Differences in cardiovascular event rates between atorvastatin and simvastatin among new users: managed-care experience

ABSTRACT

Objective: Recent clinical trials and observational studies have suggested that reduction in low-density lipoprotein cholesterol (LDL-C) does not account for all differences among statins’ effects on cardiovascular (CV) events, but that these effects may vary with time. Using a large US managed-care claims data set for 2002–2005, we assessed whether a difference in the rate of inpatient CV event rates could be observed between new atorvastatin and simvastatin users taking doses with comparable LDL-C-lowering potency, when prior risk factors are controlled and varying observation periods are employed.

Research design and methods: Eligible patients had a 6-month period of no statin use prior to the initial statin prescription, an initial statin dosage of either 20 or 40 mg of simvastatin or 10 or 20 mg of atorvastatin (the most commonly used doses of both drugs), a 0 to 3-month ‘qualifying period’ after the first prescription to allow for varying minimum lengths of statin use, and no statin switches. In the primary analysis, patients were observed until an event or significant non-adherence occurred, up to 3.5 years; in secondary analyses, maximum 3-month, 6-month and 1-year observation periods were used. The primary endpoint was the first inpatient admission due to a CV event after the end of the qualifying period; multivariate Cox regression analysis controlled for a variety of demographic and CV risk characteristics and statin type.

Results: At baseline, simvastatin users had significantly higher observed risk factors and higher subsequent, unadjusted CV event rates. In the primary Cox regression analyses, the CV event hazard rates for atorvastatin ranged from 0.899 (1-month qualifying period, p = 0.027) to 0.936 (3-month qualifying period, p = 0.33) versus simvastatin. Cox-based hazard rates for atorvastatin during 3-month to 1-year observation periods ranged from 0.908 to 0.915 for the 0-day qualifying period and from 0.851 to 0.884 for the 1-month qualifying period cohort (all p < 0.05); rates for the 3-month qualifying period cohort remained non-significant.

Limitations: Since this was not a prospective randomized study, there is the potential for unobserved risk factors to be responsible for some or all of the differences observed.

Conclusions: These results indicate an association between atorvastatin use and lower CV event rates, particularly in the first year of use, when observable risk factor differences are controlled. The implied absolute risk reduction of 2–3 events per 1000 patients per year may be considered clinically significant when viewed relative to major clinical trial results.

Key words: :

• Atorvastatin
• Cardiovascular outcomes
• Managed-care data
• Simvastatin

Acknowledgments

Declaration of interest: Formatting the manuscript for submission was provided by Envision Pharma and funded by Pfizer Inc. No content development support was provided. The authors acknowledge the programming assistance of Gordon Siu and Vivian Zhou (both employees of Pfizer Inc), and the comments and advice of Barbara LePetri, MD, Jack Mardekian, PhD, Michael Gaffney, PhD, Larry Liu, MD, PhD, Andreas Kuznik PhD, and Susan Shiff, PhD (all current or past employees of Pfizer Inc). R.J.W. and S.Z. are employees of Pfizer. R.A.V. has consulted for Pfizer but was not remunerated directly for his involvement in this research.