for LDL-C levels for patients with very high CV risk will be achieved. Statin regime similarly affects achievement of goals for high risk patients. Even if the specific target is not met, the Cholesterol Treatment Trialists’ (CCT) Collaboration findings that the risk of occlusive events and CV death decreases with every 1 mmol/l reduction in LDL-C [3], suggest that every reduction in LDL-C is worthwhile.  It should be noted that no data on adverse effects are available in the database and that the definition of high risk patients in VOYAGER differs slightly from the definition in the guidelines.


References

1. Rosensen RS. Statins: can the new generation make an impression? Expert Opin Emerg Drugs 2004;9:269e79.
2. LaRosa J, Grundy SM, Waters DD, et al. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med 2005;352: 1425e35.
3. Cholesterol Treatment Trialists’ (CTT) Collaboration. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170 000 participants in 26 randomised trials. Lancet 2010;376:1670e81.
4. Reiner Z, Catapano AL, De Backer G, et al. ESC/EAS guidelines for the management of dyslipidaemias: the task force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European
Atherosclerosis Society (EAS). Eur Heart J 2011;32:1769e818.
5. Nicholls SJ, Brandrup-Wognsen G, Palmer M, Barter PJ. 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;105:69e76.


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