Global variation of risk thresholds for initiating statins for primary prevention of cardiovascular disease: a benefit-harm balance modelling study

Abstract Background We previously showed that the 10-year cardiovascular disease (CVD) risk threshold to initiate statins for primary prevention depends on the baseline CVD risk, age, sex, and the incidence of statin-related harm outcome and competing risk for non-CVD death. As these factors appear to vary across countries, we aimed in this study to determine country-specific thresholds and provide guidelines a quantitative benefit-harm assessment method for local adaptation. Methods For each of the 186 countries included, we replicated the benefit-harm balance analysis using an exponential model to determine the thresholds to initiate statin use for populations aged 40 to 75 years, with no history of CVD. The analyses took data inputs from a priori studies, including statin effect estimates (network meta-analysis), patient preferences (survey), and baseline incidence of harm outcomes and competing risk for non-CVD (global burden of disease study). We estimated the risk thresholds above which the benefits of statins were more likely to outweigh the harms using a stochastic approach to account for statistical uncertainty of the input parameters. Results The 5th and 95th percentiles of the 10-year risk thresholds above which the benefits of statins outweigh the harms across 186 countries ranged between 14 and 20% in men and 19–24% in women, depending on age (i.e., 90% of the country-specific thresholds were in the ranges stated). The median risk thresholds varied from 14 to 18.5% in men and 19 to 22% in women. The between-country variability of the thresholds was slightly attenuated when further adjusted for age resulting, for example, in a 5th and 95th percentiles of 14–16% for ages 40–44 years and 17–21% for ages 70–74 years in men. Some countries, especially the islands of the Western Pacific Region, had higher thresholds to achieve net benefit of statins at 25–36% 10-year CVD risks. Conclusions This extensive benefit-harm analysis modeling shows that a single CVD risk threshold, irrespective of age, sex and country, is not appropriate to initiate statin use globally. Instead, countries need to carefully determine thresholds, considering the national or subnational contexts, to optimize benefits of statins while minimizing related harms and economic burden.

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Net benefit of statins for primary prevention of cardiovascular disease in people 75 years or older: a benefit–harm balance modeling study

Therapeutic Advances in Chronic Disease ◽

10.1177/2040622319877745 ◽

2019 ◽

Vol 10 ◽

pp. 204062231987774 ◽

Cited By ~ 1

Author(s):

Henock G. Yebyo ◽

Hélène E. Aschmann ◽

Dominik Menges ◽

Cynthia M. Boyd ◽

Milo A. Puhan

Keyword(s):

Cardiovascular Disease ◽

Primary Prevention ◽

Patient Preferences ◽

Observational Studies ◽

Age Groups ◽

Exponential Model ◽

Statistical Uncertainty ◽

Net Benefit ◽

Cvd Risk ◽

History Of

Background: We determined the risk thresholds above which statin use would be more likely to provide a net benefit for people over the age of 75 years without history of cardiovascular disease (CVD). Methods: An exponential model was used to estimate the differences in expected benefit and harms in people treated with statins over a 10-year horizon versus not treated. The analysis was repeated 100,000 times to consider the statistical uncertainty and produce a distribution of the benefit–harm balance index from which we determined the 10-year CVD risk threshold where benefits outweighed the harms. We considered treatment estimates from trials and observational studies, baseline risks, patient preferences, and competing risks of non-CVD death, and statistical uncertainty. Results: Based on average preferences, statins were more likely to provide a net benefit at a 10-year CVD risk of 24% and 25% for men aged 75–79 years and 80–84 years, respectively, and 21% for women in both age groups. However, these thresholds varied significantly depending on differences in individual patient preferences for the statin-related outcomes, with interquartile ranges of 21–33% and 23–36% for men aged 75–79 years and 80–84 years, respectively, as well as 20–32% and 21–32% for women aged 75–79 years and 80–84 years, respectively. Conclusions: Statins would more likely provide a net benefit for primary prevention in older people taking the average preferences if their CVD risk is well above 20%. However, the thresholds could be much higher or lower depending on preferences of individual patients, which suggests more emphasis should be placed on individual-based decision-making, instead of recommending statins for everyone based on a single or a small number of thresholds.

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Prediction of Cardiovascular Disease Mortality in a Middle Eastern Country: Performance of the Globorisk and Score Functions in Four Population-Based Cohort Studies of Iran

International Journal of Health Policy and Management ◽

10.34172/ijhpm.2020.103 ◽

2020 ◽

Author(s):

Noushin Fahimfar ◽

Akbar Fotouhi ◽

Mohammad Ali Mansournia ◽

Reza Malekzadeh ◽

Nizal Sarrafzadegan ◽

...

Keyword(s):

Cardiovascular Disease ◽

Middle Eastern ◽

Score Function ◽

Population Based ◽

Clinical Usefulness ◽

Limited Information ◽

Net Benefit ◽

Cvd Risk ◽

Risk Of Death ◽

Risk Threshold

Background: Considering the importance of cardiovascular disease (CVD) risk prediction for healthcare systems and the limited information available in the Middle East, we evaluated the SCORE and Globorisk models to predict CVD death in a country of this region. Methods: We included 24 427 participants (11 187 men) aged 40-80 years from four population-based cohorts in Iran. Updating approaches were used to recalibrate the baseline survival and the overall effect of the predictors of the models. We assessed the models’ discrimination using C-index and then compared the observed with the predicted risk of death using calibration plots. The sensitivity and specificity of the models were estimated at the risk thresholds of 3%, 5%, 7%, and 10%. An agreement between models was assessed using the intra-class correlation coefficient (ICC). We applied decision analysis to provide perception into the consequences of using the models in general practice; for this reason, the clinical usefulness of the models was assessed using the net benefit (NB) and decision curve analysis. The NB is a sensitivity penalized by a weighted false positive (FP) rate in population level. Results: After 154 522 person-years of follow-up, 437 cardiovascular deaths (280 men) occurred. The 10-year observed risks were 4.2% (95% CI: 3.7%-4.8%) in men and 2.1% (1.8-2%.5%) in women. The c-index for SCORE function was 0.784 (0.756-0.812) in men and 0.780 (0.744-0.815) in women. Corresponding values for Globorisk were 0.793 (0.766- 0.820) and 0.793 (0.757-0.829). The deviation of the calibration slopes from one reflected a need for recalibration; after which, the predicted-to-observed ratio for both models was 1.02 in men and 0.95 in women. Models showed good agreement (ICC 0.93 in men, and 0.89 in women). Decision curve showed that using both models results in the same clinical usefulness at the risk threshold of 5%, in both men and women; however, at the risk threshold of 10%, Globorisk had better clinical usefulness in women (Difference: 8%, 95% CI: 4%-13%). Conclusion: Original Globorisk and SCORE models overestimate the CVD risk in Iranian populations resulting in a high number of people who need intervention. Recalibration could adopt these models to precisely predict CVD mortality. Globorisk showed better performance clinically, only among high-risk women.

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Aspirin for primary prevention: yes or no?

Journal of Primary Health Care ◽

10.1071/hc10092 ◽

2010 ◽

Vol 2 (2) ◽

pp. 92 ◽

Cited By ~ 4

Author(s):

Vanessa Selak ◽

C Raina Elley ◽

Sue Wells ◽

Anthony Rodgers ◽

Norman Sharpe

Keyword(s):

Blood Pressure ◽

Cardiovascular Disease ◽

Primary Prevention ◽

Meta Analysis ◽

Risk Category ◽

Age Group ◽

Blood Pressure Lowering ◽

Net Benefit ◽

Cvd Risk ◽

Pressure Lowering

AIM: To assess benefit versus harm of aspirin for cardiovascular disease (CVD) primary prevention by age group, gender and risk category and to interpret these results in light of current New Zealand CVD risk assessment and management guidelines. METHODS: Rates of benefit (avoided vascular events) and harm (additional major extracranial bleeds) for each gender and age group were calculated from data from the six randomised controlled trials included in the Anti-Thrombotic Trialists’ (ATT) Collaboration meta-analysis. These rates were applied to CVD risk categories to calculate the net benefit or net harm likely to occur from the use of aspirin in primary prevention of CVD as monotherapy and when added to lipid and blood pressure–lowering therapies. RESULTS: Benefits of aspirin monotherapy outweigh the harms for both men and women aged up to 80 years with calculated five-year CVD risk >15% in primary prevention. Harm may outweigh benefit for primary prevention for those over 80 years. For men 70–79 years the benefit of aspirin in primary prevention is marginal when added to lipid and blood pressure–lowering therapies. DISCUSSION: The recent ATT Collaboration meta-analysis has raised doubts about the relative safety of aspirin in primary prevention of CVD. However, modelling by risk category and age group suggests that current guidelines are justified in recommending aspirin for primary prevention of CVD in those with five-year CVD risk ≥15% up to the age of 80 years. For men 70–79, consider lipid and blood pressure - lowering therapies first then reassess whether aspirin adds additional net benefit. KEYWORDS: Aspirin; primary prevention; cardiovascular disease; cardiovascular risk

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Clinical Prediction Models for Primary Prevention of Cardiovascular Disease: Validity in Independent Cohorts

10.1101/2021.01.31.21250871 ◽

2021 ◽

Author(s):

Gaurav Gulati ◽

Riley J Brazil ◽

Jason Nelson ◽

David van Klaveren ◽

Christine M. Lundquist ◽

...

Keyword(s):

Cardiovascular Disease ◽

Decision Making ◽

Primary Prevention ◽

Prediction Models ◽

Model Updating ◽

Clinical Prediction ◽

Net Benefit ◽

Clinical Prediction Models ◽

C Statistic ◽

Prevention Of Cardiovascular Disease

AbstractBackgroundClinical prediction models (CPMs) are used to inform treatment decisions for the primary prevention of cardiovascular disease. We aimed to assess the performance of such CPMs in fully independent cohorts.Methods and Results63 models predicting outcomes for patients at risk of cardiovascular disease from the Tufts PACE CPM Registry were selected for external validation on publicly available data from up to 4 broadly inclusive primary prevention clinical trials. For each CPM-trial pair, we assessed model discrimination, calibration, and net benefit. Results were stratified based on the relatedness of derivation and validation cohorts, and net benefit was reassessed after updating model intercept, slope, or complete re-estimation. The median c statistic of the CPMs decreased from 0.77 (IQR 0.72-0.78) in the derivation cohorts to 0.63 (IQR 0.58-0.66) when externally validated. The validation c-statistic was higher when derivation and validation cohorts were considered related than when they were distantly related (0.67 vs 0.60, p < 0.001). The calibration slope was also higher in related cohorts than distantly related cohorts (0.69 vs 0.58, p < 0.001). Net benefit analysis suggested substantial likelihood of harm when models were externally applied, but this likelihood decreased after model updating.ConclusionsDiscrimination and calibration decrease significantly when CPMs for primary prevention of cardiovascular disease are tested in external populations, particularly when the population is only distantly related to the derivation population. Poorly calibrated predictions lead to poor decision making. Model updating can reduce the likelihood of harmful decision making, and is needed to realize the full potential of risk-based decision making in new settings.

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Abstract MP41: Implications of the Use of the New ACC/AHA Guidelines for Cardiovascular Disease Prevention in a Brazilian Cohort - The Elsa Brasil Study

Circulation ◽

10.1161/circ.131.suppl_1.mp41 ◽

2015 ◽

Vol 131 (suppl_1) ◽

Author(s):

Marcio S Bittencourt ◽

Isabela Bensenor ◽

Dora Chor ◽

Paulo Vasconcelos ◽

Paulo Lotufo

Keyword(s):

Cardiovascular Disease ◽

Primary Prevention ◽

Prediction Model ◽

Urban Areas ◽

Absolute Risk ◽

Adult Health ◽

Older Individuals ◽

Cvd Risk ◽

The Impact ◽

Brazilian Cohort

Introduction: The 2013 American College of Cardiology / American Heart Association (ACC/AHA) guidelines developed a new prediction model for cardiovascular disease (CVD) and suggested the use of a lower threshold of 7.5% 10 year hard CVD risk for primary prevention. The implications of the use of this model in other cohort and admixed races has not yet been tested. The current study sought to evaluate the potential impact of its use in a large Brazilian cohort. Methods: We have included 15105 participants of the (Brazilian Longitudinal Study of Adult Health) ELSA-Brasil study, a multicenter prospective study that enrolled civil servants aged 35 to 74 years in 6 different urban areas in brazil. We have calculated the both the Framingham risk score (FRS) and the new risk prediction model to the entire cohort, and estimated the impact of changing current recommendations based on the FRS and lipid targets to the new recommendations based on the absolute risk estimated by the new model. Results: The mean age was 52±9.1 years, with 8218 (54%) women. The race distribution included 52% white, 16% black, 28% mixed (brown), and 4% of other. While 19.2% (95% CI: 18.4 to 19.6) of the cohort would require statins for primary prevention accordion to prior recommendations, the new guidelines would recommend treatment for approximately 40.2% (95%CI: 39.4 to 41.0) of the cohort. A substantial increase in the population in whom statins are recommended occurred for males, from 23.3% (95%CI: 22.6 to 24.0%) to 55.7% (95%CI: 54.9 to 56.5), as well as females, from 16.6 (95%CI: 16.0 to 17.2) to 27.1 (95%CI: 26.4 to 27.8), and across all races and age levels (figure). Conclusion: The new ACC/AHA guidelines for primary prevention would approximately double the proportion of Brazilian adults in whom statins are indicated, mostly among older individuals. The epidemiological and economical impact of this changes are not yet known.

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Current 10-year atherosclerotic cardiovascular disease risk threshold for statin eligibility is cost-effective for primary prevention

Evidence-Based Medicine ◽

10.1136/ebmed-2015-110277 ◽

2015 ◽

Vol 20 (6) ◽

pp. 230-230

Author(s):

Joseph Yeboah

Keyword(s):

Cardiovascular Disease ◽

Primary Prevention ◽

Disease Risk ◽

Cardiovascular Disease Risk ◽

Cost Effective ◽

Atherosclerotic Cardiovascular Disease ◽

Risk Threshold ◽

Atherosclerotic Cardiovascular Disease Risk

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Evaluation of academic detailing visits on GP knowledge and practice for statin use and management

Australian Journal of Primary Health ◽

10.1071/py20062 ◽

2020 ◽

Vol 26 (6) ◽

pp. 492

Author(s):

Isla Hains ◽

Natalie Raffoul ◽

Jeannie Yoo

Keyword(s):

Cardiovascular Disease ◽

Education Program ◽

Academic Detailing ◽

Cvd Risk ◽

Lipid Management ◽

National Education ◽

Management Algorithm ◽

Knowledge And Practice ◽

And Control ◽

Statin Use

Dyslipidaemia is a major risk factor for cardiovascular disease (CVD) and is routinely managed by GPs. Lipid-modifying medicines, commonly statins, are used to treat dyslipidaemia and prevent CVD in high-risk individuals. A national education program for over 8000 Australian GPs was delivered and evaluated. The program aimed to optimise the use of statins and provide GPs with an Australian-developed statin-associated muscle symptoms (SAMS) management algorithm supporting assessment and management of suspected SAMS. Retrospective pre-test and control questionnaires were administered to measure changes in knowledge and intended practice following the education program. A total of 226 participant GPs and 150 control GPs completed the questionnaires. The program led to positive changes in GP knowledge and intended practice around the use of absolute CVD risk to make prescribing decisions. Participant GPs demonstrated increased knowledge, compared with control GPs, about the use of CVD risk calculators as the most effective approach to lipid management, and adequately trialling a statin before considering a second agent. One of the greatest improvements in participant GP-intended practice related to the assessment and management of suspected SAMS, with participant GPs more likely to appropriately identify and manage suspected SAMS than control GPs.

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