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Role of Statin Therapy in Primary Prevention of Cardiovascular Disease in Elderly Patients.

ABSTRACT: PURPOSE OF REVIEW:Hypercholesterolemia and statin treatment are nowadays common among people older than 75 years, but clinical heterogeneity in this increasing age group is wide, and treatment decisions may differ from those in younger patients. Aim is to discuss the presentation, modifying factors, and treatment decisions of hypercholesterolemia (usually with statins) in older persons and focusing on primary prevention. RECENT FINDINGS:There are no randomized controlled trials in persons older than 80 years at baseline. Randomized controlled trial findings in younger patients and 75+ subgroups and in observational studies support treatment in secondary prevention of atherosclerotic cardiovascular disease (ASCVD), but trial evidence in primary prevention is less clear. Available data do not imply specific harms in older patients, and, therefore, also, judicious primary prevention is possible. However, persons older than 75 years are biologically a very heterogeneous group with frequent frailty, comorbid conditions, and multiple concomitant drugs. All these, as well as personal preferences, must be taken into account in treatment decisions. Statin treatment is only one way to prevent ASCVD in older people. Treatment of hypercholesterolemia should be started far before 75-80 years, and there is no need to discontinue statin treatment due to chronological age alone. After 75 years, treatment should be started in patients with ASCVD and judiciously in primary prevention. Like all prevention, statin treatment should be discontinued when palliative treatment is started. Ongoing and planned trials in 70+ individuals will give more information about primary prevention in older persons.

SUBMITTER: Strandberg TE

PROVIDER: S-EPMC6527904 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Role of Statin Therapy in Primary Prevention of Cardiovascular Disease in Elderly Patients.

Strandberg Timo E TE

Current atherosclerosis reports 20190520 8

<h4>Purpose of review</h4>Hypercholesterolemia and statin treatment are nowadays common among people older than 75 years, but clinical heterogeneity in this increasing age group is wide, and treatment decisions may differ from those in younger patients. Aim is to discuss the presentation, modifying factors, and treatment decisions of hypercholesterolemia (usually with statins) in older persons and focusing on primary prevention.<h4>Recent findings</h4>There are no randomized controlled trials in ...[more]

PMID: 31111235

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Project description:BackgroundStatins are an important intervention for primary and secondary cardiovascular disease (CVD) prevention. We aimed to establish the variation in primary preventive treatment for CVD with statins in the English population.MethodsCross sectional analyses of 6155 English primary care practices with 40,017,963 patients in 2006/7. Linear regression was used to model prescribing rates of statins for primary CVD prevention as a function of IMD (index of multiple deprivation) quintile, proportion of population from an ethnic minority, and age over 65 years. Defined Daily Doses (DDD) were used to calculate the numbers of patients receiving a statin. Statin prescriptions were allocated to primary and secondary prevention based on the prevalence of CVD and stroke.ResultsWe estimated that 10.5% (s.d.3.7%) of the registered population were dispensed a statin for any indication and that 6.3% (s.d. 3.0%) received a statin for primary CVD prevention. The regression model explained 21.2% of the variation in estimates of prescribing for primary prevention. Practices with higher prevalence of hypertension (β co-efficient 0.299 p <0.001) and diabetes (β co-efficient 0.566 p < 0.001) prescribed more statins for primary prevention. Practices with higher levels of ethnicity (β co-efficient-0.026 p <0.001), greater deprivation (β co-efficient -0.152 p < 0.001) older patients (β co-efficient -0.032 p 0.002), larger lists (β co-efficient -0.085, p < 0.001) and were more rural (β co-efficient -0.121, p0.026) prescribed fewer statins. In a small proportion of practices (0.5%) estimated prescribing rates for statins were so low that insufficient prescriptions were issued to meet the predicted secondary prevention requirements of their registered population.ConclusionsAbsolute estimated prescribing rates for primary prevention of CVD were 6.3% of the population. There was evidence of social inequalities in statin prescribing for primary prevention. These findings support the recent introduction of a financial incentive for primary prevention of CVD in England.

Project description:The American College of Cardiology and the American Heart Association (ACC/AHA) cholesterol treatment guidelines have wide-scale implications for treating adults without history of atherosclerotic cardiovascular disease (ASCVD) with statins.To estimate the cost-effectiveness of various 10-year ASCVD risk thresholds that could be used in the ACC/AHA cholesterol treatment guidelines.Microsimulation model, including lifetime time horizon, US societal perspective, 3% discount rate for costs, and health outcomes. In the model, hypothetical individuals from a representative US population aged 40 to 75 years received statin treatment, experienced ASCVD events, and died from ASCVD-related or non-ASCVD-related causes based on ASCVD natural history and statin treatment parameters. Data sources for model parameters included National Health and Nutrition Examination Surveys, large clinical trials and meta-analyses for statin benefits and treatment, and other published sources.Estimated ASCVD events prevented and incremental costs per quality-adjusted life-year (QALY) gained.In the base-case scenario, the current ASCVD threshold of 7.5% or higher, which was estimated to be associated with 48% of adults treated with statins, had an incremental cost-effectiveness ratio (ICER) of $37,000/QALY compared with a 10% or higher threshold. More lenient ASCVD thresholds of 4.0% or higher (61% of adults treated) and 3.0% or higher (67% of adults treated) had ICERs of $81,000/QALY and $140,000/QALY, respectively. Shifting from a 7.5% or higher ASCVD risk threshold to a 3.0% or higher ASCVD risk threshold was estimated to be associated with an additional 161,560 cardiovascular disease events averted. Cost-effectiveness results were sensitive to changes in the disutility associated with taking a pill daily, statin price, and the risk of statin-induced diabetes. In probabilistic sensitivity analysis, there was a higher than 93% chance that the optimal ASCVD threshold was 5.0% or lower using a cost-effectiveness threshold of $100,000/QALY.In this microsimulation model of US adults aged 45 to 75 years [corrected], the current 10-year ASCVD risk threshold (?7.5% risk threshold) used in the ACC/AHA cholesterol treatment guidelines has an acceptable cost-effectiveness profile (ICER, $37,000/QALY), but more lenient ASCVD thresholds would be optimal using cost-effectiveness thresholds of $100,000/QALY (?4.0% risk threshold) or $150,000/QALY (?3.0% risk threshold). The optimal ASCVD threshold was sensitive to patient preferences for taking a pill daily, changes to statin price, and the risk of statin-induced diabetes.

Project description:INTRODUCTION:Previous research has shown that statin adherence for the primary prevention of CVD is lower compared to secondary prevention populations. Therefore the aim of this systematic review was to review predictors of statin adherence for the primary prevention of CVD. METHODS:A systematic search of papers published between Jan 1984 and May 2017 was conducted in PubMed, PsycINFO, EMbase and CINAHL databases. A study was eligible for inclusion if; 1) it was a study of the general population or of patients with familial hypercholesterolemia, hypertension, diabetes or arthritis; 2) statins were prescribed; 3) adherence was defined and measured as the extent to which patients followed their statin regimen during the period of prescription, and 4) it was an original trial or observational study (excluding case reports). A study was subsequently excluded if 1) results were not presented separately for primary prevention; 2) it was a trial of an intervention (for example patient education). Papers were reviewed by two researchers and consensus agreed with a third. A quality assessment (QA) tool was used to formally assess each included article. To evaluate the effect of predictors, data were quantitatively and qualitatively synthesised. RESULTS:In total 19 studies met the inclusion criteria and nine were evaluated as high quality using the QA tool. The proportion of patients classed as "adherent" ranged from 17.8% to 79.2%. Potential predictors of statin adherence included traditional risk factors for CVD such as age, being male, diabetes and hypertension. Income associated with adherence more strongly in men than women, and highly educated men were more likely and highly educated women less likely to be adherent. Alcohol misuse and high BMI associated with non-adherence. There was no association between polypharmacy and statin adherence. The evidence base for the effect of other lifestyle factors and health beliefs on statin adherence was limited. CONCLUSION:Current evidence suggests that patients with more traditional risk factors for CVD are more likely to be adherent to statins. The implications for future research are discussed.

Project description:ImportanceFor primary prevention of atherosclerotic cardiovascular disease (ASCVD), the 2021 European Society of Cardiology (ESC) guidelines on statin use (hereafter European-ESC) recommend a new risk model (Systematic Coronary Risk Evaluation 2 [European-SCORE2]) as well as new age-specific treatment thresholds (≥7.5% 10-year ASCVD risk if aged 40-49 years and ≥10% if aged 50-69 years).ObjectiveTo compare the clinical performance of the 2021 European-ESC, American College of Cardiology/American Heart Association (hereafter US-ACC/AHA), UK National Institute for Health and Care Excellence (UK-NICE), and 2019 ESC/European Atherosclerosis Society (EAS) guidelines in apparently healthy individuals.Design, setting, and participantsThis population-based contemporary cohort study included 66 909 individuals from the Copenhagen General Population Study. Participants were aged 40 to 69 years and were free of ASCVD, diabetes, chronic kidney disease, and statin use at baseline in 2003 to 2015. Mean follow-up time was 9.2 years. Data were analyzed from November 2021 to April 2022.ExposuresStatin treatment according to guideline criteria.Main outcomes and measuresCalibration of risk calculators, statin eligibility, sensitivity, and specificity for ASCVD events according to guideline criteria.ResultsDuring follow-up, a range of 2962 to 4277 nonfatal and fatal ASCVD events was observed, as defined by the 2021 European-SCORE2, US pooled cohort equations (PCE), and UK-QRISK3 models, and 180 fatal ASCVD events were noted as defined by the 2019 European-SCORE1 model. European-SCORE2 was slightly better calibrated with a predicted/observed ASCVD event ratio of 0.8 vs 1.3 for US-PCE, 1.3 for UK-QRISK3, and 5.8 for European-SCORE1. For primary prevention class I recommendations in individuals aged 40 to 69 years, 2862 of 66 909 (4%) qualified for statins according to the 2021 European-ESC guidelines compared with 23 029 (34%) with US-ACC/AHA, 17 659 (26%) with UK-NICE, and 13 496 (20%) with 2019 European-ESC/EAS guidelines, with associated sensitivities for detecting future European-SCORE2-defined ASCVD events of 12%, 60%, 51%, and 36%, respectively. The sensitivity of the European-ESC guidelines was improved considerably by lowering the treatment thresholds, resulting in smaller losses in specificity. To obtain similar clinical performance with the 2021 European-ESC guidelines as in the other guidelines, the threshold with European-SCORE2 should be reduced to 5% overall to match US-ACC/AHA, to 6% to match UK-NICE, and to 7% to match 2019 European-ESC/EAS guidelines.Conclusions and relevanceDespite an improved European-SCORE2 prediction model, the new treatment thresholds in the 2021 European-ESC guidelines dramatically reduce eligibility for primary prevention with statins in low-risk European countries. Using lower treatment thresholds can improve overall guideline performance.

Project description:BackgroundIn view of evidence that statin therapy increases risk of diabetes, the balance of benefit and risk of these drugs in primary prevention has become controversial. We undertook an analysis of participants from the JUPITER trial to address the balance of vascular benefits and diabetes hazard of statin use.MethodsIn the randomised, double-blind JUPITER trial, 17,603 men and women without previous cardiovascular disease or diabetes were randomly assigned to rosuvastatin 20 mg or placebo and followed up for up to 5 years for the primary endpoint (myocardial infarction, stroke, admission to hospital for unstable angina, arterial revascularisation, or cardiovascular death) and the protocol-prespecified secondary endpoints of venous thromboembolism, all-cause mortality, and incident physician-reported diabetes. In this analysis, participants were stratified on the basis of having none or at least one of four major risk factors for developing diabetes: metabolic syndrome, impaired fasting glucose, body-mass index 30 kg/m(2) or higher, or glycated haemoglobin A(1c) greater than 6%. The trial is registered at ClinicalTrials.gov, NCT00239681.FindingsTrial participants with one or more major diabetes risk factor (n=11,508) were at higher risk of developing diabetes than were those without a major risk factor (n=6095). In individuals with one or more risk factors, statin allocation was associated with a 39% reduction in the primary endpoint (hazard ratio [HR] 0·61, 95% CI 0·47-0·79, p=0·0001), a 36% reduction in venous thromboembolism (0·64, 0·39-1·06, p=0·08), a 17% reduction in total mortality (0·83, 0·64-1·07, p=0·15), and a 28% increase in diabetes (1·28, 1·07-1·54, p=0·01). Thus, for those with diabetes risk factors, a total of 134 vascular events or deaths were avoided for every 54 new cases of diabetes diagnosed. For trial participants with no major diabetes risk factors, statin allocation was associated with a 52% reduction in the primary endpoint (HR 0·48, 95% CI 0·33-0·68, p=0·0001), a 53% reduction in venous thromboembolism (0·47, 0·21-1·03, p=0·05), a 22% reduction in total mortality (0·78, 0·59-1·03, p=0·08), and no increase in diabetes (0·99, 0·45-2·21, p=0·99). For such individuals, a total of 86 vascular events or deaths were avoided with no new cases of diabetes diagnosed. In analysis limited to the 486 participants who developed diabetes during follow-up (270 on rosuvastatin vs 216 on placebo; HR 1·25, 95% CI 1·05-1·49, p=0·01), the point estimate of cardiovascular risk reduction associated with statin therapy (HR 0·63, 95% CI 0·25-1·60) was consistent with that for the trial as a whole (0·56, 0·46-0·69). By comparison with placebo, statins accelerated the average time to diagnosis of diabetes by 5·4 weeks (84·3 [SD 47·8] weeks on rosuvastatin vs 89·7 [50·4] weeks on placebo).InterpretationIn the JUPITER primary prevention trial, the cardiovascular and mortality benefits of statin therapy exceed the diabetes hazard, including in participants at high risk of developing diabetes.FundingAstraZeneca.

Project description:BackgroundBenefit-targeted statin prescribing may be superior to risk-targeted statin prescribing (the current standard), but the impact and efficiency of this approach are unclear.Methods and resultsWe analyzed the National Health and Nutrition Examination Survey (NHANES) using an open-source model (the Prevention Impact and Efficiency Model) to compare targeting of statin therapy according to expected benefit (benefit-targeted) versus baseline risk (risk-targeted) in terms of projected population-level impact and efficiency. Impact was defined as relative % reduction in atherosclerotic cardiovascular disease in the US population for the given strategy compared to current statin treatment patterns; and efficiency as the number needed to treat over 10 years (NNT10, average and maximum) to prevent each atherosclerotic cardiovascular disease event. Benefit-targeted moderate-intensity statin therapy at a treatment threshold of 2.3% expected 10-year absolute risk reduction could produce a 5.7% impact (95% confidence interval, 4.8-6.7). This is approximately equivalent to the potential impact of risk-targeted therapy at a treatment threshold of 5% 10-year atherosclerotic cardiovascular disease risk (5.6% impact [4.7-6.6]). Whereas the estimated maximum NNT10 is much improved for benefit-targeted versus risk-targeted therapy at these equivalent-impact thresholds (43.5 vs 180), the average NNT10 is nearly equivalent (24.2 vs 24.6). Reaching 10% impact (half the Healthy People 2020 impact objective, loosely defined) is theoretically possible with benefit-targeted moderate-intensity statins of persons with expected absolute risk reduction >2.3% if we expand age eligibility and account for treatment of all persons with diabetes mellitus or with low-density lipoprotein >190 mg/dL (impact=12.4%; average NNT10=23.0).ConclusionsBenefit-based targeting of statin therapy provides modest gains in efficiency over risk-based prescribing and could theoretically help attain approximately half of the Healthy People 2020 impact goal with reasonable efficiency.

Dataset Information

Role of Statin Therapy in Primary Prevention of Cardiovascular Disease in Elderly Patients.

Publications

Role of Statin Therapy in Primary Prevention of Cardiovascular Disease in Elderly Patients.

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