COVID-19–Specific Strategies for the Treatment of ST-Segment Elevation Myocardial Infarction in China

Corresponding Author

Every 40 s a person in the United States has an acute coronary syndrome, of which ∼30% comprise ST-segment elevation myocardial infarction (STEMI) (1). For STEMI patients, the clinical advantage of primary percutaneous coronary intervention (PPCI) over fibrinolytic therapy (FT) including reducing mortality, nonfatal reinfarction, and intracranial hemorrhage has been demonstrated since the early 1990s. Guidelines therefore recommend PPCI as the preferred reperfusion therapy for STEMI when provided in a timely fashion.

The coronavirus disease-2019 (COVID-19) pandemic has strained health care resources globally, radically altering patient lifestyles, and discouraging and/or delaying patients from presenting for medical treatment. In the United States and Europe, there has been a dramatic reduction in STEMI volume (2,3). Symptom onset to first-medical-contact (S-FMC) time has also sharply increased during this period (4). In addition, areas with significant COVID-19 outbreaks have had to rethink systems of care, with some institutions and countries considering or even implementing a strategy of FT over PPCI due to concerns of (scarce) resource allocation, conservation of personal protective equipment, as well as challenges in transfer of patients to facilities that perform PPCI (5).

In this issue of the Journal, Xiang et al. (6) expand on the impact of the COVID-19 outbreak using data from 1,372 Chest Pain Centers in China (CPCC). To our knowledge, the use of data from this remarkable collaborative database is novel; however, detailed descriptions of the included patients, sites, and outcomes are limited, reminding us to be circumspect with conclusions drawn from the presented data. During the outbreak period, CCPC modified the suggested STEMI protocol in areas affected by the outbreak to recommend FT as the preferred reperfusion strategy for patients with unconfirmed COVID-19 status to mitigate the risk of exposure and to minimize delays in coronary reperfusion. Data from 4 weeks before (pre-outbreak) and 4 weeks after (outbreak) the CPCC STEMI protocol change were compared. The associations between presentation during the COVID-19 outbreak period (especially within the Hubei province which was China’s COVID-19 major epicenter) and several process and outcome variables including number of weekly STEMI cases, reperfusion strategy, key treatment time points, in-hospital mortality, in-hospital heart failure, and in-hospital bleeding were compared.

A noteworthy total of 28,189 STEMI patients (of which almost 90% met inclusion criteria of having complete data) were treated during the sampling period. Within the present analysis, the investigators found a 26% reduction in the weekly total of hospitalized STEMI cases during the COVID-19 outbreak, with an even greater reduction in Hubei (62%). As expected due to the national recommendation to adopt a strategy of FT, in the COVID-19 outbreak period, the odds of PPCI were lower and the odds of FT were higher; this finding was even more pronounced in Hubei. Parameters such as S-FMC, first medical contact–to–needle (FMC-N), and first medical contact–to–wire (FMC-W, equating to door-balloon time) were prolonged during the outbreak period, especially in the epicenter. In Hubei, the FMC-W and FMC-N times were ∼20 min longer; in non-Hubei provinces, the FMC-W and FMC-N times were only delayed by ∼5 min. The negative impact of the outbreak on the odds of timely reperfusion (odds ratio: 0.81; 95% confidence interval: 0.76 to 0.86) is described, and in conjunction with this were observed increases in both the odds of in-hospital mortality and in-hospital heart failure.

One of the greatest challenges of observational research is discerning the “effect” of the exposure of interest from underlying secular (or other) trends. So in a sense, this analysis is best used in descriptive terms, rather than as an attempt to ascribe causation to any one of the multiple moving parts (e.g., the evolution of the outbreak itself, the change in reperfusion protocol, or the regional differences in patterns of disease and care). In the pre-outbreak and outbreak periods in both Hubei and non-Hubei provinces, the proportion of cases with S-FMC ≤12 h was similar. However, the majority (∼55%) of patients presenting with STEMI were categorized as “walk-in” patients and another ∼30% were “transfers.” Even in the defined pre-outbreak period, PPCI was not offered to ∼20% of patients presenting with STEMI. While at first blush 20% of STEMI patients not receiving PPCI seems high, in comparison to prior studies from China, this represents substantial improvement over time (7). Perhaps the overriding lesson from this analysis is the importance of reperfusion therapies for STEMI as a whole, with modifications based upon the specific care patterns within regional networks and systems, and individualized to the patient.

FT as an alternative to PPCI has trade-offs. With the increased use of FT during the outbreak, a difference in effective reperfusion would be expected given the known benefit of PPCI over FT. Further, STEMI mimickers, such as myopericarditis, are not uncommon in COVID-19 disease, with only ∼60% of COVID-19 STEMI patients having a culprit lesion identified on angiography (8,9). Administration of FT to the 40% of patients without a culprit lesion has a nontrivial probability of causing bleeding complications without achieving reperfusion at the epicardial level. An exception would be if the goal of FT is to target another COVID-19–related pathophysiologic explanation of STEMI such as in situ thrombosis or microvascular plugging; however, the true incidence of this phenomenon is unclear, and the specific role of FT in this situation is as yet unproven. Widespread adaptation of FT as the preferred reperfusion approach may therefore unnecessarily expose many patients to bleeding risk. The low total number of patients with bleeding events in this report despite increasing adoption of FT suggests potential under-reporting of these outcomes, which are not are readily ascertained as outcomes such as overall mortality. Thus, it is our opinion that especially in areas with adequate personal protective equipment and timely access to PPCI, PPCI should remain the preferred method of revascularization for STEMI patients, irrespective of COVID-19 status (10).

Through their work, Xiang et al. (6) have added to the growing evidence base that COVID-19 epicenters have had a decline in hospitalized STEMI cases, in conjunction with increases in time to reperfusion. This reduction in timeliness of reperfusion during the pandemic is likely further exacerbated in health care systems with limited access to PPCI at baseline. Despite a protocol-based recommendation to change to a strategy of FT to attempt to reduce these delays in reperfusion, increases in mortality and heart failure were still observed. The old adage of “time is muscle” therefore remains true, pandemic or not.