Uptake of non-statin lipid-lowering therapies for secondary prevention in community practice.

Nearly two-thirds of individuals with atherosclerotic cardiovascular disease (ASCVD) do not reach target low-density lipoprotein cholesterol despite statin therapy. Three novel lipid-lowering therapies have proven to further reduce ASCVD beyond statins, including: ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), and icosapent ethyl. This study evaluated the use of these three agents in 728,423 individuals with ASCVD from 89 US health systems from 01/2018 through 03/2021 using the electronic health record. As of 2021, only 6.0% of ASCVD patients were on ezetimibe, 1.6% were on a PCSK9i, and 1.3% on icosapent ethyl, with utilization only marginally increasing over the study period. Addressing the underutilization of non-statin lipid-lowering therapy for secondary prevention is a critical step in improving the treatment gap of patients with residual risk of ASCVD.

Longitudinal and secular trends in total cholesterol levels and impact of lipid-lowering drug use among Norwegian women and men born in 1905-1977 in the population-based Tromsø Study 1979-2016.

OBJECTIVES: Elevated blood cholesterol is a modifiable risk factor for cardiovascular disease. Cholesterol level surveillance is necessary to study population disease burden, consider priorities for prevention and intervention and understand the effect of diet, lifestyle and treatment. Previous studies show a cholesterol decline in recent decades but lack data to follow individuals born in different decades throughout life. METHODS: We investigated changes in age-specific and birth cohort-specific total cholesterol (TC) levels in 43 710 women and men born in 1905-1977 (aged 20-95 years at screening) in the population-based Tromsø Study. Fifty-nine per cent of the participants had more than one and up to six repeated TC measurements during 1979-2016. Linear mixed models were used to test for time trends. RESULTS: Mean TC decreased during 1979-2016 in both women and men and in all age groups. The decrease in TC in age group 40-49 years was 1.2 mmol/L in women and 1.0 mmol/L in men. Both the 80th and the 20th percentile of the population TC distribution decreased in both sexes and all age groups. Longitudinal analysis showed that TC increased with age to a peak around middle age followed by a decrease. At any given age, TC significantly decreased with increase in year born. Lipid-lowering drug use was rare in 1994, increased thereafter, but was low (<3% in women and <5% in men) among those younger than 50 years in all surveys. Between 1994 and 2016, lipid-lowering drug treatment in individuals 50 years and older explained 21% and 28% of the decrease in TC levels in women and men, respectively. CONCLUSIONS: We found a substantial decrease in mean TC levels in the general population between 1979 and 2016 in all age groups. In birth cohorts, TC increased with age to a peak around middle age followed by a decrease.

Randomized controlled trial of different aspirin regimens for reduction of niacin-induced flushing.

PURPOSE: Results of a study to test the hypothesis that taking niacin simultaneously with different forms of aspirin would reduce the occurrence of niacin-induced flushing are reported. METHODS: Traditionally, taking enteral absorbed aspirin 30 minutes before a niacin dose has been shown to reduce flushing by 30-50% relative to nonuse of aspirin. The objective of the study was to evaluate the efficacy of enteral absorbed and orally dissolved aspirin, taken at the same time as niacin, in reducing the frequency of moderate-to-severe flushing. In a prospective, double-blind, placebo-controlled crossover trial, healthy adult male and female volunteers were asked to take aspirin or a placebo (both agents were taken in both orally dissolved and swallowed formulations) immediately before niacin administration. Subjects then self-evaluated flushing symptoms on a validated scale. RESULTS: Simultaneous administration of swallowed aspirin and niacin reduced moderate-to-severe flushing events by a mean of 36.1%, from 2.35 to 1.5 events per subject (p = 0.003), relative to event rates with use of niacin alone. In a subset of subjects who had experienced moderate-to-severe flushing symptoms despite taking swallowed aspirin, flushing in response to subsequent niacin use was decreased by 20.5% (p = 0.05) with coadministration of orally dissolved aspirin and by 18.0% with a regimen containing both orally dissolved and swallowed aspirin (p = 0.03). CONCLUSION: Novel regimens of niacin and aspirin, including orally dissolved aspirin, were effective in reducing niacin-induced flushing in a small sample of healthy adult volunteers.

Pharmacological treatment of hypertension and hyperlipidemia in Izhevsk, Russia.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death in Russia. Hypertension and hyperlipidemia are important risk factors for CVD that are modifiable by pharmacological treatment and life-style changes. We aimed to characterize the extent of the problem in a typical Russian city by examining the prevalence, treatment and control rates of hypertension and hyperlipidemia and investigating whether the specific pharmacological regimes used were comparable with guidelines from a country with much lower CVD rates. METHODS: The Izhevsk Family Study II included a cross-sectional survey of a population sample of 1068 men, aged 25-60 years conducted in Izhevsk, Russia (2008-2009). Blood pressure and total cholesterol were measured and self-reported medication use was recorded by a clinician. We compared drug treatments with the Russian and Canadian treatment guidelines for hypertension and hyperlipidemia. RESULTS: The prevalence of hypertension was 61 % (age-standardised prevalence 51 %), with 66 % of those with hypertension aware of their diagnosis and 50 % of those aware taking treatment. 17 % of those taking treatment achieved blood pressure control. The majority (59 %) of those taking treatment were not doing so regularly. Prevalence of hyperlipidemia was 45 % (age-standardised prevalence 40 %), however less than 2 % of those with hyperlipidemia were taking any treatment. Types of lipid-lowering and anti-hypertensive medications prescribed were broadly in line with Russian and Canadian guidelines. CONCLUSION: The prevalence of hypertension and hyperlipidemia is high in Izhevsk while the proportion of those treated and attaining treatment targets is very low. Prescribed medications were concurrent with those in Canada, but adherence is a major issue.

Endothelial Effect of Statin Therapy at a High Dose Versus Low Dose Associated with Ezetimibe / Efeito Endotelial da Terapia com Estatina em Alta Dose versus Baixa Dose Associada à Ezetimiba

Abstract Background: The effect of statins on the endothelial function in humans remains under discussion. Particularly, it is still unclear if the improvement in endothelial function is due to a reduction in LDL-cholesterol or to an arterial pleiotropic effect. Objective: To test the hypothesis that modulation of the endothelial function promoted by statins is primarily mediated by the degree of reduction in LDL-cholesterol, independent of the dose of statin administered. Methods: Randomized clinical trial with two groups of lipid-lowering treatment (16 patients/each) and one placebo group (14 patients). The two active groups were designed to promote a similar degree of reduction in LDL-cholesterol: the first used statin at a high dose (80 mg, simvastatin 80 group) and the second used statin at a low dose (10 mg) associated with ezetimibe (10 mg, simvastatin 10/ezetimibe group) to optimize the hypolipidemic effect. The endothelial function was assessed by flow-mediated vasodilation (FMV) before and 8 weeks after treatment. Results: The decrease in LDL-cholesterol was similar between the groups simvastatin 80 and simvastatin 10/ezetimibe (27% ± 31% and 30% ± 29%, respectively, p = 0.75). The simvastatin 80 group presented an increase in FMV from 8.4% ± 4.3% at baseline to 11% ± 4.2% after 8 weeks (p = 0.02). Similarly, the group simvastatin 10/ezetimibe showed improvement in FMV from 7.3% ± 3.9% to 12% ± 4.4% (p = 0.001). The placebo group showed no variation in LDL-cholesterol level or endothelial function. Conclusion: The improvement in endothelial function with statin seems to depend more on a reduction in LDL-cholesterol levels, independent of the dose of statin administered, than on pleiotropic mechanisms.

Resumo Fundamento: O efeito das estatinas na função endotelial em seres humanos permanece em discussão. Particularmente, ainda carece resposta se a melhora na função endotelial deve-se à redução do LDL-colesterol ou a um efeito pleiotrópico arterial. Objetivo: Testar a hipótese de que a modulação da função endotelial promovida por estatinas é prioritariamente mediada pelo grau de redução do LDL-colesterol, independente da dose de estatina utilizada. Métodos: Ensaio clínico randomizado com dois grupos de tratamento hipolipemiante (16 pacientes/cada) e um grupo placebo (14 pacientes). Os dois grupos ativos foram desenhados para promover graus semelhantes de redução de LDL-colesterol: o primeiro utilizou estatina em alta dose (80 mg, grupo sinvastatina 80) e o segundo em baixa dose (10 mg) associada a ezetimiba (10 mg, grupo sinvastatina 10/ezetimiba) para otimizar o efeito hipolipemiante. A função endotelial foi analisada pela vasodilatação mediada por fluxo (VMF) antes e após 8 semanas de tratamento. Resultados: A redução no LDL-colesterol foi semelhante entre os grupos sinvastatina 80 e sinvastatina 10/ezetimiba (27% ± 31% e 30% ± 29%, respectivamente, p = 0,75). O grupo sinvastatina 80 apresentou incremento da VMF de 8,4% ± 4,3% no basal para 11% ± 4,2% após 8 semanas (p = 0,02). Da mesma forma, o grupo sinvastatina 10/ezetimiba apresentou melhora da VMF de 7,3% ± 3,9% para 12% ± 4,4% (p = 0,001). O grupo placebo não apresentou variação no nível de LDL-colesterol ou da função endotelial. Conclusão: A melhora da função endotelial com uso de estatina parece depender mais da redução do LDL-colesterol, independente da dose de estatina utilizada, do que de mecanismos pleiotrópicos.