Number Needed to Treat for Repatha (Evolocumab)
The number needed to treat (NNT) for Repatha (evolocumab) is 67 over 2.2 years to prevent one major cardiovascular event in patients with atherosclerotic cardiovascular disease. 1, 2
Evidence for NNT with Repatha
- The FOURIER trial, which evaluated evolocumab in 27,564 patients with atherosclerotic cardiovascular disease on background statin therapy, demonstrated an absolute risk reduction (ARR) of 1.5% for the composite primary endpoint of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization over 2.2 years 1
- This translates to an NNT of 67 over 2.2 years to prevent one major cardiovascular event 1, 2
- For the key secondary endpoint (composite of cardiovascular death, myocardial infarction, or stroke), evolocumab showed a 20% relative risk reduction (HR: 0.80; 95% CI: 0.73-0.88) with event rates of 5.9% vs. 7.4% (placebo), also yielding an NNT of 67 1
Comparison with Other Lipid-Lowering Therapies
- Alirocumab (another PCSK9 inhibitor) demonstrated a similar NNT of 63 over 2.8 years in the ODYSSEY OUTCOMES trial 1
- In contrast, ezetimibe plus simvastatin showed an NNT of 50 over 6 years in the IMPROVE-IT trial for secondary prevention 1
- The NNT for ezetimibe was more favorable in patients with diabetes, with an absolute risk reduction of 5.5% over 7 years (NNT of approximately 18) 1
Factors Affecting NNT for Repatha
- The NNT for evolocumab appears consistent across various subgroups, including patients with the lowest baseline LDL-C levels (median 74 mg/dL) 2
- Long-term follow-up studies suggest that the clinical benefits of evolocumab may increase over time, potentially improving the NNT with extended treatment 3, 4
- Patients at very high risk (e.g., those with recent myocardial infarction, multiple events, or peripheral artery disease) may experience greater absolute benefits, resulting in a more favorable NNT 3
Mechanism and Efficacy
- Evolocumab is a monoclonal antibody that inhibits PCSK9, increasing the number of LDL receptors available to clear circulating LDL-C 1
- It reduces LDL-C levels by approximately 60% when added to statin therapy 5, 2, 4
- The FOURIER trial demonstrated that evolocumab lowered median LDL-C from 92 mg/dL to 30 mg/dL 2
- This significant LDL-C reduction is maintained long-term, with studies showing consistent 56-57% reductions for up to 5 years 4
Safety Considerations
- The safety profile of evolocumab is generally favorable, with no significant differences in adverse events compared to placebo except for injection site reactions (2.1% vs. 1.6%) 1, 2
- No increase in new-onset diabetes or neurocognitive events was observed in clinical trials 2
- Long-term safety data from the OSLER-1 trial (up to 5 years) showed consistent safety with yearly serious adverse event rates ranging from 6.9% to 7.9% 4
- Treatment persistence rates exceed 90% in real-world studies, suggesting good tolerability 3
Clinical Implications
- The 2018 AHA/ACC cholesterol guidelines recognize the role of PCSK9 inhibitors for secondary prevention in high-risk patients not achieving adequate LDL-C lowering with maximally tolerated statin therapy 1
- Evolocumab is FDA-approved to reduce the risk of MI, stroke, and coronary revascularization in adults with established cardiovascular disease 1
- The medication is administered subcutaneously either as 140 mg every 2 weeks or 420 mg once monthly 1
- The consistent benefit across subgroups suggests that the NNT of 67 is applicable to a broad range of patients with established atherosclerotic cardiovascular disease 2