The Effect of the Lockdown on Patients With Myocardial Infarction During the COVID-19 Pandemic

A Systematic Review and Meta-Analysis

Background: The phenomenon of declining numbers of patients presenting with myocardial infarction was reported from the beginning of the COVID-19 pandemic onward. It was thought that measures introduced to stem the pandemic, such as the lockdown, contributed to this development. However, the data on hospital admissions, delay times, and mortality are not consistent.

Methods: Our systematic literature review and meta-analysis embraced studies reporting the number of hospital admissions of patients with ST-segment elevation myocardial infarction (STEMI) and/or non-ST-segment elevation myocardial infarction (NSTEMI) during lockdown episodes. We also collected data on patient- and system-related delay times and on mortality.

Results: Data from 27 studies on a total of 81 163 patients were included in our meta-analysis. We found that the number of hospital admissions of patients with myocardial infarction was significantly lower during the lockdown than before the pandemic (incidence rate ratio [IRR] = 0.516 [0.403; 0.660], I² = 98%). This was true both for patients with STEMI (IRR = 0.620 [0.514; 0.746], I² = 96%) and for patients with NSTEMI (IRR = 0.454 [0.354; 0.584], I² = 96%). However, we found no significant difference in the time from hospital admission to cardiac catheterization, or in mortality, in relation to the time from symptom onset to first medical contact.

Conclusion: In this study, we have shown that the lockdown due to COVID-19 was associated with a marked decline in the number of hospital admissions of patients with myocardial infarction. As no significant effect on delay times or mortality was observed, it seems that timely medical care continued to be delivered.

Since the early phases of the SARS-CoV-2 outbreak, there have been reports that the coronavirus-19 (COVID-19) pandemic negatively influences individual health behavior, medical supply, and health care (1, 2). In this context, patients with an acute disease that requires swift medical care, such as acute myocardial infarction, represent a particularly vulnerable population. There have been many reports from around the world of declining admission rates of patients with acute myocardial infarction. It has been suggested that, for example, social distancing measures, lockdown, and the fear of SARS-CoV-2 infection through contact with healthcare workers might have delayed medical attention to myocardial infarction patients. In this context, the effect of the pandemic on patient- and system-related delay times for myocardial infarction patients, e.g., the time from symptom onset to first medical contact, is relevant; however, the data are not consistent. To evaluate this issue further, we performed a meta-analysis of hospitalization rates, patient- and system-related delay times, and mortality in patients with acute myocardial infarction who presented to a hospital during a COVID-19-related lockdown.

Methods

Data acquisition and study selection

In a selective literature survey, the databases of PubMed, Embase, and Web of Science were searched for reports of the novel coronavirus (SARS-CoV-2) in the period December 2019 to April 2021. Combinations of the keywords “COVID” or “coronavirus” or “SARS-CoV” and “STEMI” or “NSTEMI” or “acute coronary syndrome” or “myocardial infarction” and “lockdown”, or “social distancing” or “curfew” were used for this purpose. A detailed description of the methods used can be found in the eMethods.

Results

Literature search and assessment of study quality

Using the search algorithm described above, we identified 267 studies in the three databases. Of these, 124 were duplicates. Moreover, 91 studies were not related to the research question and were thus excluded. The remaining 52 articles were assessed for eligibility. Eight studies had to be excluded for reasons of poor quality, and 17 further studies were removed owing to a lack of data on numbers of STEMI and NSTEMI admissions. The remaining 27 studies were included in the quantitative synthesis (eFigure 1; Table) (3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29). As evaluated using the NIH Study Quality Assessment Tool, 13 studies were of “fair” quality, while 14 studies were rated “good” (Table).

Figure 1

Forest plot: incidence rate ratio

Table

Study characteristics

eFigure 1

PRISMA flowchart

Patients

In total, 81 163 patients with myocardial infarction from 27 studies were included in our meta-analysis. Of these, 71 061 patients were in the pre-lockdown group and 10 102 in the lockdown group. Patient characteristics could be extracted from 11 studies. The patients included for analysis had an average age of 68 years; 69% of them were male. Assessment of cardiovascular risk factors showed that 50% of patients had arterial hypertension, 28% had dyslipidemia, 27% had diabetes mellitus, 21% had coronary artery disease, and 26% either were former or current smokers (weighted arithmetic means). The patient characteristics are summarized in eTable 1.

eTable

Study patient characteristics

Admission rates of patients with myocardial infarction

The hospitalization rates could be extracted from all 27 studies. While before the lockdown the mean daily number of admissions of patients with myocardial infarction was 40.6, only 14.7 patients per day presented to hospital because of myocardial infarction during lockdown. This decline of approximately 64% reveals a significant decrease in the admission rate of patients with myocardial infarction during COVID-19-related lockdown (incidence rate ratio [IRR] = 0.516 [95% confidence interval: 0.403; 0.660], I2 = 98%; Figure 1). Subgroup analysis showed that admission rates of both STEMI patients (IRR = 0.620 [0.514; 0.746], I2 = 96%, eFigure 2) and NSTEMI patients (IRR = 0.454 [0.354; 0.584], I2 = 97%; eFigure 3) declined significantly. The corresponding funnel plots are shown in eFigures 6–8. Because the high heterogeneity and the funnel plots indicate a reporting bias, the trim-and-fill method was applied. However, this did not change our results (trim-and-fill: STEMI & NSTEMI, IRR = 0.498 [0.397; 0.626]; STEMI, IRR = 0.610 [0.510; 0.730]; NSTEMI, IRR = 0.454 [0.355; 0.581]).

Figure 2

Forest plot: mortality

eFigure 2

Forest plot: incidence rate ratio for STEMI patients

eFigure 3

Forest plot: incidence rate ratio for NSTEMI patients

Analysis of patient- and system-related delay times of STEMI patients

The analysis of patient-related delay time showed no significant difference between the two groups in terms of the time from symptom onset to first medical contact (time to FMC, in minutes), which was investigated in nine studies (MD = 21.8 [-5.3; 48.9], I² = 85%; eFigure 4). Moreover, also in nine studies, system-related delay times were not significantly different before and during the COVID-19-associated lockdown (MD = 2.4 [-1.7; 6.5], I² = 80%; eFigure 5), as measured by the time from admission to cardiac catheterization (door-to-balloon time, in minutes). The corresponding funnel plots can be found in eFigures 9–10. Application of the trim-and-fill method did not lead to different results (trim-and-fill; time to FMC: MD = -8.4 [-37.5; 20.8]; door-to-balloon time: MD = 1.3 [-2.8; 5.4]).

eFigure 4

Forest plot: time from symptom onset to first medical contact

eFigure 5

Forest plot: time from hospital admission to cardiac catheterization

Mortality of patients with myocardial infarction

We further evaluated the effect of lockdown on the mortality of patients with acute myocardial infarction. We found no significant difference in mortality between the lockdown group (190 out of 3261 patients, 5.8%) and the pre-lockdown group (2269 out of 50 020 patients, 4.5%) (odds ratio [OR] = 1.113 [0.935; 1.324], I2 = 2%; Figure 2, eFigure 11). There was still no significant difference after application of the trim-and-fill method (trim-and-fill: mortality, OR = 1.113 [0.935; 1.324]).

Discussion

This is the first meta-analysis exploring the effect of lockdown on admission rates of myocardial infarction patients during the COVID-19 pandemic. We showed that admission rates of STEMI and NSTEMI patients declined significantly during lockdown phases of the pandemic. However, we did not find any alteration of patient- and system-related delay times in STEMI patients. Moreover, mortality was not increased in myocardial infarction patients referred during lockdown.

Admission rates of myocardial infarction patients during the COVID-19 pandemic

Early in the COVID-19 outbreak, healthcare professionals began to observe reductions in admissions of patients with myocardial infarction (30, 31). Various factors, among others the fear of infection with SARS-CoV-2 in the hospital and social isolation measures, have been suggested as possible reasons for this phenomenon (6, 26, 27, 33, 36, 37, 38). Those patients who were admitted during the pandemic appeared to be in worse clinical condition (15, 23, 32, 33, 34, 35). Accordingly, a recently published meta-analysis demonstrates significant increases in the incidence and mortality of out-of-hospital cardiac arrest (OHCA) during the COVID-19 pandemic (39). This suggests that the increased OHCA may have made a relevant contribution to the reduced admission rates for patients with myocardial infarction, especially STEMI. However, since our meta-analysis demonstrates that presentations of NSTEMI patients also declined significantly, it seems likely that factors other than OHCA also contribute to the phenomenon of the missing myocardial infarction patients.

Effect of lockdown on admission rates of myocardial infarction patients

The potential adverse effects of lockdown measures on the medical care of myocardial infarction patients has been discussed since the initial phase of the pandemic, but reports have been conflicting (3, 29, e1). In a recently published study that prospectively evaluated the outcomes of STEMI patients hospitalized during lockdown, “admission during lockdown” was identified as the sole predictor of intentionally delayed presentation (35). Our meta-analysis shows that the number of myocardial infarction patients admitted to the hospital declined significantly during lockdown. Previous studies simply observed a reduction in the number of NSTEMI admitted, while admissions of STEMI patients remained constant (5, 15). This suggests that NSTEMI patients, whose symptoms are usually less severe than those experienced by patients with STEMI, are at risk of their medical needs not being met. However, our meta-analysis demonstrates that on a global scale, the incidence of both STEMI and NSTEMI admissions declined significantly during lockdown episodes. It thus appears that all patients suffering from acute myocardial infarction are exposed to the risk of inadequate medical care during periods of lockdown.

Effect of lockdown on delay times of myocardial infarction patients

Measures of social distancing and isolation are suspected to worsen the outcome of patients with myocardial infarction by prolonging the total ischemia time (3, 5, 18, 25). In the early phase of the pandemic, even increased preclinical use of fibrinolysis in STEMI patients was propagated in order to minimize the time to reperfusion (e2). However, no increased use of fibrinolysis during the pandemic was documented in the studies included in our analysis (5, 16, 18, 24, 26, 27). To evaluate whether delay times and, consequently, total ischemia times of myocardial infarction patients were prolonged during periods of lockdown, we performed meta-analyses for times from symptom onset to FMC (patient-related delay) and door-to-balloon times (system-related delay). We found that neither changed significantly during lockdown, suggesting that timely medical treatment could be maintained despite the measures imposed at this time.

Effect of lockdown on mortality of myocardial infarction patients

Data on the effect of lockdown-associated social distancing measures on the mortality of myocardial infarction patients are sparse. The results of a recently published meta-analysis suggest that mortality in STEMI patients did not increase during the COVID-19 pandemic (40). However, this meta-analysis included studies with mortality data from outside defined periods of lockdown, which may have evened out the effect of social distancing measures (40). Through our systematic review of the literature, nine studies reporting mortality rates of patients suffering from myocardial infarction were identified and included in our meta-analysis. Although the death rates were 5.8% (190 of 3261 patients) in the lockdown group and 4.5% (2269 of 50 200 patients) in the pre-lockdown group, the difference was not significant. This suggests that lockdown measures did not aggravate mortality in myocardial infarction patients. This may be attributable to the swift actions taken by cardiological societies (e.g., campaigns to raise awareness of the symptoms of myocardial infarction) and by the medical system as a whole, as well as to the adjustment of clinical treatment algorithms in response to the pandemic (e3, e4). However, all of the studies included in our meta-analysis on mortality contain exclusively data on in-hospital mortality, so no conclusions regarding longer-term outcomes can be drawn. We have to await the results of large prospective studies with longer follow-up. In this regard, a monocentric prospective study analyzing the survival of STEMI patients admitted before, during, and after lockdown showed that after median follow-up of 142 days, survival was significantly lower only in the lockdown group (35).

Moreover, none of the studies included in our meta-analysis looked at the number of patients with OHCA, although some findings suggest that a certain proportion of the myocardial infarction patients “missing” during the pandemic could be accounted for by an increase in OHCA events. For example, an Italian study reported that a significant decline in hospitalization of patients with myocardial infarction during the initial phase of the pandemic was accompanied by a significant rise in fatal myocardial infarction-related events outside the hospital setting (e5). However, further studies, particularly in other countries, are necessary to verify these results.

Effect of regional circumstances on myocardial infarction patients

Since the COVID-19 pandemic is a global, dynamically developing event, regional differences have to be taken into account when discussing the pandemic’s effects on myocardial infarction patients. In contrast to countries such as Germany, where numbers of infections were low during the initial phase of the pandemic, studies from nations hit harder by the pandemic, such as Spain and China, reported dramatically longer times from symptom onset to FMC as well as increased door-to-balloon times (24, 41, e6). This clearly shows that the effects of regional differences on population-level health behavior have to be taken into account in the management of myocardial infarction patients during the continuing pandemic. In our meta-analysis, the highest decline in the incidence of admission of myocardial infarction patients was found in studies from India (7, 12, 16). Unfortunately, no data on delay times and mortality rates could be extracted from these studies. A recently published meta-analysis comparing the impact of the COVID-19 pandemic on the care of STEMI patients in Western and Eastern countries showed that while mortality rose significantly in Eastern centers, there was no difference in Western centers. Moreover, mortality rates were significantly higher in hospitals located in low-income countries (all of them Eastern centers). In contrast, no relevant difference was found for hospitals in high-income countries (e7). Since the studies in our meta-analysis were predominantly conducted at Western centers, our results suggest that the reduced number of admission during lockdown in this population group are associated neither with prolonged patient-related or system-related delay times nor with higher (short-term) mortality. This may be attributable to swift adaptation of emergency medical processes, implementation of information campaigns by the cardiological societies, and sufficient access to medical care. However, it remains to be clarified to what extent OHCA events affected mortality among myocardial infarction patients.

Limitations

As our meta-analysis incorporated data from various observational studies, it naturally has limitations. The majority of the studies included contained only skewed data for the delay times, which were adjusted using the Box–Cox method as appropriate (40, e8). Use of this method may in some cases entail imprecision in calculating the standard deviation, a feature innate to this method. Additionally, the differing cohort sizes influence the weighting of the individual studies, an inherent limitation of meta-analyses. Calculations of the statistical measure I² and the p-value of the associated chi-square test revealed high heterogeneity among the studies included. This is presumably related to the fact that the studies originate from different countries with:

• Different health care systems
• Differing access to health care
• Different strategies for combating and containing the pandemic

Moreover, the study periods of the included studies vary. This results from our study design and may contribute to the heterogeneity. Due to the high heterogeneity and the exploratory character of this study, our results must be viewed as hypothesis generating. Nevertheless, because our aim was to give an unbiased insight into the impact of lockdown on myocardial infarction patients, all relevant data available were included.

Conclusion

This is the first meta-analysis evaluating the effect of lockdown on patients with myocardial infarction admitted during the COVID-19 pandemic. We have shown that the incidence of hospitalization of patients with myocardial infarction declined significantly during the lockdown. This was true for both patients with STEMI and those with NSTEMI. Intriguingly, we found no relevant effect of social distancing measures on patient-related delay times, system-related delay times, or mortality. This suggests that, overall, timely medical care of myocardial infarction patients could be maintained.

Research support

This work was supported by the Kaltenbach Doctoral Scholarship of the German Heart Foundation (Deutsche Herzstiftung) (LS), and local funding from Ulm University Hospital and the University of Ulm, Germany.

Acknowledgment

The authors thank Dr. Katharina Krempel for her critical review of the manuscript.

Conflict of interest statement
The authors declare that no conflict of interest exists.

Manuscript received on 17 January 2021, revised version accepted on 26 May 2021

Corresponding author
Dr. Manuel Rattka
Klinik für Innere Medizin II, Abteilung für Kardiologie
Pneumologie und internistische Intensivmedizin, Universitätsklinikum Ulm
Albert Einstein Allee 23, 89081 Ulm, Germany

Cite this as:
Baumhardt M, Dreyhaupt J, Winsauer C, Stuhler L, Thiessen K, Stephan T, Markovic S, Rottbauer W, Imhof A, Rattka M: The effect of the lockdown on patients with myocardial infarction during the COVID-19 pandemic—a systematic review and meta-analysis. Dtsch Arztebl Int 2021; 118: 447–53. DOI: 10.3238/arztebl.m2021.0253

►Supplementary material

eReferences, eMethods, eTables, eFigures: www.aerzteblatt-international.de/m2021.0253

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