Research published in AACC’s Clinical Chemistry journal shows that a test can identify patients with a history of cardiovascular disease who are at high risk of another heart attack or death and would benefit from treatment with the drug vorapaxar. This study and two others on tests that predict risk of adverse cardiovascular events are featured in the Cardiovascular Disease issue of Clinical Chemistry.
In the U.S. every year, cardiovascular disease leads to 735,000 heart attacks—210,000 of which occur in people who have already had a heart attack. One of the primary ways to prevent recurrent heart attacks is antiplatelet therapy, which stops the formation and growth of clots that block arteries. Vorapaxar is a new, powerful antiplatelet drug developed to improve on the efficacy of standard treatments in this class (such as aspirin). However, although vorapaxar greatly reduces the risk of another heart attack or death, clinical trials have also shown that 4.2 percent of patients on this drug experience the serious side effect of moderate to severe bleeding.
In the study, a team of researchers demonstrated that a high sensitivity cardiac troponin I (hs-cTnI) test can identify patients who are most likely to respond to vorapaxar, which could help to minimize the number of individuals who receive this drug unnecessarily and experience bleeding. Led by David A. Morrow, MD, of Brigham and Women’s Hospital in Boston, Massachusetts, the researchers measured hs-cTnI in 15,833 patients from a vorapaxar clinical trial who had a prior heart attack, stroke, or peripheral arterial disease. Out of this sample group, patients with an hs-cTnI concentration >26 ng/L had a 3-year rate of death, heart attack, or stroke of 18.6 percent, compared with only a 5 percent rate in patients with hs-cTnI levels <1.9 ng/L. The researchers also found that, for the patients at high risk of recurring cardiovascular events (hs-cTnI >26 ng/L), treatment with vorapaxar reduced this risk by 1.86 percent, while in low risk patients (hs-cTnI <1.9 ng/L), vorapaxar only reduced this risk by an additional 0.25 percent.
Overall, only 7.3 percent of the study group fell in the high risk category that benefited significantly from vorapaxar. Although vorapaxar is approved for use in all patients who have had a heart attack, these results indicate that this drug could potentially be more effective if targeted toward the subset of patients who have elevated hs-cTnI results.
“This study quantifies the magnitude of benefit with more potent antithrombotic secondary preventive therapy in patients with increased [hs-cTnI],” said Morrow. “This finding is of particular relevance for novel therapies such as vorapaxar for which the decision to implement additional therapy balances the potential absolute gains versus risk of bleeding, and cost.”
Two other tests in this issue of Clinical Chemistry could also improve treatment for cardiovascular disease by more accurately identifying patients with a history of heart disease who are at risk of death, as well as by predicting which healthy individuals are at risk of developing this condition.
With the first test, researchers from Duke University in Durham, North Carolina, led by Svati H. Shah, MD, found that glycoprotein acetylation (GlycA)—an indicator of systemic inflammation—is strongly associated with mortality in patients with a history of cardiovascular disease. Shah’s team measured GlycA in 7,617 individuals from a cardiac catheterization biorepository. Over a mean time of 7 years, the researchers found that patients with elevated GlycA levels had a 37 percent greater chance of cardiovascular death. Interestingly, they also determined that a rise in GlycA is associated with a reduction in the benefits of high-density lipoprotein (HDL), i.e. the good cholesterol. Individuals in the study with high HDL but low GlycA had a <5 percent chance of death in 5 years. However, patients with both high HDL and GlycA had a 35 percent chance of death in 5 years. These results indicate that a test for GlycA could help healthcare providers to identify heart disease patients who, in spite of high HDL levels, are at risk of death and in need of therapeutic intervention.
With the second test, researchers led by Stephan J.L. Bakker, MD, PhD, of the University Medical Center Groningen in Groningen, Netherlands, show that increased concentrations of N-terminal fragment prosomatostatin (NT-proSST) are associated with an increased risk of cardiovascular disease and death in the general population. The researchers measured blood concentrations of NT-proSST in 8,134 healthy men and women, ages 28-75 years old, from the Prevention of Renal and Vascular End-stage Disease study. After 10.5 years, higher values of NT-proSST were associated with a 22 percent greater risk of developing cardiovascular disease and a 32 percent increased chance of mortality, respectively. A test for NT-proSST could therefore identify healthy individuals who should implement lifestyle changes to prevent the onset of heart disease.
Fred S. Apple, Louise Cullen, G. Michael Felker, Geoffrey Ginsburg, David Morrow. Cardiovascular Disease: Impact of Biomarkers, Proteomics, and Genomics. Clinical Chemistry, 2016; 63 (1): 1 DOI: 10.1373/clinchem.2016.263350