Also at very low achieved LDL-c is ‘the lower better’ for cardiovascular risk

ESC 2017 - Barcelona

News - Aug. 27, 2017

New analysis examines how low cholesterol can safely go (FOURIER)

Presented at the ESC congress 2017 by:Robert Patrick GIUGLIANO (Boston, MA, USA)


Intitial results of the FOURIER study showed that the PCSK9 antibody evolocumab lowered LDL-c levels significantly to a median of 0.8 mmol/L, as well as the risk of cardiovascular events during a median follow-up of 2.2 years.

During the ESC data of new analyses of the FOURIER trial were presented, in which efficacy and safety were evaluated in relation tot he achieved LDL-c level at month 1 (25.982 patients). Patients were categorized into 5 groups: 1) <0.5 mM (20 mg/dL), 2) 0.5-1.3 mM (20-49 mg/dL), 3) 1.3-1.8 mM (50-69 mg/dL), 4) 1.8-2.6 mM (70-99 mg/dL) and 5) ≥2.6 mM (≥100 mg/dL), the latter of which functioned as a reference group. Moreover, in the EBBINGHAUS population cognition was evaluated.

Main results

  • A linear relation between LDL-c at week 4 and the corrected frequentie of events was seen (P=0.0001). The lowest LDL-c group had 31% risk reduction of the composite endpoint of CV death, myocardial infarction and stroke (HR 0.69, 95% CI 0.56-0.85), and the highest group had 10% lower risk (HR 0.90, 95% CI 0.78-1.04).
  • The rate of 10 safety events, among which cognition, were comparable among all groups.
  • Exploratory analyses in patiënten <0.26 mM LDL-c at week 4 (n=504) showed that in this group the number of events further reduced (HR for CVD, MI, stroke, unstable angina, coronary revascularization 0.69, 95%CI 0.49-0.97, P=0.03 and for CVD, MI and stroke 0.59, 95%CI 0.37-0.92, P=0.02). No safety signals were observed in this group.


LDL-c can be lowered to unprecendented low levels, when using statins and PCSK9 inhibitors. A strong linear relationship was seen between achieved LDL-c levels and number of CV events, even below 0.26 mM LDL-c, without safety concerns up to 2.2 years. These data suggest that LDL-c must be lowered even further than is currently recommended for patients with atherosclerotic CVD.

Giugliano therefore emphasized during the press conference that the “lower the better” really seems true. He also noted that the exploratory data of the extremely low LDL-c group show a fantastic result that may support guideline recommendations to go as low as possible with LDL-c.

- Our reporting is based on the information provided at the ESC congress -

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