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Targeted Treatment against Lipoprotein (a): The Coming Breakthrough in Lipid Lowering Therapy.

ABSTRACT: Atherosclerotic cardiovascular diseases (ASCVD) are a very important cause of premature death. The most important risk factor for ASCVD is lipid disorders. The incidence of lipid disorders and ASCVD is constantly increasing, which means that new methods of prevention and treatment of these diseases are still being searched for. In the management of patients with lipid disorders, the primary goal of therapy is to lower the serum LDL-C concentration. Despite the available effective lipid-lowering therapies, the risk of ASCVD is still increased in some patients. A high level of serum lipoprotein (a) (Lp(a)) is a risk factor for ASCVD independent of serum LDL-C concentration. About 20% of Europeans have elevated serum Lp(a) levels, requiring treatment to reduce serum Lp(a) concentrations in addition to LDL-C. Currently available lipid lowering drugs do not sufficiently reduce serum Lp(a) levels. Hence, drugs based on RNA technology, such as pelacarsen, olpasiran, SLN360 and LY3819469, are undergoing clinical trials. These drugs are very effective in lowering the serum Lp(a) concentration and have a satisfactory safety profile, which means that in the near future they will fill an important gap in the armamentarium of lipid-lowering drugs.

SUBMITTER: Sosnowska B

PROVIDER: S-EPMC9781646 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Targeted Treatment against Lipoprotein (a): The Coming Breakthrough in Lipid Lowering Therapy.

Sosnowska Bożena B Surma Stanisław S Banach Maciej M

Pharmaceuticals (Basel, Switzerland) 20221216 12

Atherosclerotic cardiovascular diseases (ASCVD) are a very important cause of premature death. The most important risk factor for ASCVD is lipid disorders. The incidence of lipid disorders and ASCVD is constantly increasing, which means that new methods of prevention and treatment of these diseases are still being searched for. In the management of patients with lipid disorders, the primary goal of therapy is to lower the serum LDL-C concentration. Despite the available effective lipid-lowering ...[more]

PMID: 36559024

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Project description:ObjectiveElevated lipoprotein(a) [Lp(a)] is a risk factor for atherosclerotic cardiovascular disease (ASCVD) and has no approved pharmacotherapies. Limited real-world data exists on the proportion of patients with available Lp(a) test results, characteristics of these patients, and their use of lipid lowering therapies (LLTs) for secondary prevention (SP) and primary prevention (PP) of ASCVD.MethodsPatients with measured Lp(a) receiving LLTs for SP or PP of ASCVD were identified in the Optum Clinformatics® Data Mart database. Lp(a) distribution and LLT utilization including persistence and adherence were assessed. Logistic regression was used to assess the association between Lp(a) levels and low-density lipoprotein cholesterol (LDL-C) levels after index LLT, adjusting for baseline characteristics.ResultsOverall, 2154 SP and 7179 PP patients met eligibility criteria. Of patients with available laboratory data, only 0.7% (SP) and 0.6% (PP) had Lp(a) test results. In the SP cohort, Lp(a) levels ≥125 nmol/L and ≥175 nmol/L were 26.4% and 17.6%, respectively, and the mean (SD) Lp(a) levels (overall SP cohort 90.4 [97.9] nmol/L) were highest in Black patients (123.4 [117.4]; p<0.001). Statin monotherapy was the most frequently prescribed LLT in SP patients overall (89.4%). Median (interquartile range [IQR]) persistence of LLTs was 227 (91, 649) days and 33.6% achieved ≥80% proportion of days covered (PDC). Patients with Lp(a) ≥175 nmol/L had 2.1 times greater odds of having elevated LDL-C (≥70 mg/dL) post-LLT than those with Lp(a) <175 nmol/L (p = 0.031). Similar findings were observed in the PP population.ConclusionsLp(a) screening was rare. Elevated Lp(a) was observed in more than one-quarter of patients receiving LLTs, with the highest mean Lp(a) levels observed in Black patients. Low adherence to LLTs was prevalent and at least half of patients failed to achieve their respective LDL-C target thresholds despite treatment. Finally, high Lp(a) levels were associated with worse LDL-C control.

Project description:ᅟ: The present study comprised 17,096 Chinese hypertensive dyslipidemia patients who received lipid-lowering treatment for > 3 months in order to investigate blood pressure (BP) as well as low-density lipoprotein cholesterol (LDL-C) goal attainment rates in Chinese hypertensive dyslipidemia patients on antidyslipidemia drugs. The factors that interfered with BP, or BP and LDL-C goal attainment rates and antihypertensive treatment patterns, were analyzed. In total, 89.9% of the 17,096 hypertensive dyslipidemia patients received antihypertensive medications mainly consisting of a calcium channel blocker (CCB) (48.7%), an angiotensin receptor antagonist (ARB) (25.4%) and an angiotensin-converting enzyme inhibitor (ACEI) (15.1%). In cardiology departments, usage rates of β-blockers (19.2%) were unusually high compared to other departments (4.0-8.3%), whereas thiazide diuretics were prescribed at the lowest rate (0.3% vs 1.2-3.6%). The overall goal attainment rates for combined BP and LDL-C as well as BP or LDL-C targets were 22.9, 31.9 and 60.1%, respectively. The lowest BP, LDL-C and BP combined with LDL-C goal attainment rates were achieved in endocrine departments (19.9, 48.9 and 12.4%, respectively). Combination therapies showed no benefit particularly for BP goal achievement. A multivariate logistic regression analysis showed that age < 65 years, alcohol consumption, diabetes, coronary heart disease (CHD), cerebrovascular disease (CVD), chronic kidney disease (CKD), body mass index (BMI) ≥ 28 kg/m2 and not achieving total cholesterol goals were independent predictors for achieving BP, LDL-C or combined BP and LDL-C goals. In summary, the BP and LDL-C goal achievement rates in Chinese dyslipidemia outpatients with hypertension were low, especially in endocrine departments. Combination therapies were not associated with improvement of the goal achievement rates. TRIAL REGISTRATION: Clinical trial registration number NCT01732952.

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Targeted Treatment against Lipoprotein (a): The Coming Breakthrough in Lipid Lowering Therapy.

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Targeted Treatment against Lipoprotein (a): The Coming Breakthrough in Lipid Lowering Therapy.

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