Can intensive LDL-C lowering reduce the risk of recurrent CV events?

How cumulative LDL-C exposure impacts CV risk

As cumulative LDL-C exposure increases over time, LDL-C accumulates within the artery wall, increasing plaque burden and the likelihood of clinically significant atherosclerosis and cardiovascular events (here). Lowering LDL-C levels and maintaining them over time slows plaque progression and substantially reduces lifetime ASCVD risk (here).

Early, intensive and sustained LDL-C lowering matters (here, here).

The latest NHFA/CSANZ and ESC/EAS guidelines recommend achieving LDL-C <1.4 mmol/L and ≥50% reduction from baseline, with further benefit gained from treating to the lowest achievable level (here, here).

In the SWEDEHEART registry, early addition of ezetimibe to statin therapy after MI was associated with lower MACE incidence than later or no ezetimibe initiation. At 1 year, compared with early combination therapy (≤12 weeks after hospital discharge), the risk of MACE was significantly higher for late (13 weeks to 16 months after hospital discharge) and no ezetimibe initiation (weighted risk differences: 0.6% [95% CI: 0.1%–1.1%; P<0.01] and 0.7% [95% CI: 0.2%–1.3%; P<0.01], respectively) (here).

Identifying patients who remain above LDL-C goal despite lipid-lowering therapy is an important consideration. For patients who remain above goal despite statin and ezetimibe, both NHFA/CSANZ and ESC/EAS guidelines recommend treatment intensification with a PCSK9 inhibitor (here, here).

FOURIER: rapid and sustained LDL-C reductions and CV outcomes benefit with Repatha^®(here)

The landmark FOURIER trial evaluated Repatha^® added to optimised statin therapy (± ezetimibe) in 27,564 patients with established ASCVD over a median follow-up of 2.2 years, providing important insights into the effects of LDL-C lowering on CV outcomes (here).

In the FOURIER open-label extension (FOURIER-OLE)*, patients originally randomised to Repatha® had a 15% lower risk of the primary composite endpoint vs those originally randomised to placebo, despite both groups receiving Repatha® during the extension (HR: 0.85; 95% CI: 0.75–0.96; p=0.008) (here).

(*Limitations of FOURIER-OLE include the absence of a concurrent placebo arm, lack of randomisation during the extension period, and cardiovascular outcomes being prespecified but considered exploratory. P values were nominal and not adjusted for multiplicity.)

Long-term LDL-C lowering with Repatha® was associated with persistently low rates of adverse events for >8 years (here). In clinical studies, the incidence of adverse events was similar between Repatha® and control groups (here). The adverse reactions associated with Repatha® were usually mild to moderate. Common adverse reactions occurring (≥ 1/100 to < 1/10) are nausea, injection site reactions, influenza, nasopharyngitis, upper respiratory tract infection, arthralgia, back pain and rash (here).

Add Repatha^®: the only available PCSK9 inhibitor in Australia with proven CV outcomes benefit^(here, here, here, here)

(^As of June 2026.)

Repatha^® is PBS reimbursed for your FH and non-FH patients with ASCVD (here). Check your patient’s eligibility for Repatha® in two easy steps using the simple PBS navigator. 

Visit www.repatha.com.au for more information and resources

Repatha^® is indicated as an adjunct to diet and exercise in: Prevention of CV events (MI, stroke and coronary revascularisation) in adults with established CVD in combination with an optimally dosed statin and/or other lipid-lowering therapies; Primary hypercholesterolaemia (heterozygous familial hypercholesterolaemia and non-familial hypercholesterolaemia) in adults, given in combination with an optimally dosed statin and/or other lipid-lowering therapies, or alone or in combination with other lipid-lowering therapies in statin-intolerant patients; Homozygous familial hypercholesterolaemia 12 years and above given in combination with other lipid-lowering therapies (here).

SWEDEHEART Study Design: The SWEDEHEART registry study was an observational, nationwide cohort study in Sweden of lipid-lowering therapy–naive patients hospitalised for MI (N=35,826) who were discharged on statin therapy. Patients were classified according to timing of ezetimibe initiation relative to discharge: early combination therapy (ezetimibe added within 12 weeks of discharge; reference group), late combination therapy (ezetimibe added between 13 weeks and 16 months after discharge), or no ezetimibe (statin monotherapy). The primary outcome was major adverse cardiovascular events (MACE), consisting of all-cause death, nonfatal MI, and nonfatal stroke (here).

FOURIER Study Design: The FOURIER trial was a randomised, double-blind, placebo-controlled trial in patients with ASCVD (n=27,564) with LDL-C levels of ≥1.8 mmol/L (fasting) or non-HDL-C ≥2.59 mmol/L who were receiving optimised statin therapy ± ezetimibe. Patients were randomised 1:1 to receive either Repatha® SC 140 mg Q2W or 420mg QM (n=13,784) or placebo SC Q2W or QM (n=13,780) and followed for a median of 2.2 years. The primary efficacy endpoint was the composite of CV death, MI, stroke, hospitalisation for UA, or coronary revascularisation. The key secondary efficacy endpoint was the composite of CV death, MI, or stroke.(here, here)

Refer to full Product Information before prescribing; available from Amgen Australia Pty Ltd, Ph: 1800 803 638 or at www.amgen.com.au/Repatha.PI

For more information on Repatha® or to report an adverse event or product complaint involving Repatha®, please contact Amgen Medical Information on 1800 803 638 or visit www.amgenmedinfo.com.au.

Abbreviations: ARR, absolute risk reduction; ASCVD, atherosclerotic cardiovascular disease; CI, confidence interval; CV, cardiovascular; CVD, cardiovascular disease; ESC/EAS, European Society of Cardiology and European Atherosclerosis Society; FH, familial hypercholesterolaemia; HDL-C, high-density lipoprotein cholesterol; HR, hazard ratio; LDL-C, low-density lipoprotein cholesterol; MACE, major adverse cardiovascular events; MI, myocardial infarction; NHFA/CSANZ, National Heart Foundation of Australia and Cardiac Society of Australia and New Zealand; PBS, Pharmaceutical Benefits Scheme; PCSK9, proprotein convertase subtilisin/kexin type 9; Q2W, every 2 weeks; QM, every month; SC, subcutaneous; UA, unstable angina.

Amgen Australia Pty Ltd. ABN 31 051 057 428, Sydney NSW 2000. © 2026 Amgen Inc. All rights reserved. AMGREP3750. AUS-145-26-80148. Date of preparation: September 2026.