Cholesterol Guidelines for Multi Ethnic CVD Prevention
Cholesterol Guidelines for Multi Ethnic CVD Prevention
The study design for the MESA study has been published elsewhere. A brief description of the MESA cohort, collection of data, event adjudication, and how the ASCVD events were calibrated in this analysis is attached as an appendix (Appendix B).
Only MESA participants aged 40 to 75 years during the baseline examination were included in these analyses. Descriptive statistics of all MESA participants who were not on statins during the baseline examination and have complete data for assessing statin eligibility under the NCEP/ATP III and 2013 ACC/AHA cholesterol guidelines are presented as mean (SD) for continuous variables and percentages for categorical variables. Ten-year ATP III risk was calculated for each participant. Under the NCEP/ATP III cholesterol guidelines (2001 and the 2004 update), all T2DM patients as well as individuals with (a) 2+ risk factors with calculated 10-year CHD risk of >20% and low-density lipoprotein cholesterol (LDLc) >100 mg/dL, (b) 2+ risk factors with 10-year risk 10% to 20% and LDLc ≥130 mg/dL, (c) 2+ risk factors with 10-year risk <10% and LDLc ≥160 mg/dL, and (d) LDLc ≥190 mg/dL are eligible for statin therapy for primary prevention. The optional recommendation of 2+ risk factors with calculated CHD risk 10% to 20% and LDLc ≥100 mg/dL was also included as a sensitivity analysis to estimate statin eligibility under the old guidelines.
The new pooled ASCVD risk estimator was also used to calculate the estimated 10-year ASCVD risk for each MESA participant. The 10-year ASCVD risk for Hispanics and Chinese participants was estimated using the pooled ASCVD risk equation for whites. Under the 2013 AHA/ACC cholesterol guidelines, all T2DM patients (age 40–75 years), participants with LDLc ≥190 mg/dL, and all participants with calculated new pooled risk score ≥7.5% are eligible for statin therapy for primary prevention. The optional recommendation of statin therapy for individuals with ASCVD risk 5% to 7.5% was also included for sensitivity analysis. The difference between the number who qualified for statin therapy under the new guidelines and the number who qualified for statin therapy under the NCEP/ATP III (old guideline) was used as the additional number of participants who will qualify for statin therapy under the current guidelines (newly eligible) (n = 1,742). The rate at which ASCVD events accumulated in the newly eligible MESA subcohort was analyzed with a Kaplan-Meier plot and a Poisson rate model. Robust SEs were used for the Poisson regression.
Relative risk estimates based on the type and dose of statins administered in selected clinical trials were applied to the calibrated 10-year ASCVD and T2DM events that occurred in participants who qualified under (a) NECP/ATP III, (b) new ACC/AHA, and (c) newly eligible MESA cohorts to provide estimates of the reduction in ASCVD and increment in T2DM that would have occurred due to statin therapy in this MESA subcohort (Table I).
The accurate duration of therapy of all the MESA participants who were not on statins at the baseline examination but took statins during the follow-up period could not be determined. We therefore undertook a sensitivity analysis in which we considered the observed events to have occurred while (1) 100% of each subcohort took statins throughout the follow-up period and (2) none of the participants in each of the subcohort took statins during the follow-up period, to provide the extreme bounds of the estimates in our main analysis.
Classification of statin intensity and their corresponding relative risk estimates in published clinical trials were based on the 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults. Estimates from the Cochrane Collaboration Meta-Analysis were used for the effects of moderate intensity therapy on ASCVD events. The relative risk estimate for high-intensity statins was obtained by combining data from the Cochrane Collaboration Meta-Analysis and Mills et al. The effects of statin therapy on incident T2DM were obtained by eliminating high-intensity statin studies from risk estimate provided in the meta-analysis by Sattar et al for moderate-intensity statin therapy (odds ratio 1.08, (1.01–1.15), I = 1.5%), and by taking a weighted average of the JUPITER and CORONA studies for high-intensity statin therapy. The expected change in the number of events was calculated by multiplying the number of calibrated events by (risk ratio − 1). The 95% prediction intervals were calculated from the 95% CIs in clinical trials.
Number needed to treat (NNT; number of participants who need to be treated with statins over a 10-year period to prevent 1 ASCVD event) and number needed to harm (NNH; number of participants who need to be treated with statins over a 10-year period to cause 1 T2DM) were calculated.
The statistical analysis was performed using STATA 12.0 (STATACORP LP) and Excel 2010 (Microsoft).
The authors are solely responsible for all the analyses, the drafting and editing of the paper and its final contents.
Methods
Study Population and Data Collection
The study design for the MESA study has been published elsewhere. A brief description of the MESA cohort, collection of data, event adjudication, and how the ASCVD events were calibrated in this analysis is attached as an appendix (Appendix B).
Statistical Analysis
Only MESA participants aged 40 to 75 years during the baseline examination were included in these analyses. Descriptive statistics of all MESA participants who were not on statins during the baseline examination and have complete data for assessing statin eligibility under the NCEP/ATP III and 2013 ACC/AHA cholesterol guidelines are presented as mean (SD) for continuous variables and percentages for categorical variables. Ten-year ATP III risk was calculated for each participant. Under the NCEP/ATP III cholesterol guidelines (2001 and the 2004 update), all T2DM patients as well as individuals with (a) 2+ risk factors with calculated 10-year CHD risk of >20% and low-density lipoprotein cholesterol (LDLc) >100 mg/dL, (b) 2+ risk factors with 10-year risk 10% to 20% and LDLc ≥130 mg/dL, (c) 2+ risk factors with 10-year risk <10% and LDLc ≥160 mg/dL, and (d) LDLc ≥190 mg/dL are eligible for statin therapy for primary prevention. The optional recommendation of 2+ risk factors with calculated CHD risk 10% to 20% and LDLc ≥100 mg/dL was also included as a sensitivity analysis to estimate statin eligibility under the old guidelines.
The new pooled ASCVD risk estimator was also used to calculate the estimated 10-year ASCVD risk for each MESA participant. The 10-year ASCVD risk for Hispanics and Chinese participants was estimated using the pooled ASCVD risk equation for whites. Under the 2013 AHA/ACC cholesterol guidelines, all T2DM patients (age 40–75 years), participants with LDLc ≥190 mg/dL, and all participants with calculated new pooled risk score ≥7.5% are eligible for statin therapy for primary prevention. The optional recommendation of statin therapy for individuals with ASCVD risk 5% to 7.5% was also included for sensitivity analysis. The difference between the number who qualified for statin therapy under the new guidelines and the number who qualified for statin therapy under the NCEP/ATP III (old guideline) was used as the additional number of participants who will qualify for statin therapy under the current guidelines (newly eligible) (n = 1,742). The rate at which ASCVD events accumulated in the newly eligible MESA subcohort was analyzed with a Kaplan-Meier plot and a Poisson rate model. Robust SEs were used for the Poisson regression.
Relative risk estimates based on the type and dose of statins administered in selected clinical trials were applied to the calibrated 10-year ASCVD and T2DM events that occurred in participants who qualified under (a) NECP/ATP III, (b) new ACC/AHA, and (c) newly eligible MESA cohorts to provide estimates of the reduction in ASCVD and increment in T2DM that would have occurred due to statin therapy in this MESA subcohort (Table I).
The accurate duration of therapy of all the MESA participants who were not on statins at the baseline examination but took statins during the follow-up period could not be determined. We therefore undertook a sensitivity analysis in which we considered the observed events to have occurred while (1) 100% of each subcohort took statins throughout the follow-up period and (2) none of the participants in each of the subcohort took statins during the follow-up period, to provide the extreme bounds of the estimates in our main analysis.
Classification of statin intensity and their corresponding relative risk estimates in published clinical trials were based on the 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults. Estimates from the Cochrane Collaboration Meta-Analysis were used for the effects of moderate intensity therapy on ASCVD events. The relative risk estimate for high-intensity statins was obtained by combining data from the Cochrane Collaboration Meta-Analysis and Mills et al. The effects of statin therapy on incident T2DM were obtained by eliminating high-intensity statin studies from risk estimate provided in the meta-analysis by Sattar et al for moderate-intensity statin therapy (odds ratio 1.08, (1.01–1.15), I = 1.5%), and by taking a weighted average of the JUPITER and CORONA studies for high-intensity statin therapy. The expected change in the number of events was calculated by multiplying the number of calibrated events by (risk ratio − 1). The 95% prediction intervals were calculated from the 95% CIs in clinical trials.
Number needed to treat (NNT; number of participants who need to be treated with statins over a 10-year period to prevent 1 ASCVD event) and number needed to harm (NNH; number of participants who need to be treated with statins over a 10-year period to cause 1 T2DM) were calculated.
The statistical analysis was performed using STATA 12.0 (STATACORP LP) and Excel 2010 (Microsoft).
The authors are solely responsible for all the analyses, the drafting and editing of the paper and its final contents.
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