Use Of Statins In Primary Prevention Research Articles

126 A Student Pilot for A Feasibility Study of the Theoretical 3S Trial (SPFT3S): GP and Ethics Committee Members Questionnaire

Abstract Introduction Emerging research suggests that statin use for primary prevention in people without diabetes aged 75 and older has no benefit. This study aims to determine the feasibility of the theoretical Stop Statin Study (3S), a double-blind randomised controlled trial carried out in general practice, which would test this hypothesis. 50% of trial patients would stop taking statins for 5 years in an event driven study. The questionnaires aim to identify the attitudes of general practitioners (GPs) and ethics committee members (ECMs) regarding stopping statins for 5 years in patients aged 75 and older without diabetes or history of cardiovascular disease and their willingness to allow patients to participate in the 3S study. Method Questionnaires comprised of 6 questions were designed. 4 students distributed the questionnaire and it was completed by 19 GPs based at 8 practices in the North-East of England. 31 ECMs (12 expert and 19 lay) responded by email. Results 95% of GPs who completed the survey would agree to their patients participating in the theoretical study with 47% of GPs indicating that their willingness to participate in the study is patient dependent. 95% of GPs would also consider stopping statins in this population group if sufficient research had been carried out or if the guidelines were changed. 42% of GPs have a negative attitude to prescribing statins in this population group. All the ECMs would approve the study, citing over-prescribing and polypharmacy as their reason. Conclusions The majority of GPs will participate in the theoretical 3S study, if their patients are willing to participate. There is already a negative perception amongst GPs towards the use of statins in elderly people without disease. The 3S study appears to be feasible from the GP and ethics perspective but would require a larger feasibility study.

Recommendations and associated levels of evidence for statin use in primary prevention of cardiovascular disease: a comparison at population level of the ESC, ACC/AHA, USPSTF, and CCS Guidelines

Abstract Background It is unclear to what extent the 2019 European Society of Cardiology (ESC), 2018 American College of Cardiology/ American Heart Association (ACC/AHA), 2016 US Preventive Services Task Force (USPSTF), and 2016 Canadian Cardiovascular Society (CCS) guidelines differ in assigning levels of evidence and classes of recommendations (LOE/class) to lipid-lowering treatment recommendations in primary prevention of cardiovascular disease (CVD). Purpose To compare LOE/class from four commonly used guidelines at population level. Methods A total of 7262 participants, aged 45–75 years of age and without history of CVD, from the prospective population-based Rotterdam Study were included. Per guideline, proportions of the population recommended statin therapy by LOE/class, sensitivity and specificity, and numbers needed to treat at 10 years (NNT10y) were calculated. Results Mean age was 61.1 (SD 6.9) years, and 58.2% were women. ESC, ACC/AHA, USPSTF and CCS strongly recommended statin use for a respective 33.8%, 48.1%, and 40.2% and 73.0% of the eligible population based on high-quality evidence, while in an additional 55.3%, 7.1%, 8.4% and 9.2% of participants statins use could or should be considered based on varying LOE/class. The sensitivity for treatment recommendations supported with strong, high quality evidence was 61.6% for ESC (“IA”), 74.6% for ACC/AHA (“IA or IB”), 69.4% for USPSTF (“USPSTF-B”) and 92.5% for CCS (“strong”). Specificity was highest for the ACC/AHA at 46.8% and lowest for ESC at 11.4%. Estimated NNT10y for those with the strongest LOE/class were comparable across all guidelines, ranging from 18 to 26 for moderate-intensity statin use, and 11 to 16 for high-intensity statin use. NNT10y reflective of recommendations supported with moderate strength of LOE/class varied substantially among guidelines for both moderate-intensity and high-intensity statin use, ranging from 33 for ESC and USPSTF to 91 for CCS. Conclusions Assigned LOE/class varied greatly among four clinical practice guidelines for primary prevention of CVD. Efforts for harmonized and comparable evidence grading system for clinical practice guidelines in primary prevention of CVD may reduce ambiguity, and reinforce updated evidence-based recommendations for appropriate treatment of populations for whom clear evidence for benefit of statin use is available. Funding Acknowledgement Type of funding source: None

Updated treatment thresholds in the 2019 ESC/EAS dyslipidaemia guidelines substantially expand indications for statin use for primary prevention at population level: results from the Rotterdam Study

Abstract Background In the recent update of the ESC/EAS practice guidelines for the management of dyslipidaemias, indications for statin treatment in primary prevention have been expanded to those at lower cardiovascular disease (CVD) risk and with lower LDL levels, as well as to those 65 to 75 years of age according to their level of predicted CVD risk. Purpose To compare the implications of the 2016 and 2019 ESC/EAS guidelines and determine the extent to which these updates affect treatment recommendations at population level. Methods We calculated 10-year CVD risk following the 2016 and 2019 ESC/EAS guideline recommendations and proportions of individuals qualifying for statin treatment categories per guideline. The study population included 7262 participants free of CVD, aged 45 to 75 years, from the Dutch prospective population-based Rotterdam Study. Results Mean (SD) age was 61.1 (6.9) years and 58.2% were women. Diabetes was present in 8.4% of the participants, 24.7% were smokers, mean LDL was 3.7 (0.9) mmol/L, and mean blood pressure was 137/80 (20/11) mmHg. Next to lifestyle changes, the 2016 and 2019 ESC/EAS guidelines recommend statin treatment in 13.2% (N=961) and 37.7% (N=2738) of the total population and consider statin treatment in 37.0% (N=2689) and 51.4% (N=3733), respectively. When stratified by 5-year age groups, the 2016 and 2019 ESC/EAS guidelines overall suggest a respective 29.7% (N=411) and 60.7% (N=839) of adults aged 45–55 years to be considered for statin treatment. While adults with an estimated 10-year SCORE risk of fatal CVD <1% and LDL <4.9 mmol/L were deemed to be at sufficiently low risk in the 2016 ESC/EAS guidelines and hence were suggested only lifestyle advice to modify their cardiovascular risk, in the 2019 update, 517 individuals (i.e. 37.4% of 1383 adults aged 45–55 years) were considered for statin treatment. The 2016 ESC/EAS guidelines did not provide treatment recommendations for individuals aged >65 years, while the 2019 ESC/EAS guidelines recommend statin treatment in 69.2% (N=1430) and considers treatment in another 27.7% (N=571) among the study population aged 65–75 years (N=2065). Conclusions Updated treatment recommendations in the 2019 ESC/EAS dyslipidaemia guideline substantially expand statin treatment to asymptomatic individuals aged 45–55 at low risk, and individuals aged 65–75 years. Whether the broadening of statin indications in asymptomatic low-risk individuals and those aged 65–75 years will lead to greater uptake of primary prevention efforts and thereby long-term lowering of the burden of CVD in Europe, remains to be investigated. Funding Acknowledgement Type of funding source: None

Effects of Statin Use for Primary Prevention among Adults Aged 75 Years and Older in the National Health Insurance Service Senior Cohort (2002-2015).

BackgroundThis study aimed to identify adverse events and mortality in adults aged 75 years and older who were initially prescribed statins for primary prevention.MethodsThis retrospective study analyzed the data from the National Health Insurance Corporation–Senior Cohort from 2002 to 2015. An exact block matched model was constructed from statin user and statin non-user groups. ResultsThe study sample comprised 1,370 older adults (mean age, 78 years), with 685 statin non-users matched to 685 new statin users. Compared to non-users, the adjusted hazard ratios (HRs) of new statin users were 0.83 (p=0.04) for all-cause mortality, 1.24 (p=0.03) for major adverse cardiovascular events, and 1.18 (p=0.06) for new-onset diabetes mellitus. In a sub-analysis of statin use duration, longer statin use (>5 years) was associated with a significantly lower risk of all-cause mortality (HR=0.76, p=0.01) but not with major adverse cardiovascular events (HR=0.88, p=0.36) or new-onset diabetes mellitus (HR=0.95, p=0.78) after adjusting for age, sex, body mass index, diabetes mellitus, hypertension, aspirin use, and antiplatelet use. ConclusionOur findings suggested that statins started for primary prevention in older adults aged 75 years and older had an advantageous effect on all-cause mortality only if used for at least 5 years.

Statin Use in Primary Prevention of Atherosclerotic Cardiovascular Disease According to 5 Major Guidelines for Sensitivity, Specificity, and Number Needed to Treat

Five major guidelines on statin use for primary prevention of atherosclerotic cardiovascular disease (ASCVD) have been published since 2014: the National Institute for Health and Care Excellence (NICE; 2014), US Preventive Services Task Force (USPSTF; 2016), Canadian Cardiovascular Society (CCS; 2016), European Society of Cardiology/European Atherosclerosis Society (ESC/EAS; 2016), and American College of Cardiology/American Heart Association (ACC/AHA; 2018). To compare the sensitivity, specificity, and estimated number needed to treat (NNT10) to prevent 1 ASCVD event in 10 years according to statin criteria from the 5 guidelines. Population-based contemporary cohort study. Analyses were performed in the Copenhagen General Population Study, with a mean follow-up time of 10.9 years. We included 45 750 individuals aged 40 to 75 years. The participants were enrolled between 2003 and 2009 and were all free of ASCVD at baseline. Data were analyzed between January 1, 2019, and August 4, 2019. Statin treatment according to guideline criteria. We assumed a 25% relative reduction of ASCVD events per 38 mg/dL (to convert to millimoles per liter, multiply by 0.0259) reduction in low-density lipoprotein cholesterol. Sensitivity and specificity for ASCVD events and the NNT10 to prevent 1 ASCVD event according to guideline criteria. Median age at baseline examination was 56 years, and 43% of participants were men (n = 19 870 of 45 750). During follow-up, we observed 4156 ASCVD events. Overall, 44% of individuals in Copenhagen General Population Study were statin eligible with CCS (n = 19 953 of 45 750), 42% with ACC/AHA (n = 19 400 of 45 750), 40% with NICE (n = 19 400 of 45 750), 31% with USPSTF (n = 13 966 of 45 750), and 15% with ESC/EAS (n = 6870 of 45 750). Sensitivity and specificity for ASCVD events were 68% (n = 2815 of 4156) and 59% (n = 24 456 of 41 594) for CCS, 70% (n = 2889 of 4156) and 60% (n = 25 083 of 41 594) for ACC/AHA, 68% (n = 2815 of 4156) and 63% (n = 26 213 of 41 594) for NICE, 57% (n = 2377 of 4156) and 72% (n = 30 005 of 41 594) for USPSTF, and 24% (n = 1001 of 4156) and 86% (n = 35 725 of 41 594) for ESC/EAS. The NNT10 to prevent 1 ASCVD using moderate-intensity and high-intensity statin therapy, respectively, was 32 and 21 for CCS criteria, 30 and 20 for ACC/AHA criteria, 30 and 20 for NICE criteria, 27 and 18 for USPSTF criteria, and 29 and 20 for ESC/EAS criteria. With similar NNT10 to prevent 1 event, the CCS, ACC/AHA, and NICE guidelines correctly assign statin therapy to many more of the individuals who later develop ASCVD compared with the USPSTF and ESC/EAS guidelines. Our results therefore suggest that the CCS, ACC/AHA, or NICE guidelines may be preferred for primary prevention.

Statin Use in Primary Prevention: A Simple Trial-Based Approach Compared With Guideline-Recommended Risk Algorithms for Selection of Eligible Patients

BackgroundCardiovascular disease risk assessment tools help identify individuals likely to benefit from preventative therapies. In this study we compared outcomes using the American College of Cardiology/American Heart Association (ACC/AHA) risk algorithm and the Framingham Risk Score (FRS) tool in the Heart Outcomes Prevention Evaluation (HOPE)-3 study. MethodsWe compared outcomes using the ACC/AHA algorithm and the FRS with those seen in HOPE-3, which randomized participants to 10 mg rosuvastatin or placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke; second coprimary outcome additionally included heart failure, cardiac arrest, and revascularization. ResultsRelative risks using risk scores were similar to those observed in the HOPE-3. Hazards ratios for the first coprimary outcome according to risk categories of ≤ 10%, 10%-20%, and ≥ 20% using the ACC/AHA algorithm were 0.82 (95% confidence interval [CI], 0.53-1.28), 0.72 (95% CI, 0.53-0.96), and 0.72 (95% CI, 0.55-0.93), and absolute risk reduction (ARR) of 0.18%, 1.33%, and 1.85%, respectively, over a median of 5.6 years. Corresponding results using the FRS were 0.69 (95% CI, 0.36-1.35), 0.73 (95% CI, 0.52-1.01), and 0.75 (95% CI, 0.60- 0.94); and ARR of 1.32%, 0.61%, and 1.43%. Hazard ratios for the second coprimary outcome were 0.77 (95% CI, 0.51-1.14), 0.73 (95% CI, 0.56-0.95), and 0.74 (95% CI, 0.58-0.94); and ARR of 0.36%, 1.49%, and 1.85%, using the ACC/AHA algorithm and 0.76 (95% CI, 0.41-1.41), 0.70 (95% CI, 0.52-0.95), and 0.76 (95% CI, 0.62-0.94); and ARR of 1.08%, 0.83%, and 1.56% using the FRS. ConclusionsThe pragmatic HOPE-3 trial approach identifies in an ethnically diverse primary prevention population individuals at intermediate risk who benefit from statin therapy using simple clinical characteristics without the need for complex, currently used risk assessment tools.

Abstract 101: Cost-Effectiveness and Decision Analysis of Polygenic Risk Scores in Statin Use for Primary Prevention

Research Objective: Polygenic risk scores can improve prediction of first-time cardiovascular disease (CVD). Prediction of future events is the central factor in statin use in current guidelines Therefore, we hypothesized that if polygenic risk scores were added to current risk scores, statin use could become more efficient. We performed a cost-effectiveness analysis to see if genomic testing could be a cost-effective way to prevent CVD. Study Design: Decision-analytic model of genomic testing for statin decision-making. Data sources: Published literature Time Horizon: Lifetime Perspective: Third-party payer Intervention: Statin decision-making based on current guidelines or based on current guidelines augmented with genetic testing in all Americans ages 40-75 with estimated 10-year CVD risk of 5-20%. Population Studied: Primary prevention population in the United States. Outcome Measures: Quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios (ICERs), and total 10-year spending. Principal Findings: At $200 per genetic test and $144 for a year of medium-strength statin use, full adherence to the current guidelines are estimated to cost $66,155 per QALY saved. Genetic testing would be $263,000 per additional QALY saved. These results are sensitive to improvements in genetic prediction and cost of genetic testing. Conclusions: Genomic testing to improve statin use is cost-effective for a very large number of Americans at current prices.

Assessing gaps in cholesterol treatment guidelines for primary prevention of cardiovascular disease based on available randomised clinical trial evidence: The Rotterdam Study.

BackgroundThe purpose of this study was to determine how American College of Cardiology/American Heart Association (ACC/AHA) 2013 and European Society of Cardiology 2016 guidelines for the primary prevention of atherosclerotic cardiovascular disease (CVD) compare in reflecting the totality of accrued randomised clinical trial evidence for statin treatment at population level.MethodsFrom 1997–2008, 7279 participants aged 45–75 years, free of atherosclerotic cardiovascular disease, from the population-based Rotterdam Study were included. For each participant, we compared eligibility for each one of 11 randomised clinical trials on statin use in primary prevention of CVD, with recommendations on lipid-lowering therapy from the ACC/AHA and European Society of Cardiology (ESC) guidelines. Atherosclerotic cardiovascular disease incidence and cardiovascular disease mortality rates were calculated.ResultsThe proportion of participants eligible for each trial ranged from 0.4% for ALLHAT-LLT to 30.8% for MEGA. The likelihood of being recommended for lipid-lowering treatment was lowest for those eligible for low-to-intermediate risk RCTs (HOPE-3, MEGA, and JUPITER), and highest for high-risk individuals with diabetes (MRC/BHF HPS, CARDS, and ASPEN) or elderly PROSPER. Eligibility for an increasing number of randomised clinical trials correlated with a greater likelihood of being recommended lipid-lowering treatment by either guideline (p < 0.001 for both guidelines).ConclusionCompared to RCTs done in high risk populations, randomised clinical trials targeting low-to-intermediate risk populations are less well-reflected in the ACC/AHA, and even less so in the ESC guideline recommendations. Importantly, the low-to-intermediate risk population targeted by HOPE-3, the most recent randomised clinical trial in this field, is not well-captured by the current European prevention guidelines and should be specifically considered in future iterations of the guidelines.

Frequency of Guideline-Based Statin Therapy in Adults With Congenital Heart Disease

We aimed to evaluate atherosclerotic cardiovascular disease (ASCVD) risk estimates and guideline-based statin use for primary prevention of ASCVD in adults with congenital heart disease (ACHD). This was a case-controlled, retrospective study of 248 cases and 744 age- and gender-matched controls at a tertiary care referral center. ASCVD risk scores were calculated and used to assess indication for statin treatment for primary prevention per the 2013 American College of Cardiology and American Heart Association guideline on assessment of cardiovascular risk. There were no differences in average 10-year ASCVD risk scores between ACHD cases (4.6% ± 6.6%) and matched controls (5.1% ± 6.7%, p = 0.32). ACHD cases had lower total cholesterol (183 ± 38 vs 192.6 ± 35.3 mg/dL, p < 0.001) and were less likely to smoke (8.1% vs 14.6%, p = 0.008), yet had lower high density lipoprotein (52.6 ± 17.2 vs 55.3 ± 17.1 mg/dL, p = 0.03) and higher hypertension rates (38.7% vs 28.5%, p = 0.003). However, only 42.3% ACHD cases with a primary prevention statin indication were appropriately prescribed therapy as compared with 59.0% of controls (p = 0.04). In conclusion, ACHD cases have a similar 10-year ASCVD risk score than age- and gender-matched peers, but ACHD cases are less likely than their peers to be prescribed statin therapy for primary prevention per guideline-based recommendations.

Cardiovascular Risk and Statin Eligibility of Young Adults After an MI: Partners YOUNG-MI Registry

BackgroundDespite significant progress in primary prevention, the rate of MI has not declined in young adults. ObjectivesThe purpose of this study was to evaluate statin eligibility based on the 2013 American College of Cardiology/American Heart Association guidelines for treatment of blood cholesterol and 2016 U.S. Preventive Services Task Force recommendations for statin use in primary prevention in a cohort of adults who experienced a first-time myocardial infarction (MI) at a young age. MethodsThe YOUNG-MI registry is a retrospective cohort from 2 large academic centers, which includes patients who experienced an MI at age ≤50 years. Diagnosis of type 1 MI was adjudicated by study physicians. Pooled cohort risk equations were used to estimate atherosclerotic cardiovascular disease risk score based on data available prior to MI or at the time of presentation. ResultsOf 1,685 patients meeting inclusion criteria, 210 (12.5%) were on statin therapy prior to MI and were excluded. Among the remaining 1,475 individuals, the median age was 45 years, there were 294 (20%) women, and 846 (57%) had ST-segment elevation MI. At least 1 cardiovascular risk factor was present in 1,225 (83%) patients. The median 10-year atherosclerotic cardiovascular disease risk score of the cohort was 4.8% (interquartile range: 2.8% to 8.0%). Only 724 (49%) and 430 (29%) would have met criteria for statin eligibility per the 2013 American College of Cardiology/American Heart Association guidelines and 2016 U.S. Preventive Services Task Force recommendations, respectively. This finding was even more pronounced in women, in whom 184 (63%) were not eligible for statins by either guideline, compared with 549 (46%) men (p < 0.001). ConclusionsThe vast majority of adults who present with an MI at a young age would not have met current guideline-based treatment thresholds for statin therapy prior to their MI. These findings highlight the need for better risk assessment tools among young adults.

Statins for Primary Prevention of Cardiovascular Events and Mortality in Older Men.

We sought to determine whether statin use for primary prevention is associated with a lower risk of cardiovascular events or mortality in older men. Prospective cohort study. Physicians' Health Study participants. 7,213 male physicians ≥70years without a history of cardiovascular disease (CVD). Multivariable propensity score for statin use with greedy matching (1:1) to minimize confounding by indication. Median baseline age was 77 (70-102), median follow-up was 7years. Non-users were matched to 1,130 statin users. Statin use was associated with an 18% lower risk of all-cause mortality, HR 0.82 (95% CI 0.69-0.98) and non-significant lower risk of CVD events, HR 0.86 (95% CI 0.70-1.06) and stroke, HR 0.70 (95% CI 0.45-1.09). In subgroup analyses, results did not change according to age group at baseline (70-76 or >76years) or functional status. There was a suggestion that those >76 at baseline did not benefit from statins for mortality, HR 1.14 (95% CI 0.89-1.47), compared to those 70-76 at baseline, HR 0.83 (95% CI 0.61-1.11); however the CIs overlap between the two groups, suggesting no difference. Statin users with elevated total cholesterol had fewer major CVD events than non-users, HR 0.68 (95% CI 0.50-0.94) and HR 1.43 (95% CI 0.99-2.07)), respectively. Statin use was associated with a significant lower risk of mortality in older male physicians ≥70 and a nonsignificant lower risk of CVD events. Results did not change in those who were >76years at baseline or according to functional status. There was a suggestion that those with elevated total cholesterol may benefit. Further work is needed to determine which older individuals will benefit from statins as primary prevention.

Evaluating the Impact and Cost-Effectiveness of Statin Use Guidelines for Primary Prevention of Coronary Heart Disease and Stroke.

Statins are effective in the primary prevention of atherosclerotic cardiovascular disease. The 2013 American College of Cardiology/American Heart Association (ACC/AHA) guideline expands recommended statin use, but its cost-effectiveness has not been compared with other guidelines. We used the Cardiovascular Disease Policy Model to estimate the cost-effectiveness of the ACC/AHA guideline relative to current use, Adult Treatment Panel III guidelines, and universal statin use in all men 45 to 74 years of age and women 55 to 74 years of age over a 10-year horizon from 2016 to 2025. Sensitivity analyses varied costs, risks, and benefits. Main outcomes were incremental cost-effectiveness ratios and numbers needed to treat for 10 years per quality-adjusted life-year gained. Each approach produces substantial benefits and net cost savings relative to the status quo. Full adherence to the Adult Treatment Panel III guideline would result in 8.8 million more statin users than the status quo, at a number needed to treat for 10 years per quality-adjusted life-year gained of 35. The ACC/AHA guideline would potentially result in up to 12.3 million more statin users than the Adult Treatment Panel III guideline, with a marginal number needed to treat for 10 years per quality-adjusted life-year gained of 68. Moderate-intensity statin use in all men 45 to 74 years of age and women 55 to 74 years of age would result in 28.9 million more statin users than the ACC/AHA guideline, with a marginal number needed to treat for 10 years per quality-adjusted life-year gained of 108. In all cases, benefits would be greater in men than women. Results vary moderately with different risk thresholds for instituting statins and statin toxicity estimates but depend greatly on the disutility caused by daily medication use (pill burden). At a population level, the ACC/AHA guideline for expanded statin use for primary prevention is projected to treat more people, to save more lives, and to cost less compared with Adult Treatment Panel III in both men and women. Whether individuals benefit from long-term statin use for primary prevention depends more on the disutility associated with pill burden than their degree of cardiovascular risk.

Point-of-care testing to promote cardiovascular disease risk assessment: A proof of concept study.

Updated cholesterol guidelines emphasize multivariable cardiovascular disease (CVD) risk estimation to guide treatment decision-making in primary prevention. This study tested the preliminary feasibility, acceptability and efficacy of point-of-care testing (POCT) and quantitative CVD risk assessment in high-risk adults to increase guideline-recommended statin use in primary prevention. Participants were aged 40–75 years, without CVD or diabetes mellitus, and potentially-eligible for consideration of statins based on estimated 10-year CVD risk from last-measured risk factor levels in the electronic health record. We performed POCT to facilitate quantitative CVD risk assessment with the Pooled Cohort Equations immediately before a scheduled primary care provider (PCP) visit. Outcomes were: physician documentation of a CVD risk discussion and statin prescription on the study date. We also assessed acceptability of the intervention through structured questionnaire. We recruited 18 participants (8 from an academic practice and 10 from a federally-qualified health clinic). After the intervention, 83% of participants discussed CVD risk with their PCP, 47% received a statin recommendation from their PCP, and 29% received a new statin prescription during the PCP visit. Participants reported high levels of satisfaction with the intervention. This study demonstrates that in initial testing pre-visit POCT and quantitative CVD risk assessment appears to be a feasible and acceptable intervention that may promote guideline-recommended statin initiation in primary prevention. Future research with an adequately powered trial is warranted to determine the effectiveness of this approach in clinical practice.

92 Primary care prescriptions for statins in england 1998–2015

IntroductionStatins are widely prescribed for the prevention of cardiovascular events. A change in 2014 of the National Institute for Health and Care Excellence (NICE) guidelines for the primary prevention of...

Cardiovascular Risk Stratification and Statin Eligibility Based on the Brazilian vs. North American Guidelines on Blood Cholesterol Management.

Background:The best way to select individuals for lipid-lowering treatment in the population is controversial.Objective:In healthy individuals in primary prevention:to assess the relationship between cardiovascular risk categorized according to the V Brazilian Guideline on Dyslipidemia and the risk calculated by the pooled cohort equations (PCE);to compare the proportion of individuals eligible for statins, according to different criteria.Methods:In individuals aged 40-75 years consecutively submitted to routine health assessment at one single center, four criteria of eligibility for statin were defined: BR-1, BR-2 (LDL-c above or at least 30 mg/dL above the goal recommended by the Brazilian Guideline, respectively), USA-1 and USA-2 (10-year risk estimated by the PCE ≥ 5.0% or ≥ 7.5%, respectively).Results:The final sample consisted of 13,947 individuals (48 ± 6 years, 71% men). Most individuals at intermediate or high risk based on the V Brazilian Guideline had a low risk calculated by the PCE, and more than 70% of those who were considered at high risk had this categorization because of the presence of aggravating factors. Among women, 24%, 17%, 4% and 2% were eligible for statin use according to the BR-1, BR-2, USA-1 and USA-2 criteria, respectively (p < 0.01). The respective figures for men were 75%, 58%, 31% and 17% (p < 0.01). Eighty-five percent of women and 60% of men who were eligible for statin based on the BR-1 criterion would not be candidates for statin based on the USA-1 criterion.Conclusions:As compared to the North American Guideline, the V Brazilian Guideline considers a substantially higher proportion of the population as eligible for statin use in primary prevention. This results from discrepancies between the risk stratified by the Brazilian Guideline and that calculated by the PCE, particularly because of the risk reclassification based on aggravating factors.

Assessing potential population impact of statin treatment for primary prevention of atherosclerotic cardiovascular diseases in the USA: population-based modelling study

ObjectiveNew cholesterol treatment guidelines from American College of Cardiology/American Heart Association recommend statin treatment for more of US population to prevent atherosclerotic cardiovascular disease (ASCVD). It is important to assess...

Limitations of the SCORE-guided European guidelines on cardiovascular disease prevention.

Recently, primary prevention with statins was liberalized in the USA and UK but restricted in many comparable European countries. Supported by risk-benefit and cost-effectiveness analyses, the 2013 ACC/AHA (American College of Cardiology/American Heart Association)1 and 2014 UK-NICE (National Institute for Health and Care Excellence)2 risk assessment and prevention guidelines lowered the risk threshold above which primary prevention with statins should be considered. In contrast, the 2016 update of the European guidelines on cardiovascular disease prevention in clinical practice,3 issued jointly by the European Society of Cardiology (ESC) and nine other societies, continued a conservative position on statin use in primary prevention by preserving the high-risk decision threshold introduced in 2003: 5% 10-year risk for fatal atherosclerotic cardiovascular disease (ASCVD) estimated by SCORE (Systematic Coronary Risk Evaluation).4 The 5% high-risk threshold introduced by the SCORE-based 2003 ESC prevention guidelines4 was chosen because 5% 10-year risk for fatal ASCVD was considered to equate with 20% 10-year risk for fatal and non-fatal coronary heart disease (CHD) arbitrarily defined as high-risk under previous ESC guidelines. No rationale was provided for choosing ≥20% 10-year CHD risk as high risk when introduced in 1994,5 neither for preserving it as ≥5% 10-year risk for fatal ASCVD.4 Hence, except for UK and possibly a few other European countries, the most important threshold for initiating primary prevention with statins has not been revised in Europe for more than 20 years, during which time long-awaited generic and inexpensive statins became available, and their efficacy and safety convincingly documented. Considering that the prevalence and treatment costs of ASCVD remain high, such a development would normally favour a more widespread use of statins in primary prevention. However, because SCORE depends solely on the ultimate cause of death, in countries with declining ASCVD mortality it is becoming harder …

Statin adherence and risk of acute cardiovascular events among women: a cohort study accounting for time-dependent confounding affected by previous adherence

ObjectivesPrevious studies on the effect of statin adherence on cardiovascular events in the primary prevention of cardiovascular disease have adjusted for time-dependent confounding, but potentially introduced bias into their estimates...

Long-Term Outcomes of Short-Term Statin Use in Healthy Adults: A Retrospective Cohort Study.

Data suggest that the beneficial cardiovascular effects of statins are maximized after the first year of statin use; yet, the timeline of statin-associated adverse events is not well delineated. To examine the associations of short-term statin use (≤1year) with short- and long-term adverse events and beneficial cardiovascular outcomes in a 'healthy' cohort. A cohort study of a healthy Tricare population (fiscal year [FY] 2002 through FY 2011) who have no cardiovascular disease, major comorbidities requiring medications, or functional limitations. Statin users used statins for 90-365days during FY 2005 as their only prescription medication. Nonusers had medical encounters but did not receive prescription medications during FY 2005, and did not receive any statins throughout the study period from FY 2002 to FY 2011. Outcomes were the occurrence of major acute cardiovascular events, diabetes mellitus and its complications, kidney diseases, musculoskeletal diseases, obesity, cataracts, malignancy, and death. We matched 1525 statin users to 1525 nonusers. During the follow-up period (FY 2006 to FY 2011), statin users had significantly higher odds of developing diabetes and diabetic complications that persisted throughout follow-up (odds ratio [OR] 1.93, 95% confidence interval [CI] 1.55-2.41 and OR 2.15, 95% CI 1.20-3.86, respectively). Short-term statin use was not associated with decreased odds of major acute cardiovascular events (OR 1.17, 95% CI 0.72-1.92). There were no differences in risks of kidney diseases, musculoskeletal diseases, or malignancy. Short-term statin use for primary prevention in this healthy cohort was associated with an increased risk of long-term diabetes and diabetic complications without cardiovascular benefits. Further study using pragmatic studies and prospective observational studies appropriately equipped to eliminate unidentified confounders are urgently needed.

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.