Moderate Statin Research Articles

Switching, Persistence and Adherence to Statin Therapy: a Retrospective Cohort Study Using the Australian National Pharmacy Data.

Statins are widely prescribed for the primary and secondary prevention of cardiovascular disease (CVD), but their effectiveness is dependent on the level of adherence and persistence. This study aimed to explore the patterns of switching, adherence and persistence among the Australian general population with newly dispensed statins. A retrospective cohort study was conducted using a random sample of data from the Australian national prescription claims data. Switching, adherence to and persistence with statins were assessed for people starting statins from 1 January 2015 to 31 December 2019. Switching was defined as either switching to another intensity of statin, to another statin or to a non-statin agent. Non-persistence to treatment was defined as discontinuation (i.e. ≥90days with no statin) of coverage. Adherence was measured using proportion of days covered (PDC), and patients with PDC < 0.80 were considered non-adherent. Cox proportional hazard models were used to compare discontinuation, switching and reinitiation between different statins. A cohort of 141,062 people dispensed statins and followed over a median duration of 2.5years were included. Of the cohort, 29.3% switched statin intensity, 28.4% switched statin type, 3.7% switched to ezetimibe and in 2.7%, ezetimibe was added as combination therapy during the study period. Overall, 58.8% discontinued statins based on the 90-day gap criteria, of whom 55.2% restarted. The proportion of people non-adherent was 24.0% at 6 months to 49.0% at 5 years. People on low and moderate intensity statins were more likely to discontinue compared to those on high-intensity statins (hazard ratio [HR] 1.20, 95% confidence interval [CI] 1.09-1.31), (HR 1.28, 95%CI 1.14-1.42), respectively. Compared to maintaining same statin type and intensity, switching statins, which includes up-titration (HR 0.77, 95%CI 0.70 to 0.86) was associated with less likelihood of discontinuation after reinitiation. Long-term persistence and adherence to statins remains generally poor among Australians, which limits the effectiveness of these medicines and the consequent health impact they may provide for individuals (and by extension, the population impact when poor persistence and adherence is considered in the statin-taking population). Switching between statins is prevalent in one third of statin users, although any clinical benefit of the observed switching trend is unknown. This, combined with the high volume of statin prescriptions, highlights the need for better strategies to address poor persistence and adherence.

Intensity of statin therapy and muscle symptoms: a network meta-analysis of 153 000 patients

ObjectiveTo estimate relative risk (RR) of statin-associated musculoskeletal symptoms by statin therapy intensity.SettingNetwork meta-analysis assessing multicentre randomised controlled trials (RCTs) across several countries.ParticipantsPubMed, Web of Science, Cochrane database and ClinicalTrials.gov...

Patient"s awareness of recommended LDL-C goals in primary prevention and observed achievement

Abstract Funding Acknowledgements Type of funding sources: None. Introduction The novel 2019 ESC/EAS Guidelines on lipids recommend more intensive reduction on LDL-C across CV risk categories in comparison with the 2016 edition. Purpose This cross-sectional observation study aims to assess whether patients on lipid lowering therapy, as a primary prevention measure, are aware of the new set goals and if they achieved them. Methods Patients, taking currently any statin as a primary prevention measure, visiting the Emergency Department of a tertiary hospital in northern Greece were invited to participate by answering a short questionnaire followed by a phone call to provide the exact lab results or other details. Results In total 412 eligible patients (54.1% female) were enrolled from January to October 2020 (mean age 61 ± 13 years old). Mean duration of statin prescription was about 8 years (7.8 ± 5 years). The majority (381, 92.5%) of patients reported lab tests yearly while most of them (394, 95.6%) were being followed up in outpatient clinics or private offices. Patients were allocated into CV categories: low (48, 11.7%), medium (239, 58.0%), high (108, 26.2%) and very high (17, 4.1%). The estimated 10-year risk of CV death was calculated using SCORE. Almost two thirds of the patients (282, 68.4%) were taking moderate intensity statins (as monotherapy) while one out of ten (45, 10.9%) was taking a statin plus ezetimibe combination. No patient was prescribed a PCSK9 inhibitor. Only two out of five (171, 41.5%) patients reached the LDL-C goal, though differences were noted between risk categories with almost half of the low and medium CV risk patients achieving the desired LDL-L level: low (23, 47.9%), medium (124, 51.9%), high (21, 19.4%) and very high (3, 17.6%). No significant difference was observed in terms of potency of statin. As expected, patients taking a statin and ezetimibe combination achieved lower LDL-C levels, with almost two thirds (31 out of 45 patients, 68.9%) reaching the goal. No information could be collected regarding why patients not reaching the goal were not offered a statin of higher potency and/or dosing, a combination with ezetimibe or a PCSK9 inhibitor. Disturbingly enough, none of the patient was aware that the LDL-C goals recommended by scientific societies had been lowered in 2019, while only 29 patients (7.0%) could recall discussing LDL-C goals with their physician. Moreover, merely three patients could remember the calculation of any CV risk score. The majority of the patients (379, 92.0%) reported that they would like to know their personal CV risk score and their LDL-C goal. Conclusions Greek primary prevention patients taking statins are overall unaware of the novel set LDL-C goals and it seems that they have not been offered a total CV risk score assessment. Hardly acceptable attainment of LDL-C goals was observed. Further research is warranted to assess the barriers that obstruct a satisfactory goal achievement. Abstract Figure.

Three-dimensional ultrasound imaging: An effective method to detect the effect of moderate intensity statin treatment in slowing carotid plaque progression.

We aimed to evaluate the feasibility of three-dimensional ultrasound imaging (3DUS) in assessing the therapeutic effect of moderate-intensity statin therapy on carotid atherosclerotic plaques. Patients with carotid plaques were recruited to the study from January 2016 to September 2018, and were divided into two groups based on whether or not they were taking statins. All participants underwent 3DUS of their carotid plaques at baseline, then 3months and 2 years after initial examination. The changes of the carotid plaques were compared between the two groups. Were included 97 patients (57 males and 40 females), 65.26 ± 9.53 year-old with 67 into the statin group and 30 in the control group. The baseline levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were lower in the statin group than in the control group (3.79 ± 0.78 mmol/L vs 4.50 ± 1.12 mmol/L; 2.01 ± 0.62 mmol/L vs 2.58 ± 0.91 mmol/L, P< .05). There was no significant difference in the change of total plaque volume (TPV) detected by 3D-US between the statin (median [interquartile range]: 0 [-30-20] mm3 ) and the control group (0 [-22.5-25] mm3 ) at 3months. Over 2 years, the TPV increased faster in the control group (+70 [25-150] mm3 ), than in the statin group (15 [-57.5-90) mm3 , P< .05). 3DUS can be an effective tool to observe the development of carotid plaques and the effect of statin treatment.

Comparative effect of physical exercise versus statins on improving arterial stiffness in patients with high cardiometabolic risk: A network meta-analysis.

The comparative analysis of the effect of several doses of statins against different intensities of physical exercise on arterial stiffness (a measure of cardiovascular risk) could shed light for clinicians on which method is most effective in preventing cardiovascular disease (CVD) and be used to inform shared decision-making between doctors and patients. This study was aimed at analyzing the effect, in high cardiometabolic risk patients, of different statins doses and exercise intensities on arterial stiffness (a measure of cardiovascular risk) by integrating all available direct and indirect evidence in network meta-analyses. We systematically searched MEDLINE, Embase, SPORTDiscus, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Web of Science databases from their inception to February 28, 2020; for unpublished trials, we also searched ClinicalTrials.gov. We searched for studies concerning the effect of statins or physical exercise on arterial stiffness, measured by pulse wave velocity (PWV). For methodological quality assessment, Cochrane Collaboration's tool for assessing risk of bias (RoB2) was used. A network geometry graph was used to assess the strength of the evidence. Comparative evaluation of the interventions effect was performed by conducting a standard pairwise meta-analysis and a network meta-analysis (NMA) for direct and indirect comparisons between interventions and control/nonintervention. A total of 22 studies were included in the analyses (18 randomized controlled trials (RCTs) and 4 nonrandomized experimental studies), including 1,307 patients with high cardiometabolic risk from Asia (3 studies), Oceania (2 studies), Europe (10 studies), North America (5 studies), and South America (2 studies). The overall risk of bias assessed with RoB2 was high in all included studies. For standard pairwise meta-analysis and NMA, high-intensity exercise versus control (mean difference (MD) -0.56; 95% CI: -1.01, -0.11; p = 0.015 and -0.62; 95% CI: -1.20, -0.04; p = 0.038, respectively) and moderate statin dose versus control (MD -0.80, 95% CI: -1.59, -0.01; p = 0.048 and -0.73, 95% CI: -1.30, -0.15; p = 0.014, respectively) showed significant MDs. When nonrandomized experimental studies were excluded, the effect on high-intensity exercise versus control and moderate statin dose versus was slightly modified. The main limitation of this study was that the magnitude of the effect of the exercise interventions could be underestimated due to regression toward the mean bias because the baseline cardiometabolic risk profile of patients in the physical exercise intervention trials was healthier than those in the statins ones; consequently, more modest improvements in physical exercise interventions compared to statins interventions can be expected. Additionally, we might consider as limitations the small study sizes, the heterogeneous patient groups, the focus on a proxy endpoint (PWV), and the high risk of bias. In this NMA, we found that although many patients could benefit from statins for reducing CVD risk, our results support that, considering the beneficial effects of high-intensity exercise on arterial stiffness, it would be worthwhile to refocus our attention on this type of exercise as an effective tool for the prevention of CVD. PROSPERO CRD42019123120.

Assessment of Lipid Profile and Serum Creatinine Kinase in Subjects with Hyperlipidemia on Moderate Intensity Statin Therapy Attending a Postgraduate Teaching Hospital in South India

Atherosclerosis of large and medium sized arteries are believed to be the major reason behind the development of Coronary Artery Diseases and Hyperlipidemia has been found to be one of the most important contributing factors. Appropriate lifestyle changes along with proper drug therapy lead to a considerable reduction in mortality rate due to coronary artery disease. Reduction of LDL Cholesterol is the primary goal of cholesterol-lowering therapy, but most of the patients are usually unable to achieve the treatment goals with lifestyle modifications alone; and in such situations, drug therapy is essential to prevent the disease progression and further future complications. The aim of the study was to demonstrate impact of three moderate intensity statins on lipid profile and biomarker representing muscle toxicity. It was a prospective observational study conducted in a tertiary care teaching hospital in south India. Patients of both gender falling the age group between 30 and 70 years with newly diagnosed Hyperlipidemia attending the Department of Medicine OPD, were enrolled in the study. Total 229 participants were enrolled in study and all the drug treatment were found to be effective in achieving the treatment goal; at the same time Rosuvastatin 10 mg treatment group exhibited better efficacy along with minimal muscle toxicity.

Effect of PCSK9 inhibitor on lipoprotein particles in patients with acute coronary syndromes

BackgroundTo assess the effects of proprotein convertase subtilisin/kexin type 9 inhibitor (evolocumab) on lipoprotein particles subfractions with Nuclear Magnetic Resonance spectroscopy in patients with acute coronary syndromes.MethodsA total of 99 consecutive patients with ACS were enrolled and assigned to either the experimental group (n = 54) or the control group (n = 45). The combination therapy of PCSK9 inhibitor (Repatha®, 140 mg, q2w) and moderate statin (Rosuvastatin, 10 mg, qn) was administered in the experimental group, with statin monotherapy (Rosuvastatin, 10 mg, qn) in the control group. The therapeutic effects on lipoprotein particle subfractions were assessed with NMR spectroscopy after 8 weeks treatment, and the achievement of LDL-C therapeutic target in both groups were analyzed.ResultsIn the experimental group, after 8 weeks of evolocumab combination treatment, the concentrations of blood lipids (TC, LDL-C and its subfractions [LDL-1 to 6], VLDL-C and its subfractions [VLDL-1 to 5], IDL-C, and HDL-C), lipoprotein particles, and their subfractions [VLDL-P, IDL-P, LDL-P, and its subfractions [LDL-P1 to 6], apoB, and LP(a)] demonstrated therapeutic benefits with statistical significance (P < 0.05). The decrease in total LDL-P concentrations was mainly due to a decreased concentration of small-sized LDL particles (LDL-P 5 + 6), which was significantly more prominent than the decrease in medium-sized LDL-P (LDL-P3 + 4) and large-sized LDL-P (LDL-P1 + 2) (P < 0.001). According to lipid control target recommended by the latest China Cholesterol Education Program Expert Consensus in 2019, after 8 weeks treatment, 96.3% patients in the experimental group and 13.3% in the control group had achieved the LDL-C therapeutic target (P < 0.01).ConclusionsEvolocumab combination treatment for 8 weeks significantly improves the plasma lipid profiles in ACS patients, and significantly decrease the concentration of lipoprotein particles which might contribute to the pathonesis of atherosclerosis.

Statin Use in Older Adults with Stable Atherosclerotic Cardiovascular Disease.

Older adults (>75 years of age) represent two-thirds of atherosclerotic cardiovascular disease (ASCVD) deaths. The 2013 and 2018 American multi-society cholesterol guidelines recommend using at least moderate intensity statins for older adults with ASCVD. We examined annual trends and statin prescribing patterns in a multiethnic population of older adults with ASCVD. Retrospective longitudinal study using electronic health record (EHR) data from 2007 to 2018. A large multi-specialty health system in Northern California. A total of 24,651 adults older than 75 years with ASCVD. Statin prescriptions for older adults with known ASCVD were trended over time. Multivariable regression models were used to identify predictors of statin prescription (logistic) after controlling for relevant demographic and clinical factors. The study cohort included 24,651 patients older than 75 years; 48% were women. Although prescriptions for moderate/high intensity statins increased over time for adults over 75, fewer than half of the patients (45%) received moderate/high intensity statins in 2018. Women (odds ratio (OR) = 0.77; 95% confidence interval (CI) = 0.74, 0.80), patients who had heart failure (OR = 0.69; 95% CI = 0.65, 0.74), those with dementia (OR = 0.88; 95% CI = 0.82, 0.95) and patients who were underweight (OR = 0.64; 95% CI = 0.57, 0.73) were less likely to receive moderate/high intensity statins. Despite increasing prescription rates between 2007 and 2018, guideline-recommended statins remained underused in older adults with ASCVD, with more pronounced disparities among women and those with certain comorbidities. Future studies are warranted to examine reasons for statin underuse in older adults with ASCVD.

Applicability of the REDUCE-IT trial to the FAST-MI registry. Are the results of randomized trials relevant in routine clinical practice?

The REDUCE-IT data revealed robust CVD reduction with a strategy comprising of high dose omega-3 icosapent ethyl. In order to evaluate the applicability of REDUCE-IT, we applied the inclusion and exclusion criteria in the French Registry on Acute ST- elevation and non-ST-elevation Myocardial Infarction (FAST-MI). We included patients over 45 years, who had detailed lipid values 11.1 months after hospitalization for MI. We compared the applicability of REDUCE-IT [TG between 150 and 500 mg/dl and an LDL-C between 40 and 100 mg/dl while treated with statin therapy] in the FAST-MI registry. 12.5% of the patients met the eligibility criteria for REDUCE-IT. The differences between the REDUCE-IT like and REDUCE-IT excluded samples were related to age, male gender, body mass index, current smoking, hypertension, and the percentage of diabetic patients. In the REDUCE-IT like sample, the mean values of total cholesterol, TG (median) and the HDL-C were respectively 159, 192, 43 and the LDL-C value was 72 mg/dl. The distribution of the statin regimens in the REDUCE-IT like sample was as follows: 65.3%, 32.4% and 2.3% had high, moderate and low intensity statin therapy. The distribution of TG categories in the REDUCE-IT like sample was as follows: 55.3% (150-199), 36.0% (200-299) and 8.7% (300-500 mg/dl). The subgroup with TGs greater than 200 mg/dl and HDL-C less than 35 mg/dl was 16.1% in the REDUCE-IT like group and 2.1% in the REDUCE-IT excluded group ( P < 0.001). The cardiovascular event rate (death, nonfatal MI, nonfatal stroke) was respectively 36.7 for the FAST-MI REDUCE-IT like group and 36.9 per 1000 persons-years (CVD death, nonfatal MI, nonfatal stroke) for the REDUCE-IT trial. If the results of REDUCE-IT are applied to patients hospitalized for a myocardial infarction in France, on top of statins, 12.5% of these patients could benefit from a strategy of high dose omega-3 icosapent ethyl.

Abstract 13588: Cardiovascular Outcomes in Patients With Established Atherosclerosis and LDLR Loss of Function: Results From the FOURIER Trial

Introduction: Patients with loss of function (LoF) mutations of the LDL receptor gene (LDLR) have lifelong elevations in LDL-C. We investigated their risk of cardiovascular (CV) events compared with patients with intact LDLR function. Methods: We performed a prospective genetic cohort analysis from the FOURIER trial including all 14,297 patients who consented for genetic testing, passed QC, and were of European ancestry. All patients had established ASCVD and were on moderate or high intensity statin therapy. Whole exome sequencing was performed and LoF mutations in LDLR were identified using LOFTEE, a tool for detecting protein-truncating variants. Polygenic risk for CAD was also calculated for each patient using a previously validated 27-SNP genetic risk score, with high and low risk defined as above and below the median. The primary endpoint was a composite of CV death, myocardial infarction, stroke, unstable angina, or coronary revascularization. Results: There were 111 (0.8%) patients identified with an LDLR LoF mutation, representing an approximately 4-fold enrichment compared to the general population. These patients had mean baseline LDL-C levels 62 mg/dl higher than those without an identified LDLR LoF mutation (160 vs. 98 mg/dl, p&lt;0.0001) and a 70% increased risk of CV events (HR 1.70 [1.04-2.79], p=0.03) ( Figure, a ). When polygenic risk for CAD was combined with LDLR mutation status there was a significant gradient of risk identified (p-trend=0.001). Patients without a monogenic LDLR mutation or high polygenic risk had a 2.5-year KM event rate of 8.6%; those with either one had a 10.0-12.9% event rate; those with both had a 17.1% event rate ( Figure, b ). Conclusion: ASCVD patients with LDLR LoF mutations have persistently elevated LDL-C and increased CV risk despite intensive statin therapy. The combination of a monogenic LDLR mutation with high polygenic risk for CAD appears additive in this secondary prevention cohort.

Abstract 13200: Relationship Between Baseline Low-Density Lipoprotein Cholesterol and Percent Low-Density Lipoprotein Cholesterol Reduction With Evolocumab in the FOURIER (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Patients With Elevated Risk) Trial

Introduction: The FOURIER trial demonstrated that the PCSK9 inhibitor evolocumab robustly reduced LDL-C amongst patients on moderate or high intensity statins. We investigated whether the magnitude of the percentage LDL-C reduction is consistent across baseline LDL-C levels. Methods: FOURIER enrolled 27,564 patients with ASCVD and an LDL-C ≥70 mg/dl or a non-HDL-C ≥100 mg/dl on optimized statin therapy at the time of enrollment. The % LDL-C reduction from baseline to 12 wks was examined in patients on study drug through 12 wks (N=25,847) using a quadratic regression model including terms for treatment (evolocumab vs. placebo), baseline LDL-C and [LDL-C] 2 , and interaction terms. Stratified analyses were done for patients on high vs. moderate intensity statin. Results: Overall, compared with placebo, evolocumab reduced LDL-C by 61% (95% CI 61-62%). Patients with lower baseline LDL-C had significantly greater % LDL-C reductions (Figure top; P&lt;0.001 for interaction between baseline LDL-C and % LDL-C reduction with evolocumab). Among patients with a baseline LDL-C of 70 mg/dL, LDL-C reduction was 68% (95% CI 67-69%) vs. 54% (95% CI 53-55%) in patients with a baseline LDL-C of 130 mg/dl. When stratified by concomitant statin intensity, similar relationships were observed (Figure middle &amp; bottom). Conclusions: The magnitude of % LDL-C reduction with evolocumab is greater in patients with lower baseline LDL-C levels. These data are encouraging for the use of PCSK9 inhibition even for patients at the lower end of LDL-C.

High risk US adults with untreated hyperlipidaemia in NHANES: estimated reduction in cardiovascular events with statin treatment

Abstract Introduction Dyslipidemia is widely prevalent. Despite guidelines that recommend statin therapy for high-risk patients, many of these patents are untreated. This gap in care must be urgently closed. Purpose We analyzed data from the National Health and Nutrition Examination Survey (NHANES) in order to: (1) ascertain the number of high-risk individuals with dyslipidaemia not receiving lipid lowering therapy in the United States; and (2) estimate the reduction in acute cardiovascular (CV) events if those individuals were treated with either moderate or high potency statins in order to achieve at minimum a 30% or 50% reduction in LDL-C levels. Methods Data from NHANES participants who had fasting blood serum data available, including lipids, were included in our analysis (n=14,888). Statistical analyses were performed in the R language. Coronary heart disease (CHD) risk was assessed using NCEP ATP III criteria, and participants were categorized as being at high, intermediate, or low CHD risk. Data from seven surveys from 2003–4 to 2015–6 was used and extrapolations to the US adult population (50 states plus the District of Columbia) were performed using the direct method to the US Census 2000 population. Results We identified 1162 adults (age 20–79) who were high-risk and untreated despite being hyperlipidaemic (LDLC ≥100mg/dL). We estimated they represent 12.8 million individuals in the US 2015–16 population. Without lipid modification and hypothecating 10-year risks of CV events in this group of 20, 25, 30, 35 and 40%, respectively, predicted numbers of CV events are 2.6M, 3.2M, 3.9M, 4.5M, and 5.1M. Moderate-intensity statins reduce LDLC by 30–40% and high-intensity statins by 50–60%. Using untreated LDL-C values from all NHANES surveys we calculated predicted absolute reductions in LDL-C would be at least 42 mg/dL if a moderate-intensity statin was used and at least 70 mg/dL if a high-intensity statin was used, with reductions in CV risk of at least 27% and 46%, respectively. In this group of untreated high-risk individuals, predicted numbers of CV events that could be prevented by moderate-intensity statin for 10 years range from at least 0.7M to at least 1.4M, and with high-intensity statin use for 10 years from at least 1.2M to at least 2.3M, depending on the level of untreated risk. With Numbers Needed to Treat (NTT) between 5 and 18, use of statin treatment in this group would be highly beneficial and cost-effective. Conclusions There are a large number of untreated high-risk individuals with dyslipidaemia in the US. Use of moderate and high dose statin therapy in these patients for 10 years would reduce CV risk by at least 27% and 47%, respectively. Among untreated high-risk patients, the NNTs for moderate and high dose statin therapy are 9–18 and 5–11, respectively, depending on 10-year level of CV risk. The quality of life and socioeconomic implications of these estimates are substantial. Funding Acknowledgement Type of funding source: None

Do European patients with peripeheral arterial disease receive optimal lipid lowering therapy and achieve LDL-C goals? Results from the DA VINCI study

Abstract Background 2016 and 2019 EAS/ESC dyslipidemia guidelines recommend lipid lowering therapy (LLT) to reduce LDL-C in patients with peripheral arterial disease (PAD) with or without established cardiovascular (CV) disease, and recommend target LDL-C goals based on individual CV risk. Data regarding the implementation of these guidelines in clinical practice across Europe is currently lacking. Purpose Describe LLT and achievement of the target LDL-C goals recommended in EAS/ESC dyslipidemia guidelines in patients with PAD. Methods The cross-sectional Da Vinci study enrolled consenting adults who had received LLT in the 12 months prior to the study visit and had at least one LDL-C measurement in the 14 months prior to the study visit, seen in a primary or secondary care setting across 18 European countries. Patients with coronary, peripheral and cerebral disease were enrolled at a ratio of 1:2:2. FH patients with prior CV events were excluded. Data were collected from medical records at a single visit between Jun '17–Nov '18, including LLT and most recent LDL-C. Primary outcome was LDL-C goal attainment ≥28 days after starting most recent LLT (treatment-stabilised LLT). Results Of 5888 patients enrolled, 2794 met our definition of atherosclerotic cardiovascular disease (ASCVD). Of these ASCVD patients, 1036 (37%) had PAD. 31% (323/1036) of PAD patients were female and mean (SD) age was 69 (9.4) years. Concomitant CV risk factors included diabetes mellitus (473/1036 patients [46%]), hypertension (809/1036 [78%]) and smoking (794/1036 [77%]). 26% (271/1036) of patients with PAD also had coronary vascular disease and 12% (122/1036) also had cerebrovascular disease. At the visit date, approximately half (497/1036 [48%]) of all PAD patients were receiving moderate intensity statins and 41% (421/1036) were receiving high intensity statins. 818 (73%) of the PAD patients had a treatment-stabilised LDL-C measurement (median, 2.20 mmol/L), of whom 40% (326/818) achieved the 2016 EAS/ESC LDL-C goal of 1.8 mmol/L and only 19% (159/818) achieved the 2019 goal of 1.4mmol/L. Conclusions European patients with PAD are not treated as per EAS/ESC recommendations, with a large proportion receiving suboptimal LLT and fewer than half achieving target LDL-C levels. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Amgen

Differences in lipid treatment patterns in women versus men in a large cohort of patients with atherosclerotic cardiovascular disease in Ontario, Canada

Abstract Background/Introduction The prevalence of ischaemic heart disease is lower in women vs men in Canada. Studies have shown that women are more likely to be underdiagnosed and less likely to receive guideline-recommended treatments than men. Women receiving lipid-lowering therapies (LLTs) are also less likely to attain treatment goals vs men. Purpose We analysed use of LLTs and attainment of low-density lipoprotein cholesterol (LDL-C) treatment goals in a recent longitudinal cohort of patients with ASCVD with public drug coverage in Ontario to describe differences observed between female and male patients. Methods Patients ≥65 years with a primary ASCVD event/procedure between 1 Apr 2005 and 31 Mar 2016, treated with an LLT and with index and follow up LDL-C values were identified from claims data at the Institute for Clinical Evaluative Sciences data repository. Patients were assessed over a 1 year follow up period for LDL-C goal attainment (&amp;lt;2.0 mmol/L or 50% reduction from index LDL-C as per Canadian Cardiovascular Society Guidelines) and analysed by LLT category. Results 143,302 patients with ASCVD ≥65 years on LLTs were identified of which 41% were female. A higher proportion of female vs male patients were prescribed low (3% vs 2%) and medium intensity statins (51% vs 44%) compared with high intensity statins (43% vs 52%). A higher proportion of women failed to attain LDL-C goal compared to men (33% vs 24%) (Figure). When analysed by low, moderate or high intensity statin, 65%, 35%, and 27% of female patients and 49%, 25% and 19% of male patients failed to attain LDL-C goal at follow up. Conclusions In this retrospective study, women with a diagnosis of ASCVD were more frequently treated with low/moderate intensity statins whereas men were more frequently treated with high intensity statins. Approximately 2 of 3 women and 3 of 4 men receiving statin treatment attained LDL-C goal during the 1-year follow up period. Overall, there appear to be treatment differences between female and male patients with ASCVD, with males receiving higher intensity statin therapy and attaining LDL-C goal more frequently. Further research is needed to determine why these discrepancies exist. This study made use of de-identified data from the ICES Data Repository, which is managed by the Institute for Clinical Evaluative Sciences with support from its funders and partners: Canada's Strategy for Patient-Oriented Research (SPOR), the Ontario SPOR Support Unit, the Canadian Institutes of Health Research and the Government of Ontario. The opinions, results and conclusions reported are those of the authors. No endorsement by ICES or any of its funders or partners is intended or should be inferred. Parts of this material are based on data and/or information compiled and provided by CIHI. However, the analyses, conclusions, opinions and statements expressed in the material are those of the author(s), and not necessarily those of CIHI. Figure 1 Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Amgen Canada Inc

Are the results of clinical trials relevant in the real world? The applicability of REDUCE-IT to the FAST-MI Registry

Abstract Background Large clinical trials are often criticized for testing therapeutic strategies in selected populations. The REDUCE-IT data revealed robust atherosclerotic cardiovascular risk reduction with a strategy comprising of high dose omega-3 icosapent ethyl versus placebo in statin treated patients with triglyceride values (TG) between 150 and 499 mg/dl and controlled LDL-C (41–100 mg/ dl). Purpose In order to evaluate the applicability of REDUCE-IT in a French population, we applied the inclusion and exclusion criteria in the French Registry on Acute ST- elevation and non-ST-elevation Myocardial Infarction (FAST-MI) [2010 and 2015]. Methods From the FAST-MI registry, we included patients over 45 years, who had detailed lipid values post-acute hospitalization [11.1 months (median) after hospitalization for myocardial infarction]. We thus compared the applicability of REDUCE-IT [in patients with TG between 150 (or 200) and 500 mg/dl and an LDL-C between 40 and 100 mg/dl while treated with statin therapy] in the FAST-MI registry focusing on the general characteristics, the risk factors, and the cardiovascular prognosis i.e. the rate of total mortality, myocardial infarction and stroke. Results 12.5% of the patients (5.5% if TG between 200 and 500 mg/dl) met the eligibility criteria for REDUCE-IT. The differences between the REDUCE-IT like (n=472) and REDUCE-IT excluded (n=3317) samples were related to age (61 vs 65, NS), male gender (79.5% vs 73.8%, p&amp;lt;0.01), body mass index in kg/m2 (28 vs 26.2, p&amp;lt;0.001), current smoking (45% vs 31.4%, p&amp;lt;0.001), hypertension (56.5% vs 50.2%, p&amp;lt;0.01), and the percentage of diabetic patients (29.5% vs 15.6%, p&amp;lt;0.001). In the REDUCE-IT like sample, the mean values of total cholesterol, TG (median) and the HDL-C were respectively 159, 192, 43 and the LDL-C value was 72 mg/dl. The distribution of the statin regimens in the REDUCE-IT like sample was as follows: 65.3%, 32.4% and 2.3% had high, moderate and low intensity statin therapy. The distribution of TG categories in the REDUCE-IT like sample was as follows: 55.3% (150–199), 36.0% (200–299) and 8.7% (300–500 mg/dl). The subgroup with TGs greater than 200 mg/dl and HDL-C less than 35 mg/dl was 16.1% in the REDUCE-IT like group and 2.1% in the REDUCE-IT excluded group (p&amp;lt;0.001). The cardiovascular event rate (death, nonfatal MI, nonfatal stroke) was respectively 36.7 for the FAST-MI REDUCE-IT like group and 36.9 persons-years (CVD death, nonfatal MI, nonfatal stroke) for the REDUCE-IT trial. Conclusion The cardiovascular residual risk related to elevated TG in the applicable patient population in the FAST-MI registry was similar to the risk in REDUCE-IT. If the results of REDUCE-IT are applied to patients hospitalized for a myocardial infarction in France, on top of statins, 12.5% of these patients could benefit from a strategy of high dose omega-3 icosapent ethyl on top of contemporary medical therapy to improve their future cardiovascular health. Funding Acknowledgement Type of funding source: None

Clinical implications of the log linear association between LDL-C lowering and cardiovascular risk reduction: Greatest benefits when LDL-C >100 mg/dl.

The log linear association between on-treatment LDL-C levels and ASCVD events is amplified in higher risk patient subgroups of statin versus placebo trials. Update previous systematic review to evaluate how the log linear association influences the magnitude of cardiovascular risk reduction from intensifying LDL-C lowering therapy. MEDLINE/PubMED, Clinical trials.gov, and author files were searched from 1/1/2005 through 10/30/2019 for subgroup analyses of cardiovascular outcomes trials of moderate versus high intensity statin, ezetimibe, and PCSK9 mAbs with an ASCVD endpoint (nonfatal myocardial infarction or stroke, cardiovascular death). Annualized ASCVD event rates were used to extrapolate 5-year ASCVD risk for each treatment group reported in subgroup analyses, which were grouped into a priori risk groups according to annualized placebo/control rates of ≥4%, 3-3.9%, or <3% ASCVD risk. Data were pooled using a random-effects model. Weighted least-squares regression was used to fit linear and log-linear models. Systematic review identified 96 treatment subgroups from 2 trials of moderate versus high intensity statin, 2 trials of a PCSK9 mAb versus placebo, and 1 trial of ezetimibe versus placebo. A log linear association between on-treatment LDL-C and ASCVD risk represents the association between on-treatment LDL-C levels and ASCVD event rates, especially in higher risk subgroups. Greater relative and absolute cardiovascular risk reductions from LDL-C lowering were observed when baseline LDL-C was >100 mg/dl and in extremely high risk ASCVD patient groups. Greater cardiovascular and mortality risk reduction benefits from intensifying LDL-C lowering therapy may be expected in those with LDL-C ≥100 mg/dl, or in extremely high risk patient groups. When baseline LDL-C <100 mg/dl, the log linear association between LDL-C and event rates suggests that treatment options other than further LDL-C lowering should also be considered for optimal risk reduction.

DA VINCI study: Change in approach to cholesterol management will be needed to reduce the implementation gap between guidelines and clinical practice in Europe

DA VINCI study: Change in approach to cholesterol management will be needed to reduce the implementation gap between guidelines and clinical practice in Europe

Profile of use and access to statins in patients with coronary arterial disease in an outpatient clinic of a teaching hospital

Objective The aim of the study is to describe statin use pattern and access among individuals with coronary artery disease of a secondary care service of the Brazilian Unified Health System. Methods This is a cross-sectional study carried out in a multi-professional outpatient cardiology clinic at a public, university, and general hospital in the state of Minas Gerais, Brazil. The level of adherence to the recommendations of intensity of the statin therapy of Brazilian and American dyslipidemia guidelines was established. The prescribed statin, adherence to treatment, access, and clinically relevant drug interactions with statins were identified. Access to statin was analyzed through the availability and acquisition capacity realms. Results The sample consisted of 148 patients who were selected from April 2018 to February 2019. Approximately 90% of patients were under 75 years old. The most prevalent cardiovascular diagnoses were acute myocardial infarction with ST-segment elevation and without ST-segment elevation. All patients had a very high cardiovascular risk. Polypharmacy and cardiovascular polypharmacy were identified in 91.2% and 74.3% of patients, respectively. We identified that 90.6% of the patients used a moderate-intensity statin, and simvastatin was the most common stain used. The level of adherence to the recommendations of Brazilian and American dyslipidemia guidelines for statin use was 9.4% and 21.6%, respectively. Total free access to statins by the Unified Health System was 44.6%, with 52.1% of respondents reporting that they received statins at the health center, 25.7% through the popular pharmacy program via copayment, and 33.8% from a private pharmacy. Conclusion The level of adherence to the recommendations of U.S. and Brazilian guidelines of dyslipidemia for statin use was low. Most patients used a moderate intensity statin, despite having a high cardiovascular risk. Simvastatin was the most prescribed statin.

584-P: Optimal Utilisation of Statins in Real-World Settings

Aim: The purpose of this retrospective data analysis is to assess prescription practices including appropriate use and dose of statins in patients with T2DM. Methods: This is an observational retrospective data analysis of T2DM patients with dyslipidemia and who were on statin treatment for at least 6 months. Data for this study was obtained from EMRs of diabetes and endocrinology specialty outpatient clinics (n=35), pan India between Jan 2018 and May 2019. Patients aged &amp;lt;40 and &amp;gt;75 years were excluded from the analysis. Patient’s record with demographics, medical history, prescriptions (antidiabetes and statin drugs) and lab investigations data were collected. Results: Of the total 45,205 diabetes patients, 15023(33%) were on statins. The mean age was 53.2 years, 64% were males and 36% were females. Final analysis included 4099 patients between ages 40 and 75 years on statin drugs along with antidiabetes drugs. Mean HbA1c, fasting and post-prandial blood glucose was 8.5%, 173mg/dL and 257 mg/dL, respectively. The lipid profile TC, TG, HDL, and LDL was 174mg/dL, 188 mg/dL, 41 mg/dL, and 107 mg/dL, respectively. Low-intensity statins (2539[62%]) were the most common prescriptions followed by moderate (1402[34%]) and high (158[4%]) intensity statins. Rosuvastatin (2615[64%]) was most commonly prescribed followed by atorvastatin (1302[32%]), and non-statin fenofibrate (182[4%]). 4% of the patients on low-intensity statins at the first visit moved to moderate or high dose intensity statins. In contrast, 2% of patients on moderate dose moved to low dose intensity. Conclusion: In endocrine clinic population with 45205 patients only 33% of patients were on statins. In the population between 40 and 75, a majority were on low-intensity statins with relatively very few progressing to moderate and high-intensity statin. The low uptake of statins and low dose use indicates the need to increase awareness of appropriate patient selection and correct dose of statin use in the clinic population including referral and tertiary care clinics. Disclosure S.G. Krishna: None. S. Das: None. N. Nk: None. S.P. Manohar: None. N. Bs: None. D. Mc: None. S. Shah: None. A. Ahmed: None. M. Chavan: None. S. Sathyakumar: None. V.K. Kolukula: None.

P0260CLINICAL PROFILE OF PATIENTS INITIATING EVOLOCUMAB IN SPANISH NEPHROLOGY UNITS: A RESTROSPECTIVE, OBSERVATIONAL STUDY IN CLINICAL PRACTICE (RETOSS-NEPHRO)

Abstract Background and Aims Cardiovascular disease is the primary cause of morbidity and mortality in patients with chronic kidney disease (CKD). Evolocumab is a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9) and lowers serum low density lipoprotein cholesterol (LDL-C) levels. Evolocumab is indicated for adult patients with hypercholesterolaemia or mixed dyslipidaemia who are unable to reach LDL-C goals with the maximum tolerated dose of statin or are statin intolerant. This study was conducted to describe clinical characteristics, reasons for therapy initiation and treatment effects in patients treated with evolocumab in Spanish Nephrology units. Method Retrospective, observational, chart review of consecutive patients initiating evolocumab (Feb-2016 to Aug-2018) in 15 Spanish Nephrology Units. Patient characteristics, lipid modifying therapies and lipid profiles over time were retrospectively collected at 24 weeks pre- and 12±4 weeks post-evolocumab initiation. Results 60 patients were enrolled: 53.3% women; mean (SD) age, 56.9 (12.8) years; mean (SD) body mass index, 28.0 (4.7) kg/m2; 45.0% had familial hypercholesterolemia (FH) (5.0% homozygous, 23.3% heterozygous, 16.7% undetermined FH); from the total population, 35% were in primary prevention and 65.0% started evolocumab after previous Atherosclerotic Cardiovascular Disease [ASCVD]. Regarding renal function, mean (SD) eGFR was 62.6 (30.0) ml/min/1.73m2; 51.7% of patients had eGFR &amp;lt;60 ml/min/1.73m2 (CKD stage&amp;gt;2), 50.0% had proteinuria (&amp;gt;300 mg/g) and 10.0% had nephrotic syndrome. Other CV risk factors were hypertension (75.0%), diabetes (25.0%), and smoking (21.7%); 40.0% of patients were statin intolerant. At evolocumab initiation, 41.7% of patients were on a high intensity statin, 18.3% on moderate intensity statin and 50.0% were receiving ezetimibe. Mean (SD) LDL-C at evolocumab initiation was 179.7 (62.9) mg/dL (53.4% of patients with LDL-C≥160; 29.3% ≥190). Mean (SD) baseline HDL-C and total cholesterol were 48.5 (15.0) mg/dL and 273.1 (82.7) mg/dL, respectively. After 12 weeks, evolocumab resulted in LDL-C reductions of 60.1%, to a mean (SD) of 72.7 (80.3) mg/dL, with similar results observed in patients in primary/secondary prevention, with CKD stage &amp;gt;2/≤2 or with/without proteinuria. Conversely, patients with/without FH showed significant differences between their reductions (46.6% vs 76.6%, respectively, p=0.0276). At week 12, 90.0% of patients reached LDL-C levels &amp;lt;100 mg/dL, 70.0% &amp;lt;70 mg/dL, and 55.0% &amp;lt;55mg/dL, while eGFR levels and statin use remained stable. Conclusion In Spanish Nephrology Units, evolocumab was predominantly prescribed in patients with FH, ASCVD and/or CKD stage &amp;gt;2. Initial evolocumab use was aligned with ESC/EAS dyslipidaemia guidelines, but with higher baseline LDL-C levels than the recommended thresholds. After 12 weeks of evolocumab treatment, LDL–C levels were more than halved and the majority of patients achieved both the 2016 and 2019 EAS/ESC targets of LDL-C control.