Improving statin treatment strategies to reduce LDL-cholesterol: factors associated with targets' attainment in subjects with and without type 2 diabetes

Cardiovasc Diabetol. 2021 Jul 16;20(1):144. doi: 10.1186/s12933-021-01338-y.

Abstract

Background: This cross-sectional study aimed to identify actionable factors to improve LDL-cholesterol target achievement and overcome underuse of lipid-lowering treatments in high- or very-high-cardiovascular risk patients.

Methods: We evaluated healthcare records of 934,332 subjects from North-Italy, including subjects with available lipid profile and being on statin treatments up to December 2018. A 6-month-period defined adherence with proportion-of-days-covered ≥ 80%. Treatment was classified as high-intensity-statin (HIS) + ezetimibe, HIS-alone, non-HIS (NHIS) + ezetimibe or NHIS alone.

Results: We included 27,374 subjects without and 10,459 with diabetes. Among these, 30% and 36% were on secondary prevention, respectively. Adherence was high (78-100%) and increased with treatment intensity and in secondary prevention. Treatment intensity increased in secondary prevention, but only 42% were on HIS. 2019-guidelines LDL-cholesterol targets were achieved in few patients and more often among those with diabetes (7.4% vs. 10.7%, p < 0.001). Patients in secondary prevention had mean LDL-cholesterol levels aligned slightly above 70 mg/dl (range between 68 and 73 mg/dl and between 73 and 85 mg/dl in patients with and without diabetes, respectively). Moreover, the differences in mean LDL-cholesterol levels observed across patients using treatments with well-stablished different LDL-lowering effect were null or much smaller than expected (HIS vs. NHIS from - 3 to - 11%, p < 0.001, HIS + ezetimibe vs. HIS-from - 4 to + 5% n.s.). These findings, given the observational design of the study, might suggest that a "treat to absolute LDL-cholesterol levels" approach (e.g., targeting LDLc of 70 mg/dl) was mainly used by physicians rather than an approach to also achieve the recommended 50% reduction in LDL-cholesterol levels. Our analyses suggested that female sex, younger age, higher HDL-c, and elevated triglycerides are those factors delaying prescription of statin treatments, both in patients with and without diabetes and in those on secondary prevention.

Conclusions: Among patients on statin treatment and high adherence, only a small proportion of patients achieved LDL-cholesterol targets. Late initiation of high-intensity treatments, particularly among those with misperceived low-risk (e.g., female subjects or those with high HDL-cholesterol), appears as pivotal factors needing to be modified to improve CVD prevention.

Keywords: Cardiovascular prevention; Ezetimibe; Gender; HDL; PCSK9; Statins.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Cardiovascular Diseases / diagnosis
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / prevention & control*
  • Cholesterol, LDL / blood*
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / epidemiology*
  • Down-Regulation
  • Dyslipidemias / blood
  • Dyslipidemias / diagnosis
  • Dyslipidemias / drug therapy*
  • Dyslipidemias / epidemiology
  • Ezetimibe / therapeutic use
  • Female
  • Heart Disease Risk Factors
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Italy / epidemiology
  • Male
  • Medication Adherence
  • Middle Aged
  • Primary Prevention
  • Retrospective Studies
  • Risk Assessment
  • Secondary Prevention
  • Time Factors
  • Treatment Outcome

Substances

  • Biomarkers
  • Cholesterol, LDL
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Ezetimibe