Warfarin Tied to Progressive Coronary Artery Calcification

By Marilynn Larkin

NEW YORK (Reuters Health) – Warfarin use is independently associated with calcific effects on coronary arteries, regardless of changes in atheroma volume, concomitant statin use or renal function, researchers say.

“Although in recent times we’ve seen a splurge in the number of newer oral anticoagulants on the market, warfarin still remains the most commonly prescribed oral anticoagulant to date for treating a range of disorders,” Dr. Rishi Puri of the Quebec Heart and Lung Institute at Laval Hospital told Reuters Health.

“However, several lines of investigation . . . highlight warfarin’s pro-calcific effects,” he said by email. While other studies show a significant association between warfarin use and arterial calcification at a single time point, “our study was unique in that serial coronary intravascular ultrasound was employed.”

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In a post hoc analysis of eight prospective randomized trials, Dr. Puri and colleagues compared serial changes in coronary percent atheroma volume (PAV) and calcium index (CaI) in matched arterial segments of patients treated with and without warfarin, as well as other cardiovascular-related medications.

As reported online July 19 in JACC: Cardiovascular Imaging, 171 patients (mean age 58, 73% men) were treated with warfarin for 18 to 24 months and 4,129 were not; 73% of the study population received statins prior to the study and 97% received concomitant statins.

A propensity score weighting method was applied to the findings to account for significant differences in baseline characteristics between the two groups. Patients in the warfarin-treated group were older, more likely to be men, had a higher body mass index and a higher incidence of prior stroke, atrial fibrillation, and aspirin use.

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Similarly, given the large difference in sample size between the warfarin and no-warfarin group, a sensitivity analysis was performed on the CaI data.

Participants had an overall 0.41 increase in PAV (p=0.001 compared with baseline) and an overall 0.04 increase in CaI (p<0.001 compared with baseline) during the study period. After adjustment, no significant difference in annualized PAV was found with (0.33) or without (0.25) warfarin treatment (p=0.17).

By contrast, a significantly greater annualized increase in CaI was seen in warfarin-treated (median 0.03) compared with nonwarfarin-treated patients (median 0.02, p<0.001).

The sensitivity analysis, which evaluated a 1:1 matched cohort with 164 patients per group, also found significantly greater annualized changes in CaI in warfarin-treated compared with non-warfarin treated patients.

In a multivariate model, warfarin was independently associated with increasing CaI (odds ratio, 1.16).

Summing up, Dr. Puri said, “Irrespective of the degree of plaque present at baseline and its change, and what other medical therapies were concomitantly prescribed - including statins, which we know stabilize lipid-laden arteries by inducing plaque regression and corresponding fibrosis and calcification - the use of warfarin, over an average time period of just 18-24 months, was an independent predictor of coronary plaque calcification.”

“We don’t know whether these pro-calcific effects of warfarin are actually harmful over the longer term by promoting a more ‘vulnerable’ plaque phenotype,” he noted. “We’ve learned that not all calcium is the same when it comes to human coronary arteries, given the beneficial effects of statins in regressing plaque by removing lipid from the arterial wall while inducing calcification.”

“Our findings are especially intriguing,” he added, “given the increasing choice that physicians now have in terms of anticoagulant options, which are often prescribed for many years, and for some, representing a lifelong therapy.”

“Further research needs to be undertaken evaluating the effects of the newer oral anticoagulants on the arterial vasculature,” Dr. Puri concluded. “If and until we know more about the clinical implications of our findings, physicians should continue to prescribe warfarin according to the clinical indication at hand.”

Editorialist Dr. Chris Reutelingsperger of the Cardiovascular Research Institute Maastricht, the Netherlands, told Reuters Health, “Clinicians should be aware of this potential side effect of warfarin so they can tailor their therapeutic decision making more precisely.”

“These insights also underpin how important it is to comprehend fully the dynamics and pathological consequences of vascular calcification,” he said by email. “The awareness that its incidence and severity increase with the aging population should create a sense of urgency for better understanding of vascular calcification.”

SOURCE: https://bit.ly/2uq9iM5 and https://bit.ly/2gXbXbH

JACC: Cardiovasc Imaging 2017.

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