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September 5, 2026HerzOpen Access

Predicting LDL-cholesterol reduction variability on statin–ezetimibe therapy: insights from “Jena auf Ziel”

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Why the study?

To assess individual variations in LDL-C response and investigate associations between baseline plasma surrogate markers of cholesterol metabolism and LDL-C reductions on combined lipid-lowering therapy.

Does atorvastatin and ezetimibe combination therapy reduce LDL-C consistently across different baseline cholesterol metabolism phenotypes in patients with STEMI?

Population

42 lipid-lowering therapy-naive STEMI patients

Comparison

Early combination therapy with atorvastatin 80 mg and ezetimibe 10 mg across quartiles of cholesterol metabolism markers

Design

Secondary analysis of a prospective cohort study

Follow-up

4-6 weeks

Key result

Upfront dual therapy with atorvastatin 80mg and ezetimibe 10mg achieved a median LDL-C reduction of 65.28% with no significant association between baseline cholesterol metabolism markers and treatment response.

Authors

UMUmidakhon MakhmudovaDLDieter LütjohannFHFranz Haertel

Discussion

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Overview

May support upfront dual statin-ezetimibe in STEMI for consistent LDL-C lowering; hypothesis-generating on independence from metabolism markers, needing RCT confirmation.

Key Points

  • To evaluate individual variability in LDL-C reduction and determine whether baseline surrogate markers of cholesterol absorption and synthesis predict treatment response to upfront dual statin–ezetimibe therapy.
  • Conducted a secondary analysis of the prospective Jena auf Ziel (JaZ) cohort study in 42 treatment-naïve patients presenting with ST-elevation myocardial infarction (STEMI).
  • Initiated upfront combination therapy with atorvastatin 80 mg and ezetimibe 10 mg upon hospital admission.
  • Measured baseline plasma markers of cholesterol absorption (sitosterol, campesterol, cholestanol) and synthesis (lathosterol), assessing LDL-C reductions after 4–6 weeks.
  • Upfront dual therapy reduced LDL-C by 47.7% to 92.5% across all patients at 6 weeks, with a median reduction exceeding 60% across all quartiles of cholesterol absorption and synthesis markers.
  • No statistically significant differences in percentage LDL-C reduction occurred across quartiles of sitosterol, campesterol, cholestanol, or lathosterol ratios to cholesterol.
  • Pearson correlation analysis revealed a modest association where higher baseline sitosterol:cholesterol ratios correlated with slightly less pronounced LDL-C reductions.

Study Design

Type

Cohort (n=42)

Multicenter

No

Structured PICO

Does atorvastatin and ezetimibe combination therapy reduce LDL-C consistently across different baseline cholesterol metabolism phenotypes in patients with STEMI?

P
Population
42 lipid-lowering therapy-naïve patients with ST-elevation myocardial infarction treated with upfront combination therapy and followed for 6 weeks.
I
Intervention
Atorvastatin 80 mg and ezetimibe 10 mg initiated on admission for 4-6 weeks
O
Outcome
LDL-C reduction from baseline and its association with baseline plasma surrogate markers of cholesterol metabolism (absorption and synthesis) after 4-6 weekssurrogate

Upfront dual therapy with atorvastatin and ezetimibe in STEMI patients achieves robust LDL-C reduction with low interindividual variability, regardless of baseline cholesterol metabolism markers.

Limitations

  • Small sample size which may have limited statistical power
  • Secondary analysis without prior power calculations
  • Only evaluated short-term response to treatment
  • Observational study without a control group
  • small sample size
  • short-term response evaluation
  • observational study with no control group
  • secondary analysis without prior power calculations

Cite This Study

Makhmudova et al. (2026) conducted a cohort in ST-segment elevation myocardial infarction (STEMI) (n=42). Atorvastatin and ezetimibe was evaluated on LDL-C reduction from baseline. Upfront dual therapy with atorvastatin 80mg and ezetimibe 10mg achieved a median LDL-C reduction of 65.28% with no significant association between baseline cholesterol metabolism markers and treatment response.

synapsesocial.com/papers/6a9bd48c6b95aff0620ec546https://doi.org/10.1007/s00059-026-05393-7
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