LDL-c goal attainment after STEMI with early combination therapy
Intensive lipid-lowering therapy for early achievement of guideline-recommended LDL-cholesterol levels in patients with ST-elevation myocardial infarction (“Jena auf Ziel”)
Introduction and methods
The Swedish SWEDEHEART registry recently showed that 17% of patients with a recent MI achieved the LDL-c target recommended in the 2019 ESC/EAS Guidelines for the management of dyslipidaemias (i.e., LDL-c <1.4 mmol/L (<55 mg/dL)), while the remaining 83% would be eligible for expanded lipid-lowering therapy . The 2019 ESC/EAS Guidelines call for high-intensity statin therapy, and if the target is not achieved within 4–6 weeks, add-on therapy with ezetimibe and thereafter a PCSK9i are recommended . Yet, early use of combination lipid-lowering therapy, consisting of a high-intensity statin and ezetimibe, is effective in reducing LDL-c levels [3-7].
Aim of the study
The study aim was to attain the LDL-c target in patients hospitalized for STEMI by treating them with combination lipid-lowering therapy (consisting of atorvastatin 80 mg and ezetimibe 10 mg) as first-line therapy, escalated with either bempedoic acid or a PCSK9i if the target was not reached.
The JaZ (“Jena auf Ziel”) study was a prospective cohort study in 85 patients who were admitted with STEMI to the Jena University Hospital in Jena, Germany from January through December 2021. Upon admission, patients received combination therapy with atorvastatin 80 mg and ezetimibe 10 mg. During the hospital stay, they were educated about CV risk modification. During follow-up, the lipid-lowering therapy was escalated with bempedoic acid or a PCSK9i if needed in order to achieve the recommended LDL-c target in all patients. Patient empowerment was used to increase therapy adherence. The authors also evaluated adverse events of this lipid-lowering strategy.
The primary outcome was achievement of the 2019 ESC/EAS Guidelines–recommended LDL-c target for MI patients (<1.4 mmol/L (<55 mg/dL).
LDL-c target attainment
- On admission, mean (± SD) LDL-c level was 3.2 ± 1.2 mmol/L (123.4 ± 44.9 mg/dL). Of the 85 patients, 5 (5.9%) had an LDL-c level < 1.4 mmol/L , 75 (88.2%) had an LDL-c level >1.8 mmol/L, 61 (71.8%) had LDL-c >2.6 mmol/L, and 7 (8.2%) had LDL-c >4.9 mmol/L.
- Early initiation of combination lipid-lowering therapy reduced mean LDL-c level to 1.7 ± 0.8 mmol/L (65.7 ± 34.8 mg/dL) at discharge. At this time, 33 patients (38.8%) achieved the LDL-c target of <1.4 mmol/L.
- At the first follow-up visit (4–6 weeks after discharge), mean LDL-c level was 1.2 ± 0.4 mmol/L (46.4 ± 15.5 mg/dL). Another 35 patients (41.2%) attained the recommended LDL-c target, which meant that a total of 68 patients (80%) reached the LDL-c goal.
- In the remaining 17 patients (20%), lipid-lowering therapy was optimized: 2 patients were switched from atorvastatin 80 mg to rosuvastatin 40 mg, 8 were treated with bempedoic acid in addition to atorvastatin 80 mg and ezetimibe 10 mg (additional 15% LDL-c reduction), 6 additionally received a PCSK9i (additional 68% LDL-c reduction), and compliance issues were addressed in 1 patient.
- At the last follow-up visit (12 months after index event), all patients reached the LDL-c target; at the time, mean LDL-c level was 1.1 ± 0.3 mmol/L (42.5 ± 11.6 mg/dL).
- During follow-up, few adverse events of the combination lipid-lowering therapy were reported, including muscle pain (n=2), dizziness (n=2), and elevation of liver enzyme levels (n=1).
In this single-center prospective cohort study, early initiation of combination lipid-lowering therapy with a high-intensity statin (atorvastatin 80 mg) and ezetimibe 10 mg resulted in attainment of the 2019 ESC/EAS Guidelines–recommended LDL-c target at the first follow-up visit in 80% of the patients hospitalized for STEMI. After escalation of therapy with bempedoic acid or a PCSK9i if needed, all patients reached the recommended LDL-c target. The combination lipid-lowering therapy was well tolerated.
The authors point out that in the 2019 ESC/EAS Guidelines, statins alone are first-line lipid-lowering therapy to reduce ASCVD risk and ezetimibe and PCSK9is should be initiated only when the LDL-c target is not met at follow-up. However, when taking the high inter-individual variability in LDL-c reduction into account, amongst others, “early initiation of combined lipid-lowering therapy with a high-intensity statin and ezetimibe appears to be a logical therapeutic strategy.”