Statin eligibility in primary prevention: new model identifies low-risk/high-benefit individuals

Thanassoulis G, Williams K, Kimler Altobelli K, et al.
Circulation 2016;published online ahead of print

Background

Currently, the following approaches are used to define statin eligibility for primary CV prevention:

1. The guidelines recommended risk-based approach according to the predicted 10-year CV risk [1,2]
2. The use of novel markers for risk stratification [3,4]
3. The use of inclusion criteria of relevant randomised trials [5,6]

Each approach has advantages and disadvantages, and all exclude certain groups of individuals at lower CV risk. Yet, there are data showing that statin therapy with the objective of prevention remains cost-effective even at lower risk thresholds [7], and that the relative benefit of statin therapy is greater at lower levels of risk [8].
This study compared two approaches for the determination of statin eligibility in primary prevention:

• the 10-year risk-based approach based on guidelines (individuals with a 10-year pooled cohorts equation risk ≥ 7.5% and LDL-C ≥ 70 mg/dL)
• an individualised benefit approach based on the predicted 10-year absolute risk reduction (ARR₁₀ ≥ 2.3%) from RCT data, with the objective to target the individuals for whom the greatest benefit is expected

Included in the analysis were 2,134 participants representing 71.8 million American residents potentially eligible for statins in primary prevention from the National Health and Nutrition Examination Survey for the years 2005–2010 [9].

Main results

Statin eligibility was:

• according to the guidelines approach: 21% (15.0 million; 95% CI: 12.7-17.3 million)
• according to the individualised approach: 34% (24.6 million; 95% CI: 21.0-28.1 million)

The mean 10-year predicted risk was:

• according to the guidelines approach: 13.9% (range: 7.5% - 43.5%)
• according to the individualised approach: 10.9% (range: 3.7% - 43.5%)

The expected ARR₁₀ from statins was:

• according to the guidelines approach: 4.8% (range: 2.3% - 10.6%), corresponding to a NNT₁₀ of 21 (range: 9-44)
• according to the individualised approach: 4.0% (range: 2.3%-10.6%), corresponding to a NNT₁₀ of 25 (range: 9-44)

Of the 24.6 million individuals with an expected ARR₁₀ ≥ 2.3%:
- 15.0 million were at high risk and statin-eligible under the 2013 guidelines
- 9.5 million were at lower risk and not statin-eligible under the 2013 guidelines
The latter (lower risk) group included:  

• 5.7 million individuals (60%) who would be eligible for at least 1 statin RCT in primary prevention
• younger individuals (mean age = 55.2 years vs. 62.5 years in the high-risk group; P<0.001)
• individuals with higher LDL-C (140 mg/dL vs. 133 mg/dL in the high-risk group; P=0.013)
• individuals at lower pooled cohorts equation risk (6% vs 14%; P<0.001)

• Estimates of ASCVD events prevented in 10 years:

• with the risk-based approach: 728,572 ASCVD events
• with the individualised-benefit approach: 995,080 ASCVD events (increase in prevented ASCVD events by 36.6%)

Conclusion

In a large primary prevention cohort, an individualised statin benefit approach identified lower-risk individuals with equal or greater expected benefit from statins compared with higher-risk individuals. The individualised statin benefit approach supports the extension of statin eligibility in primary prevention to younger individuals with higher LDL-C values and lower risk based on conventional risk stratification.

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