Lipid-lowering Therapy For Primary Prevention Research Articles

Initiation of lipid-lowering therapy as primary prevention of cardiovascular disease in the elderly.

This study aimed to analyse the initiation adherence phase to lipid-lowering therapy for primary prevention of cardiovascular disease in a Spanish population aged 70 years or older. The secondary objective was to identify the determinants of initiation and early discontinuation. This was an observational study conducted in the CArdiovascular Risk factors for HEalth Service research (CARhES) cohort. People aged 70 and older with a first prescription of a lipid-lowering drug and without a previous major adverse cardiovascular event (MACE) were selected (2018-2021). Data on sociodemographics, clinical conditions, drugs and use of health services were collected from clinical and administrative electronic databases. The study population was classified into: non-initiation, early discontinuation (i.e., discontinuation after the first dispensing) and initiation with more than one dispensing. Their characteristics were compared. Determinants of initiation and early discontinuation were explored. Among the 15 019 people studied, 80.2% initiated the medication, 11.2% showed an early discontinuation and 8.6% were non-initiators. An older age or conditions such as dementia, diabetes or depression reduced the likelihood of initiation, while obesity and a high pharmacological burden increased it. People over 90 years of age or those prescribed a statin in combination were more likely to have an early discontinuation. Non-initiation and early discontinuation are common among older people prescribed lipid-lowering drugs as primary prevention of cardiovascular disease for the first time. The presence of chronic pathologies other than cardiovascular ones should be considered when assessing whether or not to prescribe these drugs in the elderly.

LDL-C Reduction With Lipid-Lowering Therapy for Primary Prevention of Major Vascular Events Among Older Individuals

BackgroundReducing low-density lipoprotein (LDL) cholesterol with lipid-lowering therapy has consistently been shown to lower the risk of cardiovascular disease in primary prevention trials where the majority of individuals are aged <70 years. For older individuals, however, evidence is less clear. ObjectivesIn this study, the authors sought to compare the clinical effectiveness of lowering LDL cholesterol by means of lipid-lowering therapy for primary prevention of cardiovascular disease among older and younger individuals in a Danish nationwide cohort. MethodsWe included individuals aged ≥50 years who had initiated lipid-lowering therapy from January 1, 2008, to October 31, 2017, had no history of atherosclerotic cardiovascular disease, and had a baseline and a within-1-year LDL cholesterol measurement. We assessed the associated risk of major vascular events among older individuals (≥70 years) by HRs per 1 mmol/L reduction in LDL cholesterol compared with younger individuals (<70 years). ResultsFor both the 16,035 older and the 49,155 younger individuals, the median LDL cholesterol reduction was 1.7 mmol/L. Each 1 mmol/L reduction in LDL cholesterol in older individuals was significantly associated with a 23% lower risk of major vascular events (HR: 0.77; 95% CI: 0.71-0.83), which was equal to that of younger individuals (HR: 0.76; 95% CI: 0.71-0.80; P value for difference = 0.79). Similar results were observed across all secondary analyses. ConclusionsOur study supports a relative clinical benefit of lowering LDL cholesterol for primary prevention of major vascular events in individuals aged ≥70 years similarly as in individuals aged <70 years.

Comparison of the European and US guidelines for lipid-lowering therapy in primary prevention of cardiovascular disease.

Population-wide impacts of new guidelines in the primary prevention of atherosclerotic cardiovascular disease (ASCVD) should be explored in independent cohorts. Assess and compare the lipid-lowering therapy eligibility and predictive classification performance of 2016 and 2021 European Society of Cardiology (ESC), 2019 American Heart Association/American College of Cardiology (AHA/ACC), and 2022 US Preventive Services Task Force (USPSTF) guidelines. Participants from the CoLaus|PsyCoLaus study, without ASCVD and not taking lipid-lowering therapy at baseline. Derivation of 10-year risk for ASCVD using Systematic COronary Risk Evaluation (SCORE1), SCORE2 [including SCORE2-Older Persons (SCORE2-OP)], and pooled cohort equation. Computation of the number of people eligible for lipid-lowering therapy based on each guideline and assessment of discrimination and calibration metrics of the risk models using first incident ASCVD as an outcome. Among 4,092 individuals, 158 (3.9%) experienced an incident ASCVD during a median follow-up of 9 years (interquartile range, 1.1). Lipid-lowering therapy was recommended or considered in 40.2% (95% confidence interval, 38.2-42.2), 26.4% (24.6-28.2), 28.6% (26.7-30.5), and 22.6% (20.9-24.4) of women and in 62.1% (59.8-64.3), 58.7% (56.4-61.0), 52.6% (50.3-54.9), and 48.4% (46.1-50.7) of men according to the 2016 ESC, 2021 ESC, 2019 AHA/ACC, and 2022 USPSTF guidelines, respectively. 43.3 and 46.7% of women facing an incident ASCVD were not eligible for lipid-lowering therapy at baseline according to the 2021 ESC and 2022 USPSTF, compared with 21.7 and 38.3% using the 2016 ESC and 2019 AHA/ACC, respectively. Both the 2022 USPSTF and 2021 ESC guidelines particularly reduced lipid-lowering therapy eligibility in women. Nearly half of women who faced an incident ASCVD were not eligible for lipid-lowering therapy.

Lipid-Lowering Therapy for Primary Prevention of Cardiovascular Disease: A Nationwide Analysis of 440,721 Patients

Lead Author's Financial Disclosures AAK was supported by the National Heart, Lung, And Blood Institute of the National Institutes of Health under Award Number T32HL12547. The content is solely the responsibility of the authors and does not necessarily represent the official view of the National Institutes of Health. Study Funding Esperion Therapeutics, Inc. Background/Synopsis Statins are indicated for the primary prevention of atherosclerotic cardiovascular disease (ASCVD) in adults with diabetes mellitus (DM), elevated 10-year risk, and those with LDL-C ≥190 mg/dL. Contemporary treatment patterns in community practice are not well described. Objective/Purpose To explore the use and dosing of statin therapy and use of several classes of non-statin lipid lowering therapies (LLT) in adults recommended for statins in primary prevention. Methods We identified adults recommended for primary prevention statin therapy who received outpatient care in 90 US health systems between 2017 and 2018 using a de-identified, electronic health record dataset; Cerner Real World Data. Primary prevention populations included: DM and age 40-75, calculated 10-year ASCVD risk ≥7.5% and age 40-75, and those with LDL-C ≥190 mg/dL or familial hypercholesterolemia based on diagnosis code. Medication data, including self-reported use of supplements, were examined. Based on the 2013 ACC/AHA Cholesterol Guideline (what was active at the time), patients were classified as: on appropriate- intensity statin, on under-dosed statin, or not on a statin. Results We identified 440,721 patients recommended for statins (median age 63 years, 50.1% male, and 75.5% white race), including (by mutually exclusive, hierarchical order) 308,620 (70%) patients with DM, 125,411 (28.5%) with a 10-year risk ≥7.5%, and 6,690 (1.5%) with LDL-C ≥190 mg/dL. Overall, 211,295 (47.9%) were on appropriate statin therapy, 29,039 (6.6%) were on lower-than-recommended statin intensity, and 200,387 (45.5%) were not on any statin (Figure). People with DM had the relative highest percent utilization of appropriate-dose statin (53.8%), while only 35.4% of those recommended for 10-year risk were on appropriate- dose statin, and only 12% of those with LDL-C ≥190 mg/dL were treated appropriately (Figure). Utilization of non-statin LLT was low overall across all three groups (15.8%). However, nearly one in ten (9.4%) of those recommended for primary prevention reported taking non-prescription Omega-3/fish oil supplements (Figure). Conclusions Over half of primary prevention patients at high risk for ASCVD in the US are not on appropriate-dose, guideline-recommended statin therapy. Of these, the majority were not on any statin. Non-statin LDL-C lowering medication use was also low. Despite no data for cardiovascular benefit, a substantial number of adults were taking non-prescription fish oil. There remains a strong national need to improve overall utilization and evaluate barriers to prescription/uptake of evidence based LLT in all patients eligible for primary prevention. AAK was supported by the National Heart, Lung, And Blood Institute of the National Institutes of Health under Award Number T32HL12547. The content is solely the responsibility of the authors and does not necessarily represent the official view of the National Institutes of Health.

Appointment of lipid-lowering therapy in the Russian population: comparison of SCORE and SCORE2 (according to the ESSE-RF study)

Aim. In 2021, the European Society of Cardiology (ESC) guidelines for the prevention of cardiovascular diseases (CVDs) were published, where a new SCORE2 CVD risk assessment model was introduced. In our work, we compared approaches to determine the indications for initiating lipid-lowering therapy in the Russian population aged 25-64 years according to the guidelines for the diagnosis and treatment of lipid metabolism disorders of the Russian National Atherosclerosis Society (2020) and ESC guidelines for CVD prevention (2021).Material and methods. The ESSE-RF epidemiological study was conducted in 12 Russian regions. All participants signed informed consent and completed approved questionnaires. We performed anthropometric and blood pressure (BP) measurements, as well as fasting blood sampling. In total, 20665 people aged 25-64 years were examined. The analysis included data from 19546 respondents (women, 12325 (63,1%)).Results. Of the 19546 participants, 3828 (19,6%) were classified as high or very high CV risk based on the 9 criteria: BP ≥180/110 mm Hg, total cholesterol &gt;8,0 mmol/l, low-density lipoprotein (LDL) &gt;4,9 mmol/l, lipid-lowering therapy, chronic kidney disease (CKD) with glomerular filtration rate &lt;60 ml/min/1,73 m2, type 2 diabetes, previous stroke and/or myocardial infarction. Of 3828 people, lipidlowering therapy was indicated in 3758 (98%) (criteria for LDL ≥1,8 mmol/l and LDL ≥1,4 mmol/l, respectively, high and very high risk). In addition, 5519 individuals aged &lt;40 years were excluded from further analysis due to the lower age threshold of models. For 10199 participants aged &gt;40 years without established CVD, diabetes, CKD, cardiovascular risk stratification was performed according to the SCORE and SCORE2. Of them, according to the Russian National Atherosclerosis Society (2020) and ESC 2021 guidelines, lipid-lowering therapy was indicated for 701 and 9487 participants, respectively.Conclusion. Using the new approach proposed by the ESC in 2021, the number of patients aged 40-64 years without CVD, diabetes and CKD with indications for lipidlowering therapy for primary prevention in Russia increases by 14 times compared with the 2020 Russian National Atherosclerosis Society guidelines.

Lipid-Lowering Therapy for Primary Cardiovascular Prevention in Older Adults. Consensus Statement of the Russian Association of Gerontologists and Geriatricians, National Society on Atherosclerosis, Russian Society of Cardiology, Association of Clinical Pharmacologists

Completed randomized clinical studies did not have a sufficient statistical power for demonstrating clearly the efficacy of lipid-lowering therapy for primary prevention in patients aged 75 years and older and did not evaluate the effect of lipid-lowering therapy on development and course of key geriatric syndromes. Age-related alterations of skeletal muscles, cognitive decline, senile asthenia, comorbidities, polypragmasy, potential changes in drug pharmacokinetics and pharmacodynamics, and impaired renal function may adversely affect the benefit to harm ratio of statins in older patients. Key questions for administration of a lipid-lowering therapy for primary prevention in patients aged 75 years and older are: 1. Does the relationship between increased low-density lipoprotein cholesterol (LDL CS) and death rate persist? 2. Does a benefit from decreasing the level of LDL CS persist? 3. Is the lipid-lowering therapy safe? 4. What scales for risk stratification and determining indications for lipid-lowering therapy should be used?

Lipid-lowering therapy for primary prevention of premature atherosclerotic coronary artery disease: Eligibility, utilization, target achievement, and predictors of initiation

ObjectivesDespite advances in screening and prevention, rates of premature coronary artery disease (CAD) have been stagnant. The goals of this study were to investigate the barriers to early risk detection and preventive treatment in patients with premature CAD. In particular, we: 1) assessed the performance of the latest versions of major international guidelines in detection of risk of premature CAD and eligibility for preventive treatment; and, 2) investigated real-life utilization of primary prevention with lipid-lowering therapies in these patients. MethodsWe included patients in the Study to Avoid cardioVascular Events in British Columbia (SAVE BC), an observational study of patients with premature (males ​≤ ​50 years, females ​≤ ​55 years) angiographically confirmed CAD. Eligibility for primary prevention and treatment received were assessed retrospectively based on information recorded prior to or at the index presentation with CAD. ResultsOf 417 patients (28.1% females) who met the criteria, 94.3% had at least one major cardiovascular risk factor. In the retrospective risk assessment, 41.7%, 61.4%, and 34.3% (p ​< ​0.001) of patients met criteria for initiation of statin therapy, and an additional 13.9%, 8.4%, and 46.8% may be considered for treatment using the American College of Cardiology/American Heart Association, Canadian Cardiovascular Society, and European Society of Cardiology guidelines, respectively. Only 17.1% of patients received statins and 11.0% achieved guideline-recommended lipid goals before presentation. Diabetes and elevated plasma lipid levels were positively associated with treatment initiation, while smoking was associated with non-treatment. ConclusionsThe current versions of major guidelines fail to recognize many patients who develop premature CAD as being at risk. The vast majority of these patients, including patients who have guideline-directed indications, do not receive lipid-lowering therapy before presenting with CAD. Our findings highlight the need for more effective screening and prevention strategies for premature CAD.

Abstract 16281: Comparison of Guideline Recommendations and Trial Evidence for Statins in Primary Prevention of Cardiovascular Disease in a Population-based Cohort: The Rotterdam Study

Introduction: The 2013 ACC/AHA and the 2012 European Society of Cardiology (ESC) guidelines recommend lipid-lowering treatment for primary prevention based on cardiovascular disease (CVD) risk. Randomized clinical trials for statin use in primary prevention, however, included participants with specific risk factor profiles. Hypothesis: For most individuals in the general population recommended for primary prevention of CVD with statins direct trial evidence is available. Evidence of benefit may be available for persons currently not recommended treatment. Methods: We used data from 8925 participants (57% women), aged 45-79, free of CVD from the population-based Rotterdam Study to compare treatment recommendations by the ACC/AHA and ESC guidelines, with eligibility for any of 10 major statin trials. Results: The ACC/AHA guidelines recommend statin use in 3196 (83.2%) men and 2611 (51.4%) women; the ESC guidelines in 1992 (51.8%) men and 1702 (33.4%) women (95.3% overlap with ACC/AHA). A total of 2243 (58.4%) men and 2438 (48.0%) women met the eligibility criteria for at the least one trial. Guideline recommendations and trial eligibility overlapped for 2245 (25.2%) participants (Figure). A total of 2480 (27.8%) participants would be considered for statin initiation solely by the ACC/AHA and/or ESC guidelines, while 1180 (13.2%) would have been eligible for at the least one trial and would not be recommended for statin therapy based on the guidelines (Figure). Correspondence of guideline recommendations with trial eligibility varied greatly by trial, with virtual complete alignment for trials done in individuals with diabetes, while for trials done in individuals with hypercholesterolemia alignment was poor. Conclusions: For the majority of persons recommended for lipid-lowering therapy in primary prevention, efficacy of statins has been established. Statins have been proven efficacious in many persons currently not recommended for treatment.

Improving adherence to lipid-lowering therapy in a community pharmacy intervention program: a cost-effectiveness analysis.

Pharmaceutical care in community pharmacies has been shown to improve adherence to chronic therapies. Long-term impact on clinical outcomes or medical cost savings, however, remains understudied. To estimate the cost-effectiveness of a pharmaceutical care intervention program in Dutch community pharmacies that improved patients' adherence to lipid-lowering therapy. An economic evaluation was performed using a time-dependent Markov model from the health care payer perspective. Participants were patients initiating lipid-lowering therapy for primary prevention (40%) or secondary prevention (60%) of cardiovascular events (CVEs). The intervention was the pharmaceutical care program MeMO (Medication Monitoring and Optimisation) in 9 community pharmacies in the Netherlands, based on continuous monitoring and optimization of lipid-lowering therapy in new patients. The follow-up period of the program was 1 year. The main outcome of the intervention program was discontinuation of lipid-lowering therapy. This outcome was extrapolated in the economic model to lifelong costs, quality of life, reductions in cardiovascular events, and incremental cost-effectiveness ratios. Patients in the MeMO program had a lower risk for therapy discontinuation, RR = 0.49 (0.37 to 0.66); the effectiveness was similar in primary and secondary prevention. In a cohort of 1,000 primary and secondary prevention patients, the MeMO program resulted in a reduction of 7 nonfatal strokes, 2 fatal strokes, 16 nonfatal myocardial infarctions (MIs), 7 fatal MIs, and 16 revascularizations over patients' lifetime. Additional medication, disease management, and intervention costs in the MeMO program were €411,000; the cost savings due to reduced CVEs were €443,000. The MeMO program resulted in 84 quality-adjusted life-years (QALYs) gained and net cost savings of €32,000. Clinical benefits and cost savings were highest in the secondary prevention population. Pharmaceutical care in community pharmacies can improve statin therapy adherence, resulting in better prevention of CVEs. The MeMO program resulted in considerable clinical benefits and net cost savings. Programs by community pharmacies targeted at improving adherence may provide good value for money, and health care insurers should consider reimbursing these activities.

Primary prevention in high-risk dyslipidemic patients without an established cardiovascular disease: Undertreatment and rationale for lipid-lowering therapy

Background Recent updated guidelines expand the usage of lipid-lowering therapy for primary prevention in high-risk individuals without an established cardiovascular disease (CVD). In contrast to secondary prevention, the extent of the target population and the utilization of lipid-lowering drugs are insufficiently clear. We examine the implementation of statin therapy as primary prevention in high-risk patients without a known CVD and discuss the rationale for the management of dyslipidemia in this population. Methods Records of 371 consecutive patients without an established CVD who were hospitalized in an internal medicine department between January and June 2005 were evaluated for CVD-equivalent high-risk factors (diabetes mellitus, stroke of carotid origin, peripheral vascular disease, abdominal aortic aneurysm, or Framingham 10-year risk score ≥ 20%). Demographic and clinical data, in addition to lipid profile and usage of statin drugs prior to and during hospitalization, were analyzed. Results Of the 371 non-cardiovascular patients, 88 (24%) were defined as high-risk individuals eligible for statin therapy as primary prevention of CVD. Their mean age was 71 ± 11 years and their mean LDL-C level was 132 ± 30 mg/dL. Seventeen patients (19%) were treated with statin drugs prior to admission and only two more patients (19/88, 22%) received statins in addition during hospitalization. Patients treated with statins had non-significantly higher LDL-C levels. Conclusions There is considerable undertreatment of high-risk patients without an established CVD with lipid-lowering drugs. There is also sub-optimal implementation of guidelines in clinical practice, despite well-established evidence of the benefits of statins in the primary prevention of CVD for high-risk individuals with average cholesterol levels, diabetes mellitus, and in elderly patients, as represented by our study population.

Women with a low Framingham risk score and a family history of premature coronary heart disease have a high prevalence of subclinical coronary atherosclerosis

The Framingham risk estimation (FRE) serves as the basis for identifying which asymptomatic adults should be treated with aspirin and lipid-lowering therapy in primary prevention. However, the FRE generally yields low estimates of 10-year "hard" coronary heart disease (CHD) event risk with few women (< 70 years) qualifying for preventive pharmacologic therapy despite relatively high lifetime risk. We postulated that traditional risk factor assessment might fail to identify a sizeable portion of women with a sibling history for premature CHD as having advanced subclinical atherosclerosis. We studied 102 asymptomatic women (mean age 51 +/- 7 years) who were the sisters of a proband hospitalized with documented premature CHD. Participants underwent risk factor assessment and multidetector computed tomography for coronary artery calcium (CAC) scoring. Based on FRE prediction of 10-year risk for hard CHD events, participants were classified as low risk (< 10%) (n = 100), intermediate risk (10%-20%) (n = 2), or high risk (> 20%) (n = 0). Significant subclinical atherosclerosis was defined as age-sex adjusted > 75th percentile CAC scores. Ninety-eight percent were at low risk (mean FRE of only 2% +/- 2%). However, 40% had detectable CAC, 12% had CAC > 100, and 6% had CAC > or = 400. Based on CAC score percentiles, 32% had significant subclinical atherosclerosis and 17% ranked above the 90th percentile. Among women classified as low risk by FRE, a third had significant subclinical atherosclerosis. Sisters of probands with premature CHD appear to be a high-risk group and may warrant noninvasive screening for subclinical atherosclerosis to appropriately target individuals for more aggressive primary prevention therapy than what is currently recommended.

Prevention of cardiovascular events in elderly hypercholesterolemic patients

The management of hyperlipidemia in the elderly patient is a major problem, given the frequency of dyslipidemias and cardiovascular disorders in this age group. Therapy must take current uncertainties into account and, in the absence of therapeutic studies carried out in the elderly, is typically based upon a case-by-case approach. Raised cholesterol levels remain a significant risk factor for coronary heart disease (CHD) in the elderly. Although the relative risk of CHD tends to diminish with increasing age, this reduction is accompanied by an increase in absolute risk (ie, the number of events) as the frequency of the illness increases markedly with age. The results of major outcome studies with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins), when analyzed according to patient age, indicate that the benefits of these agents are not merely confined to younger individuals. However, the elderly form a unique patient population--the proportion of women is greater and the profile of cardiovascular illnesses is characterized, among others, by a greater incidence of cerebrovascular accidents. Problems relating to poor tolerability and comorbidity (which may give rise to drug-drug interactions) also occur more frequently in this age group. Moreover, the potential widespread treatment of hyperlipidemia in the elderly has profound economic implications. Under these circumstances, the clinical practice recommendations depend upon a reasonable extrapolation of epidemiologic and therapeutic data obtained from middle-aged men. At present, treatment is therefore aimed at patients with the most severe forms of hyperlipidemia, generally in the secondary prevention setting, taking into account the patient's life expectancy. The results of ongoing studies will determine the benefits of lipid-lowering therapy for primary prevention of CHD in the elderly.

Trials of lipid-lowering therapy in primary prevention of coronary heart disease.

The effectiveness of lipid-regulating therapy in the primary prevention of coronary heart disease requires further investigation. The only data available are from trials conducted before the advent of more potent lipid-regulating agents, but several large trials currently in progress are expected to provide valuable evidence about the role of lipid-regulating intervention in primary prevention.