The maxim that lower is better for LDL cholesterol continues to hold true, event at jaw-droppingly low levels of less than 10mg/DL, in a new analysis of data from the FOURIER trial.
The Further Cardiovascular outcomes Research with PCSK9 inhibition in subject with elevated risk (Fourier) trial was the pivotal efficacy and safety study for the proprotein convertase subtilisin- kexin type 9 (PCSK9) inhibitor evolocumb (Repatha) and enrolled patients with atherosclerotic cardiovascular disease and LDL cholesterol levels of at least 70 mg/d.
Among 25,982 FOURIER patients with a measured LDL cholesterol level after 4 weeks on treatment and no study event as of then, 31% had their LDL cholesterol cut to 20-49 mg/dl, 8% achieved a LDL cholesterol level of 10-19 mg/dl, and 2% reached a remarkable LDL cholesterol level of below 10 mg/ dl, as low as herbivores such as rabbits and deer.
After a median follow-up of 26 months, the incidence of the study’s primary endpoint (cardiovascular death, MI stroke, hospitalization for unstable angina, or coronary revascularization) dropped by a statistically significant 15% in patients with an achieved LDL cholesterol of 20-49 mg/dl, compared with patients whose four weeks LDL cholesterol was at or above 100mg/dl (primarily patients randomized to the study’s control arm), by 24% in all patients with LDL cholesterol less than 20 mg/dl and by 31% in the 2% of patients whose LDL cholesterol levels fell below 10 mg/dl.
These strikingly improved event rates at the lowest levels of LDL cholesterol occurred with no signal of excess adverse events , said at the annual congress of the European Society of Cardiology.
In contrast, the 13% of patents whose achieved LDL cholesterol was 50-69 mg/dl had an event rate just 6% below the referent group of 100 mg/dl or more, a non-significant difference. Existing cholesterol management guidelines that set LDL cholesterol target for secondary prevention have used a level below 70 mg/dl as the target, such as the European Society of Cardiology’s 2016 guidelines.
The data suggest that we should target considerably lower LDL cholesterol than is currently recommended for our patients with atherosclerotic cardiovascular disease.
While FOURIER’s event curve continued to drop as LDL cholesterol fell below 10 mg/dl , the study’s wide-ranging safety assessment showed no signal of harm at the lowest level. This “gives us some reassurance it’s safe. We saw benefits that continues down to the lowest LDL levels, so it’s hard to pick a LDL target. I no longer feel comfortable treating my patients to just less than 70 mg/dl. I’m not sure what is the optimal LDL target, but I think it needs to be lower than that.”
To achieved such ultralow LDL levels, most patients need treatment with a PCSK9 inhibitor plus at least one and perhaps two additional cholesterol-lowering drugs, a statin and ezetimibe.