Intensive Statin Treatment Research Articles

The impact of SLCO1B1 rs4149056 on LDL-C target achievement after lipid lowering therapy optimization in men and women with familial hypercholesterolemia.

FH women are less likely to receive intensive statin treatment and to obtain a 50% reduction of LDL-C from baseline compared to men with FH. SLCO1B1 rs4149056 might influence statin therapy compliance and thus LDL-C target achievement. Our aim was to evaluate the impact of SLCO1B1 rs4149056 on LDL-C target achievement after lipid lowering therapy (LLT) optimization in men and women with FH. This was a retrospective observational study involving 412 FH subjects with a probable or defined clinical diagnosis of FH who had had genetic analysis from June 2016 to September 2022. Biochemical analysis was obtained from all subjects at baseline and at the last follow-up after LLT optimization. After LLT optimization the percentage of FH subjects on high-intensity statins decreased from the M/SLCO1B1- group to the W/SLCO1B1+ group and the same was found in LDL-C target distribution (for both p for trend < 0.01). The prevalence of SASE fear increased from the M/SLCO1B1- group to the W/SLCO1B1+ group and the same was observed in reported myalgia distribution (for both p for trend < 0.01). Logistic regression analysis showed that the W/SCLO1B1-, M/SCLO1B1+ and W/SCLO1B1+ groups were inversely associated with LDL-C target achievement (p for trend < 0.001) and the W/SCLO1B1+ group exhibited the strongest association. A low prevalence of FH women with SLCO1B1 rs4149056 were on high intensity statins and they rarely achieved LDL-C target. The genotype effect of SLCO1B1 rs4149056 could be more pronounced in FH women than men.

1071 Examining Blood Lipid Profiles and Lipid Lowering Therapy in Carotid Surgery Patients in a 1-Year Follow-Up Study

Abstract Aim Stroke patients are at a high risk of future major adverse cardiovascular events. Focusing on lipid lowering therapy (LLT), current ESVS and NICE guidelines advise high intensity statin (HIS) treatment with a target LDL-C of less than 1.8mmol/L. Method This is a retrospective cohort study on 205 patients who underwent carotid endarterectomy or stenting from 01/01/18 to 31/12/20 at Leeds Vascular Institute. Prescriptions and lipid profiles prior to intervention, at discharge, and 1-year post-intervention were recorded. Differences between time points were assessed using the McNemar test. Results There were 137 men, the median age was 73, and 175 patients underwent carotid endarterectomy. Increases in prescriptions of statins (65%vs93%, p&amp;lt;0.001) and HIS (47%vs83%, p&amp;lt;0.001) were observed at discharge compared to pre-intervention but no differences were seen at 1 year. At 1 year, 8 patients were not on statin therapy; 6 were intolerant and 3 were prescribed Ezetimibe. At 1 year, there was a significant improvement in median LDL-C (2.4mmol/L IQR (1.9-3.3) vs. 1.6mmol/L (1.2-2.0)), and proportion of patients reaching target LDL-C of &amp;lt;1.8mmol/L (21%vs59%,p = 0.003) compared to pre-admission. In patients with LDL-C≥1.8mmol/L, 92% had scope for LLT up-titration. No significant differences were noted in the proportion of patients who underwent lipid profile monitoring prior to admission and at 1 year. Conclusions Admission to our local vascular unit is associated with an increase in the guideline-directed prescription of LLT, and subsequently attainment of target LDL-C. Reasons for suboptimal lipid monitoring in the community need to be understood to allow for optimal risk reduction.

1478-P: Polygenic Risk Score Predicts Incident Cardiovascular Disease in People with Diabetes at Borderline or Intermediate 10-Year ASCVD Risk

People with type 2 diabetes (T2D) and 10-year atherosclerotic cardiovascular disease (ASCVD) of 20% or higher are recommended for intense lipid management. However, the role of genetic predisposition to ASCVD on determining the intensity of statin therapy in patients with T2D at borderline (5-7.5%) or intermediate (7.5-20%) risk for incident ASCVD is unclear. We aimed to investigate the utility of polygenic risk score (PRS) in predicting incident ASCVD in people with T2D at borderline and intermediate risk from UK Biobank. We calculated 10-year ASCVD risk using pooled cohort risk equations and PRS for coronary artery disease by Bayesian regression (PRS-CS) in participants of UK Biobank. We performed time-to-event analysis for incident ASCVD and assessed improvement of C-statistic when PRS was added to 10-year ASCVD risk. In addition, risk of ASCVD was estimated for those who were in the top 20 percentile of PRS compared to the remainders. During a median follow-up of 9 years, the incidence of ASCVD in people with T2D was 5.9% and 8.6% in borderline (N=2511) and intermediate (N=8292) group, respectively. The normalized mean PRS for those who developed ASCVD was higher in each group: 0.20±0.96 vs −0.02±1.01 in borderline and 0.20±1.02 vs −0.02±0.99 in intermediate group (all P&amp;lt;0.01). Adding PRS to 10-year ASCVD risk improved the C statistic from 0.51 (95% CI 0.46-0.55) to 0.57 (0.52-0.62) in borderline and from 0.55 (0.53-0.57) to 0.58 (0.56-0.60) in intermediate group. Standardized PRS was associated with incident ASCVD in each group: HR 1.22 (CI 1.05-1.45, P&amp;lt;0.05) and 1.24 (1.15-1.34, P&amp;lt;0.001). Moreover, those who were in the top 20 percentile had increased risk of ASCVD: HR 1.63 (1.14-2.33, P&amp;lt;0.01) and 1.43 (1.21-1.70, P&amp;lt;0.001), respectively. In conclusion, genetic information in people with T2D at borderline and intermediate ASCVD risk could be used to identify those who are at higher risk for incident ASCVD and require high intensity statin treatment. Disclosure J.Choi: None. H.Lee: None. J.S.Lee: None. T.Rhee: None. K.Park: None. S.Kwak: None. Funding National Human Genome Research Institute (FAIN U01HG011723)

The effect of intensive statin therapy in non-symptomatic intracranial arteries: The STAMINA-MRI sub-study.

Pleiotropic effects of statins result in the stabilization of symptomatic intracranial arterial plaque. However, little is known about the effect of statins in non-symptomatic cerebral arteries. We hypothesized that intensive statin therapy could produce a change in the non-symptomatic cerebral arteries. This is a sub-study of a prospective observational study under the title of "Intensive Statin Treatment in Acute Ischemic Stroke Patients with Intracranial Atherosclerosis: a High-Resolution Magnetic Resonance Imaging (HR-MRI) study." Patients with statin-naive acute ischemic stroke who had symptomatic intracranial artery stenosis (above 50%) were recruited for this study. HR-MRI was performed to assess the patients' cerebral arterial status before and 6 months after the statin therapy. To demonstrate the effect of statins in the non-symptomatic segment of intracranial cerebral arteries, we excluded symptomatic segments from the data to be analyzed. We compared the morphological changes using cerebrovascular morphometry. A total of 54 patients (mean age: 62.9 ± 14.4 years, 59.3% women) were included in this study. Intensive statin therapy produced significant morphological changes of overall cerebral arteries. Among the morphological features, the arterial luminal area showed the highest number of significant changes with a range from 5.7 and 6.7%. Systolic blood pressure (SBP) was an independent factor associated with relative changes in posterior circulation bed maximal diameter percentage change (beta -0.21, 95% confidence interval -0.36 to -0.07, p = 0.005). Intensive statin therapy produced a favorable morphological change in cerebral arteries of not only the target arterial segment but also non-symptomatic arterial segments. The change in cerebral arterial luminal diameter was influenced by the baseline SBP and was dependent on the topographic distribution of the cerebral arteries.Clinical Trial Registration: ClinicalTrials.gov, identifier NCT02458755.

Statin Treatment Intensity, Discontinuation, and Long-Term Outcome in Patients With Acute Myocardial Infarction and Impaired Kidney Function.

Statin dosage in patients with acute myocardial infarction (AMI) and concomitant kidney dysfunction is a clinical dilemma. We studied discontinuation during the first year after an AMI and long-term outcome in patients receiving high versus low-moderate intensity statin treatment, in relation to kidney function. For the intention-to-treat analysis (ITT-A), we included all patients admitted to Swedish coronary care units for a first AMI between 2005 and 2016 that survived in-hospital, had known creatinine, and initiated statin therapy (N = 112,727). High intensity was initiated in 38.7% and low-moderate in 61.3%. In patients with estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m 2 , 25% discontinued treatment the first year; however, the discontinuation rate was similar regardless of the statin intensity. After excluding patients who died, changed therapy, or were nonadherent during the first year, 84,705 remained for the on-treatment analysis (OT-A). Patients were followed for 12.6 (median 5.6) years. In patients with eGFR 30-59 mL/min, high-intensity statin was associated with lower risk for the composite death, reinfarction, or stroke both in ITT-A (hazard ratio [HR] 0.93; 95% confidence interval, 0.87-0.99) and OT-A (HR 0.90; 0.83-0.99); the interaction test for OT-A indicated no heterogeneity for the eGFR < 60 mL/min group ( P = 0.46). Similar associations were seen for all-cause mortality. We confirm that high-intensity statin treatment is associated with improved long-term outcome after AMI in patients with reduced kidney function. Most patients with reduced kidney function initiated on high-intensity statins are persistent after 1 year and equally persistent as patients initiated on low-moderate intensity.

TCT-577 Lipoprotein(a) and Intracoronary Imaging After Intensive Statin Treatment

TCT-577 Lipoprotein(a) and Intracoronary Imaging After Intensive Statin Treatment

Assessment of statin adherence in patients who underwent percutaneous coronary intervention

Background and Aims : Statin therapy is one of the cornerstone part of coronary artery disease treatment. Current guidelines recommends high intensity statin treatment for primary and secondary prevention of CV events and in daily clinical pratice, discontuniation of statins is a frequent problem.We aimed to evaluate the status and associated factors of statin adherence in patients underwent percutaneous coronary intervention (PCI).

Familial hypercholesterolemia in China requires greater efforts

Familial hypercholesterolemia in China requires greater efforts

Intensive vs non-intensive statin pretreatment before percutaneous coronary intervention in Chinese patients: A meta-analysis of randomized controlled trials.

BACKGROUNDThe results of intensive statin pretreatment before percutaneous coronary intervention (PCI) is inconsistent between Chinese and Western populations, and there are no corresponding meta-analyses involving hard clinical endpoints in the available published literature.AIMTo evaluate the efficacy and safety of high-dose statin loading before PCI in Chinese patients through a meta-analysis.METHODSRelevant studies were identified by searching the electronic databases of PubMed, Embase and Cochrane’s Library to December 2019. The outcomes included an assessment of major adverse cardiovascular event (MACE), non-fatal myocardial infarction (MI), cardiac death, target vessel revascularization (TVR), myalgia /myasthenia and abnormal alanine aminotransferase (ALT) in all enrolled patients. Random effect model and fixed effect model were applied to combine the data, which were further analyzed by χ2 test and I2 test. The main outcomes were then analyzed through the use of relative risks (RR) and its 95% confidence interval (95%CI).RESULTSEleven studies involving 3123 individuals were included. Compared with patients receiving placebo or no statin treatment before surgery, intensive statin treatment was associated with a clear reduction of risk of MACE (RR = 0.44, 95%CI: 0.31-0.61, P < 0.00001). However, compared with the patients receiving moderate-intensity statin before surgery, no advantage to intensive statin treatment was seen (RR = 1.04, 95%CI: 0.82-1.31, P = 0.74). In addition, no significant difference was observed between intensive statin therapy and non-intensive statin therapy on the incidence of TVR (RR = 0.43, 95%CI: 0.18-1.02, P = 0.06) , myalgia /myasthenia (RR = 1.35, 95%CI: 0.30-5.95, P = 0.69) and abnormal alanine aminotransferase (RR = 1.47, 95%CI: 0.54-4.02, P = 0.45) except non-fatal MI (RR = 0.54, 95%CI: 0.33-0.88, P = 0.01).CONCLUSIONCompared with placebo or no statin pretreatment, intensive statin before PCI displayed reduced incidence of MACE. However, there was no significant benefit between high and moderate-intensity statin. In addition, no significant difference was observed between intensive statin therapy and non-intensive statin therapy on the incidence of TVR, myalgia/myasthenia and abnormal alanine aminotransferase except non-fatal MI.

Alirocumab after acute coronary syndrome in patients with a history of heart failure.

AimsPatients with heart failure (HF) have not been shown to benefit from statins. In a post hoc analysis, we evaluated outcomes in ODYSSEY OUTCOMES in patients with vs. without a history of HF randomized to the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor alirocumab or placebo.Methods and resultsAmong 18 924 patients with recent acute coronary syndrome (ACS) receiving intensive or maximum-tolerated statin treatment, the primary outcome of major adverse cardiovascular events (MACE) was compared in patients with or without a history of HF. The pre-specified secondary outcome of hospitalization for HF was also analysed. Overall, 2815 (14.9%) patients had a history of HF. Alirocumab reduced low-density lipoprotein cholesterol and lipoprotein(a) similarly in patients with or without HF. Overall, alirocumab reduced MACE compared with placebo [hazard ratio (HR): 0.85; 95% confidence interval (CI): 0.78–0.93; P = 0.0001]. This effect was observed among patients without a history of HF (HR: 0.78; 95% CI: 0.70–0.86; P < 0.0001), but not in those with a history of HF (HR: 1.17; 95% CI: 0.97–1.40; P = 0.10) (P interaction = 0.0001). Alirocumab did not reduce hospitalization for HF, overall or in patients with or without prior HF.ConclusionAlirocumab reduced MACE in patients without a history of HF but not in patients with a history of HF. Alirocumab did not reduce hospitalizations for HF in either group. Patients with a history of HF are a high-risk group that does not appear to benefit from PCSK9 inhibition after ACS.

Comparison of the Efficacy and Safety of Atorvastatin 40 mg/ω-3 Fatty Acids 4 g Fixed-dose Combination and Atorvastatin 40 mg Monotherapy in Hypertriglyceridemic Patients who Poorly Respond to Atorvastatin 40 mg Monotherapy: An 8-week, Multicenter, Randomized, Double-blind Phase III Study

PurposeResidual cardiovascular risk in patients with hypertriglyceridemia, despite optimal low-density lipoprotein cholesterol levels being achieved with intensive statin treatment, is a global health issue. The purpose of this study was to investigate the efficacy and tolerability of treatment with a combination of high-dose atorvastatin/Ω-3 fatty acid compared to atorvastatin + placebo in patients with hypertriglyceridemia who did not respond to statin treatment. MethodsIn this multicenter, randomized, double-blind, placebo-controlled study, patients who had residual hypertriglyceridemia after a 4-week run-in period of atorvastatin treatment were randomly assigned to receive UI-018 (fixed-dose combination atorvastatin/Ω-3 fatty acid 40 mg/4 g) or atorvastatin 40 mg + placebo (control). The primary efficacy end points were the percentage change from baseline in non–high density lipoprotein cholesterol (non–HDL-C) level at the end of treatment and the adverse events recorded during treatment. A secondary end point was the percentage change from baseline in triglyceride level. FindingsAfter 8 weeks of treatment, the percentage changes from baseline in non–HDL-C (–4.4% vs +0.6%; p = 0.02) and triglycerides (–18.5% vs +0.9%; p < 0.01) were significantly greater in the UI-018 group (n = 101) than in the control group (n = 99). These changes were present in subgroups of advanced age (≥65 years), status (body mass index ≥25 kg/m2), or without diabetes. The prevalences of adverse events did not differ between the 2 treatment groups. ImplicationsIn patients with residual hypertriglyceridemia despite receiving statin treatment, a combination of high-dose atorvastatin/Ω-3 fatty acid was associated with a greater reduction of triglyceride and non–HDL-C compared with atorvastatin + placebo, without significant adverse events.

The relationship between genotype of familial hypercholesterolemia and the efficacy of PCSK9 inhibitors

Objective: This study intends to explore the difference in the efficacy of PCSK9 inhibitors in patients with different FH phenotypes by analyzing the level of blood lipids before and after treatment with PCSK9 inhibitors in patients with familial hypercholesterolemia (FH) with different allele grades. Methods: Patients with FH phenotype, who admitted to Beijing Anzhen Hospital from January 2019 to October 2020, were enrolled. Age, sex and other clinical information were collected from enrolled, and the pathogenic genes were detected by the second generation sequencing technique. The patients were divided into five groups according to the number of alleles involved and the degree of gene damage: single allele-null mutation group, single allele-defect mutation group, multi-allele-null mutation group, multi-allele-defect mutation group and no major pathogenic gene mutation group. The results of blood lipids were collected before medication, 4-6 weeks of intensive statin treatment and one month after combined treatment with PCSK9 inhibitor (PCSK9i). The LDL-C level were compared among groups. ASCVD risk stratification was performed in all patients, and the proportion of LDL-C level reaching the corresponding risk stratification target value of each genotype group after treatment was analyzed. Results: A total of 66 patients with FH phenotype were included, including 47 males (71.2%) and 19 females (28.8%),the mean age was(43.1±13.4 years). There were 7 cases in single allele-null mutation group (10.6%), 25 cases in single allele-defect mutation group (37.9%), 8 cases in multi-allele-null mutation group (12.1%), 18 cases in multi-allele-defect mutation group (27.3%) and 8 cases in no major pathogenic mutation group (12.1%). The degree of LDL-C reduction post combined PCSK9 inhibitor therapy was as follows: single allele mutation group>no major pathogenic mutation group>multi-allele mutation group, general distribution was in the range of 0-90.0%. Two groups of single allele mutation and no major pathogenic mutation group>50.0%>multi-allele mutation group. Under the combined treatment of PCSK9 inhibitors, the further decrease of LDL-C was in the order of single allele mutation group>non-major pathogenic mutant group>multi-allele mutation group. The efficacy of combined therapy on reducing LDL-C at 1 month after treatment decreased with the increase of baseline LDL-C level (r = 0.46, P<0.001) in patients with FH phenotype. In addition, the further decrease of LDL-C level post high-intensity statin therapy combined with PCSK9 inhibitors decreased with the increase of baseline LDL-C levels (r = 0.40, P<0.001). The degree of LDL-C decrease was high and stable by statin combined with PCSK9 inhibitor therapy in single allele mutation group. In the single allele-defect mutant group, the decrease of LDL-C increased with the increase of baseline LDL-C level post intensive statin treatment and combined PCSK9 inhibitor treatment ((r=0.54, P=0.009); r=0.45,P=0.030), and the further decrease of LDL-C level decreased with the increase of baseline LDL-C level in single allele-defect mutant group post combined therapy with PCSK9 inhibitor (r=0.43, P=0.040). The decrease of LDL-C in patients with the multi-allele mutation group varied with different pathogenic gene loci and combinations post combined therapy with PCSK9 inhibitor. There was no significant difference in the level of blood lipids between the group without major pathogenic gene mutation and the group with single allele mutation before and after treatment. The percentage of patients achieving LDL-C goals with different genotypes of phenotypic FH were as follows: single allele mutation group (86.7%), non-major pathogenic mutant group (75.0%) and multi-allele mutation grou (<5.0%). Conclusions: All patients with different FH phenotypes could benefit from the intensive lipid-lowering therapy with statins and PCSK9 inhibitors, however, there are significant differences in the efficacy of lowering LDL-C in Chinese patients with FH phenotype with different molecular etiologies. Therefore, the pathogenic gene analysis may suggest the lipid-lowering effect of PCSK9 inhibitors in patients with FH.

Relation of insulin treatment for type 2 diabetes to the risk of major adverse cardiovascular events after acute coronary syndrome: an analysis of the BETonMACE randomized clinical trial

BackgroundIn stable patients with type 2 diabetes (T2D), insulin treatment is associated with elevated risk for major adverse cardiovascular events (MACE). Patients with acute coronary syndrome (ACS) and T2D are at particularly high risk for recurrent MACE despite evidence-based therapies. It is uncertain to what extent this risk is further magnified in patients with recent ACS who are treated with insulin. We examined the relationship of insulin use to risk of MACE and modification of that risk by apabetalone, a bromodomain and extra-terminal (BET) protein inhibitor.MethodsThe analysis utilized data from the BETonMACE phase 3 trial that compared apabetalone to placebo in patients with T2D, low HDL cholesterol, andACS. The primary MACE outcome (cardiovascular death, myocardial infarction, or stroke) was examined according to insulin treatment and assigned study treatment. Multivariable Cox regression was used to determine whether insulin use was independently associated with the risk of MACE.ResultsAmong 2418 patients followed for median 26.5 months, 829 (34.2%) were treated with insulin. Despite high utilization of evidence-based treatments including coronary revascularization, intensive statin treatment, and dual antiplatelet therapy, the 3-year incidence of MACE in the placebo group was elevated among insulin-treated patients (20.4%) compared to those not-treated with insulin (12.8%, P = 0.0001). Insulin treatment remained strongly associated with the risk of MACE (HR 2.10, 95% CI 1.42–3.10, P = 0.0002) after adjustment for demographic, clinical, and treatment variables. Apabetalone had a consistent, favorable effect on MACE in insulin-treated and not insulin-treated patients.ConclusionInsulin-treated patients with T2D, low HDL cholesterol, and ACS are at high risk for recurrent MACE despite the use of evidence-based, contemporary therapies. A strong association of insulin treatment with risk of MACE persists after adjustment for other characteristics associated with MACE. There is unmet need for additional treatments to mitigate this risk.Trial registration ClinicalTrials.gov NCT02586155, registered October 26, 2015

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.

Risk of Recurrent Coronary Events in Patients With Familial Hypercholesterolemia; A 10-Years Prospective Study.

Background and Aim: Real world evidence on long term treatment of patients with familial hypercholesterolemia (FH) is important. We studied the effects of intensive lipid lowering medication (LLM) and optimized lifestyle in the study TTTFH–Treat To Target FH. Materials and Methods: Adults with a first known total cholesterol of mean (95% CI) 9.8 mmol/L (9.5, 10.1) were included consecutively in their routine consultation during 2006. Of the patients 86.4% had a pathogenic FH-mutation and the remaining were clinically diagnosed. We included 357 patients and 279 met for follow-up after median 10.0 (min 8.1, max 12.8) years. Results: Mean (95% CI) low density lipoprotein (LDL-C) was reduced from 3.9 (3.8, 4.1) to 3.0 (2.9, 3.2). More men than women used high intensity statin treatment, 85.2 and 60.8%, respectively. Women (n = 129) had higher LDL-C; 3.3 mmol/L (3.0, 3.5), than men; (n = 144) 2.8 mmol/L (2.6, 3.0), p = 0.004. Add-on PCSK9 inhibitors (n = 25) reduced mean LDL-C to 2.0 (1.4, 2.6) mmol/L. At enrollment 57 patients (20.4%) had established atherosclerotic cardiovascular disease (ASCVD), and 46 (80.4%) of them experienced a new event during the study period. Similarly, 222 (79.6%) patients had no detectable ASCVD at enrollment, and 29 of them (13.1%) experienced a first-time event during the study period. Conclusion: A mean LDL-C of 3.0 mmol/L was achievable in FH, treated intensively at a specialized clinic with few users of PCSK9 inhibitors. LDL-C was higher (0.5 mmol/L) in women than in men. In patients with ASCVD at enrollment, most (80.7%) experienced a new ASCVD event in the study period. The FH patients in primary prevention had more moderate CV risk, 13% in ten years.

Clinical Efficacy and Safety of Alirocumab After Acute Coronary Syndrome According to Achieved Level of Low-Density Lipoprotein Cholesterol: A Propensity Score-Matched Analysis of the ODYSSEY OUTCOMES Trial.

Recent international guidelines have lowered recommended target levels of low-density lipoprotein cholesterol (LDL-C) for patients at very high risk for major adverse cardiovascular events (MACE). However, uncertainty persists whether additional benefit results from achieved LDL-C levels below the conventional targets. Inferences from previous analyses are limited because patients who achieve lower versus higher LDL-C on lipid-lowering therapy differ in other characteristics prognostic for MACE and because few achieved very low LDL-C levels. To overcome these limitations, we performed a propensity score-matching analysis of the ODYSSEY OUTCOMES trial (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) which compared alirocumab with placebo in 18 924 patients with recent acute coronary syndrome receiving intensive or maximum-tolerated statin treatment. Patients on alirocumab were classified in prespecified strata of LDL-C achieved at 4 months of treatment: <25 (n=3357), 25 to 50 (n=3692), or >50 mg/dL (n=2197). For each stratum, MACE (coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or hospitalization for unstable angina) after month 4 was compared in patients receiving placebo with similar baseline characteristics and adherence by using 1:1 propensity score matching. Across achieved LDL-C strata of the alirocumab group, patients differed by baseline LDL-C, lipoprotein(a), use of intensive statin therapy, study medication adherence, and other demographic, medical history, biometric, and laboratory criteria. After propensity score matching, characteristics were similar in corresponding patients of the alirocumab and placebo groups. Treatment hazard ratio, 95% CI, and absolute risk reduction (number per 100 patient-years) for MACE were similar in those with achieved LDL-C <25 mg/dL (hazard ratio, 0.74 [95% CI, 0.62-0.89]; absolute risk reduction, 0.92) or 25 to 50 mg/dL (hazard ratio, 0.74 [95% CI, 0.64-0.87]; absolute risk reduction, 1.05). Patients with achieved LDL-C >50 mg/dL had poorer adherence and derived less benefit (hazard ratio, 0.87 [95% CI, 0.73-1.04]; absolute risk reduction, 0.62). No safety concerns were associated with a limited period of LDL-C levels <15 mg/dL. After accounting for differences in baseline characteristics and adherence, patients treated with alirocumab who achieved LDL-C levels <25 mg/dL had a reduction in the risk of MACE that was similar to that of patients who achieved LDL-C levels of 25 to 50 mg/dL. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01663402.

COMPARISON OF REAL WORLD LIPID PROFILE OF PATIENTS WITH TYPE 2 DIABETES AND GUIDELINE RECOMMENDATIONS.

SUMMARYDiabetes is a major risk factor for cardiovascular disease. Despite recommendations and available therapeutic options, patients with diabetes do not always reach the recommended lipid levels. In this study, our aim was to compare the real world lipid profile of type 2 diabetes patients with guideline recommendations for dyslipidemia. Four hundred and sixty eight consecutive patients referred to Outpatient Diabetes Clinic of Istanbul Medeniyet University were recruited. Patient anthropometric measurements (height, weight, waist circumference), biochemical test results (LDL cholesterol (LDL-c), triglycerides, HDL cholesterol, HbA1c) and treatment modalities were recorded. Patients were stratified into cardiovascular risk categories according to the risk factors and their treatment dose was compared to the recommendations. Among 468 patients, 56 (12%) patients had coronary heart disease (CHD). Thirty-four percent of these patients were not on statin treatment (n=19) and their mean LDL-c level was 114±29 mg/dL (2.9±0.75 mmol/L). Nineteen percent of these patients were on high intensity statin treatment (atorvastatin 40-80 mg, rosuvastatin 20 mg). Only four patients with CHD had LDL-c levels <70 mg/dL (1.8 mmol/L). Four hundred and twelve patients had no CHD. In these patients, the mean LDL-c level was 132±38 mg/dL (3.4±0.9 mmol/L). Eighty (19%) patients had LDL-c level lower than 100 mg/dL (2.5 mmol/L). Overall 82% (n=384) of the cohort had not achieved treatment goal. In conclusion, a more pronounced approach for statin treatment is needed in diabetes patients for both primary and secondary prevention of cardiovascular diseases.

Socioeconomic status, secondary prevention activities during the first year after a myocardial infarction and target attainments

Abstract Background Socioeconomic status (SES) is a strong predictor of recurrent events post-myocardial infarction (MI) with unclear underlying mechanisms. To what extent SES is associated with secondary prevention activities (SPAs) and attainment of quality-of-care treatment goals is unknown. Purpose We aimed to assess the association between SES and SPAs during the first year post-MI and attained treatment targets at the 1-year follow-up. Methods Nationwide Swedeheart registry-based cohort study on 30,191 18–76 year old 11–15 month survivors of a first MI (8,180 women) 2006–2013. Complementary individual-level clinical data and data on SES (age and gender stratified quintiles of disposable income, level of education, and marital status), were linked from other national registries. Associations between SES and the outcomes were estimated in multivariable logistic regression models with basic adjustment for potential registry-related confounding. Results The associations between all indicators of SES and attendance to patient education and physical training programs were strong, moderate for dietary program attendance but absent for participation in smoking cessation program (Table 1). Higher SES was also associated with repeated lipid profile measurements and the highest vs lowest income with intensified statin therapy. Correspondingly, higher SES was associated with having achieved target levels of LDL-C, blood pressure, and HbA1c as well as with persistence to and being on high intensity statin treatment (Figure 1). Further, higher SES was strongly associated with having quit smoking. No association with income was however observed regarding the weekly physical activity goal. Conclusions Higher SES was strongly associated with most SPAs including programs aiming at life style change and risk factor control as well as with attainment of corresponding secondary prevention targets. This may be explanatory for higher long-term risk of recurrent disease. Figure 1. Target Attainment Forest Plots Funding Acknowledgement Type of funding source: Other. Main funding source(s): Stockholm City Council and The Swedish Heart and Lung Association

Non-Adherence to Statin Treatment in Older Patients with Peripheral Arterial Disease Depending on Persistence Status.

The effectiveness of statins in secondary prevention of peripheral arterial disease (PAD) largely depends on patients’ adherence to treatment. The aims of our study were: (a) to analyze non-adherence during the whole follow-up in persistent patients, and only during persistence for non-persistent patients; (b) to identify factors associated with non-adherence separately among persistent and non-persistent patients. A cohort of 8330 statin users aged ≥65 years, in whom PAD was newly diagnosed between January 2012–December 2012, included 5353 patients persistent with statin treatment, and 2977 subjects who became non-persistent during the 5-year follow-up. Non-adherence was defined using the proportion of days covered <80%. Patient- and statin-related characteristics associated with non-adherence were identified with binary logistic regression. A significantly higher proportion of non-adherent patients was found among non-persistent patients compared to persistent subjects (43.6% vs. 29.6%; p < 0.001). Associated with non-adherence in both persistent and non-persistent patients was high intensity statin treatment, while in non-persistent patients, it was employment and increasing number of medications. In patients with a poor adherence during their persistent period, an increased risk for discontinuation may be expected. However, there is also non-adherence among persistent patients. There are differences in factors associated with non-adherence depending on patients’ persistence.

Relationship between arterial remodelling and serial changes in coronary atherosclerosis by intravascular ultrasound: an analysis of the IBIS-4 study.

Arterial remodelling is an important determinant of coronary atherosclerosis. Assessment of the remodelling index, comparing a lesion to a local reference site, is a suboptimal correlate of serial vascular changes. We assessed a novel approach which, unlike the local-reference approach, uses the entire artery's global remodelling as reference. Serial (baseline and 13 months) intravascular ultrasound was performed in 146 non-infarct-related arteries of 82 patients treated with high-intensity statin. Arteries were divided into 3-mm segments (n = 1479), and focal remodelling was characterized in individual segments at both timepoints applying the global arterial reference approach. First, we compared preceding vascular changes in relation to follow-up remodelling. Second, we examined whether baseline remodelling predicts subsequent plaque progression/regression. At follow-up, segments with constrictive vs. compensatory or expansive remodelling had greater preceding reduction of vessel area (-0.67 vs. -0.38 vs. -0.002mm2; P < 0.001) and lumen area (-0.82 vs. -0.09 vs. 0.40mm2; P < 0.001). Overall, we found significant regression in percent atheroma volume (PAV) [-0.80% (-1.41 to -0.19)]. Segments with constrictive remodelling at baseline had greater subsequent PAV regression vs. modest regression in the compensatory, and PAV progression in the expansive remodelling group (-6.14% vs. -0.71% vs. 2.26%; P < 0.001). Lesion-level analyses (n = 118) showed no differences when remodelling was defined by the local reference approach at baseline or follow-up. Remodelling assessment using a global arterial reference approach, but not the commonly used, local reference site approach, correlated reasonably well with serial changes in arterial dimensions and identified arterial segments with subsequent PAV progression despite intensive statin treatment and overall atheroma regression.