In the Journals

TINSAL-CVD: Salsalate fails to reduce progression of noncalcified coronary plaque volume

Adding salsalate to current therapies for CHD does not reduce the progression of noncalcified coronary plaque volume in overweight and obese patients using statins, according to data published in JAMA Cardiology.

Thomas H. Hauser, MD, MPH, from the division of cardiovascular medicine, department of medicine at Beth Israel Deaconess Medical Center in Boston, and colleagues randomly assigned 257 patients (mean age, 61 years; 94% men) to salsalate (n = 129) or placebo (n =128) between September 2008 and July 2012 to determine whether targeting inflammation with salsalate reduced progression of noncalcified coronary artery plaque in patients with stable CHD receiving statins. Plaque progression was assessed by multidetector CT angiography.

Salsalate was administered at 3.5 g daily in two doses (three 500-mg tablets in first dose and four 500-mg tablets in second dose). The primary endpoint was change in volume of noncalcified plaque at end of follow-up compared with baseline.

Targeting inflammation

The researchers were able to evaluate 318 segments in 84 participants in the salsalate group and 343 segments in 89 participants in the placebo group. Hauser and colleagues reported that there was no difference in change in total noncalcified plaque volume (mean difference, –1 mm3; 95% CI, –11 to 9) between the two groups.

In addition, no overall progression in plaque components was observed in either group. Serious adverse events were similar in both groups, but renal events occurred only in the salsalate group. Nonserious adverse events that occurred more often in the salsalate group compared with the placebo group were atrial arrhythmia and tinnitus.

Paul Ridker

Paul M. Ridker

 “It remains unknown if salsalate treatment earlier in disease might reduce initiation or progression of initial lesions. Further evidence is needed to support whether targeting inflammation may be a valuable therapeutic intervention for cardiometabolic complications of obesity,” the researchers wrote.

Neutral studies matter

Paul M. Ridker, MD, MPH, director of the Center for Cardiovascular Disease Prevention and Eugene Braunwald professor of medicine at Brigham and Women’s Hospital, wrote in a related editorial that despite its neutral findings, TINSAL-CVD represents a major step in understanding salsalate’s effects on vasculature and suggested that further research should assess whether initiating salsalate therapy earlier in the disease process would produce different results.

The lack of progression of noncalcified plaque in the placebo group “represents an important reality of current cardiovascular care,” Ridker wrote.

“All participants in TINSAL-CVD were appropriately treated with statin therapy, and these agents have been shown not only to slow atherosclerotic progression overall but also to reverse progression in some patients,” Ridker wrote. by Tracey Romero

Disclosure: Amneal Pharmaceuticals and Caraco Pharmaceutical Laboratories provided salsalate and placebo for the study. Hauser reports receiving personal fees from the Harvard Cardiovascular Research Institute. Please see the full study for a list of the other researchers’ relevant financial disclosures. Ridker reports being listed as a co-inventor on patents held by Brigham and Women’s Hospital relating to the use of inflammatory biomarkers in CVD and diabetes that have been licensed to AstraZeneca and Siemens; and serving as principal investigator and chairman of a trial funded by Novartis.

Adding salsalate to current therapies for CHD does not reduce the progression of noncalcified coronary plaque volume in overweight and obese patients using statins, according to data published in JAMA Cardiology.

Thomas H. Hauser, MD, MPH, from the division of cardiovascular medicine, department of medicine at Beth Israel Deaconess Medical Center in Boston, and colleagues randomly assigned 257 patients (mean age, 61 years; 94% men) to salsalate (n = 129) or placebo (n =128) between September 2008 and July 2012 to determine whether targeting inflammation with salsalate reduced progression of noncalcified coronary artery plaque in patients with stable CHD receiving statins. Plaque progression was assessed by multidetector CT angiography.

Salsalate was administered at 3.5 g daily in two doses (three 500-mg tablets in first dose and four 500-mg tablets in second dose). The primary endpoint was change in volume of noncalcified plaque at end of follow-up compared with baseline.

Targeting inflammation

The researchers were able to evaluate 318 segments in 84 participants in the salsalate group and 343 segments in 89 participants in the placebo group. Hauser and colleagues reported that there was no difference in change in total noncalcified plaque volume (mean difference, –1 mm3; 95% CI, –11 to 9) between the two groups.

In addition, no overall progression in plaque components was observed in either group. Serious adverse events were similar in both groups, but renal events occurred only in the salsalate group. Nonserious adverse events that occurred more often in the salsalate group compared with the placebo group were atrial arrhythmia and tinnitus.

Paul Ridker

Paul M. Ridker

 “It remains unknown if salsalate treatment earlier in disease might reduce initiation or progression of initial lesions. Further evidence is needed to support whether targeting inflammation may be a valuable therapeutic intervention for cardiometabolic complications of obesity,” the researchers wrote.

Neutral studies matter

Paul M. Ridker, MD, MPH, director of the Center for Cardiovascular Disease Prevention and Eugene Braunwald professor of medicine at Brigham and Women’s Hospital, wrote in a related editorial that despite its neutral findings, TINSAL-CVD represents a major step in understanding salsalate’s effects on vasculature and suggested that further research should assess whether initiating salsalate therapy earlier in the disease process would produce different results.

The lack of progression of noncalcified plaque in the placebo group “represents an important reality of current cardiovascular care,” Ridker wrote.

“All participants in TINSAL-CVD were appropriately treated with statin therapy, and these agents have been shown not only to slow atherosclerotic progression overall but also to reverse progression in some patients,” Ridker wrote. by Tracey Romero

Disclosure: Amneal Pharmaceuticals and Caraco Pharmaceutical Laboratories provided salsalate and placebo for the study. Hauser reports receiving personal fees from the Harvard Cardiovascular Research Institute. Please see the full study for a list of the other researchers’ relevant financial disclosures. Ridker reports being listed as a co-inventor on patents held by Brigham and Women’s Hospital relating to the use of inflammatory biomarkers in CVD and diabetes that have been licensed to AstraZeneca and Siemens; and serving as principal investigator and chairman of a trial funded by Novartis.