Erratum: Leiter et al. Review of Evolocumab for the Reduction of LDL Cholesterol and Secondary Prevention of Atherosclerotic Cardiovascular Disease. Reviews in Cardiovascular Medicine. 2024; 25: 190.

[This corrects the article DOI: 10.31083/j.rcm2505190.].

Atherosclerosis quantification and cardiovascular risk: the ISCHEMIA trial.

BACKGROUND AND AIMS: The aim of this study was to determine the prognostic value of coronary computed tomography angiography (CCTA)-derived atherosclerotic plaque analysis in ISCHEMIA. METHODS: Atherosclerosis imaging quantitative computed tomography (AI-QCT) was performed on all available baseline CCTAs to quantify plaque volume, composition, and distribution. Multivariable Cox regression was used to examine the association between baseline risk factors (age, sex, smoking, diabetes, hypertension, ejection fraction, prior coronary disease, estimated glomerular filtration rate, and statin use), number of diseased vessels, atherosclerotic plaque characteristics determined by AI-QCT, and a composite primary outcome of cardiovascular death or myocardial infarction over a median follow-up of 3.3 (interquartile range 2.2-4.4) years. The predictive value of plaque quantification over risk factors was compared in an area under the curve (AUC) analysis. RESULTS: Analysable CCTA data were available from 3711 participants (mean age 64 years, 21% female, 79% multivessel coronary artery disease). Amongst the AI-QCT variables, total plaque volume was most strongly associated with the primary outcome (adjusted hazard ratio 1.56, 95% confidence interval 1.25-1.97 per interquartile range increase [559 mm3]; P = .001). The addition of AI-QCT plaque quantification and characterization to baseline risk factors improved the model's predictive value for the primary outcome at 6 months (AUC 0.688 vs. 0.637; P = .006), at 2 years (AUC 0.660 vs. 0.617; P = .003), and at 4 years of follow-up (AUC 0.654 vs. 0.608; P = .002). The findings were similar for the other reported outcomes. CONCLUSIONS: In ISCHEMIA, total plaque volume was associated with cardiovascular death or myocardial infarction. In this highly diseased, high-risk population, enhanced assessment of atherosclerotic burden using AI-QCT-derived measures of plaque volume and composition modestly improved event prediction.

Traditional and Novel Markers: Target of Treatment vs Marker of Risk.

In this article we discuss lipid-related markers associated with cardiovascular (CV) risk, and emphasize the significance of low-density lipoprotein (LDL) cholesterol (LDL-C), non-high-density lipoprotein cholesterol, and apolipoprotein B100. LDL-C, a traditional CV risk factor, correlates directly with atherosclerotic CV disease. However, LDL-C alone, usually estimated using the Friedewald equation, might not capture the entire risk profile. Therefore, triglycerides (TGs) and lipoprotein(a) [Lp(a)] should be measured as part of a complete CV risk assessment. Although TGs represent potential markers of increased CV risk, their role as direct causal agents remains inconclusive. Elevated TG levels suggest a greater cholesterol presence in non-LDL particles, necessitating the use of non-high-density lipoprotein cholesterol or apolipoprotein B100, rather than solely LDL-C, to ensure an accurate CV risk assessment. Lp(a), however, is a genetically determined particle resembling LDL, linked with various significant CV diseases. Its role in CV risk is potentially because of its added inflammatory and prothrombotic properties. Certain medications (most notably proprotein convertase subtilisin/kexin type 9 inhibitors and novel small interfering RNA molecules) can reduce Lp(a) levels. Whether this confers a benefit in preventing CV outcomes requires validation from ongoing trials. Although LDL-C remains a crucial metric, health care professionals must acknowledge its limitations and understand the emerging significance of TGs and Lp(a) in CV risk assessment. This article underscores the need to reevaluate traditional lipid markers in light of emerging evidence on TGs and Lp(a) to promote a more comprehensive approach to CV risk assessment.

Adoption of the PREVENT (Predicting Risk of Cardiovascular Disease EVENTs) Risk Algorithm: Potential International Implications.

Background: The PREVENT (Predicting Risk of cardiovascular disease EVENTs risk algorithm was developed to better reflect the impact of metabolic factors on cardiovascular risk. Objectives: The purpose of this study was to compare the relative performance of PREVENT with standard comparator algorithms (Framingham risk score, pooled cohort equation, SCORE2 [Systematic COronary Risk Evaluation2]) for risk stratification emphasizing the implications of weighing chronic kidney disease. Methods: A simulated cohort was created of males and females aged 40 to 75 years with and without other traditional risk factors and either normal estimated glomerular filtration rates (eGFR 90 or 60 ml/min/1.73 m2) or abnormal eGFR (45 or 30 ml/min/1.73 m2). The concordance and reclassification rates were calculated for each category of risk with emphasis on subjects characterized as moderate risk by the standard comparator algorithms. Results: PREVENT demonstrated increased risk with progressive decreases in eGFR. When the standard comparator algorithms identified moderate risk, PREVENT was concordant in 6% to 88% of simulations. In simulations with normal eGFR, PREVENT identified a lower risk in 18% to 88% and a higher risk in 0% to 12% of simulations. Conversely, with abnormal eGFR, PREVENT identified lower risk in 0% to 26% and higher risk in 4% to 94% of simulations. Conclusions: PREVENT substantially reclassifies risk and has the potential to alter prevention practice patterns. The tendency to assign a lower risk compared to standard algorithms when eGFR is normal may diminish implementation of preventive therapy. National health care systems need to monitor whether such changes improve overall public health.

Review of Evolocumab for the Reduction of LDL Cholesterol and Secondary Prevention of Atherosclerotic Cardiovascular Disease.

Elevated low-density lipoprotein cholesterol (LDL-C) is a major causal factor for atherosclerotic cardiovascular disease (ASCVD), the leading cause of mortality worldwide. Statins are the recommended first-line lipid-lowering therapy (LLT) for patients with primary hypercholesterolemia and established ASCVD, with LLT intensification recommended in the substantial proportion of patients who do not achieve levels below guideline-recommended LDL-C thresholds with statin treatment alone. The proprotein convertase subtilisin/kexin type 9 inhibitor monoclonal antibody evolocumab has demonstrated significant LDL-C reductions of > 60% in the clinical trial and open-label extension settings, with LDL-C reductions observed early post-evolocumab initiation and maintained long term, during up to 8.4 years of follow-up. Evolocumab therapy, when added to a statin, also conferred a significant reduction in major cardiovascular (CV) events, including a 20% reduction in the composite of CV death, myocardial infarction (MI), or stroke. The absolute benefits were enhanced among various patient types at high and very high risk for secondary ASCVD (e.g., with recent MI, multiple events or peripheral artery disease). Importantly, evolocumab treatment resulted in incremental CV risk reductions during the extended follow-up, including a 23% reduction in CV mortality and no apparent LDL-C level below which there is no further CV risk reduction. Hence, the evolocumab clinical data support the need for early and significant LDL-C lowering, especially in vulnerable ASCVD patients, in order to derive the greatest benefit in the long term. Importantly, evolocumab had no impact on any treatment emergent adverse events apart from a small increase in local injection site reactions. A growing body of real-world evidence (RWE) for evolocumab in heterogeneous populations is consistent with the trial data, including robust LDL-C reductions below guideline-recommended thresholds, a favourable safety profile even at the lowest levels of LDL-C achieved, and a high treatment persistence rate of > 90%. Altogether, this review highlights findings from 50 clinical trials and RWE studies in > 51,000 patients treated with evolocumab, to demonstrate the potential of evolocumab to address the healthcare gap in LDL-C reduction and secondary prevention of ASCVD in a variety of high- and very high-risk patients.

Canadian Cost-Effectiveness of Coronary Artery Calcium Screening Based on the Multi-Ethnic Study of Atherosclerosis.

Background: Cost-effectiveness of testing for coronary artery calcium (CAC) relative to other treatment strategies is not established in Canada. Objectives: The purpose of this study was to evaluate the cost-effectiveness of using CAC score-guided statin treatment compared with universal statin therapy among intermediate-risk, primary prevention patients eligible for statins. Methods: A state transition, microsimulation model used data from Canadian sources and the Multi-Ethnic Study of Atherosclerosis to simulate clinical and economic consequences of cardiovascular disease from a Canadian publicly funded health care system perspective. In the CAC score-guided treatment arm, statins were started when CAC ≥1. Outcome of interest was the incremental cost-effectiveness ratio at 5 and 10 years; an incremental cost-effectiveness ratio <$50,000 per quality-adjusted life year (QALY) gained was considered cost-effective. Sensitivity analyses examined uncertainty in model parameters. Results: Compared with universal statin treatment at 5 and 10 years, CAC score-guided statin treatment was projected to increase mean costs by $326 (95% CI: $325-$326) and $172 (95% CI: $169-$175), increase mean QALYs by 0.01 (95% CI: 0.01-0.01) and 0.02 (95% CI: 0.02-0.02), and cost $54,492 (95% CI: $52,342-$56,816) and $8,118 (95% CI: $7,968-$8,279) per QALY gained, respectively. The model was most sensitive to statin cost, CAC testing cost, adherence to statin monitoring, and disutility associated with daily statin use. At 5 years, CAC score-guided statin treatment was cost-effective when CAC test costs ranged from $80 to $160 in different scenarios. Conclusions: CAC score-guided statin initiation in comparison to universal statin treatment was borderline cost-neutral at 5 years and cost-effective at 10 years in statin-eligible Canadian patients at intermediate cardiovascular disease risk.

Factors Associated With Coronary Angiography Performed Within 6 Months of Randomization to the Conservative Strategy in the ISCHEMIA Trial.

BACKGROUND: ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) did not find an overall reduction in cardiovascular events with an initial invasive versus conservative management strategy in chronic coronary disease; however, there were conservative strategy participants who underwent invasive coronary angiography early postrandomization (within 6 months). Identifying factors associated with angiography in conservative strategy participants will inform clinical decision-making in patients with chronic coronary disease. METHODS: Factors independently associated with angiography performed within 6 months of randomization were identified using Fine and Gray proportional subdistribution hazard models, including demographics, region of randomization, medical history, risk factor control, symptoms, ischemia severity, coronary anatomy based on protocol-mandated coronary computed tomography angiography, and medication use. RESULTS: Among 2591 conservative strategy participants, angiography within 6 months of randomization occurred in 8.7% (4.7% for a suspected primary end point event, 1.6% for persistent symptoms, and 2.6% due to protocol nonadherence) and was associated with the following baseline characteristics: enrollment in Europe versus Asia (hazard ratio [HR], 1.81 [95% CI, 1.14-2.86]), daily and weekly versus no angina (HR, 5.97 [95% CI, 2.78-12.86] and 2.63 [95% CI, 1.51-4.58], respectively), poor to fair versus good to excellent health status (HR, 2.02 [95% CI, 1.23-3.32]) assessed with Seattle Angina Questionnaire, and new/more frequent angina prerandomization (HR, 1.80 [95% CI, 1.34-2.40]). Baseline low-density lipoprotein cholesterol <70 mg/dL was associated with a lower risk of angiography (HR, 0.65 [95% CI, 0.46-0.91) but not baseline ischemia severity nor the presence of multivessel or proximal left anterior descending artery stenosis >70% on coronary computed tomography angiography. CONCLUSIONS: Among ISCHEMIA participants randomized to the conservative strategy, angiography within 6 months of randomization was performed in <10% of patients. It was associated with frequent or increasing baseline angina and poor quality of life but not with objective markers of disease severity. Well-controlled baseline low-density lipoprotein cholesterol was associated with a reduced likelihood of angiography. These findings point to the importance of a comprehensive assessment of symptoms and a review of guideline-directed medical therapy goals when deciding the initial treatment strategy for chronic coronary disease. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01471522.

Consideration and Application of Lipoprotein(a) in the Risk Assessment of Atherosclerotic Cardiovascular Disease Risk in Adults.

Lipoprotein(a) (Lp[a]) is an low-density lipoprotein (LDL)-like particle in which apolipoprotein (apo) B is covalently bound to a plasminogen-like molecule called apo(a). A High level of Lp(a) has been demonstrated to be an independent, causal, and prevalent risk factor for atherosclerotic cardiovascular disease (ASCVD), as well as aortic valve disease, through mechanisms that promote atherogenesis, inflammation, and thrombosis. With reliable and accessible assays, Lp(a) level has been established to be associated linearly with the risk for ASCVD. The 2021 Canadian Cardiovascular Society Dyslipidemia Guidelines recommend measuring an Lp(a) level once in a person's lifetime as part of the initial lipid screening. The aim of this review is to provide an update and overview of the utility and application of Lp(a) level in the assessment and treatment of adults at risk for ASCVD, consistent with this guideline recommendation.

La lipoprotéine(a), ou Lp(a), est une lipoprotéine de basse densité dans laquelle l'apolipoprotéine B est liée de manière covalente à une molécule semblable au plasminogène, l'apolipoprotéine(a). On a démontré qu'un taux élevé de Lp(a) est un facteur de risque indépendant, causal et fréquent d'athérosclérose cardiovasculaire (ASCV) et de valvulopathie aortique, en raison de mécanismes qui favorisent l'athérogénèse, l'inflammation et la thrombose. Des épreuves fiables et accessibles ont permis d'établir que le taux de Lp(a) était associé de façon linéaire à un risque d'ASCV. Dans ses lignes directrices de 2021 sur la prise en charge de la dyslipidémie, la Société cardiovasculaire du Canada recommande de mesurer le taux de Lp(a) une fois au cours de la vie d'une personne, dans le cadre du dépistage initial des lipides. Le présent article vise à fournir une mise à jour et un compte rendu de l'utilité et de l'application du taux de Lp(a) dans l'évaluation et le traitement des adultes présentant un risque d'ASCV, conformément à cette recommandation issue des lignes directrices.

Effects of adaptive or fixed thresholds and different platforms on the assessment of plaque characteristics using coronary computed tomography angiography.

BACKGROUND: Coronary computed tomography angiography (CCTA) is used to evaluate components of atherosclerosis. Either adaptive or diverse, fixed Hounsfield Units (HU) are used to define components such as low attenuation (LAP), mixed (MP) and calcified plaque (CP). Comparisons of different platforms and different thresholding approaches have not been extensively evaluated. We compare two fixed threshold options to an adaptive threshold option within a specific platform and to fixed threshold options measured with another platform. METHODS: Coronary segments (n â€‹= â€‹24) of good image quality, with well-defined boundaries and representing a broad range of atheroma were analyzed for LAP, MP and CP. Thresholds for LAP vs MP and MP vs CP were either Fixed30/350, Fixed75/350 or based on an automatically determined Adaptive option. Pearson correlation and Bland-Altman analyses were undertaken. RESULTS: Within a single platform, measures were highly correlated irrespective of use of Adaptive or Fixed30/350 and Fixed75/350 thresholds (R â€‹≥ â€‹0.819, p â€‹< â€‹0.000001). The correlation slope for measures of LAP progressively diminished comparing the Adaptive versus Fixed30/350 and the Fixed75/350 versus the Fixed30/350 approaches but bias was small. Between-platform comparisons yielded less optimal results, particularly with respect to measures of LAP and with one platform yielding both very small LAP volumes and very small ranges of volumes. CONCLUSION: Measures of plaque components are highly correlated irrespective of use of Adaptive or Fixed threshold approaches within a given platform. But measures are more affected by the specific proprietary algorithms employed than by specific thresholding options, especially for LAP.

Angiographic characteristics of patients with STEMI and COVID-19: Insights from NACMI registry.

BACKGROUND: To date, there has been no independent core lab angiographic analysis of patients with COVID-19 and STEMI. The study characterized the angiographic parameters of patients with COVID-19 and STEMI. METHODS: Angiograms of patients with COVID-19 and STEMI from the North American COVID-19 Myocardial Infarction (NACMI) Registry were sent to a Core Laboratory in Vancouver, Canada. Culprit lesion(s), Thrombolysis In Myocardial Infarction (TIMI) flow, Thrombus Grade Burden (TGB), and percutaneous coronary intervention (PCI) outcome were assessed. RESULTS: From 234 patients, 74% had one culprit lesion, 14% had multiple culprits and 12% had no culprit identified. Multivessel thrombotic disease and multivessel CAD were found in 27% and 53% of patients, respectively. Stent thrombosis accounted for 12% of the presentations and occurred in 55% of patients with previous coronary stents. Of the 182 who underwent PCI, 60 (33%) had unsuccessful PCI due to post-PCI TIMI flow <3 (43/60), residual high thrombus burden (41/60) and/or thrombus related complications (27/60). In-hospital mortality for successful, partially successful, and unsuccessful PCI was 14%, 13%, and 27%, respectively. Unsuccessful PCI was associated with increased risk of in-hospital mortality (risk ratio [RR] 1.96; 95% CI: 1.05-3.66, P = .03); in the adjusted model this estimate was attenuated (RR: 1.24; 95% CI: 0.65-2.34, P = .51). CONCLUSION: In patients with COVID-19 and STEMI, thrombus burden was pervasive with notable rates of multivessel thrombotic disease and stent thrombosis. Post-PCI, persistent thrombus and sub-optimal TIMI 3 flow rates led to one-third of the PCI's being unsuccessful, which decreased over time but remained an important predictor of in-hospital mortality.

Efficacy and safety of bempedoic acid in patients with heterozygous familial hypercholesterolemia: analysis of pooled patient-level data from phase 3 clinical trials.

BACKGROUND: Patients with heterozygous familial hypercholesterolemia (HeFH) often cannot reach guideline-recommended low-density lipoprotein cholesterol (LDL-C) goals despite multidrug therapy. OBJECTIVE: To evaluate the efficacy and safety of bempedoic acid as an add-on therapy for lowering LDL-C in patients with HeFH. METHODS: Pooled data from two 52-week phase 3 clinical trials of patients with atherosclerotic cardiovascular disease and/or HeFH receiving maximally tolerated statin therapy (randomized 2:1 to bempedoic acid or placebo) were analyzed by HeFH status. Endpoints included changes from baseline to week 12 (and up to week 52) in LDL-C and other lipid parameters, achievement of LDL-C goals, and safety. RESULTS: A total of 217 (bempedoic acid, 146; placebo, 71) patients with HeFH and 2,792 (bempedoic acid, 1,864; placebo, 928) without HeFH were included (mean baseline LDL-C, 172.8 mg/dL and 102.6 mg/dL, respectively). Bempedoic acid significantly lowered LDL-C at week 12 vs. placebo regardless of HeFH status (with HeFH, -21.2%; without HeFH, -18.2% [both P<0.0001]). Bempedoic acid significantly reduced other lipid parameters and high-sensitivity C-reactive protein vs. placebo regardless of HeFH status (all P≤0.01). Among patients with HeFH treated with bempedoic acid, 32% and 27% achieved LDL-C <100 mg/dL at weeks 12 and 52, respectively. Overall treatment-emergent adverse event incidence was comparable across all four groups (74.7-77.5%). CONCLUSION: Bempedoic acid significantly lowered LDL-C levels vs. placebo and was generally well tolerated in all patients, with no new safety findings in patients with HeFH, despite more intensive lipid-lowering therapy in patients with vs. without HeFH.

The effectiveness of sodium-glucose co-transporter 2 inhibitors on cardiorenal outcomes: an updated systematic review and meta-analysis.

BACKGROUND: The 2022 Canadian Cardiovascular Society (CCS) cardiorenal guideline provided clinical recommendations on sodium-glucose co-transport 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) use. Since then, additional trials of relevance for SGLT2i have been published. This update re-evaluates the clinical recommendations for using SGLTi and their indirect comparison with existing evidence on GLP-1RA as compared to the standard of care to reduce cardiorenal morbidity and mortality. METHODS: We updated our existing search and screening of the literature from September 2021 to April 2023 for randomized controlled trials of SGLT2i and GLP-1RA with placebo control. We conducted risk of bias assessment, data extraction and updated our meta-analysis of studies with similar interventions and components. The certainty of the evidence was determined using GRADE. RESULTS: Evidence from three new trials and additional results from an updated existing trial on SGLT2i met our inclusion criteria after an updated search. Across all the included studies, the total sample size was 151,023 adults, with 90,943 in SGLT2i trials and 60,080 in GLP-1 RA trials. The mean age ranged from 59.9 to 68.4 years. Compared with standard care, the use of SGLT2i and GLP-1 RA showed significant reductions in the outcomes of cardiovascular (CV) mortality (14% & 13%), any-cause mortality (12% & 12%), major adverse CV events (MACE) (11% & 14%), heart failure (HF) hospitalization (30% & 9%), CV death or HF hospitalization (23% & 11%), and kidney composite outcome (32% & 22%). In participants with T2D, both classes demonstrated significant cardiorenal protection. But, only GLP-1RA showed a reduction in non-fatal stroke (16%) and only SGLT2i showed a reduction in HF hospitalization (30%) in this population of people living with T2D. CONCLUSIONS: This updated and comprehensive meta-analysis substantiates and strengthens the clinical recommendations of the CCS cardiorenal guidelines.

Primary and Secondary Cardiovascular and Kidney Prevention With Canagliflozin: Insights From the CANVAS Program and CREDENCE Trial.

BACKGROUND: This study evaluated the effects of canagliflozin in patients with type 2 diabetes with and without prevalent cardiovascular disease (secondary and primary prevention). METHODS AND RESULTS: This was a pooled participant-level analysis of the CANVAS (Canagliflozin Cardiovascular Assessment Study) Program and CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) trial. The CANVAS Program included participants with type 2 diabetes at elevated cardiovascular risk, whereas the CREDENCE trial included participants with type 2 diabetes and albuminuric chronic kidney disease. Hazard ratios (HRs) with interaction terms were obtained from Cox regression models to estimate relative risk reduction with canagliflozin versus placebo across the primary and secondary prevention groups. We analyzed 5616 (38.9%) and 8804 (61.1%) individuals in the primary and secondary prevention subgroups, respectively. Primary versus secondary prevention participants were on average younger (62.2 versus 63.8 years of age) and more often women (42% versus 31%). Canagliflozin reduced the risk of major adverse cardiovascular events (HR, 0.84 [95% CI, 0.76-0.94]) consistently across primary and secondary prevention subgroups (Pinteraction=0.86). Similarly, no treatment effect heterogeneity was observed with canagliflozin for hospitalization for heart failure, cardiovascular death, end-stage kidney disease, or all-cause mortality (all Pinteraction>0.5). CONCLUSIONS: Canagliflozin reduced cardiovascular and kidney outcomes with no statistical evidence of heterogeneity for the treatment effect across the primary and secondary prevention subgroups in the CANVAS Program and CREDENCE trial. Although studies on the optimal implementation of canagliflozin within these populations are warranted, these results reinforce canagliflozin's role in cardiorenal prevention and treatment in individuals with type 2 diabetes. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT01032629, NCT01989754, NCT02065791.

Sex differences in the presentation, treatment and outcomes of patients with homozygous familial hypercholesterolemia.

BACKGROUND: Homozygous familial hypercholesterolemia (HoFH) is a rare, autosomal semi-dominant lipid metabolism disorder characterized by extremely high low-density lipoprotein cholesterol (LDL-C) levels and premature cardiovascular disease. The objective of this study was to investigate sex-differences in the treatment and outcomes of patients with HoFH. METHODS: We examined clinical characteristics, lipid-lowering therapy (LLT), and cardiovascular events using descriptive statistics of patients in the Canadian HoFH registry. Major adverse cardiovascular events (MACE) were defined as the composite of cardiovascular death, non-fatal myocardial infarction, and stroke. Sex differences between continuous and categorical variables were analyzed using Mann-Whitney U test and Fisher's Exact test, respectively. RESULTS: This study included 48 patients (27 (56%) female). The median age at diagnosis in females was 14.0 (interquartile range (IQR) 9.0-30.0) and in males was 8.0 (IQR 2.0-23.0) (p = 0.07). Baseline clinical characteristics were comparable between both sexes. The median baseline LDL-C was 12.7 mmol/L (10.0-18.3) in females and 15.3 (10.5-20.0) in males (p = 0.51). Follow up LDL-C levels were 7.6 mmol/L (IQR 4.8-11.0) in females and 6.3 (IQR 4.6-7.5) in males (p = 0.1). Most patients were taking 3 or more LLTs, with comparable proportions in both sexes (p = 0.26). Apheresis was similar in both sexes, 14 (51.8%) vs. 10 (47.6%) (p = 0.2). Over a mean of 10 years of follow-up, MACE occurred in 3 females (11.1%) and 4 males (19.1%) (p = 0.2). CONCLUSION: Lipid levels and treatment were similar between sexes. MACE occurred in similar proportions between sexes, indicating that HoFH offsets the inherently lower cardiovascular risk in pre-menopausal females. Further investigation into sex-differences in HoFH in larger sample sizes is warranted.

Recommendations for statin management in primary prevention: disparities among international risk scores.

BACKGROUND AND AIMS: Statin recommendations in primary prevention depend upon risk algorithms. Moreover, with intermediate risk, risk enhancers and de-enhancers are advocated to aid decisions. The aim of this study was to compare algorithms used in North America and Europe for the identification of patients warranting statin or consideration of risk enhancers and de-enhancers. METHODS: A simulated population (n = 7680) equal in males and females, with/without smoking, aged 45-70 years, total cholesterol 3.5-7.0 mmol/L, high-density lipoprotein cholesterol 0.6-2.2 mmol/L, and systolic blood pressure 100-170 mmHg, was evaluated. High, intermediate, and low risks were determined using the Framingham Risk Score (FRS), Pooled Cohort Equation (PCE), four versions of Systematic Coronary Risk Evaluation 2 (SCORE2), and Multi-Ethnic Study of Atherosclerosis (MESA) algorithm (0-1000 Agatston Units). RESULTS: Concordance for the three levels of risk varied from 19% to 85%. Both sexes might be considered to have low, intermediate, or high risk depending on the algorithm applied, even with the same burden of risk factors. Only SCORE2 (High Risk and Very High Risk versions) identified equal proportions of males and females with high risk. Excluding MESA, the proportion with moderate risk was 25% (SCORE2, Very High Risk Region), 32% (FRS), 39% (PCE), and 45% (SCORE2, Low Risk Region). CONCLUSION: Risk algorithms differ substantially in their estimation of risk, recommendations for statin treatment, and use of ancillary testing, even in identical patients. These results highlight the limitations of currently used risk-based approaches for addressing lipid-specific risk in primary prevention.

Real-World Insights into Evolocumab Use in Patients with Hyperlipidemia Across Five Countries: Analysis from the ZERBINI Study.

INTRODUCTION: This study characterizes patients receiving evolocumab in clinical practice and assesses treatment effectiveness, safety and persistence outcomes across five countries. METHODS: This retrospective and prospective observational study enrolled patients initiated on evolocumab during August 2017 to July 2019 at 49 sites across Canada, Mexico, Colombia, Saudi Arabia and Kuwait. Medical records data were extracted within 6 months prior to (baseline) and every 3 months for 12 months post evolocumab initiation and reported as available. RESULTS: A total of 578 patients were enrolled (40.1% female, median age 60 [interquartile range (IQR) 51-68] years); 83.7% had atherosclerotic cardiovascular disease and/or familial hypercholesterolemia. Median low-density lipoprotein cholesterol (LDL-C) at baseline was 3.4 (IQR 2.7-4.2) mmol/L (131.5 [IQR 104.4-162.4] mg/dL), with 75.6% of patients receiving a statin (59.2% high intensity). Compared to baseline, the median lowest LDL-C was reduced by 70.2% and remained stable over 12 months of treatment. Guideline-recommended LDL-C thresholds < 1.8, < 1.4 and < 1.0 mmol/L (< 70, < 55 and < 40 mg/dL) were achieved by 75.3%, 63.6% and 47.4% of patients. LDL-C outcomes were consistent across high- and very high-risk patients. Background lipid-lowering therapy remained relatively stable. No serious treatment-emergent adverse events were reported, and persistence to evolocumab was 90.2% at 12 months. CONCLUSION: These findings provide real-world evidence that evolocumab use is in accordance with its international guideline-recommended place in dyslipidemia therapy, as well as confirmation of its effectiveness and safety in a heterogeneous population. Evolocumab can address a healthcare gap in the management of dyslipidemia by increasing the proportion of patients achieving LDL-C goals recommended to lower cardiovascular risk.

Epidemiology and treatment of heart failure with chronic obstructive pulmonary disease in Canadian primary care.

AIMS: Heart failure (HF) and chronic obstructive pulmonary disease (COPD) are largely managed in primary care, but their intersection in terms of disease burden, healthcare utilization, and treatment is ill-defined. METHODS AND RESULTS: We examined a retrospective cohort including all patients with HF or COPD in the Canadian Primary Care Sentinel Surveillance Network from 2010 to 2018. The population size in 2018 with HF, COPD, and HF with COPD was 15 778, 27 927, and 4768 patients, respectively. While disease incidence declined, age-sex-standardized prevalence per 100 population increased for HF alone from 2.33 to 3.63, COPD alone from 3.44 to 5.96, and COPD with HF from 12.70 to 15.67. Annual visit rates were high and stable around 8 for COPD alone but declined significantly over time for HF alone (9.3-8.1, P = 0.04) or for patients with both conditions (14.3-11.9, P = 0.006). For HF alone, cardiovascular visits were common (29.4%), while respiratory visits were infrequent (3.5%), with the majority of visits being non-cardiorespiratory. For COPD alone, respiratory and cardiovascular visits were common (16.4% and 11.3%) and the majority were again non-cardiorespiratory. For concurrent disease, 39.0% of visits were cardiorespiratory. The commonest non-cardiorespiratory visit reasons were non-specific symptoms or signs, endocrine, musculoskeletal, and mental health. In patients with HF with and without COPD, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor-neprilysin inhibitor use was similar, while mineralocorticoid receptor antagonist use was marginally higher with concurrent COPD. Beta-blocker use was initially lower with concurrent COPD compared with HF alone (69.3% vs. 74.0%), but this progressively declined by 2018 (74.5% vs. 73.5%). CONCLUSIONS: The prevalence of HF and COPD continues to rise. Although patients with either or both conditions are high utilizers of primary care, the majority of visits relate to non-cardiorespiratory comorbidities. Medical therapy for HF was similar and the initially lower beta-blocker utilization disappeared over time.