Gender Gap for ACS Care Persists Even With Better Troponin Test

Putting sex-specific thresholds of high-sensitivity cardiac troponin I (hs-cTnI) in practice led to more findings of myocardial injury in women with suspected acute coronary syndrome (ACS), but disparities in their subsequent care remained, according to a pre-specified analysis of the High-STEACS trial.

For the diagnosis of MI in people presenting to the emergency department, the switch from a uniform threshold on a standard cardiac troponin I assay to sex-specific cutoffs on hs-cTnI testing resulted in the finding of myocardial injury jumping from 16% to 22% in women, compared with a smaller increase, from 20% to 21%, among men, reported Nicholas Mills, MD, of the British Heart Foundation and University Centre for Cardiovascular Science at University of Edinburgh, Scotland, and colleagues, in the Journal of the American College of Cardiology.

In the end, implementation of sex-specific hs-cTnI thresholds to guide clinical care -- 16 ng/L in women and 34 ng/L in men -- resulted in no improvement in rates of recurrent MI or cardiovascular death at 1 year for either sex:

• 18% of women with myocardial injury according to standard troponin test
• 17% of women after implementation of sex-specific hs-cTnI thresholds (adjusted HR 1.11 vs pre-implementation, 95% CI 0.92-1.33)
• 18% of men with myocardial injury under standard troponin test
• 15% of men after implementation of sex-specific hs-cTnI thresholds (adjusted HR 0.85 vs pre-implementation, 95% CI 0.71-1.01)

High-STEACS was a stepped-wedge, cluster-randomized controlled trial of more than 48,000 consecutive patients. The High-STEACS collaborators had previously reported that adoption of their sex-specific hs-cTnI assay protocol reclassified one in six patients with myocardial injury, but with no reduction in the primary endpoint at 1 year. The trial was conducted at 10 hospitals in Scotland.

After implementation of the new sex-specific thresholds, women with myocardial injury had improved odds of undergoing coronary angiography (from 18% to 26%) and coronary revascularization (10% to 15%, P<0.001 for both).

However, with similar improvements for men (38% to 46% for angiography; 26% to 34% for revascularization, P<0.001 for both), women stayed at a disadvantage.

"Although hs-cTnI testing identified similar proportions of women and men with myocardial injury, we continue to observe major differences in their management. Women remain one-half as likely as men to receive treatment for ACS even after implementation of the hs-cTnI assay and sex-specific thresholds," according to the investigators.

Moreover, with the new hs-cTnI thresholds, women were also less likely to be prescribed secondary prevention (P<0.001 for all):

• Dual antiplatelet therapy (54% vs 67%)
• Statins (31% vs 41%)
• Beta blockers (33% vs 42%)

"A higher proportion of women had non-ischemic myocardial injury compared with men, and this might have accounted for the lower provision of therapies, because these therapies may not be indicated and there is no evidence from randomized controlled trials to guide treatment in this group of patients," Mills and colleagues suggested.

This doesn't explain everything, however, as subgroup analyses restricted to those women and men with adjudicated diagnoses of type 1 MI still showed treatment differences between sexes, the authors pointed out.

"It is clear from this study that simply improving diagnostic accuracy cannot remedy deeply embedded gender disparities in attitudes, practice, and outcomes. Simply put, if one does not act on the data, no diagnostic test will ever have additional worth," commented Allan Jaffe, MD, and Sharonne Hayes, MD, both of the Mayo Clinic in Rochester, Minnesota, in an accompanying editorial.

The duo pointed to non-significant differences in the frequency of chest discomfort and electrocardiographic changes among women and men (66% vs 74% and 27% vs 36%, respectively).

"Women have consistently been observed to present later after the onset of acute MI symptoms and to experience further delays once arriving to the emergency department, including longer triage and door-to-balloon times. The consequence of these observations may well be that women are more apt to be on the downslope of the time concentration curve, where they do not show a rapid change in pattern," they stated.

"Unless one is a patient, one may miss this change and decide that the increases are chronic and stable," Jaffe and Hayes suggested.

The High-STEACS group cautioned that their adjudicators could have underdiagnosed type 1 MI in women as their rates of coronary angiography were half those of men. "We must acknowledge that some misclassification may have occurred," they stated.

Another limitation was that the estimates of treatment efficacy were subject to residual confounding by indication: patients selected for treatment are likely to differ substantially from those who did not receive treatment, according to Mills and colleagues.

Moreover, it remains to be seen if the findings can be applied to different practices in other geographic locations.

For example, the U.S. uses high-sensitivity cardiac troponin testing more broadly, Jaffe and Hayes noted. "Diagnostic criteria may be different for patients with chronic renal failure on dialysis, the even more elderly patients presenting atypically, and the critically ill, and therefore one must be careful in extrapolating between European and American studies," they wrote.

"Thus in the United States, it may be even more important to do a history, physical, and any indicated testing to determine the etiology of the high-sensitivity cardiac troponin elevation to guide therapy," they added.

A trial comparing the use of sex-specific hs-cTnI thresholds with a uniform cutoff is underway in CODE-MI, another cluster-randomized trial.