Short answer: The labels approve Praluent, Repatha and Leqvio alongside diet and exercise to lower LDL, without requiring a statin. Two label trials tested a PCSK9 antibody in people taking no cholesterol medicine: LDL fell about 55% to 57% more than placebo on Repatha at week 12, and 48% on Praluent vs 19% on ezetimibe. Most trial participants, though, were also on a statin.
All three labels list use as an adjunct to diet and exercise to lower LDL cholesterol in adults with high cholesterol, and in some forms of familial hypercholesterolemia. Praluent and Repatha are also approved to lower the risk of heart attack, stroke and related events in adults at increased risk. None of the three labels makes a statin a condition of use.
The trial populations are a different matter. In the heart outcome trials (FOURIER for Repatha, ODYSSEY OUTCOMES for Praluent) and in the main Leqvio trials, people were taking a statin at the highest dose they could tolerate, often with other cholesterol medicines. The heart-event benefit in the labels was measured on top of a statin.
| Trial | People | Result |
|---|---|---|
| Repatha, MENDEL-2 (label, 12 weeks) | 614 adults on no cholesterol medicine, average LDL 143 mg/dL | LDL fell 55% (140 mg every 2 weeks) and 57% (420 mg monthly) more than placebo, and 37% to 38% more than ezetimibe |
| Praluent, ODYSSEY MONO (label) | 103 adults at moderate heart risk on no cholesterol medicine, average LDL 140 mg/dL | Week 12: -48% on Praluent vs -19% on ezetimibe; 30% had the dose raised to 150 mg |
| Repatha, GAUSS-3 (Nissen 2016, 24 weeks) | 218 people with muscle symptoms on statins | LDL fell about 53% to 55% on Repatha vs about 17% on ezetimibe |
| Praluent, ODYSSEY ALTERNATIVE (Moriarty 2015, 24 weeks) | 361 people unable to take at least 2 statins | LDL fell 45.0% on Praluent vs 14.6% on ezetimibe |
These trials measured LDL, not heart attacks or strokes. The Leqvio label does not include a trial in people off statins.
The labels note that a statin changes the antibodies' levels a little. The Repatha label says a high-intensity statin lowered evolocumab exposure by about 20%, which it calls not clinically meaningful. The Praluent label gives a median half-life of 17 to 20 days, reduced to 12 days with a statin, also described as not clinically meaningful.
Whether to use a PCSK9 shot alone, with a statin, or with other medicines such as ezetimibe depends on someone's heart risk, LDL goal and what they can tolerate, and is decided with the prescriber.
People on a PCSK9 shot often take a daily pill as well. Dose Track can hold both on one schedule, with the shot every 2 or 4 weeks or every 6 months and the pill each day, so missed doses of either are easy to spot when LDL results come back.
Read more on Dose Track: Praluent vs Repatha · Leqvio vs Repatha · Cholesterol · LDL cholesterol