This contemporary, international, evidence-informed guidance aims to achieve the greatest good for the greatest number of people with familial hypercholesterolaemia (FH) across different countries. ...FH, a family of monogenic defects in the hepatic LDL clearance pathway, is a preventable cause of premature coronary artery disease and death. Worldwide, 35 million people have FH, but most remain undiagnosed or undertreated. Current FH care is guided by a useful and diverse group of evidence-based guidelines, with some primarily directed at cholesterol management and some that are country-specific. However, none of these guidelines provides a comprehensive overview of FH care that includes both the lifelong components of clinical practice and strategies for implementation. Therefore, a group of international experts systematically developed this guidance to compile clinical strategies from existing evidence-based guidelines for the detection (screening, diagnosis, genetic testing and counselling) and management (risk stratification, treatment of adults or children with heterozygous or homozygous FH, therapy during pregnancy and use of apheresis) of patients with FH, update evidence-informed clinical recommendations, and develop and integrate consensus-based implementation strategies at the patient, provider and health-care system levels, with the aim of maximizing the potential benefit for at-risk patients and their families worldwide.
Purpose of Review
To review recent international and domestic definitions, considerations, and treatment algorithms for statin intolerance, and specifically, statin-associated muscle symptoms (SAMS).
...Recent Findings
Multiple organizations around the world have produced guidance documents to aid clinicians on managing statin intolerance. A common theme resides among all the guidance documents that most patients can tolerate statins. For those patients who cannot, healthcare teams need to evaluate, rechallenge, educate, and ensure adequate reduction of atherogenic lipoproteins.
Summary
Statin therapy remains the cornerstone of lipid-lowering therapies to reduce atherosclerotic cardiovascular disease (ASCVD) and reduce mortality and morbidity. The common theme throughout all these guidance documents is the importance of statin therapy to reduce ASCVD and continual adherence to treatment. Because adverse events occur and inhibit patients from achieving adequate lowering of their atherogenic lipoproteins, trial and rechallenge of statin therapy, as well as addition of non-statin therapies, especially in high-risk patients, is also undisputed. The main differences stem from laboratory monitoring and the classification of the severity of the adverse effect. Future research should focus on consistently diagnosing SAMS so that these patients can be easily identified in the electronic health records.
Guidelines provide recommendations for clinicians based on the best available evidence and informed by clinical expertise. These recommendations often fail to be utilized by clinicians hindering the ...translation of evidence into practice. The purpose of this review is to describe novel ways in which implementation science has been used to improve translation of guidelines into clinical practice in the field of lipidology.
We searched PubMed for articles related to guideline implementation in lipidology published in 2021 and 2022. Identified articles were categorized into three domains: first, poor uptake of guideline recommendations in practice; second, implementation science as a solution to improve care; and third, examples of how implementation science can be incorporated into guidelines.
The field of lipidology has identified that many guideline recommendations fail to be translated into practice and has started to utilize methods from implementation science to assess ways to shrink this gap. Future work should focus on deploying tools from implementation science to address current gaps in guideline development. Such as, developing a systematic approach to restructure guideline recommendations so they are implementable in practice and aid in clinicians' ability to easily translate them into practice.
Purpose of Review
Describe the application of implementation science to improve the detection and management of familial hypercholesterolaemia.
Recent Findings
Gaps between evidence and practice, ...such as underutilization of genetic testing, family cascade testing, failure to achieve LDL-cholesterol goals and low levels of knowledge and awareness, have been identified through clinical registry analyses and clinician surveys. Implementation science theories, models and frameworks have been applied to assess barriers and enablers in the literature specific to local contextual factors (e.g. stages of life). The effect of implementation strategies to overcome these factors has been evaluated; for example, automated identification of individuals with FH or training and education to improve statin adherence. Clinical registries were identified as a key infrastructure to monitor, evaluate and sustain improvements in care.
Summary
The expansion in evidence supporting the care of familial hypercholesterolaemia requires a similar expansion of efforts to translate new knowledge into clinical practice.
Clinical guidelines recommend statins for patients with atherosclerotic cardiovascular disease (ASCVD), but many remain untreated. The goal of this study was to assess the impact of statin use on ...recurrent major adverse cardiovascular events (MACE). This study used medical records and insurance claims from 4 health care systems in the United States. Eligible adults who survived an ASCVD hospitalization from September 2013 to September 2014 were followed for 1 year. A multivariable extended Cox model examined the outcome of time-to-first MACE, then a multivariable joint marginal model investigated the association between post-index statin use and nonfatal and fatal MACE. There were 8,168 subjects in this study; 3,866 filled a statin prescription ≤90 days before the index ASCVD event (47.33%) and 4,152 filled a statin prescription after the index ASCVD event (50.83%). These post-index statin users were younger, with more co-morbidities. There were 763 events (315/763, 41.3% terminal) experienced by 686 (8.4%) patients. The adjusted overall MACE risk reduction was 18% (HR 0.82, 95% CI 0.70 to 0.95, p = 0.007) and was more substantial in the first 180 days (HR 0.72, 95% CI 0.60 to 0.86, p <0.001). There was a nonsignificant 19% reduction in the number of nonfatal MACE (rate ratio 0.81, 95% CI 0.49 to 1.32, p = 0.394) and a 65% reduction in the risk of all-cause death (HR 0.35, 95% CI 0.22 to 0.56, p <0.001). In conclusion, we found a modest increase in statin use after an ASCVD event, with nearly half of the patients untreated. The primary benefit of statin use was protection against early death. Statin use had the greatest impact in the first 6 months after an ASCVD event; therefore, it is crucial for patients to quickly adhere to this therapy.
The cost-effectiveness of screening the U.S. population for Centers for Disease Control and Prevention (CDC) Tier 1 genomic conditions is unknown.
To estimate the cost-effectiveness of simultaneous ...genomic screening for Lynch syndrome (LS), hereditary breast and ovarian cancer syndrome (HBOC), and familial hypercholesterolemia (FH).
Decision analytic Markov model.
Published literature.
Separate age-based cohorts (ages 20 to 60 years at time of screening) of racially and ethnically representative U.S. adults.
Lifetime.
U.S. health care payer.
Population genomic screening using clinical sequencing with a restricted panel of high-evidence genes, cascade testing of first-degree relatives, and recommended preventive interventions for identified probands.
Incident breast, ovarian, and colorectal cancer cases; incident cardiovascular events; quality-adjusted survival; and costs.
Screening 100 000 unselected 30-year-olds resulted in 101 (95% uncertainty interval UI, 77 to 127) fewer overall cancer cases and 15 (95% UI, 4 to 28) fewer cardiovascular events and an increase of 495 quality-adjusted life-years (QALYs) (95% UI, 401 to 757) at an incremental cost of $33.9 million (95% UI, $27.0 million to $41.1 million). The incremental cost-effectiveness ratio was $68 600 per QALY gained (95% UI, $41 800 to $88 900).
Screening 30-, 40-, and 50-year-old cohorts was cost-effective in 99%, 88%, and 19% of probabilistic simulations, respectively, at a $100 000-per-QALY threshold. The test costs at which screening 30-, 40-, and 50-year-olds reached the $100 000-per-QALY threshold were $413, $290, and $166, respectively. Variant prevalence and adherence to preventive interventions were also highly influential parameters.
Population averages for model inputs, which were derived predominantly from European populations, vary across ancestries and health care environments.
Population genomic screening with a restricted panel of high-evidence genes associated with 3 CDC Tier 1 conditions is likely to be cost-effective in U.S. adults younger than 40 years if the testing cost is relatively low and probands have access to preventive interventions.
National Human Genome Research Institute.
•Real and imagined challenges have limited pediatric lipid screening.•Implementation science provides opportunities to shrink screening gaps in care.•Creative and collaborative efforts empower ...partnerships to improve screening.
Recent guidance by the United States Preventive Services Task Force has renewed the debate surrounding the benefits of pediatric lipid screening. This commentary reviews the evolution of the pediatric lipid screening recommendations in the United States, followed by an exploration of real and imagined challenges that prevent optimal cholesterol screening rates in children. Real challenges substantively prevent the uptake of these guidelines into practice; imagined challenges, such as identifying the best age to screen, are often context-dependent and can also be surmounted. Experiences from other countries identify potential facilitators to improving screening and additional barriers. Implementation science provides guidance on overcoming the real barriers, translating evidence-based recommendations into clinical practice, and informing the next wave of solutions to overcome these challenges.
Numerous implementation strategies to improve utilization of statins in patients with hypercholesterolemia have been utilized, with varying degrees of success. The aim of this systematic review is to ...determine the state of evidence of implementation strategies on the uptake of statins.
This systematic review identified and categorized implementation strategies, according to the Expert Recommendations for Implementing Change (ERIC) compilation, used in studies to improve statin use. We searched Ovid MEDLINE, Embase, Scopus, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and Clinicaltrials.gov from inception to October 2018. All included studies were reported in English and had at least one strategy to promote statin uptake that could be categorized using the ERIC compilation. Data extraction was completed independently, in duplicate, and disagreements were resolved by consensus. We extracted LDL-C (concentration and target achievement), statin prescribing, and statin adherence (percentage and target achievement). A total of 258 strategies were used across 86 trials. The median number of strategies used was 3 (SD 2.2, range 1-13). Implementation strategy descriptions often did not include key defining characteristics: temporality was reported in 59%, dose in 52%, affected outcome in 9%, and justification in 6%. Thirty-one trials reported at least 1 of the 3 outcomes of interest: significantly reduced LDL-C (standardized mean difference SMD - 0.17, 95% CI - 0.27 to - 0.07, p = 0.0006; odds ratio OR 1.33, 95% CI 1.13 to 1.58, p = 0.0008), increased rates of statin prescribing (OR 2.21, 95% CI 1.60 to 3.06, p < 0.0001), and improved statin adherence (SMD 0.13, 95% CI 0.06 to 0.19; p = 0.0002; OR 1.30, 95% CI 1.04 to 1.63, p = 0.023). The number of implementation strategies used per study positively influenced the efficacy outcomes.
Although studies demonstrated improved statin prescribing, statin adherence, and reduced LDL-C, no single strategy or group of strategies consistently improved outcomes.
PROSPERO CRD42018114952 .
Improving care of individuals with familial hypercholesteremia (FH) is reliant on the synthesis of evidence-based guidelines and their subsequent implementation into clinical care. This review ...describes implementation strategies, defined as methods to improve translation of evidence into FH care, that have been mapped to strategies from the Expert Recommendations for Implementing Change (ERIC) compilation.
A search using the term 'familial hypercholesterolemia' returned 1350 articles from November 2018 to July 2021. Among these, there were 153 articles related to improving FH care; 1156 were excluded and the remaining 37 were mapped to the ERIC compilation of strategies: assess for readiness and identify barriers and facilitators 9, develop and organize quality monitoring systems 14, create new clinical teams 2, facilitate relay of clinical data to providers 4, and involve patients and family members 8. There were only 8 of 37 studies that utilized an implementation science theory, model, or framework and two that explicitly addressed health disparities or equity.
The mapping of the studies to implementation strategies from the ERIC compilation provides a framework for organizing current strategies to improve FH care. This study identifies potential areas for the development of implementation strategies to target unaddressed aspects of FH care.
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