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

Lotte Kaasenbrood, Neil R. Poulter, Peter S. Sever, Helen M. Colhoun, Shona J. Livingstone, S. Matthijs Boekholdt, Sara L. Pressel, Barry R. Davis, Yolanda Van Der Graaf, Frank L J Visseren (Lead / Corresponding author)

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    Abstract

    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).

    Original languageEnglish
    Pages (from-to)213-221
    Number of pages9
    JournalCirculation: Cardiovascular Quality and Outcomes
    Volume9
    Issue number3
    Early online date11 May 2016
    DOIs
    Publication statusPublished - May 2016

    Fingerprint

    Hydroxymethylglutaryl-CoA Reductase Inhibitors
    Numbers Needed To Treat
    Type 2 Diabetes Mellitus
    Blood Vessels
    Therapeutics
    Placebos
    Confidence Intervals
    Lipids
    Pravastatin
    Antihypertensive Agents
    Calibration
    Decision Making
    Myocardial Infarction
    Clinical Trials

    Keywords

    • cardiovascular diseases
    • decision making shared
    • diabetes mellitus
    • precision medicine
    • statins HMG-CoA
    • treatment outcome

    Cite this

    Kaasenbrood, Lotte ; Poulter, Neil R. ; Sever, Peter S. ; Colhoun, Helen M. ; Livingstone, Shona J. ; Boekholdt, S. Matthijs ; Pressel, Sara L. ; Davis, Barry R. ; Van Der Graaf, Yolanda ; Visseren, Frank L J. / 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. In: Circulation: Cardiovascular Quality and Outcomes. 2016 ; Vol. 9, No. 3. pp. 213-221.
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    abstract = "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).",
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    author = "Lotte Kaasenbrood and Poulter, {Neil R.} and Sever, {Peter S.} and Colhoun, {Helen M.} and Livingstone, {Shona J.} and Boekholdt, {S. Matthijs} and Pressel, {Sara L.} and Davis, {Barry R.} and {Van Der Graaf}, Yolanda and Visseren, {Frank L J}",
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    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. / Kaasenbrood, Lotte; Poulter, Neil R.; Sever, Peter S.; Colhoun, Helen M.; Livingstone, Shona J.; Boekholdt, S. Matthijs; Pressel, Sara L.; Davis, Barry R.; Van Der Graaf, Yolanda; Visseren, Frank L J (Lead / Corresponding author).

    In: Circulation: Cardiovascular Quality and Outcomes, Vol. 9, No. 3, 05.2016, p. 213-221.

    Research output: Contribution to journalArticle

    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

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    JO - Circulation: Cardiovascular Quality and Outcomes

    JF - Circulation: Cardiovascular Quality and Outcomes

    SN - 1941-7713

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    ER -