Antidepressant reduces clotting factors after heart attack

American Heart Association
Tuesday, 12 August 2003

Treating depression in heart attack or chest pain patients reduces the chance of forming dangerous blood clots that can lead to a new heart attack, researchers report in today's rapid access issue of Circulation: Journal of the American Heart Association.

"This study is the first to show that the antidepressant sertraline inhibits platelet endothelial markers more than placebo in depressed patients after coronary events," says lead author Victor L. Serebruany, M.D., Ph.D. assistant professor of medicine at Johns Hopkins University and laboratory director for Sinai Thrombosis Center at Baltimore.

In depressed patients, platelets in the blood are stickier and more likely to form clots. Previous studies have shown that depressed patients are more likely than non-depressed patients to die of a subsequent cardiac problem after being hospitalized for a heart attack. After a heart attack, 20 percent to 25 percent of patients develop major depression, but it often goes untreated, researchers say.

"Physicians became reluctant to prescribe antidepressants after indications that some antidepressants increased the risk of dying or serious cardiovascular outcomes," says Christopher M. O'Connor, M.D., professor of medicine, chief of clinical pharmacology, and director of the heart failure program at the Duke University Medical Center in Durham, N.C.

However, a newer class of antidepressants called selective serotonin reuptake inhibitors (SSRIs), doesn't carry the same risk. SSRIs block the reuptake of the chemical serotonin into nerve cells and also block serotonin reuptake into platelets.

Last year, researchers from the multicenter study Sertraline Anti-Depressant Heart Attack Randomized Trial (SADHART) reported that the SSRI sertraline (Zoloft) was safe to use in depressed cardiac patients and was associated with fewer deaths in the six months following hospitalization for unstable angina or heart attack.

The new analysis involved a subset of 64 men and women, average age 57, enrolled in SADHART. Each was diagnosed with major clinical depression while hospitalized; about half had experienced previous episodes of major depression. Almost all were receiving other medications such as aspirin, warfarin, coumadin, clopidogrel, ticlopidine or dipyridamole to reduce clotting and the risk of a new heart attack.

"To prevent clotting after a coronary event, it is routine for patients to be treated with anti-coagulants and anti-platelet drugs. This study looked at whether adding sertraline to these standard treatments provided an additional benefit," says O'Connor, the cardiovascular principal investigator of SADHART.

Researchers measured eight factors related to blood clotting: platelet factor 4 (PF4), â-thromboglobulin (âTG), platelet/endothelial cell adhesion molecule 1 (PECAM-1), P-selectin, vascular cell adhesion molecule-1, E-selectin, thromboxane (TxB2) and prostacycline (6-keto-PGF1a). All are released into the bloodstream as platelets aggregate and are indirect markers of platelet activity and blood-vessel constriction.

Researchers performed the laboratory studies at baseline and again at six and 16 weeks after starting treatment with 50-200 mg/day of sertraline (typical doses for treating depression) or placebo.

Of the 16 measurements taken after treatment had begun, 12 indicated significantly reduced platelet activity in the patients taking sertraline, compared to only eight of 16 in the placebo group. Adding sertraline to other anti-clotting agents did not increase the risk of bleeding, Serebruany notes.

"Down the road, the big question is whether sertraline might be a beneficial cardiovascular drug, used not just to treat cardiac patients with major depression but to reduce cardiac risk in those with mild depression or no depression," O'Connor says.

The next step is a larger study to confirm these results, he adds. A study is already underway using sertraline in patients with heart failure.

Other co-authors are Alexander H. Glassman, M.D.; Alex I. Malinin, M.D.; Charles B. Nemeroff, M.D., Ph.D.; Dominique L. Musselman, M.D.; Louis T. van Zyl, M.D.; Mitchell S. Finkel, M.D.; K. Ranga R. Krishnan, M.D.; Michael Gaffney, Ph.D.; Wilma Harrison, M.D., and Robert M. Califf, M.D.

For more information, or to contact American Heart Association, see their website at: www.americanheart.org