Jordan Andrews1, Peter J Psaltis1, Ozgur Bayturan2, Mingyuan Shao3, Brian Stegman3, Mohamed Elshazly3, Samir R Kapadia3, E Murat Tuzcu3, Steven E Nissen3, Stephen J Nicholls1, Rishi Puri4. 1. Vascular Research Centre, Heart Health Theme, South Australian Health and Medical Research Institute and School of Medicine, University of Adelaide, Adelaide, Australia. 2. Celal Bayar University School of Medicine, Manisa, Turkey. 3. Cleveland Clinic Coordinating Center for Clinical Research, Cleveland, Ohio. 4. Cleveland Clinic Coordinating Center for Clinical Research, Cleveland, Ohio; Québec Heart and Lung Institute, Québec, Canada; Department of Medicine, University of Adelaide, Adelaide, Australia. Electronic address: rishi_puri@hotmail.com.
Abstract
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.
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.
Authors: Rick H van Gorp; Constance C F M J Baaten; Anxhela Habibi; Armand M G Jaminon; Frederique E C M Peeters; Peter Leenders; Harry J G M C Crijns; Johan W M Heemskerk; Chris P Reutelingsperger; Henri M Spronk; Leon J Schurgers Journal: Eur Heart J Open Date: 2021-08-06
Authors: Pietro Scicchitano; Marco Tucci; Maria Consiglia Bellino; Francesca Cortese; Annagrazia Cecere; Micaela De Palo; Francesco Massari; Pasquale Caldarola; Francesco Silvestris; Marco Matteo Ciccone Journal: Cardiovasc Drugs Ther Date: 2021-06 Impact factor: 3.727