Ticagrelor tied to acute improvement in endothelial function

By Marilynn Larkin

NEW YORK (Reuters Health) - Short-term use of ticagrelor is associated with improved microvascular endothelial function but has no effect on arterial stiffness, researchers in Canada say.

Impaired endothelial function is associated with an increased risk of cardiovascular events, whereas use of ticagrelor is associated with reduced risk. To better understand these associations, Dr. Shahar Lavi of Western University in London, Ontario, and colleagues assessed endothelial function and arterial stiffness before and after a dose of a ticagrelor. Assessments were timed to reflect the drug’s peak (two hours after administration) and trough (12 hours after the last dose) concentrations.

As reported online July 26 in JAMA Cardiology, the three-week study included 45 adults (41 men and four women) with a mean age of 64. It was funded by AstraZeneca, which markets ticagrelor as Brilinta.

Participants had abnormal endothelial function, defined as a reactive hyperemia index (RHI) of less than 2.0, and at least two cardiovascular risk factors: 27% had diabetes, 76% had dyslipidemia, and 64% had hypertension. All but one were taking aspirin; 84% were taking a statin, 76% a beta-blocker, or both.

After a dose of ticagrelor, the RHI improved at peak levels (mean, 2.02) but not at trough levels (mean, 1.74).

“Considering the twice-daily drug administration, endothelial function may be improved during the dosing cycle of ticagrelor,” the authors suggest. “However, this effect is not sustained for the duration of the 12 hours between drug dosing times and is maintained only while patients continue taking the drug.”

Ticagrelor had no effect on arterial stiffness, as determined by the normalized augmentation index.

Summing up, Dr. Lavi told Reuters Health, “Ticagrelor use has been associated with improved cardiovascular outcomes in patients with established coronary artery disease. Our study demonstrates that administration of ticagrelor to (these) patients was associated with acute improvement in endothelial function.”

“Taken together,” he said by email, “it is possible that some of the benefits observed with ticagrelor are related to its effect on vascular function.”

The clinical impact of short-term improvement in endothelial function “is unknown,” he noted. “However, it is likely that while patients are still on ticagrelor, improvement is maintained. This may be important, as endothelial function has been shown to be associated with clinical outcomes.

Dr. Ravi Dave, director of interventional cardiology at UCLA Medical Center, Santa Monica, told Reuters Health, “This is a nice study…in a small group of patients with known atherosclerotic coronary artery disease, (but) larger studies need to be done in the field.”

The benefit seen in the study “could be clinically meaningful,” he said by email, “since the patients requiring ticagrelor have significant coronary artery disease and need twice-a-day dosing.”

SOURCE: http://bit.ly/2wpAHfu

JAMA Cardiol 2017.

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