Angiography within 24 hours?
The European guidelines include a class IA recommendation for angiography within 24 hours in NSTEMI (3). This implies that the authors of the guidelines believe the intervention has been shown to be beneficial, useful and effective. As supporting evidence, the authors cite two meta-analyses (12, 13) and the TIMACS study (14), the largest of a total of ten studies that have compared early versus late angiography.
The TIMACS study included 3 031 patients and is the only one of the studies that comes close to having reasonable statistical power. However, it was discontinued prematurely due to insufficient patient recruitment and the results should be interpreted with caution. The other two references are meta-analyses where the TIMACS study was combined with three and six smaller studies, respectively, and where it contributes 56 % and 75 % of the total number of patients. It thus weighs heavily in the evidence upon which the European guidelines are based.
In the TIMACS study, the median time to angiography was 14 hours in the group that underwent early angiography versus 50 hours in the group with delayed angiography. The primary endpoint was a composite of mortality, acute myocardial infarction or stroke at six months. There was no significant effect of early angiography on the primary endpoint. Both meta-analyses reached the same conclusion.
We must question whether the European Society of Cardiology has made the correct call when none of the three publications that form the basis for the class IA recommendation of early angiography showed an effect on the studies' primary endpoint. How might this have happened? The explanation is that the class IA recommendation is based on a subgroup analysis in the TIMACS study, in which a beneficial effect of early angiography was found for the one-third of patients at highest risk, defined as a GRACE score of > 140 (Global Registry of Acute Coronary Events).
Several factors suggest that it may be inadvisable to place decisive weight on this subgroup analysis. As a general rule, one should be wary of placing too much weight on subgroup analyses, especially if the main analysis has not shown any effect. Moreover, the GRACE score was not developed to guide treatment, but to estimate the risk of mortality after an acute coronary syndrome (15). Age thus weighs heavily in this score.
Since the publication of the European guidelines in 2016, an additional meta-analysis has been published that includes three more recent studies (16). This analysis also found that angiography within 24 hours had no effect on hard clinical outcomes, but there was a significant reduction in the risk of further ischaemic episodes, and early angiography did lead to shorter hospital stays.