Author + information
- Received April 30, 2009
- Revision received August 17, 2009
- Accepted August 25, 2009
- Published online December 15, 2009.
- Matti J. Tikkanen, MD, PhD*,* (, )
- Michael Szarek, PhD†,
- Rana Fayyad, PhD†,
- Ingar Holme, PhD‡,
- Nilo B. Cater, MD†,
- Ole Faergeman, MD, DMSc§,
- John J.P. Kastelein, MD, PhD∥,
- Anders G. Olsson, MD, PhD#,
- Mogens Lytken Larsen, MD, DMSc§,
- Christina Lindahl, MD**,
- Terje R. Pedersen, MD, PhD‡,
- IDEAL Investigators
- ↵*Reprint requests and correspondence:
Dr. Matti J. Tikkanen, Department of Medicine, Division of Cardiology, Helsinki University Central Hospital, 00290 Helsinki, Finland
Objectives This post-hoc analysis of the IDEAL (Incremental Decrease in End Points Through Aggressive Lipid Lowering) trial was designed to assess the comparative treatment efficacy of high-dose atorvastatin and usual-dose simvastatin for the prevention of events subsequent to the first event, using the Wei, Lin, and Weissfeld method.
Background Time-to-first-event analysis of data is frequently utilized to provide efficacy outcome information in coronary heart disease prevention trials. However, during the course of such long-term trials, a large number of events occur subsequent to the first event, the analysis of which will be precluded by this approach.
Methods The Wei, Lin, and Weissfeld method allows the analysis of repeated occurrence of events of the same type or of entirely different natures. It regards the recurrence times as multivariate event (failure) times, and models the marginal (individual) distribution for each event with the Cox proportional hazards model.
Results In the IDEAL trial, compared with patients taking simvastatin 20 to 40 mg daily, patients receiving atorvastatin 80 mg daily had their relative risk of a first cardiovascular event reduced by 17% (p < 0.0001), of a second by 24% (p < 0.0001), of a third by 19% (p = 0.035), of a fourth by 24% (p = 0.058), and of a fifth by 28% (p = 0.117).
Conclusions Our results indicate that intensive statin therapy continues to be more effective than standard statin therapy, even beyond the first event, and suggest that clinicians should not hesitate to prescribe high-dose statin therapy for patients experiencing multiple recurrent cardiovascular events.
Continuing Medical Education (CME) is available for this article.
This study was funded by Pfizer, Inc., New York, New York. Dr. Tikkanen receives speaking and consulting honoraria from Pfizer, Merck, Orion, and AstraZeneca, and a research grant from Pfizer and Takeda. Dr. Holme receives Steering Committee honoraria from Pfizer. Dr. Faergeman receives honoraria and research grants from Pfizer, Merck, Sharpe & Dohme, and AstraZeneca. Dr. Kastelein receives consulting and lecture fees from Pfizer, AstraZeneca, Merck, and Schering-Plough. Dr. Olsson has consulting agreements with AstraZeneca, KaroBio, Merck, Sanofi-Aventis, Pfizer, and Roche. Dr. Larsen receives consultancy fees and research grants from Pfizer, Merck, Sharpe & Dohme, and AstraZeneca. Dr. Pedersen receives consultation fees and honoraria from Pfizer, Merck, Merck AG, and AstraZeneca, and research grants and Steering Committee fees from Pfizer and Merck. Drs. Cater and Fayyad are employees of Pfizer, Inc. Drs. Szarek and Lindahl were employees of Pfizer at the time of the data analysis and drafting of the paper. Dr. Szarek is currently an employee at ImClone Systems LLC.
- Received April 30, 2009.
- Revision received August 17, 2009.
- Accepted August 25, 2009.
- American College of Cardiology Foundation