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

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. Eur J Cardiovasc Prev Rehabil 16:315-320 (C) 2009 The European Society of Cardiolog

Congestive heart failure is associated with lipoprotein components in statin-treated patients with coronary heart disease Insights from the Incremental Decrease in End points Through Aggressive Lipid Lowering Trial (IDEAL)

Background: Very few, if any, studies have assessed the ability of apolipoproteins to predict new-onset of congestive heart failure (HF) in statin-treated patients with coronary heart disease (CHD). Aims: To employ the Incremental Decrease in End points Through Aggressive Lipid Lowering Trial (IDEAL) study database to assess the association of on-treatment lipoprotein components with prediction of HF events and to compare their predictive value with that of established risk factors such as hypertension and diabetes. Methods: We used Cox regression models to study the relationships between on-treatment levels of apolipoproteins A1 and B to subsequent HE Chi square information value from the log likelihood was used to compare the predictive value of lipoprotein components with established risk factors of HF. Findings: In the IDEAL study, on-treatment apolipoproteins proved to be associated with the occurrence of new-onset HE Variables related to low-density lipoprotein cholesterol (LDL-C) carried less predictive information than those related to high-density lipoprotein cholesterol (HDL-C), and apoA-1 was the single variable most strongly associated with HF. LDL-C was less predictive than both non-HDL-C (total cholesterol minus HDL-C) and apoB. The ratio of apoB to apoA-1 was most strongly related to HF after adjustment for potential confounders, among which diabetes had a stronger correlation with HF than did hypertension. ApoB/apoA-1 carried approximately 2.2 times more of the statistical information value than that of diabetes. Calculation of the net reclassification improvement index revealed that about 3.7% of the patients had to be reclassified into more correct categories of risk once apoB/apoA-1 was added to the adjustment factors. The reduction in risk by intensive lipid-lowering treatment as compared to usual-dose simvastatin was well predicted by the difference in apoB/apoA-1 on-treatment levels. Interpretation: The on-treatment ratio of apoB/apoA-1 was the strongest predictor of HF in CHD patients of both IDEAL treatment arms combined, mostly driven by the strong association with apoA-1, whereas LDL-C and non-HDL-C were less able to predict HF outcome. The predictive information value contained within apoB/apoA-1 was about 2.2 times more than that of diabetes. Between-treatment group differences in HF were to a significant extent explained by on-treatment differences in apoB/apoA-1, mostly through the changes in apoB. We argue therefore, on-treatment lipoprotein components contribute to the overall future risk of HF in statin-treated patients with CHD. (c) 2009 Published by Elsevier Ireland Lt

Lipoprotein predictors of cardiovascular events in statin-treated patients with coronary heart disease:Insights from the incremental decrease in end-points through aggressive lipid-lowering trial (IDEAL)

BACKGROUND: Few studies have looked into the ability of measurements of apolipoprotein B (apoB) and apolipoprotein A-1 (apoA-1) or apoB/apoA-1 to predict new coronary heart disease (CHD) events in patients with CHD on statin treatment. AIMS: In the IDEAL trial, to compare lipoprotein components to predict CHD events and to what degree differences in those parameters could explain the observed outcome. METHODS: We compared the ability of treatment with atorvastatin 80 mg/day to that of simvastatin 20-40 mg/day to prevent CHD events in patients with CHD and used Cox regression models to study the relationships between on-treatment levels of lipoprotein components to subsequent major coronary events (MCE). FINDINGS: Variables related to low-density lipoprotein cholesterol (LDL-C) carried more predictive information than those related to high-density lipoprotein cholesterol (HDL-C), but LDL-C was less predictive than both non-HDL-C and apoB. The ratio of apoB to apoA-1 was most strongly related to MCE. However, for estimating differences in relative risk reduction between the treatment groups, apoB and non-HDL-C were the strongest predictors. INTERPRETATION: The on-treatment level of apoB/apoA-1 was the strongest predictor of MCE in the pooled patient population, whereas apoB and non-HDL-C were best able to explain the difference in outcome between treatment groups. Measurements of apoB and apoA-1 should be more widely available for routine clinical assessment