Statin Dose Research Articles

Lipid-Lowering Therapy for Primary Prevention of Cardiovascular Disease: A Nationwide Analysis of 440,721 Patients

Lead Author's Financial Disclosures AAK was supported by the National Heart, Lung, And Blood Institute of the National Institutes of Health under Award Number T32HL12547. The content is solely the responsibility of the authors and does not necessarily represent the official view of the National Institutes of Health. Study Funding Esperion Therapeutics, Inc. Background/Synopsis Statins are indicated for the primary prevention of atherosclerotic cardiovascular disease (ASCVD) in adults with diabetes mellitus (DM), elevated 10-year risk, and those with LDL-C ≥190 mg/dL. Contemporary treatment patterns in community practice are not well described. Objective/Purpose To explore the use and dosing of statin therapy and use of several classes of non-statin lipid lowering therapies (LLT) in adults recommended for statins in primary prevention. Methods We identified adults recommended for primary prevention statin therapy who received outpatient care in 90 US health systems between 2017 and 2018 using a de-identified, electronic health record dataset; Cerner Real World Data. Primary prevention populations included: DM and age 40-75, calculated 10-year ASCVD risk ≥7.5% and age 40-75, and those with LDL-C ≥190 mg/dL or familial hypercholesterolemia based on diagnosis code. Medication data, including self-reported use of supplements, were examined. Based on the 2013 ACC/AHA Cholesterol Guideline (what was active at the time), patients were classified as: on appropriate- intensity statin, on under-dosed statin, or not on a statin. Results We identified 440,721 patients recommended for statins (median age 63 years, 50.1% male, and 75.5% white race), including (by mutually exclusive, hierarchical order) 308,620 (70%) patients with DM, 125,411 (28.5%) with a 10-year risk ≥7.5%, and 6,690 (1.5%) with LDL-C ≥190 mg/dL. Overall, 211,295 (47.9%) were on appropriate statin therapy, 29,039 (6.6%) were on lower-than-recommended statin intensity, and 200,387 (45.5%) were not on any statin (Figure). People with DM had the relative highest percent utilization of appropriate-dose statin (53.8%), while only 35.4% of those recommended for 10-year risk were on appropriate- dose statin, and only 12% of those with LDL-C ≥190 mg/dL were treated appropriately (Figure). Utilization of non-statin LLT was low overall across all three groups (15.8%). However, nearly one in ten (9.4%) of those recommended for primary prevention reported taking non-prescription Omega-3/fish oil supplements (Figure). Conclusions Over half of primary prevention patients at high risk for ASCVD in the US are not on appropriate-dose, guideline-recommended statin therapy. Of these, the majority were not on any statin. Non-statin LDL-C lowering medication use was also low. Despite no data for cardiovascular benefit, a substantial number of adults were taking non-prescription fish oil. There remains a strong national need to improve overall utilization and evaluate barriers to prescription/uptake of evidence based LLT in all patients eligible for primary prevention. AAK was supported by the National Heart, Lung, And Blood Institute of the National Institutes of Health under Award Number T32HL12547. The content is solely the responsibility of the authors and does not necessarily represent the official view of the National Institutes of Health.

Lowering LDL cholesterol in clinical practice: time for change?

Atherosclerotic cardiovascular disease (ASCVD) events are associated with cumulative exposure to LDL cholesterol. Clinical guidelines for blood cholesterol management in people with ASCVD recommend monotherapy with the highest tolerated dose of statin before consideration of additional non-statin therapy to reach the LDL cholesterol goal.1,2 Combination lipid-lowering therapy (LLT) reduces LDL cholesterol concentrations to a greater extent than doubling the statin dose.3 However, until now, no randomised clinical trial had compared the long-term clinical event outcomes of high-intensity statin monotherapy versus lower-intensity statin with ezetimibe.

Association of statin treatment with hepatocellular carcinoma risk in end-stage kidney disease patients with chronic viral hepatitis

Statin use in end-stage kidney disease (ESKD) patients are not encouraged due to low cardioprotective effects. Although the risk of hepatocellular carcinoma (HCC), a frequently occurring cancer in East Asia, is elevated in ESKD patients, the relationship between statins and HCC is not known despite its possible chemopreventive effect. The relationship between statin use and HCC development in ESKD patients with chronic hepatitis was evaluated. In total, 6165 dialysis patients with chronic hepatitis B or C were selected from a national health insurance database. Patients prescribed with ≥ 28 cumulative defined daily doses of statins during the first 3 months after dialysis commencement were defined as statin users, while those not prescribed with statins were considered as non-users. Primary outcome was the first diagnosis of HCC. Sub-distribution hazard model with inverse probability of treatment weighting was used to estimate HCC risk considering death as competing risk. During a median follow-up of 2.8 years, HCC occurred in 114 (3.2%) statin non-users and 33 (1.2%) statin users. The HCC risk was 41% lower in statin users than in non-users (sub-distribution hazard ratio, 0.59; 95% confidence interval [CI], 0.42–0.81). The weighted incidence rate of HCC was lower in statin users than in statin non-users (incidence rate difference, − 3.7; 95% CI − 5.7 to − 1.7; P < 0.001). Incidence rate ratio (IRR) was also consistent with other analyses (IRR, 0.56; 95% CI, 0.41 to 0.78; P < 0.001). Statin use was associated with a lower risk of incident HCC in dialysis patients with chronic hepatitis B or C infection.

Association of Statin Usage and the Development of Diabetes Mellitus after Acute Pancreatitis

BackgroundPatients with acute pancreatitis (AP) have at least a 2-fold higher risk for developing postpancreatitis diabetes mellitus (PPDM). No therapies have prevented PPDM. Statins were demonstrated to possibly lower the incidence and severity of AP but have not been studied to prevent PPDM. MethodsData from a commercial insurance claim database (Optum Clinformatics) were used to assess the impact of statins on patients without pre-existing DM admitted for a first episode of AP in 118,479 patients. Regular statin usage was defined as filled statin prescriptions for at least 80% of the year prior to AP. The primary outcome was defined as PPDM. We constructed a propensity score and applied inverse probability of treatment weighting to balance baseline characteristics between groups. Using Cox proportional hazards regression modeling, we estimated the risk of PPDM, accounting for competing events. ResultsWith a median of 3.5 years of follow-up, the 5-year cumulative incidence of PPDM was 7.5% (95% confidence interval [CI], 6.9% to 8.0%) among regular statin users and 12.7% (95% CI, 12.4% to 12.9%) among nonusers. Regular statin users had a 42% lower risk of developing PPDM compared with nonusers (hazard ratio, 0.58; 95% CI, 0.52 to 0.65; P < .001). Irregular statin users had a 15% lower risk of PPDM (hazard ratio, 0.85; 95% CI, 0.81 to 0.89; P < .001). Similar benefits were seen with low, moderate, and high statin doses. ConclusionsIn a large database-based study, statin usage reduced the risk of developing DM after acute pancreatitis. Further prospective studies with long-term follow-up are needed to study the impact of statins on acute pancreatitis and prevention of PPDM.

Clinical impact of statin intensity according to age in patients with acute myocardial infarction.

The available data are not sufficient to understand the clinical impact of statin intensity in elderly patients who undergo percutaneous coronary intervention (PCI) due to acute myocardial infarction (AMI). Using the COREA-AMI registry, we sought to compare the clinical impact of high- versus low-to-moderate-intensity statin in younger (<75 years old) and elderly (≥75 years old) patients. Of 10,719 patients, we included 8,096 patients treated with drug-eluting stents. All patients were classified into high-intensity versus low-to-moderate-intensity statin group according to statin type and dose at discharge. The primary end point was target-vessel failure (TVF), a composite of cardiovascular death, target-vessel MI, or target-lesion revascularization (TLR) from 1 month to 12 months after index PCI. In younger patients, high-intensity statin showed the better clinical outcomes than low-to-moderate-intensity statin (TVF: 79 [5.4%] vs. 329 [6.8%], adjusted hazard ratio [aHR] 0.76; 95% confidence interval [CI] 0.59-0.99; P = 0.038). However, in elderly patients, the incidence rates of the adverse clinical outcomes were similar between two statin-intensity groups (TVF: 38 [11.4%] vs. 131 [10.6%], aHR 1.1; 95% CI 0.76-1.59; P = 0.63). In this AMI cohort underwent PCI, high-intensity statin showed the better 1-year clinical outcomes than low-to-moderate-intensity statin in younger patients. Meanwhile, the incidence rates of adverse clinical events between high- and low-to-moderate-intensity statin were not statistically different in elderly patients. Further randomized study with large elderly population is warranted.

Statins and statin intensity in peripheral artery disease.

Background: Peripheral artery disease (PAD) affects more than 202 million people worldwide. Several studies have shown that patients with PAD are often undertreated, and that statin utilization is suboptimal. European and American guidelines highlight statins as the first-line lipid-lowering therapy to treat patients with PAD. Our objective with this meta-analysis was to further explore the impact of statins on lower extremities PAD endpoints and examine whether statin dose (high vs. low intensity) impacts outcomes. Patients and methods: We performed a systematic review and meta-analysis according to the PRISMA guidelines. Any study that presented a comparison of use of statins vs. no statins for PAD patients or studies comparing high vs. low intensity statins were considered to be potentially eligible. We excluded studies with only critical limb threatening ischemia (CLTI) patients. The Medline (PubMed) database was searched up to January 31, 2021. A random effects meta-analysis was performed. Results: In total, 39 studies and 275,670 patients were included in this meta-analysis. In total, 136,025 (49.34%) patients were on statins vs. 139,645 (50.66%) who were not on statins. Statin use was associated with a reduction in all cause-mortality by 42% (HR: 0.58, 95% CI: 0.49-0.67, p<0.01) and cardiovascular death by 43% (HR: 0.57, 95% CI: 0.40-0.74, p<0.01). Statin use was associated with an increase in amputation-free survival by 56% (HR: 0.44, 95% CI: 0.30-0.58, p<0.01). The risk of amputation and loss of patency were reduced by 35% (HR: 0.65, 95% CI: 0.41-0.89, p<0.01) and 46% (HR: 0.54, 95% CI: 0.34-0.74, p<0.01), respectively. Statin use was also associated with a reduction in the risk of major adverse cardiovascular events (MACE) by 35% (HR: 0.65, 95% CI: 0.51-0.80, p<0.01) and myocardial infarction rates by 41% (HR: 0.59, 95% CI: 0.33-0.86, p<0.01). Among patients treated with statins, the high-intensity treatment group was associated with a reduction in all cause-mortality by 36% (HR: 0.64, 95% CI: 0.54-0.74, p<0.01) compared to patients treated with low intensity statins. Conclusions: Statin treatment among patients with PAD was associated with a statistically significant reduction in all-cause mortality, cardiovascular mortality, MACE, risk for amputation, or loss of patency. Higher statin dose seems to be associated with improved outcomes.

COVID-19 and chronic kidney disease: peculiarities of treatment

Abstract. The present study aimed to characterize the management of patients with chronic kidney disease with concomitant COVID-19. Articles published in 2019-2021 in the PubMed, Scopus, and Google Scholar electronic databases were analyzed.&#x0D; As a result of this review, the following particularities of COVID-19 treatment in chronic kidney disease could be summarized. It is obligatory to continue treatment with renin-angiotensin-aldosterone system inhibitors in patients with chronic kidney disease and COVID-19. Lisinopril is considered used for avoiding the elevated renal expression of angiotensin-converting enzyme 2. Spironolactone can prevent acute lung injuries and is reasonable if the triple combination of drugs for reducing blood pressure is not effective. Low-dose rosuvastatin therapy is recommended for patients with COVID-19 and chronic kidney disease stages 3-5 treated with antiretroviral drugs such as lopinavir and ritonavir, remdesivir. Ezetimibe is reasonable to use in case of ineffective higher doses of statins and to decrease hospitalization risk.

Influence of statin treatment in a cohort of patients admitted for COVID-19

Aims and objectivesStatins have been proposed as potentially useful agents for modulating the host response in COVID-19. However, solid evidence-based recommendations are still lacking. Our aim was to study the association between statin use and clinical outcomes in a large cohort of hospitalized patients with SARS-CoV-2 infection, as well as the specific consequences of chronic treatment withdrawal during hospital admission. Material and methodsRetrospective observational study including 2191 hospitalized patients with confirmed SARS-CoV-2 infection. ResultsMean age was 68.0±17.8 years and 597 (27.3%) patients died during follow-up. A total of 827 patients (37.7% of the whole sample), received chronic treatment with statins. Even though they underwent more frequent admissions in critical care units, chronic treatment with statins was not independently associated with all-cause mortality [HR 0.95 (0.72-1.25)]. During the whole hospital admission, 371 patients (16.9%) received at least one dose of statin. Although these patients had a significantly worse clinical profile, both treatment with statins during admission [HR 1.03 (0.78-1.35)] and withdrawal of chronic statin treatment [HR 1.01 (0.78-1.30)] showed a neutral effect in mortality. However, patients treated with statins presented more frequently hepatic cytolysis, rhabdomyolysis and thrombotic/hemorrhagic events. ConclusionsIn this large cohort of hospitalized COVID-19 patients, statins were not independently associated with all-cause mortality during follow-up. Clinically relevant statin-associated adverse effects should be carefully monitored during hospital admission.

Frequency of statin-induced liver injury: A secondary analysis of previous hospital-based study

Background: Although statins are considered safe, they do have side effects with a wide range of hepatic adverse effects. The present study aims to estimate the frequency of liver injury in patients treated with various statins and to describe their clinical characteristics and outcomes. Materials and Methods: We carried out a secondary post hoc analysis of collected data from our previous study entitled “Frequency of Rhabdomyolysis in Patients Treated with Statins in Hamad General Hospital, Qatar.” Results: We identified 10 cases (1.0%) of statin-induced liver injury during the study period. Their mean age was 62±10.09 years, with 6 (60%) males and 4 (40%) females. Of the 10 patients, six patients received rosuvastatin, two patients received atorvastatin, and other two cases received simvastatin. The mean duration between the initiation of statin and the development of liver injury (latency period) was 20.40±6.91 months. Five of our patients were asymptomatic, and liver injury was discovered incidentally during routine testing of the patients during routine follow-up, while four patients developed painless jaundice and one developed muscle pain attributed to rhabdomyolysis. Statins were stopped in all patients. Nine of them were managed on an outpatient basis, while one patient with rhabdomyolysis was admitted. In all patients, other statins were reintroduced after a mean time of 7.4±3 months without recurrence of liver injury. No mortality has been reported. Conclusion: Our study demonstrated that statin-induced liver injury is a rare clinical entity that occurs regardless of the dose and type of statin, with rosuvastatin being the most causative drug. Statin-induced liver injury was asymptomatic and was discovered incidentally in 50% of our cases during routine testing, underscoring the importance of routine follow-up of liver function tests in asymptomatic patients.

Genetically predicted on-statin LDL response is associated with higher intracerebral haemorrhage risk.

Statins lower low-density lipoprotein cholesterol and are widely used for the prevention of atherosclerotic cardiovascular disease. Whether statin-induced low-density lipoprotein reduction increases risk of intracerebral haemorrhage has been debated for almost two decades. Here, we explored whether genetically predicted on-statin low-density lipoprotein response is associated with intracerebral haemorrhage risk using Mendelian randomization. Using genomic data from randomized trials, we derived a polygenic score from 35 single nucleotide polymorphisms of on-statin low-density lipoprotein response and tested it in the population-based UK Biobank. We extracted statin drug and dose information from primary care data on a subset of 225 195 UK Biobank participants covering a period of 29 years. We validated the effects of the genetic score on longitudinal low-density lipoprotein measurements with generalized mixed models and explored associations with incident intracerebral haemorrhage using Cox regression analysis. Statins were prescribed at least once to 75 973 (31%) of the study participants (mean 57 years, 55% females). Among statin users, mean low-density lipoprotein decreased by 3.45 mg/dl per year [95% confidence interval (CI): (-3.47, -3.42)] over follow-up. A higher genetic score of statin response [1 standard deviation (SD) increment] was associated with significant additional reductions in low-density lipoprotein levels [-0.05 mg/dl per year, (-0.07, -0.02)], showed concordant lipidomic effects on other lipid traits as statin use and was associated with a lower risk for incident myocardial infarction [hazard ratio per SD increment 0.98 95% CI (0.96, 0.99)] and peripheral artery disease [hazard ratio per SD increment 0.93 95% CI (0.87, 0.99)]. Over a 11-year follow-up period, a higher genetically predicted statin response among statin users was associated with higher intracerebral haemorrhage risk in a model adjusting for statin dose [hazard ratio per SD increment 1.16, 95% CI (1.05, 1.28)]. On the contrary, there was no association with intracerebral haemorrhage risk among statin non-users (P = 0.89). These results provide further support for the hypothesis that statin-induced low-density lipoprotein reduction may be causally associated with intracerebral haemorrhage risk. While the net benefit of statins for preventing vascular disease is well-established, these results provide insights about the personalized response to statin intake and the role of pharmacological low-density lipoprotein lowering in the pathogenesis of intracerebral haemorrhage.

Cost Effectiveness of Inclisiran in Atherosclerotic Cardiovascular Patients with Elevated Low-Density Lipoprotein Cholesterol Despite Statin Use: A Threshold Analysis.

BackgroundInclisiran is a novel, cholesterol-lowering therapy, with a long duration of effect, administered every 6 months (subcutaneously by a healthcare professional). In the ORION-10 trial in US patients with atherosclerotic cardiovascular disease (ASCVD) in addition to maximum tolerated statins, with or without ezetimibe, inclisiran demonstrated statistically significant reductions in low-density lipoprotein cholesterol (LDL-C) of up to 51%. This is the first peer-reviewed publication to investigate the price at which inclisiran is cost effective in the US.ObjectiveThe aim of this study was to determine the maximum price at which inclisiran is cost effective in addition to standard of care, in US patients with ASCVD, versus standard of care alone, at different willingness-to-pay thresholds.Design, Setting and ParticipantsA lifetime Markov model from the US health system perspective, including 15 health states, was used to evaluate the cost effectiveness of inclisiran. The following states were separated by time from a previous cardiovascular event (0–1 years, 1–2 years, 2+ years [‘stable’]): initial, unstable angina, myocardial infarction, and stroke. Additional states included revascularization and death (cardiovascular or non-cardiovascular causes). Baseline risk of cardivoascular events were from US database sources or published literature. Reductions in LDL-C from inclisiran were from the ORION-10 trial. LDL-C reduction was used to adjust baseline risk of cardiovascular events, based on established relationships between 1 mmol/L reduction in LDL-C and decreases in cardiovascular events, from the Cholesterol Treatment Trialists studies. The population included adults with a history of ASCVD, and LDL-C ≥ 70 mg/dL, despite maximum tolerated doses of statin therapy.InterventionsInclisiran as an adjunct to standard of care, compared with standard of care alone.Main Outcomes and MeasuresThe threshold price of inclisiran.ResultsInclisiran as an adjunct to standard of care resulted in threshold annual inclisiran prices of $6383, $9973, and $13,563 at willingness-to-pay thresholds of $50,000, $100,000, and $150,000 per quality-adjusted life-year, respectively. Probabilistic sensitivity analysis showed that at a threshold of $100,000 per QALY, inclisiran had a 100% probability of being cost effective, with an annual price below $9000. At the publicly available price of $3250 per dose, inclisiran was found to have an incremental cost-effectiveness ratio just above the $50,000 per QALY threshold, of $51,686.Conclusions and RelevanceThis study identified the price at which inclisiran is cost effective for the US health system, at generally accepted willingness-to-pay thresholds.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40256-022-00534-9.

Interactions Between Statins, Exercise, and Health: A Clinical Update

Interactions Between Statins, Exercise, and Health: A Clinical Update

A PCSK9 inhibitor induces a transient decrease in the neutrophil-lymphocyte ratio and monocyte-lymphocyte ratio in homozygous familial hypercholesterolemia patients

Background and aimsExtremely elevated levels of low-density lipoprotein-cholesterol (LDL-C) contribute to long-term chronic systemic inflammation in homozygous familial hypercholesterolemia (HoFH) patients. The aims of this study is to describe the inflammatory profile of HoFH patients and explore the effect of a PCSK9 inhibitor (PCSK9i) on a series of inflammatory biomarkers, including the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-HDL ratio (MHR), monocyte-lymphocyte ratio (MLR) and mean platelet volume-lymphocyte ratio (MPVLR). MethodsIn this prospective cohort study, 25 definitive HoFH patients on high-intensity statins plus ezetimibe were administered subcutaneous injections of 420 mg PCSK9i every 4 weeks (Q4W). The biochemical parameters and inflammatory profile were analyzed on the day before PCSK9i therapy and 3 months and 6 months after PCSK9i therapy. ResultsHoFH on the maximum tolerated statin dose plus ezetimibe displayed elevated lipid and disturbed blood biomarker profiles. After 3 months of add-on PCSK9i therapy, a significant reduction in LDL-C was observed. Moreover, the percentage and count of neutrophils, monocyte counts, MPV, and two inflammatory biomarkers, the NLR and MLR, were reduced. However, at 6 months of PCSK9i treatment, the NLR and MLR returned to pre-PCSK9i treatment levels. ConclusionsPCSK9i induces a transient decrease in the NLR and MLR in HoFH patients in a lipid-lowering independent manner.

Low-density lipoprotein cholesterol increased significantly after short-term discontinuation of atorvastatin, but did not correlate with plasma drug concentrations

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): The Dam foundation Introduction Statin non-adherence remains a prevalent challenge in cardiovascular disease prevention and robust methods to monitor adherence are needed. Large variations in low-density-lipoprotein cholesterol (LDL-C) response to a given type and dose of statin have been reported. The LDL-C response to short-term discontinuation of statins is not well defined. Moreover, the relationship between the blood concentrations of statin metabolites and LDL-C, and how clinical factors interact, are unknown. Purpose To determine changes in LDL-C at an individual and group level during four-day discontinuation of atorvastatin, and to investigate whether clinical factors and atorvastatin metabolites concentration correlate with changes in LDL-C. Methods This clinical pharmacokinetic adherence study conducted in 2021, included 60 adult participants treated with atorvastatin 20 mg (n=20), 40 mg (n=20) or 80 mg (n=20). The participants were instructed to take atorvastatin daily between 07 and 10 am the week before study start, to ensure steady state drug concentrations. The last dose of atorvastatin was taken 24 hours prior to the first blood sampling (day zero). Atorvastatin doses were omitted until after blood sampling on the fourth day. The concentrations of atorvastatin metabolites (acid and lactone forms, including 2-OH- and 4-OH metabolite) were measured by a liquid chromatography–tandem mass spectrometry assay. Paired-samples T-tests, Spearman rank correlations and linear regression analyses were performed with SPSS. Results Mean age was 65 (SD 11) years, 18 (30%) were female, 45 (75%) had cardiovascular disease and 11 (18%) had diabetes mellitus. Mean LDL-C at steady state on day zero was 1.9 (SD 0.6) mmol/L. LDL-C increased on average by 0.5 (SD 0.3) mmol/L (30%) from day zero to day four, during the period with atorvastatin discontinuation. The increase of LDL-C was significant already after the first omitted dose (day one) (Figure 1). LDL-C increased from day zero to day four in 78 out of the 80 patients (97.5%). Higher Body Mass Index was significantly associated with lager increase in LDL-C during the four-day discontinuation (B 0.02, 95% CI 0.01 to 0.04, p=0.028), whereas age, sex, kidney function, cardiovascular disease and diabetes were not. Changes in atorvastatin plus metabolites concentration from day zero to day four were not associated with changes in LDL-C during discontinuation (Figure 2). This also applied if we assessed the individual atorvastatin metabolites. Conclusion Atorvastatin discontinuation for only four days resulted in a statistically significant 30% increase of LDL-C. Atorvastatin pharmacokinetics did not correlate with change in LDL-C during the discontinuation. Even short-term non-adherence may have unfavourable consequences, and deserves further attention.

Current lipid-lowering approach and LDL target achievement in very high-risk patients: in-hospital results of a high-volume primary percutaneous coronary intervention tertiary center

Abstract Funding Acknowledgements Type of funding sources: None. Background Low-density lipoprotein-cholesterol (LDL-C) is a well-accepted causal risk factor for atherothrombotic cardiovascular disease. Several randomized controlled trials and meta-analyses have shown that lipid-lowering therapies reduce cardiovascular events and have a positive effect in reducing vulnerable plaques. In particular, the recommended target for LDL-C has become more and more stringent, moving to 1.4 mmol/l (55 mg/dl) for very high-risk patients. According to the 2019 ESC/EAS Guidelines, the current paradigm for lipid management favors a stepwise approach consisting of early initiation of high-intensity statin, followed by subsequent addition of ezetimibe, and ultimately a consideration of PCSK9 inhibitor treatment if LDL-C levels remain elevated. Methods We recruited 307 patients admitted for acute coronary syndrome (ACS) during the COVID-19 pandemic from March 2020 to December 2020. Baseline LDL-C concentration and prescribed hypolipemiant treatment at hospital admission and discharge were registered. Therefore, we included all consecutive patients identified as very-high cardiovascular risk, according to 2019 ESC guidelines. We stratified our population through variables independently associated with non-attainment of LDL-cholesterol such as hypertension, diabetes, peripheral arterial disease, clinical manifestations of ACS, number of main vessels treated, and complexity of the atherosclerotic disease. Results 274 patients were included. Mean age was 69,9 years (SD 11,4), 20,8 % were women, 23,7 % had diabetes, 16,4 % had PAD and 32,1 % suffered from valvular disease, mainly with mitral regurgitation or aortic stenosis no more than mild or moderate. Of 25.1% with a previous history of acute myocardial infarction, the 33,3% of whom didn’t have statin therapy pre-ACS index (p =0,001). At admission, medium cholesterol levels of patients that underwent previous coronary revascularization (25,5% of the total population) were 84,21 ± 31,2 mg/dL, not in range according to both 2016 and 2019 ESC guidelines. At discharge, 77,37 % of all the patients included received only statin therapy VS 22,63% with statin plus ezetimibe. In the subpopulation of patients with recurring ACS events with LDL pre-admission &amp;gt; 100 mg/dL,despite high dose statin, only 25% of this population were discharged adding ezetimibe (VS 75% who kept on the treatment of high dose statin without up-titration). Conclusions Management of dyslipidemia is frequently suboptimal and the gap between guidelines and clinical practice for lipid management across Europe has been exacerbated by the 2019 guidelines. A greater utilization of non-statin lipid-lowering therapies is likely needed to reach the LDL-C optimal target. A correct stratification of the risk class would help to identify, in a personalized perspective of treatment, patients at very high risk that would take advantage of more aggressive therapy to reach the lowest target of LDL-C ("the lower is better").

Timing of statin dose: a systematic review and meta-analysis of randomized clinical trials.

Timing of statin dose: a systematic review and meta-analysis of randomized clinical trials.

MO244: PCSK9 Inhibitors are Efficient in Treatment of Resistant Hypercholesterolemia in Nephrotic Syndrome

Abstract BACKGROUND AND AIMS Hypercholesterolemia in nephrotic syndrome is commonly resistant to statin therapy and represents an important clinical challenge both for cardiovascular risk prevention and to eliminate lipotoxic effect on podocytes. Serum PCSK9 level is elevated in nephrotic syndrome and has a key pathophysiologic role in development and persistance of hyperlipidemia. Thus, we aimed to investigate the role of PCSK9 inhibitors in control of hypercholesterolemia in patients with neprotic syndrome. METHOD Consecutive patients with nephrotic syndrome and elevated atherogenic Lp (a) (n = 4) and patients with resistant secondary glomerulonephritis with nephrotic proteinuria (n = 2) were included. In all patients, in addition to full dose statin therapy, evolocumab 420 mg s.c. monthly was introduced. Lipid levels were measured after a median of 4 (range 2–9) months after starting evolocumab. RESULTS Nephrotic syndrome was caused by focal segmental glomerulosclerosis in four patients (66.7%) and membranous nepropathy was the cause in two patients (33.3%). Median age of included patients was 49.5 (range 24–70) years. Four patients with primary cause of glomerulonephritis received specific imunosupressive treatment. During follow-up, we observed descrease in glomerular filtration rate (eGFR median 58.5 interquartile range (IQR) [46.7–98.7] mL/min/1.73 m2 versus median 47 IQR [38.25–89.25] mL/min/1.73 m2; P = .046) and persistence of proteinuria [median 11 970 IQR (3862–13 765) mg/dU versus median 10 847 (5407–14 340) mg/dU; P = .753]. However, despite persistent proteinuria and decrease in eGFR, significant decrease in total cholesterol [median 9.10 IQR (6.92–10.87) mmol/L versus median 6.81 (5.4–8.45) mmol/L; P = .028] and LDL cholesterol [median 5.40 IQR (4.12–7.25) versus median 4.04 IQR (2.70–4.60); P = .046] was observed. There was no significant difference in Lp (a) and triglyceride levels. CONCLUSION PCSK9 inhibitors are a promising new therapeutic option for hyperlipidemia in patients with nephrotic syndrome. Further research, including a larger number of patients, is needed to correctly position PCSK9 inhibitors in treatment of hyperlipidemia in patients with nephrotic syndrome.

Association of Familial Hypercholesterolemia and Statin Use With Risk of Dementia in Norway

Hypercholesterolemia, which is a cardiovascular risk factor, may also be associated with dementia risk. The benefit of statin treatment on dementia risk is controversial. To determine whether individuals with familial hypercholesterolemia (FH), who have been exposed to lifelong hypercholesterolemia, have an excess risk of dementia and whether statin use is associated with dementia risk. This was a prospective cohort study performed from 2008 to 2018 in Norway. Statistical analysis was performed from January 2021 to February 2022. This study included individuals with genetically verified FH and age-matched and sex-matched controls obtained from the general Norwegian population. Dementia was defined according to International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes F00-03 and G30. Incident cases of total dementia, vascular dementia, Alzheimer disease-dementia in Alzheimer disease, and data on lipid-lowering medication were obtained from the Norwegian Patient Registry, Cause of Death Registry, and the Norwegian Prescription Database. Hazard ratios (HRs) for risk of dementia for individuals with FH vs matched controls were calculated using Cox regression. The cumulative sum of defined daily doses (DDDs) of statins prescribed during study follow-up was calculated for individuals with FH and was analyzed as a time-varying covariate with 3 levels: 1 to 4999 DDDs, 5000 to 10 000 DDDs, and more than 10 000 DDDs. Among the 3520 individuals with FH (1863 women [52.9%]; mean [SD] age at the start of follow-up, 51.8 [11.5] years) and the 69 713 controls (36 958 women [53.0%]; mean [SD] age at the start of follow-up, 51.7 [11.5] years), 62 patients with FH (39 women [62.9%]) and 1294 controls (801 women [61.9%]) had developed dementia over the course of 10 years of follow-up. Most dementia cases occurred among individuals aged 70 years and older (39 patients with FH [62.9%] and 870 patients [67.2%] in the control group). We found no excess risk of dementia in patients with FH vs matched controls (HR for total dementia, 0.9; 95% CI, 0.7-1.2). There was no association between cumulative DDDs of statins and total dementia in patients with FH with HRs of 1.2 (95% CI, 0.4-3.8) for cumulative DDDs of 5000 to 10 000 and 1.9 (95% CI, 0.7-5.0) for cumulative DDDs greater than 10 000. These findings suggest that individuals with FH have no excess risk of dementia compared with age-matched and sex-matched controls and that there is no association between use of statins and risk of dementia in patients with FH.

From the Editor’s Desk...

From the Editor’s Desk...

A Paradigm Shift in Dyslipidemia Management in Primary Care: A 12-Month Cohort Study

PurposeLDL-lowering therapy is beneficial to reduce the risk of cardiovascular disease (CVD). Higher statin doses lower LDL-C levels and prevent CVD; however, they increase adverse events, such as muscle-related adverse events and new-onset diabetes mellitus (DM). Ezetimibe combined with statin therapy improves LDL-C–lowering levels and tolerability in patients with established CVD. We aimed to analyze the efficacy and safety of a fixed-dose rosuvastatin and ezetimibe (R+E) combination therapy in intermediate-risk patients with hypercholesterolemia and no DM after 12 months of visiting a primary physician. MethodsThis multicenter, open-label, single-arm, prospective observational study involved 5717 patients from 258 primary health care centers in Korea enrolled between 2016 and 2018. Patients had no DM or previous CVD but had cardiovascular risk factors and were taking a statin or a fixed-dose combination of E (10 mg) + R (5, 10, or 20 mg). We analyzed 700 patients using propensity score matching. FindingsA fixed-dose R+E combination therapy significantly reduced LDL-C in 5/10 mg R+E (29.35%), 10/10 mg R+E (36.19%), and 20/10 mg R+E (41.83%) compared with statin monotherapy (19.09%) at 12-month follow-up (P = 0.017). Compared with statin monotherapy, HDL-C levels increased in 5/10 mg R+E (mean change at 12 months; P = 0.004), and triglyceride levels decreased in 10/10 mg R+E (mean change at 12 months; P = 0.033). The fixed-dose R+E combination therapy was associated with fewer adverse events and a neutral effect on glucose deterioration compared with statin monotherapy at 12 months of follow-up. ImplicationsIn a possible paradigm shift, a fixed-dose R+E combination therapy may be beneficial for primary cardiovascular prevention with potent LDL-lowering efficacy and tolerability; however, further large prospective studies are needed.