Author + information
- Received November 9, 2016
- Revision received April 19, 2017
- Accepted April 20, 2017
- Published online September 3, 2018.
- Jordan Andrews, BSa,
- Peter J. Psaltis, MBBS, PhDa,
- Ozgur Bayturan, MDb,
- Mingyuan Shao, MSc,
- Brian Stegman, MDc,
- Mohamed Elshazly, MDc,
- Samir R. Kapadia, MDc,
- E. Murat Tuzcu, MDc,
- Steven E. Nissen, MDc,
- Stephen J. Nicholls, MBBS, PhDa and
- Rishi Puri, MBBS, PhDc,d,e,∗ ()
- aVascular Research Centre, Heart Health Theme, South Australian Health and Medical Research Institute and School of Medicine, University of Adelaide, Adelaide, Australia
- bCelal Bayar University School of Medicine, Manisa, Turkey
- cCleveland Clinic Coordinating Center for Clinical Research, Cleveland, Ohio
- dQuébec Heart and Lung Institute, Québec, Canada
- eDepartment of Medicine, University of Adelaide, Adelaide, Australia
- ↵∗Address for correspondence:
Dr. Rishi Puri, Québec Heart and Lung Institute, Hôpital Laval, 2725 chemin Sainte-Foy, Québec QC G1V 4G5, Canada.
Objectives This study compared serial changes in coronary percent atheroma volume (PAV) and calcium index (CaI) in patients with coronary artery disease who were treated with and without warfarin.
Background Warfarin blocks the synthesis and activity of matrix Gla protein, a vitamin K–dependent inhibitor of arterial calcification. The longitudinal impact of warfarin on serial coronary artery calcification in vivo in humans is unknown.
Methods In a post hoc patient-level analysis of 8 prospective randomized trials using serial coronary intravascular ultrasound examinations, this study compared changes in PAV and CaI in matched arterial segments in patients with coronary artery disease who were treated with (n = 171) and without (n = 4,129) warfarin during an 18- to 24-month period.
Results Patients (mean age 57.9 ± 9.2 years; male 73%; prior and concomitant 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statin) use, 73% and 97%, respectively) demonstrated overall increases in PAV of 0.41 ± 0.07% (p = 0.001 compared with baseline) and in CaI (median) of 0.04 (interquartile range [IQR]: 0.00 to 0.11; p < 0.001 compared with baseline). Following propensity-weighted adjustment for clinical trial and a range of clinical, ultrasonic, and laboratory parameters, there was no significant difference in the annualized change in PAV in the presence and absence of warfarin treatment (0.33 ± 0.05% vs. 0.25 ± 0.05%; p = 0.17). A significantly greater annualized increase in CaI was observed in warfarin-treated compared with non–warfarin-treated patients (median 0.03; IQR: 0.0 to 0.08 vs. median 0.02; IQR: 0.0 to 0.06; p < 0.001). In a sensitivity analysis evaluating a 1:1 matched cohort (n = 164 per group), significantly greater annualized changes in CaI were also observed in warfarin-treated compared with non–warfarin-treated patients. In a multivariate model, warfarin was independently associated with an increasing CaI (odds ratio: 1.16; 95% confidence interval: 1.05 to 1.28; p = 0.003).
Conclusions Warfarin therapy is associated with progressive coronary atheroma calcification independent of changes in atheroma volume. The impact of these changes on plaque stability and cardiovascular outcomes requires further investigation.
Dr. Nicholls has received research grants from Anthera, AstraZeneca, Cerenis, Eli Lilly, InfraReDx, Roche, Resverlogix, Novartis, Amgen, LipoScience, Sanofi-Regeneron, and The Medicines Company; is on the Speakers Bureau of AstraZeneca, Pfizer, Merck Schering-Plough, and Takeda; and is a consultant for and on the advisory board of AstraZeneca, Abbott, AtheroNova, Esperion, Amgen, Novartis, Omthera, CSL Behring, Boehringer Ingelheim, Pfizer, Merck Schering-Plough, Takeda, Roche, Novo Nordisk, LipoScience, and Anthera. Dr. Nissen has received research grants from Pfizer, AstraZeneca, Novartis, Roche, Daiichi-Sankyo, Takeda, Sanofi-Aventis, Resverlogix, and Eli Lilly; and is a consultant for and on the advisory board of many pharmaceutical companies, but requires them to donate all honoraria or consulting fees directly to charity so that he receives neither income nor a tax deduction. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received November 9, 2016.
- Revision received April 19, 2017.
- Accepted April 20, 2017.
- 2018 American College of Cardiology Foundation
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