Polymorphism in KIF6 Gene and Benefit From Statins After Acute Coronary SyndromesResults From the PROVE IT-TIMI 22 Study
Olga A. Iakoubova, MD, PhD*,*,
Marc S. Sabatine, MD, MPH, FACC ,
Charles M. Rowland, MS*,
Carmen H. Tong, BS*,
Joseph J. Catanese, BS*,
Koustubh Ranade, PhD ,
Katy L. Simonsen, PhD,
Todd G. Kirchgessner, PhD,
Christopher P. Cannon, MD, FACC,
James J. Devlin, PhD* and
Eugene Braunwald, MD, MACC
* Celera, Alameda, California
TIMI Study Group, Cardiovascular Division, Brigham & Women’s Hospital, Harvard Medical School, Boston, Massachusetts
Pharmaceutical Research Institute, Bristol-Myers Squibb, Princeton, New Jersey.
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Figure 1 Primary End Point According to Treatment and KIF6 719Arg Carrier Status
Kaplan-Meier estimates of the cumulative incidence of death or major cardiovascular events in the high-dose atorvastatin and standard-dose pravastatin treatment groups: (A) among carriers of the KIF6 719Arg variant; (B) among noncarriers of the KIF6 719Arg variant. The log-rank p values are based on 2 years of follow-up. The unadjusted hazard ratios (HR) and 95% confidence intervals (CI) are based on 30 months of follow-up.
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Figure 2 Time to Benefit According to KIF6 719Arg Carrier Status
Hazard ratio for death or major cardiovascular events at 30, 90, and 180 days, 2 years, and at the end of follow-up. High-dose atorvastatin therapy was compared with standard-dose pravastatin therapy according to KIF6 719Arg carrier status. The cumulative incidence of death or major cardiovascular events was estimated by the Kaplan-Meier method. CI = confidence interval.
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Figure 3 Effect of Statin Therapy According to KIF6 Trp719Arg in 3 Studies
Effect of statin therapy on fatal coronary heart disease or nonfatal myocardial infarction in the CARE trial, coronary heart disease in the WOSCOPS trial, and death or major cardiovascular events in the PROVE IT-TIMI 22 trial according to KIF6 719Arg carrier status. In both the CARE trial, a secondary prevention study, and the WOSCOPS trial, a primary prevention study, the effect of pravastatin (40 mg) was compared with placebo. In the PROVE IT-TIMI 22 trial, a secondary prevention study, the effect of atorvastatin (80 mg) was compared with pravastatin (40 mg). We used Cox proportional hazards models in the CARE and PROVE IT-TIMI 22 trials and conditional logistic regression in the nested case-control study of the WOSCOPS trial. CI = confidence interval.
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