SAN FRANCISCO – An investigational high-sensitivity troponin T assay provides prognostically meaningful information beyond that yielded by its commercially available sibling test.
The Roche high-sensitivity troponin T assay (hsTnT) excelled over the commercially available Roche Elecys fourth-generation cardiac troponin T test (cTnT) in patients presenting with high-risk non–ST-elevation acute coronary syndrome, Dr. Jonathan Grinstein reported at the annual meeting of the American College of Cardiology.
Dr. Jonathan Grinstein
The investigational test results prove strikingly useful for the subset of patients who test hsTnT-positive and cTnT-negative. In this group, the adjusted odds ratio of 30-day cardiovascular death or new MI is 6.7-fold greater than that of patients who were hsTnT negative and cTnT positive.
"Saying it another way, among this patient subgroup, who represent about 3.5% of our total study population, if one were to analyze the troponins using only the fourth-generation assay, we’d be falsely reassured regarding the likelihood of recurrent cardiovascular events in the next 30 days. In reality, this is a high-risk group," Dr. Grinstein observed.
Both assays were utilized for comparative purposes in 4,160 patients with suspected high-risk non–ST-elevation acute coronary syndrome who participated in two completed and previously reported randomized clinical trials. The studies, known as SEPIA-ACS1 TIMI 42 and EARLY ACS, had as their primary purpose the investigation of novel anticoagulants and optimal timing of administration. All subjects included in this secondary analysis had cardiac ischemia at rest for at least 10 minutes and one or more other high-risk features and underwent dual troponin T testing within 24 hours following symptom onset, explained Dr. Grinstein, a cardiology fellow and TIMI study investigator at Brigham and Women’s Hospital, Boston.
The 99th percentile standard for the investigational hsTnT assay is 14 ng/L. The 3,697 patients in the two clinical trials who met or exceeded this standard had a 30-day incidence of cardiovascular death or new MI of 9.1%, compared with a much more modest rate of 1.9% in the 463 subjects with an hsTnT level below 14 ng/L.
The relationship between hsTnT and 30-day adverse outcome was continuous: The adverse event rate was 1.9% in the 463 patients with an hsTnT below 14 ng/L, 6.4% in 532 subjects with an hsTnT of 14-50 ng/L, 8.6% in 383 patients with a level of 50-100 ng/L, 9.5% in 2,417 patients with an hsTnT of 100-1,500 ng/L, and 11% in the 365 patients with a level in excess of 1,500 ng/L, according to Dr. Grinstein.
Fifteen percent of the subjects with an hsTnT below 14 ng/L had a high TIMI risk score, compared with 36% of those with an hsTnT of 14 ng/L or more.
Overall, two-thirds of the 30-day adverse events were centrally adjudicated acute MIs and one-third were cardiovascular deaths, but the proportion of cardiovascular deaths rose in patients with higher initial hsTnT values.
In the side-by-side analysis including both the hsTnT and fourth-generation cTnT assays, 463 patients had sufficiently low values on both tests that they were categorized as dual negative; their 30-day event rate was 1.9%. Another 378 patients were hsTnT negative but cTnT positive, with an associated 1.3% event rate.
More interesting were the 146 patients who were hsTnT positive and cTnT negative; their event rate was 8.2%. The adjusted odds ratio of 30-day cardiovascular death or new MI in such patients was 6.7-fold greater than in those who were hsTnT negative and fourth-generation positive.
Among the 3,551 subjects with a high-risk score on both assays, the 30-day cardiovascular event rate was 9.1%, he added.
The hsTnT assay, now under Food and Drug Administration review, is widely available in other countries. Compared with commercially available assays in the United States, it provides greatly increased sensitivity in the detection of myocardial necrosis. There have been concerns, however, that this enhanced sensitivity might come at the expense of reduced specificity, leaving the clinical significance of low-level elevations in hsTnT debatable. This study provides reassurance on that score, Dr. Grinstein said.
The SEPIA-ACS1 TIMI 42 trial was sponsored by Sanofi-Aventis. EARLY ACS was sponsored by Schering-Plough. The troponin T assays are manufactured by Roche. Dr. Grinstein reported having no financial conflicts.