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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.

Background: Cardiovascular (CV) risk management for high-risk patients is often provided by primary care physicians (PCPs). We surveyed Canadian PCPs regarding their awareness and implementation of the 2021 Canadian Cardiovascular Society (CCS) lipid guideline recommendations for patients following an acute coronary syndrome (ACS) and those with diabetes but without CV disease. Methods: A committee of PCPs and specialists with lipid expertise, including some 2021 CCS lipid guideline coauthors, designed a survey to probe PCP awareness and practice patterns regarding CV risk management. From a national database, a total of 250 PCPs completed the survey between January and April 2022. Results: Almost all PCPs (97.2%) concurred that a post-ACS patient should be seen by their PCP within 4 weeks of hospital discharge (81.2% said within 2 weeks). Almost half (44.4%) responded that discharge summaries provided inadequate information, and 41.6% felt that lipid management post-ACS was the responsibility primarily of specialists. A total of 58.4% articulated that they face challenges when seeing a post-ACS patient, related to inadequate discharge information, complexities of polypharmacy and duration of therapies, and managing statin intolerance. A total of 63.2% and 43.6% correctly identified low-density lipoprotein cholesterol (LDL-C) intensification thresholds of 1.8 mmol/L in post-ACS patients, and 2.0 mmol/L in diabetes patients, respectively, and 81.2% incorrectly thought that proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors were indicated for patients with diabetes but without CV disease. Conclusions: One year following publication of the 2021 CCS lipid guidelines, our survey reveals knowledge gaps among responding PCPs regarding intensification thresholds and treatment options for patients post-ACS, or those with diabetes. Innovative and effective knowledge-translation programs to address these gaps are desirable. Résumé: Contexte: La prise en charge du risque cardiovasculaire (CV) chez les patients à risque élevé est souvent réalisée par les médecins en soins primaires (MSP). Nous avons donc sondé les MSP canadiens quant à leur connaissance des lignes directrices 2021 de la Société cardiovasculaire du Canada (SCC) sur les lipides et leur mise en œuvre auprès des patients ayant subi un syndrome coronarien aigu (SCA) et auprès des patients atteints de diabète qui ne présentent pas de maladie CV. Méthodologie: Un comité de MSP et de spécialistes ayant une expertise sur la question des lipides, y compris certains coauteurs des lignes directrices 2021 de la SCC sur les lipides, a conçu un sondage pour évaluer la connaissance des mesures de prise en charge du risque CV et les habitudes de pratique des MSP en la matière. Au total, 250 MSP provenant d’une banque de données nationale ont rempli le sondage entre janvier et avril 2022. Résultats: Presque tous les MSP (97,2 %) étaient d’accord pour dire que les patients ayant subi un SCA devraient avoir une consultation avec leur MSP dans les quatre semaines suivant leur congé de l’hôpital (81,2 % ont dit deux semaines). Près de la moitié des répondants (44,4 %) ont indiqué que le sommaire d’hospitalisation fournit une information inadéquate, et 41,6 % estimaient que la gestion des lipides après un SCA relevait des spécialistes. Au total, 58,4 % des répondants ont mentionné rencontrer des difficultés lors de la consultation avec un patient après une SCA, surtout quant à l’information inadéquate contenue dans le sommaire d’hospitalisation, aux complexités de la polypharmacie, à la durée des traitements et à l’intolérance aux statines. De plus, 63,2 % et 43,6 % des répondants ont correctement indiqué les seuils d’intensification du traitement pour le cholestérol à lipoprotéines de basse densité (LDL), soit 1,8 mmol/l chez les patients après un SCA et 2,0 mmol/l chez les patients diabétiques, respectivement. Par ailleurs, 81,2 % des répondants croyaient à tort que les inhibiteurs de la proprotéine convertase subtilisine/kexine de type 9 (PCSK9) étaient indiqués pour les patients diabétiques ne présentant pas de maladie CV. Conclusions: Un an après la publication des lignes directrices 2021 de la SCC sur les lipides, notre sondage montre des lacunes dans les connaissances des MSP quant aux seuils d’intensification du traitement et aux options de traitement pour les patients ayant subi un SCA ou atteints de diabète. Des programmes novateurs et efficaces de transmission du savoir sont souhaitables pour combler ces lacunes.

Abstract Background The secondary fracture prevention gap in the osteoporosis field has been previously described as a ‘crisis’. Closing this gap is increasingly important in the context of accumulating evidence showing that an incident fragility fracture is associated with an increased risk of subsequent fracture within 1–2 years, known as imminent fracture risk. The objective of this study was to use health services data to characterize the time between index fragility fractures occurring at different osteoporotic sites and subsequent fractures. Methods This retrospective observational study used de-identified health services data from the publicly funded healthcare system in Ontario, the largest province of Canada. Patients aged > 65 with an index fragility fracture occurring between 2011 and 2015 were identified from the ICES Data Repository using International Classification of Diseases (ICD)-10 codes. We examined median time to subsequent fragility fractures for osteoporotic fracture sites until the end of follow-up (2017). BMD assessment and use of osteoporosis therapies following index fracture were also characterized. Results Among 115,776 patients with an index fragility fracture, 17.8% incurred a second fragility fracture. Median time between index and second fracture occurring at any site was 555 days (interquartile range: 236–955). For each index fracture site examined, median time from index to second fracture was 3 years post index fracture. Conclusions This cohort of Canadian patients aged > 65 years who experienced a fragility fracture at any site are at imminent risk of experiencing subsequent fracture within the next 2 years and should be proactively assessed and treated.

Abstract Background Recent studies are lacking reports on mortality after non-hip fractures in adults aged > 65. Methods This retrospective, matched-cohort study used de-identified health services data from the publicly funded healthcare system in Ontario, Canada, contained in the ICES Data Repository. Patients aged 66 years and older with an index fragility fracture occurring at any osteoporotic site between 2011 and 2015 were identified from acute hospital admissions, emergency and ambulatory care using International Classification of Diseases (ICD)-10 codes and data were analyzed until 2017. Thus, follow-up ranged from 2 years to 6 years. Patients were excluded if they presented with an index fracture occurring at a non-osteoporotic fracture site, their index fracture was associated with a trauma code, or they experienced a previous fracture within 5 years prior to their index fracture. This fracture cohort was matched 1:1 to controls within a non-fracture cohort by date, sex, age, geography and comorbidities. All-cause mortality risk was assessed. Results The survival probability for up to 6 years post-fracture was significantly reduced for the fracture cohort vs matched non-fracture controls (p 65 years, a fragility fracture occurring at any site was associated with reduced survival for up to 6 years post-fracture. The greatest reduction in survival occurred within the first-year post-fracture, where mortality risk more than doubled and deaths were observed in 1 in 11 women and 1 in 7 men following a non-hip fracture and in 1 in 5 women and 1 in 3 men following a hip fracture.

This study evaluated the impact of a continuing medical education (CME) program that emphasized actionable information, motivation to act, and skills to strengthen physician recommendations for seasonal influenza vaccination in children 6 through 23 months of age for whom influenza immunization rates are suboptimal. Physicians were randomly assigned to an accredited CME program or to no CME. Participants completed pre- and post-study questionnaires. Influenza immunization rates were compared between groups. A total of 33 physicians in the CME group and 35 in the control group documented 292 and 322 healthy baby visits, respectively. Significantly more parents immunized their children against influenza after interacting with CME-trained physicians than those with no CME training (52.9% vs. 40.7%; p = 0.007). The odds ratio for vaccination after visits with CME-trained physicians was 1.52 (95% confidence interval 1.09 to 2.12; p = 0.014), which was unaffected by the socioeconomic status of parents. Parents who discussed influenza vaccination with CME-trained physicians were 20% more likely to choose an approved but publicly unfunded adjuvanted pediatric influenza vaccine. The percentages of physicians reporting the highest levels of knowledge, ability, and confidence doubled or tripled after the CME intervention. Significantly more parents immunized very young children after interacting with physicians who had undergone CME training.

This prospective cohort survey evaluated the concordance of clinicians’ perceptions of parental intentions and parents’ actual intentions to vaccinate their infants against influenza. During a routine healthy baby visit, clinicians provided parents with information about influenza, children’s vulnerability to influenza, and nonadjuvanted and adjuvanted trivalent influenza vaccines (TIV and aTIV, respectively). Before and after the clinician–parent interaction, parents were surveyed about their attitudes, their perceptions of support from significant others, and the intention to vaccinate their infant with aTIV. Clinicians were asked about their perception of parents’ intentions to choose aTIV for their children. These assessments included 24 clinicians at 15 community practices and nine public health clinics, and 207 parents. The correlation coefficients of the clinicians’ assessment of parents’ intention to vaccinate were 0.483 (p < 0.001) if the vaccine was presented as free of cost, 0.266 (p < 0.001) if the cost was $25, and 0.146 (p = 0.036) if the cost was $50, accounting for 23%, 7%, and 2% of the variance in parental intentions, respectively. The clinicians were poor at predicting parental intentions to immunize, particularly when cost was involved. Information on vaccine options and influenza infection should be provided for every eligible patient to allow parents to determine if the vaccine is appropriate for their child.

Adjuvanted trivalent influenza vaccine (aTIV) provides enhanced protection against seasonal influenza in children compared with nonadjuvanted trivalent influenza vaccine (TIV). This prospective cohort study assessed parental attitudes, beliefs, and intentions to vaccinate their infants aged 6–23 months with aTIV. Parents were surveyed before and after routine healthy baby visits, and post clinician interaction results were analyzed using multivariable logistic regression. Physicians at 15 community practice clinics and nurses at 3 public health clinics participated; 207 parents were surveyed. After clinician consultation, most parents considered immunization with aTIV to be safe (72.9%), effective (69.6%), and important (69.0%); most perceived support for vaccination from significant others (62.8%) and clinicians (81.6%); and 66.6% intended to vaccinate their infant with aTIV. Parental attitudes toward vaccinating their infant with aTIV were strongly correlated with perceptions of vaccine safety, efficacy, and importance, and these represented the strongest influence on intentions to vaccinate (odds ratio (OR) 79.25; 95% confidence interval (CI) 6.05–1037.50). Parental intentions were further influenced by perceived strength of clinician recommendation (OR 4.55, 95% CI 1.38–15.06) and social support for vaccination (OR 3.46, 95% CI 0.50–24.13). These findings may inform clinician approaches to parental education to ensure optimal seasonal pediatric influenza vaccination.

The adjuvanted trivalent influenza vaccine (aTIV) provides enhanced protection against influenza for infants but is not publicly funded (NPF). The objective of this prospective cohort study of parents with children 6 through 23 months of age was to understand how NPF status influences parental perceptions of approved but unfunded vaccines and their intentions to vaccinate. At healthy baby visits, clinicians provided parents with information about influenza and vaccination. Before and after these interactions, a research nurse assessed parents’ intentions to vaccinate their children and their beliefs about the safety, efficacy, and necessity of vaccinating their children with aTIV in both publicly funded (PF) and NPF settings. Overall, 15 community practice clinics (n = 15 physicians) and nine public health clinics (n = 9 nurses) recruited 207 parents. The percentage of parents intending to immunize their children with aTIV decreased from 72% (vaccine PF, free of charge), to 42% (NPF, $25 per dose), to 27% (NPF, $50 per dose). Funding status strongly influenced whether parents perceived immunization with aTIV to be necessary, safe, and effective. Information on influenza and influenza vaccines should be provided to parents routinely to allow for well-informed decisions on the suitability of specific influenza vaccines for their child.