Neutral atherosclerosis trial highlights effectiveness of optimal medical therapy

By Eleanor McDermid

Salsalate has no greater effect than placebo on the progression of coronary artery plaque, show the findings of the randomised TINSAL-CVD trial.

However, Allison Goldfine (Joslin Diabetes Center, Boston, Massachusetts, USA) and co-researchers say that "[w]e did not anticipate and did not observe salsalate inducing regression of established lesions."

And patients given placebo did not actually experience noncalcified coronary artery plaque progression, measured on multidetector computed tomographic angiography, during 30 months of treatment. Virtually all patients in both groups were taking a statin, with most also taking aspirin and antihypertensive medication.

"The ability to halt atherosclerotic progression with current therapies may underlie falling cardiovascular event rates seen in cardiovascular outcome trials and nationally", write the researchers in JAMA Cardiology.

In a linked commentary, Paul Ridker (Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA) agrees that the finding "represents an important reality of current cardiovascular care."

Neither the 127 patients taking salsalate 3.5 g/day nor the 124 taking placebo had a significant change in average total noncalcified plaque volume, or the fatty or fibrous components. The patients were an average age of 60.8 years at baseline, 94% were male and White, and all had stable, established coronary artery disease. Both treatment groups had an increase in calcified plaque volume and total coronary calcium score, but with no difference between them. Ridker notes that increased calcification is a known effect of statin treatment.

Salsalate is an established anti-inflammatory agent, which is routinely used to combat pain in arthritis patients. Ridker says that, given its low cost, "reliably understanding its effects on the vasculature remains a highly important topic", with the current study being a significant contribution.

The use of salsalate in TINSAL-CVD (Targeting Inflammation Using Salsalate in Cardiovascular Disease) was associated with lower neutrophil and lymphocyte counts than placebo use, but it had no effect on C-reactive protein levels - an anti-inflammatory action that Ridker says is "virtually opposite to that of statins".

He observes that "the underlying mechanisms for specific anti-inflammatory agents matter and [...] we cannot easily judge one by another."

Ridker concludes that TINSAL-CVD is an "informative neutral trial that deserves our attention". He and the researchers both note that salsalate might have different effects in patients with early atherosclerosis.

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JAMA Cardiol 2016; Advance online publication


The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
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