According to Serebruany and colleagues, more than one million individuals in the US experience ACS each year, with more than 20% of these patients also suffering from depression. Major depression in these patients, write the authors, results in a threefold increase in the risk of morbidity and mortality from CV disease. However, before the primary results from SADHART, little data existed on the safety and efficacy of SSRIs used in the treatment of depressed post-ACS patients.

In the original SADHART study, investigators found trends toward reductions in mortality and morbidity in sertraline-treated patients, although the results did not achieve statistical significance. However, taking these results with previous epidemiologic studies suggesting mortality and morbidity benefits in sertraline-treated patients, Serebruany and colleagues sought to elucidate the possible mechanisms involved in the cardiovascular benefit with the SSRI.

To do so, they analyzed platelet and endothelial activity in a subset of 64 post-ACS patients (mean age 57 years) from the original SADHART study. The subjects included in the substudy were all diagnosed with major clinical depression while hospitalized, with approximately half having experienced previous episodes of major depression. The patients were randomized to placebo or the SSRI sertraline in flexible dosages ranging from 50 mg/day to 200 mg/day for 24 weeks. Nearly all were receiving antiplatelet regimens, including aspirin and clopidogrel.

Eight platelet/endothelial biomarkers were measured in blood samples at baseline, week 6, and week 16 of the double-blind treatment period.

"The changes from baseline were statistically significant in 12 of 16 observations in the sertraline treatment group compared with only eight of 16 observations in the placebo treatment group," write Serebruany and colleagues.

At individual time points, treatment with sertraline was superior to placebo at weeks six and 16 for the biomarker TG and at 16 weeks for a second biomarker, P-selectin. The changes in the defined biomarkers were numerically greater in patients treated with sertraline, according to the investigators, noting the difference was significant in four of the 14 observations. Across the entire treatment period, statistically greater reductions in TG and a third biomarker, E-selectin, were observed in patients treated with sertraline compared with the placebo study arm.

"Based on our data, it will be very difficult if not impossible to identify a single biomarker affected by sertraline," write the investigators. "Most likely, sertraline initially targets platelet serotonin receptors and indirectly affects major platelet functions, such as adhesion, aggregation, secretion, or receptor expression."

Before the emergence of SSRIs, treating depression in patients with unstable angina or prior MI placed physicians in a precarious position.3 The older tricyclic antidepressants are known to possess serious CV side effects and are contraindicated in many patients with ACS.

The new SSRIs, however, are now well-established medications with little evidence of cardiotoxicity, said Serebruany. The safety and efficacy of the class in these patients, in conjunction with reduced platelet activity, should encourage more physicians to treat mental illness in ACS patients.