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

• DOI: 10.1186/s12933-021-01338-y
• Publication Date: 2021-07-16T07:03:41Z
• Authors: Mario Luca Morieri; Valentina Perrone; Chiara Veronesi; Luca Degli Esposti; Margherita Andretta; Mario Plebani; Gian Paolo Fadini; Saula Vigili de K...; Angelo Avogaro
• Keywords: Male; HDL; Down-Regulation; Medication Adherence; PCSK9; 03 medical and health sciences; 0302 clinical medicine; Diseases of the circulatory (Cardiovascular) system; Humans; Original Investigation; Aged; Dyslipidemias; Retrospective Studies; Aged, 80 and over; Statins; Gender; Cholesterol, LDL; Middle Aged; Ezetimibe; 3. Good health; Primary Prevention; Cardiovascular prevention; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Italy; Cardiovascular Diseases; Heart Disease Risk Factors; RC666-701; Female; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Cardiovascular prevention; Ezetimibe; Gender; HDL; PCSK9; Statins; Aged; Aged, 80 and over; Biomarkers; Cardiovascular Diseases; Cholesterol, LDL; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Down-Regulation; Dyslipidemias; Ezetimibe; Female; Heart Disease Risk Factors; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Italy; Male; Medication Adherence; Middle Aged; Primary Prevention; Retrospective Studies; Risk Assessment; Secondary Prevention; Time Factors; Treatment Outcome; Biomarkers

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.