Adherence-adjusted efficacy with intensive versus standard statin therapy in patients with acute myocardial infarction in the IDEAL study

Ingar Holme, Michael Szarek, Nilo B Cater, Ole Faergeman, John J P Kastelein, Anders G Olsson, Matti J Tikkanen, Mogens Lytken Larsen, Christina Lindahl, Terje R Pedersen, Incremental Decrease in End Points Through Aggressive Lipid Lowering Study Group

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Abstract

BACKGROUND: The Incremental Decrease in End Points through Aggressive Lipid Lowering trial showed that the primary endpoint major coronary event was reduced by 11% (0.78-1.01) using atorvastatin 80 mg versus simvastatin 20-40 mg in patients with coronary heart disease (P=0.07). Adherence was high in both treatment groups but significantly higher in patients treated with simvastatin. DESIGN: The Incremental Decrease in End Points through Aggressive Lipid Lowering was a prescription trial with a prospective randomized open label endpoint evaluation. METHODS AND RESULTS: Adherence was calculated as exposure time on prescribed drugs divided by total follow-up time until death or end of follow-up and was a potential confounder. Adjusting for categorical adherence below or above 80% by two methods revealed that the relative risk reduction of the primary endpoint was more in the region of 15% (P=0.02) than 11% as found unadjusted. Censoring at the first occurrence of a cardiovascular event rather than at death increased this estimate to 17% (P=0.02). Noncardiovascular mortality was reduced on atorvastatin treatment by 21% (1-37%) after adjustment for adherence, whereas such reduction was not observed for cardiovascular mortality. CONCLUSION: This study found that the difference in adherence between treatment groups may have underestimated the true effect of the treatment differential. Usage of prospective randomized open label endpoint evaluation design should be carefully considered when well-known treatments are compared with rather new ones and especially in segments where patients could be more vulnerable, as in the elderly. Nonadherers in a clinical trial may be at especially high risk of fatal and nonfatal endpoints from various diseases and should be carefully monitored.
Original languageEnglish
JournalEuropean Journal of Cardiovascular Prevention and Rehabilitation
Volume16
Issue number3
Pages (from-to)315-20
Number of pages5
ISSN1741-8267
DOIs
Publication statusPublished - 1. Jun 2009

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Hydroxymethylglutaryl-CoA Reductase Inhibitors
Simvastatin
Lipids
Risk Reduction Behavior
Prescriptions
Clinical Trials
Pharmaceutical Preparations

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Holme, I., Szarek, M., Cater, N. B., Faergeman, O., Kastelein, J. J. P., Olsson, A. G., ... Through Aggressive Lipid Lowering Study Group, I. D. I. E. P. (2009). Adherence-adjusted efficacy with intensive versus standard statin therapy in patients with acute myocardial infarction in the IDEAL study. European Journal of Cardiovascular Prevention and Rehabilitation, 16(3), 315-20. https://doi.org/10.1097/HJR.0b013e32832130f5
Holme, Ingar ; Szarek, Michael ; Cater, Nilo B ; Faergeman, Ole ; Kastelein, John J P ; Olsson, Anders G ; Tikkanen, Matti J ; Larsen, Mogens Lytken ; Lindahl, Christina ; Pedersen, Terje R ; Through Aggressive Lipid Lowering Study Group, Incremental Decrease in End Points. / Adherence-adjusted efficacy with intensive versus standard statin therapy in patients with acute myocardial infarction in the IDEAL study. In: European Journal of Cardiovascular Prevention and Rehabilitation. 2009 ; Vol. 16, No. 3. pp. 315-20.
@article{c4f13bb0881811debe4e000ea68e967b,
title = "Adherence-adjusted efficacy with intensive versus standard statin therapy in patients with acute myocardial infarction in the IDEAL study",
abstract = "BACKGROUND: The Incremental Decrease in End Points through Aggressive Lipid Lowering trial showed that the primary endpoint major coronary event was reduced by 11{\%} (0.78-1.01) using atorvastatin 80 mg versus simvastatin 20-40 mg in patients with coronary heart disease (P=0.07). Adherence was high in both treatment groups but significantly higher in patients treated with simvastatin. DESIGN: The Incremental Decrease in End Points through Aggressive Lipid Lowering was a prescription trial with a prospective randomized open label endpoint evaluation. METHODS AND RESULTS: Adherence was calculated as exposure time on prescribed drugs divided by total follow-up time until death or end of follow-up and was a potential confounder. Adjusting for categorical adherence below or above 80{\%} by two methods revealed that the relative risk reduction of the primary endpoint was more in the region of 15{\%} (P=0.02) than 11{\%} as found unadjusted. Censoring at the first occurrence of a cardiovascular event rather than at death increased this estimate to 17{\%} (P=0.02). Noncardiovascular mortality was reduced on atorvastatin treatment by 21{\%} (1-37{\%}) after adjustment for adherence, whereas such reduction was not observed for cardiovascular mortality. CONCLUSION: This study found that the difference in adherence between treatment groups may have underestimated the true effect of the treatment differential. Usage of prospective randomized open label endpoint evaluation design should be carefully considered when well-known treatments are compared with rather new ones and especially in segments where patients could be more vulnerable, as in the elderly. Nonadherers in a clinical trial may be at especially high risk of fatal and nonfatal endpoints from various diseases and should be carefully monitored.",
author = "Ingar Holme and Michael Szarek and Cater, {Nilo B} and Ole Faergeman and Kastelein, {John J P} and Olsson, {Anders G} and Tikkanen, {Matti J} and Larsen, {Mogens Lytken} and Christina Lindahl and Pedersen, {Terje R} and {Through Aggressive Lipid Lowering Study Group}, {Incremental Decrease in End Points}",
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Holme, I, Szarek, M, Cater, NB, Faergeman, O, Kastelein, JJP, Olsson, AG, Tikkanen, MJ, Larsen, ML, Lindahl, C, Pedersen, TR & Through Aggressive Lipid Lowering Study Group, IDIEP 2009, 'Adherence-adjusted efficacy with intensive versus standard statin therapy in patients with acute myocardial infarction in the IDEAL study', European Journal of Cardiovascular Prevention and Rehabilitation, vol. 16, no. 3, pp. 315-20. https://doi.org/10.1097/HJR.0b013e32832130f5

Adherence-adjusted efficacy with intensive versus standard statin therapy in patients with acute myocardial infarction in the IDEAL study. / Holme, Ingar; Szarek, Michael; Cater, Nilo B; Faergeman, Ole; Kastelein, John J P; Olsson, Anders G; Tikkanen, Matti J; Larsen, Mogens Lytken; Lindahl, Christina; Pedersen, Terje R; Through Aggressive Lipid Lowering Study Group, Incremental Decrease in End Points.

In: European Journal of Cardiovascular Prevention and Rehabilitation, Vol. 16, No. 3, 01.06.2009, p. 315-20.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Adherence-adjusted efficacy with intensive versus standard statin therapy in patients with acute myocardial infarction in the IDEAL study

AU - Holme, Ingar

AU - Szarek, Michael

AU - Cater, Nilo B

AU - Faergeman, Ole

AU - Kastelein, John J P

AU - Olsson, Anders G

AU - Tikkanen, Matti J

AU - Larsen, Mogens Lytken

AU - Lindahl, Christina

AU - Pedersen, Terje R

AU - Through Aggressive Lipid Lowering Study Group, Incremental Decrease in End Points

PY - 2009/6/1

Y1 - 2009/6/1

N2 - BACKGROUND: The Incremental Decrease in End Points through Aggressive Lipid Lowering trial showed that the primary endpoint major coronary event was reduced by 11% (0.78-1.01) using atorvastatin 80 mg versus simvastatin 20-40 mg in patients with coronary heart disease (P=0.07). Adherence was high in both treatment groups but significantly higher in patients treated with simvastatin. DESIGN: The Incremental Decrease in End Points through Aggressive Lipid Lowering was a prescription trial with a prospective randomized open label endpoint evaluation. METHODS AND RESULTS: Adherence was calculated as exposure time on prescribed drugs divided by total follow-up time until death or end of follow-up and was a potential confounder. Adjusting for categorical adherence below or above 80% by two methods revealed that the relative risk reduction of the primary endpoint was more in the region of 15% (P=0.02) than 11% as found unadjusted. Censoring at the first occurrence of a cardiovascular event rather than at death increased this estimate to 17% (P=0.02). Noncardiovascular mortality was reduced on atorvastatin treatment by 21% (1-37%) after adjustment for adherence, whereas such reduction was not observed for cardiovascular mortality. CONCLUSION: This study found that the difference in adherence between treatment groups may have underestimated the true effect of the treatment differential. Usage of prospective randomized open label endpoint evaluation design should be carefully considered when well-known treatments are compared with rather new ones and especially in segments where patients could be more vulnerable, as in the elderly. Nonadherers in a clinical trial may be at especially high risk of fatal and nonfatal endpoints from various diseases and should be carefully monitored.

AB - BACKGROUND: The Incremental Decrease in End Points through Aggressive Lipid Lowering trial showed that the primary endpoint major coronary event was reduced by 11% (0.78-1.01) using atorvastatin 80 mg versus simvastatin 20-40 mg in patients with coronary heart disease (P=0.07). Adherence was high in both treatment groups but significantly higher in patients treated with simvastatin. DESIGN: The Incremental Decrease in End Points through Aggressive Lipid Lowering was a prescription trial with a prospective randomized open label endpoint evaluation. METHODS AND RESULTS: Adherence was calculated as exposure time on prescribed drugs divided by total follow-up time until death or end of follow-up and was a potential confounder. Adjusting for categorical adherence below or above 80% by two methods revealed that the relative risk reduction of the primary endpoint was more in the region of 15% (P=0.02) than 11% as found unadjusted. Censoring at the first occurrence of a cardiovascular event rather than at death increased this estimate to 17% (P=0.02). Noncardiovascular mortality was reduced on atorvastatin treatment by 21% (1-37%) after adjustment for adherence, whereas such reduction was not observed for cardiovascular mortality. CONCLUSION: This study found that the difference in adherence between treatment groups may have underestimated the true effect of the treatment differential. Usage of prospective randomized open label endpoint evaluation design should be carefully considered when well-known treatments are compared with rather new ones and especially in segments where patients could be more vulnerable, as in the elderly. Nonadherers in a clinical trial may be at especially high risk of fatal and nonfatal endpoints from various diseases and should be carefully monitored.

U2 - 10.1097/HJR.0b013e32832130f5

DO - 10.1097/HJR.0b013e32832130f5

M3 - Journal article

VL - 16

SP - 315

EP - 320

JO - European Journal of Preventive Cardiology

JF - European Journal of Preventive Cardiology

SN - 2047-4873

IS - 3

ER -