Repatha Moves One Step Closer to an Expanded EU Indication: High-Risk Patients May Receive Treatment Before a First Heart Attack or Stroke

For the prevention and treatment of cardiovascular disease, the ideal time to intervene is not after a serious event has occurred, but when the risk has become clear and a heart attack or stroke has not yet happened. The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) now supports expanding the use of the cholesterol-lowering drug Repatha (evolocumab), giving some high-risk adults the opportunity to receive treatment before their first major cardiovascular event.

The CHMP adopted a positive opinion on July 23. The proposed indication covers adults with established atherosclerotic cardiovascular disease or a high risk of developing it, without continuing to require a previous heart attack, stroke, or peripheral artery disease. This change does not yet constitute formal approval and must next be reviewed by the European Commission; updated product information will be published only if it is approved.

The recommendation is based primarily on the randomized, double-blind, placebo-controlled phase 3 VESALIUS-CV trial. Clinical trial registry data show that the study enrolled 12,301 adults with coronary heart disease or elevated cardiovascular risk who had never experienced a heart attack or stroke, to determine whether intensive lowering of low-density lipoprotein cholesterol (LDL-C) could delay a first major event.

Results compiled by the American Heart Association showed that 6.2% of participants in the evolocumab group experienced the three-point major adverse cardiovascular event composite of cardiovascular death, heart attack, or ischemic stroke, compared with 8.0% in the placebo group; the hazard ratio was 0.75. Rates of the four-point event composite, which also included coronary revascularization, were 13.4% and 16.2%, respectively, with a hazard ratio of 0.81. Expressed as absolute differences, the two measures were reduced by 1.8 and 2.8 percentage points, respectively, indicating a benefit, although its magnitude must still be weighed against patients’ baseline risk and treatment burden.

The drug’s effect on blood lipids was more direct: after 48 weeks of treatment, median LDL-C fell to 45 mg/dL in the evolocumab group, compared with 109 mg/dL in the placebo group. No significant difference was observed in overall adverse-event rates, although summary data are insufficient to replace the full product labeling and cannot answer questions about rarer adverse effects, benefits in different patient populations, or long-term continued treatment.

If the indication change is approved, Repatha will be used in combination with the highest statin dose a patient can tolerate and, where appropriate, with other lipid-lowering drugs. Patients for whom statins are contraindicated or who cannot tolerate them may also receive the drug without a statin. This does not mean that all people who have not yet had a heart attack or stroke are suitable for a PCSK9 inhibitor. Rather, it moves the treatment window earlier for people with clearly established atherosclerosis or high risk who need further LDL-C reduction.