Development and validation of a model to predict absolute vascular risk reduction by moderate-intensity statin therapy in individual patients with type 2 diabetes mellitus

TY - JOUR

T1 - Development and validation of a model to predict absolute vascular risk reduction by moderate-intensity statin therapy in individual patients with type 2 diabetes mellitus

AU - Kaasenbrood, Lotte

AU - Poulter, Neil R.

AU - Sever, Peter S.

AU - Colhoun, Helen M.

AU - Livingstone, Shona J.

AU - Boekholdt, S. Matthijs

AU - Pressel, Sara L.

AU - Davis, Barry R.

AU - Van Der Graaf, Yolanda

AU - Visseren, Frank L J

N1 - © 2016 American Heart Association, Inc.

PY - 2016/5

Y1 - 2016/5

N2 - Background - In this study, we aimed to translate the average relative effect of statin therapy from trial data to the individual patient with type 2 diabetes mellitus by developing and validating a model to predict individualized absolute risk reductions (ARR) of cardiovascular events. Methods and Results - Data of 2725 patients with type 2 diabetes mellitus from the Lipid Lowering Arm of the Anglo Scandinavian Cardiac Outcomes Trial (ASCOT-LLA) study (atorvastatin 10 mg versus placebo) were used for model derivation. The model was based on 8 clinical predictors including treatment allocation (statin/placebo). Ten-year individualized ARR on major cardiovascular events by statin therapy were calculated for each patient by subtracting the estimated on-treatment risk from the estimated off-treatment risk. Predicted 10-year ARR by statin therapy was 4% (median ARR, 3.2%; interquartile range, 2.5%-4.3%; 95% confidence interval for 3.2% ARR, -1.4% to 6.8%). Addition of treatment interactions did not improve model performance. Therefore, the wide distribution in ARR was a consequence of the underlying distribution in cardiovascular risk enrolled in these trials. External validation of the model was performed in data from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT; pravastatin 40 mg versus usual care) and Collaborative Atorvastatin Diabetes Study (CARDS; atorvastatin 10 mg versus placebo) of 3878 and 2838 patients with type 2 diabetes mellitus, respectively. Model calibration was adequate in both external data sets, discrimination was moderate (ALLHAT-LLT: c-statistics, 0.64 [95% confidence interval, 0.61-0.67] and CARDS: 0.68 [95% confidence interval, 0.64-0.72]). Conclusions - ARRs of major cardiovascular events by statin therapy can be accurately estimated for individual patients with type 2 diabetes mellitus using a model based on routinely available patient characteristics. There is a wide distribution in ARR that may complement informed decision making.Clinical Trial Registration - URL: http://www.clinicaltrials.gov. Unique identifier: NCT00327418 (CARDS) and NCT00000542 (ALLHAT).

AB - Background - In this study, we aimed to translate the average relative effect of statin therapy from trial data to the individual patient with type 2 diabetes mellitus by developing and validating a model to predict individualized absolute risk reductions (ARR) of cardiovascular events. Methods and Results - Data of 2725 patients with type 2 diabetes mellitus from the Lipid Lowering Arm of the Anglo Scandinavian Cardiac Outcomes Trial (ASCOT-LLA) study (atorvastatin 10 mg versus placebo) were used for model derivation. The model was based on 8 clinical predictors including treatment allocation (statin/placebo). Ten-year individualized ARR on major cardiovascular events by statin therapy were calculated for each patient by subtracting the estimated on-treatment risk from the estimated off-treatment risk. Predicted 10-year ARR by statin therapy was 4% (median ARR, 3.2%; interquartile range, 2.5%-4.3%; 95% confidence interval for 3.2% ARR, -1.4% to 6.8%). Addition of treatment interactions did not improve model performance. Therefore, the wide distribution in ARR was a consequence of the underlying distribution in cardiovascular risk enrolled in these trials. External validation of the model was performed in data from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT; pravastatin 40 mg versus usual care) and Collaborative Atorvastatin Diabetes Study (CARDS; atorvastatin 10 mg versus placebo) of 3878 and 2838 patients with type 2 diabetes mellitus, respectively. Model calibration was adequate in both external data sets, discrimination was moderate (ALLHAT-LLT: c-statistics, 0.64 [95% confidence interval, 0.61-0.67] and CARDS: 0.68 [95% confidence interval, 0.64-0.72]). Conclusions - ARRs of major cardiovascular events by statin therapy can be accurately estimated for individual patients with type 2 diabetes mellitus using a model based on routinely available patient characteristics. There is a wide distribution in ARR that may complement informed decision making.Clinical Trial Registration - URL: http://www.clinicaltrials.gov. Unique identifier: NCT00327418 (CARDS) and NCT00000542 (ALLHAT).

KW - cardiovascular diseases

KW - decision making shared

KW - diabetes mellitus

KW - precision medicine

KW - statins HMG-CoA

KW - treatment outcome

U2 - 10.1161/CIRCOUTCOMES.115.001980

DO - 10.1161/CIRCOUTCOMES.115.001980

M3 - Article

C2 - 27174798

AN - SCOPUS:84969160333

SN - 1941-7713

VL - 9

SP - 213

EP - 221

JO - Circulation: Cardiovascular Quality and Outcomes

JF - Circulation: Cardiovascular Quality and Outcomes

IS - 3

ER -