Tactics and features of the use of instrumental and drug treatment methods in hospitalized patients with COVID-19 and myocardial infarction with ST segment elevation: a literature review

Relevance

As the consequences of the COVID-19 pandemic are studied, increasing information is emerging about the non-respiratory effects of coronavirus infection. Controlled studies have established that the virus causing COVID-19, SARS-CoV-2, most frequently affects multiple organ systems, particularly the lungs and heart [1].

Signs of myocardial injury based on criteria such as elevated levels of cardiac biomarkers, especially high-sensitivity troponin and/or creatine kinase-MB, are common in patients with COVID-19 infection. A meta-analysis by cardiologists from Brown University (Providence, USA) included 26 studies involving 11,685 patients with confirmed COVID-19, revealing that the prevalence of significant myocardial injury, as diagnosed by elevated cardiac-specific enzyme levels, ranged from 5% to 38% depending on the criteria used, averaging over 20% [2].

Similar data were obtained in a retrospective study conducted by cardiologists from Saint Luke's Mid America Heart Institute and the University of Missouri-Kansas City (Missouri, USA). In the study by Sammour YM et al. [3], data from 32,636 COVID-19 patients included in the American Heart Association's (AHA) COVID-19 Cardiovascular Disease Registry were analyzed. From the overall cohort, 6,234 patients (19.4%) had cardiac troponin measured from a venous blood sample (drawn from the cubital/antecubital vein); the mean age was 68.7 ± 16.0 years, 56.5% were male, and 51.5% were Caucasian. A cardiac troponin elevation of more than five times the upper limit of normal was recorded in 1,365 patients (21.6%) of this subgroup. In the multicenter study (55 centers), the mean rate of invasive coronary angiography performance was 0.1% (adjusted OR 1.5). Echocardiography with left ventricular ejection fraction (LVEF) assessment was performed in 25.5% of cases (adjusted OR 3.0). Admission to the intensive care unit was noted in 41.7% of patients (adjusted OR 2.2). In-hospital mortality was 20.9% (adjusted OR 1.7). Analytical reviews on this issue have shown that significant myocardial injury, accompanied by elevated cardiac troponin (cTn) levels, is associated with adverse outcomes in patients with SARS-CoV-2 infection [4]. Possible causes of heart damage in these conditions may include myocarditis, acute myocardial infarction (MI), stress cardiomyopathy, cardiac arrhythmia, sepsis-related myocardial injury, pulmonary embolism, and endothelial and systemic involvement [5]. Among these, acute MI is a primary diagnosis that must be promptly diagnosed to optimize treatment and outcomes. Type 1 acute MI is a diagnosis for which established care protocols are used, including invasive management with coronary angiography and timely revascularization to optimize outcomes, especially in ST-elevation MI (STEMI) and high-risk non-ST-elevation MI (NSTEMI) [6]. In patients with COVID-19 with suspected acute MI, an additional clinical challenge arises: the risk of unwarranted diagnostic and therapeutic interventions increases, as several COVID-associated changes can mimic MI in the absence of obstructive coronary artery disease (MINOCA) [7].

Studies by morphologists during the COVID period have established that in patients with acute coronary syndrome (ACS), besides plaque rupture and thrombosis, other pathogenetic factors are involved in the development of acute myocardial injury in COVID-19. According to data from the European Society of Cardiology (ESC) Working Group on Cellular Biology of the Heart, the primary causes of heart damage in COVID-19 are:
a) Coagulopathy with micro- (and, to a lesser extent, macro-) vascular occlusion;
b) Direct infection of myocardial cells;
c) Effects of the cytokine storm;
d) Mechanisms related to coagulopathy-induced damage [8].

The probable mechanisms of myocardial injury in COVID-19 are multifactorial and include:

1. Hyperinflammation and cytokine storms mediated by pathological T-cells and monocytes, leading to myocarditis;

2. Heart failure and hypoxemia, leading to cardiomyocyte injury;

3. Downregulation of ACE2 expression and reduction of protective signaling pathways in cardiomyocytes;

4. Hypercoagulability and development of coronary microvascular thrombosis;

5. Diffuse endothelial injury and "endothelialitis" in multiple organs, including the heart;

6. Stress-associated disturbances (hypoxia, tachycardia, hypotension), leading to coronary atherosclerotic plaque rupture/erosion or to a supply–demand mismatch of myocardial oxygen [2].

According to specialists from an Iranian interventional cardiology center, the development of ST-segment elevation myocardial infarction (STEMI) in patients with COVID-19 is characterized by specific angiographic findings – massive and multivessel thrombosis, often independent of atherosclerotic coronary artery disease, which is associated with an unfavorable prognosis and creates new therapeutic challenges [9]. Baseline demographic, clinical, and procedural characteristics of patients were obtained, including from national registries of myocardial infarction associated with COVID-19. In particular, data from the North American COVID-19 Myocardial Infarction Registry were used. Univariate logistic regression was performed using candidate predictor criteria, and multivariate logistic regression was conducted using backward stepwise selection for independent predictors of in-hospital mortality. In-hospital mortality occurred in 118 of 425 (28%) patients [10]. Eight clinical variables identifiable at the time of STEMI diagnosis (respiratory rate >35 per minute, cardiogenic shock, oxygen saturation <93%, age >55 years, presence of infiltrates on chest X-ray, history of cardiovascular disease, diabetes, and dyspnea) were incorporated into a model with an assigned weighted numerical value for each. In-hospital mortality increased exponentially as the integrated risk score increased (Cochran-Armitage test). The predictive model demonstrated good discriminatory ability (c-statistic = 0.81) and satisfactory calibration (Hosmer-Lemeshow test). An increase in risk category was directly associated with a rise in in-hospital mortality – from 3.6% in the low-risk group to 60% in the very high-risk group [10].

Canadian cardiologists from the Division of Cardiology, College of Medicine, University of Saskatchewan (Shavadia JS et al.) analyzed data from the North American COVID-19 Myocardial Infarction Registry, including 853 patients with STEMI and COVID-19 registered in the USA, of which 112 (13%) were included in the registry [11]. The registry included adult (≥18 years) patients hospitalized from March 1, 2020, to December 31, 2021, meeting the following inclusion criteria: (1) ST-segment elevation in 2 contiguous leads (or new left bundle branch block), (2) ischemic symptoms equivalent, and (3) confirmed or suspected COVID-19 infection. Covariates included in the model were: year of registry inclusion, country, sex, age <66 years, overweight or obese status (by body mass index), Caucasian race, current smoking status, hypertension, diabetes, prior myocardial infarction, history of stroke or transient ischemic attack, signs of congestive heart failure, presence of pulmonary infiltrates, and development of shock during percutaneous coronary intervention (PCI). Clinical outcomes for patients included in the study in the USA (n=741) compared to Canada (n=112) differed as follows: in-hospital mortality was 28% (n=209) vs. 16% (n=18); stroke rate – 1.8% (n=13) vs. 0% (n=0); recurrent myocardial infarction – 2% (n=15) vs. 0% (n=0). The composite endpoint (mortality, stroke, or recurrent myocardial infarction) was recorded in 30% of patients in the USA (n=225) and 16% of patients in Canada (n=18). According to the analysis, the risk of in-hospital mortality was significantly higher in unvaccinated compared to vaccinated patients with STEMI-COVID (OR 4.7). Currently, as worldwide, the COVID-19 pandemic necessitates the justification of hospital care systems using an Incident Management System, which ensures the possibility of timely access to reperfusion therapy. Primary percutaneous coronary intervention was monitored as the reperfusion strategy, with no difference in door-to-balloon (D2B) time (see Table 1).

Table 1
Reperfusion in patients undergoing angiography

Data are presented as n (%) and diagrams using appropriate Pearson's exact tests, χ2, and Fisher's tests. The authors concluded that differences in morbidity and reperfusion strategy for STEMI-COVID patients are evident, with no reported cases of in-hospital death noted in the USA compared to Canada. Vaccination, regardless of region, appeared to be associated with a significant reduction in the risk of in-hospital mortality [11].

In an analysis led by the Thrombolysis in Myocardial Infarction (TIMI) Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School (Boston, Massachusetts) [12], data from the American Heart Association's COVID-19 Cardiovascular Disease Registry from January 14 to November 30, 2020, collected at 105 medical centers, were used. Patient characteristics, resource utilization, and outcomes were summarized and compared by country. Out of 15,621 COVID-19 hospitalizations – 54 (0.35%) patients with acute myocardial infarction were hospitalized. Among STEMI patients, transthoracic echocardiography was performed in the majority (n=40, 74.1%), but coronary angiography was performed in only a third (n=18, 33.3%). Half of all patients with COVID-19 and STEMI (n=27, 50.0%) did not receive any primary reperfusion therapy. The rate of shock of any etiology was significantly higher in ST-segment elevation myocardial infarction (STEMI) patients compared to non-STEMI patients (47% vs. 14%). Similarly, STEMI patients more frequently experienced cardiac arrest (22% vs. 4.8%), acute heart failure (17% vs. 1.4%), and need for renal replacement therapy (11% vs. 4.3%). Differences were statistically significant for all compared indicators. In-hospital mortality was 41% in STEMI patients compared to 16% in non-STEMI patients (significant). The authors concluded that STEMI in hospitalized patients with COVID-19 is rare but associated with adverse in-hospital outcomes [12].

Initial results from the analysis of the North American COVID-19 Myocardial Infarction Registry were presented by Garcia S et al. [13], staff of the Minneapolis Heart Institute Foundation (Minneapolis, Minnesota). It included STEMI patients with confirmed COVID-19 infection (COVID+ group) or with suspected (Patients Under Investigation, PUI group) COVID-19 infection. A control cohort (Control group) of age- and sex-matched STEMI patients without COVID-19, treated in the pre-COVID period (2015–2019), was formed. Patients were matched to the STEMI+COVID-19 group in a 2:1 ratio and used to compare treatment strategies and clinical outcomes. The primary outcome was in-hospital death, stroke, recurrent myocardial infarction, or unplanned repeat revascularization. As of December 6, 2020, 1,185 patients were included in the North American COVID-19 Myocardial Infarction Registry (NACMI) (230 COVID+ patients, 495 PUI patients) and 460 control patients. COVID+ patients were more frequently from ethnic minorities (Hispanic 23%, Black 24%) and had a higher prevalence of diabetes (46%). COVID+ patients more frequently presented with cardiogenic shock (18%) but less frequently underwent invasive angiography (78%) (all p <0.001 compared to control patients). Among COVID+ patients who underwent angiography, 71% underwent primary PCI (pPCI), and 20% received medical therapy (significant compared to control patients). The primary outcome occurred in 36% of COVID+ patients, 13% of PUI patients, and 5% of control patients (p <0.001 compared to control patients). The authors concluded that patients with COVID-19 and STEMI represent a high-risk group with consistently adverse clinical outcomes. Meanwhile, pPCI in patients with this infection is technically feasible and remains the predominant reperfusion strategy, consistent with current clinical guidelines.

Data from the Swiss SARS-CoV-2 Cardiovascular Disease Consortium were analyzed in a study by staff from the Department of Cardiology, Inselspital, Bern University Hospital, Bern, Switzerland, Koskinas KC et al. [14]. From March 2020 to February 2022, 538 patients were included in the study, including 122 cases of acute cardiovascular events and 416 controls. The mean age was 68.0 ± 14.7 years, and 75% were predominantly male. Compared to the control situation, SARS-COV-2-positive patients more frequently presented with acute heart failure (35% vs. 17%) or persistent arrhythmia (31% vs. 9%), but less frequently with acute coronary syndrome (26% vs. 53%) or severe aortic stenosis (4% vs. 18%). Mortality was significantly higher in cases compared to controls in-hospital (16% vs. 1%), at 30 days (19.0% vs. 2.2%), and at 1 year (28.7% vs. 7.6%). This was driven primarily (up to 30 days) and exclusively (at one-year follow-up) by higher non-cardiovascular mortality, accompanied by a greater level of renal function deterioration. The researchers concluded that patients hospitalized for acute cardiovascular events with SARS-COV-2 infection had higher all-cause mortality over the entire one-year follow-up period. The study results indicate the need for an early and comprehensive interdisciplinary approach with simultaneous correction of both cardiac and non-cardiac disorders, as well as the advisability of long-term dynamic monitoring of patients with manifest cardiovascular diseases complicated by SARS-CoV-2 infection.

The mortality of patients with ST-segment elevation myocardial infarction (STEMI) hospitalized during COVID-19 infection during the national lockdown in Italy was analyzed based on data from a nationwide administrative database. The analysis included STEMI patients hospitalized during quarantine restrictions (March 11 – May 3, 2020), with subsequent comparison with similar time intervals over the preceding five years. The study was conducted by staff from the Cardio-Thoracic and Vascular Medicine and Surgery Department, San Camillo-Forlanini Hospital (Rome, Italy) [15]. During treatment, it was found that the observed rates of 30-day and 6-month all-cause mortality in STEMI patients with and without COVID-19 infection during quarantine were compared with the expected mortality according to the trend of the previous 5 years. During the study period in Italy, 32,910 hospitalizations for STEMI were recorded. In 2020, 4,048 STEMI patients were hospitalized, of whom 170 (4.2%) had confirmed COVID-19, and 3,878 (95.8%) did not. According to the five-year trend analysis, the expected 30-day and 6-month all-cause mortality rates for 2020 were 9.2% and 12.6%, respectively, while the actually observed mortality reached 10.8% and 14.4%. When excluding STEMI patients with confirmed COVID-19, mortality rates corresponded to the expected values of the five-year period. After multivariate adjustment, the presence of COVID-19 remained an independent predictor of all-cause mortality at 30 days (adjusted odds ratio 4.5) and 6 months (OR 3.6).

In a study conducted under the auspices of the Paris Cardiovascular Research Center (PARCC) in 2021, data from a nationwide survey in France were used. Information on STEMI patients admitted to 65 centers for emergency revascularization between March 1 and May 31, 2020, was analyzed, with comparison to the same period in 2019. The primary endpoint was in-hospital mortality or the development of fatal or non-fatal mechanical complications of acute myocardial infarction. A total of 6,306 patients were included in the analysis. It was found that during the peak of the pandemic, there was a decrease in the number of STEMI hospitalizations by 13.9 ± 6.6% per week. In 2020, the delay from symptom onset to PCI was longer compared to 2019 (270 min [interquartile range 150–705] vs. 245 min [140–646]). The increase in total ischemic time was mainly due to prolongation of the interval from symptom onset to first medical contact (121 min [60–360] in 2020 vs. 150 min [62–420] in 2019). In 2020, there was a higher frequency of mechanical complications of myocardial infarction (1.7% vs. 0.9%), leading to an increase in the frequency of achieving the primary endpoint – 129 patients (7.6%) in 2020 compared to 112 patients (5.6%) in 2019. No significant differences were found in the rates of orotracheal intubation, in-hospital cardiac arrest, ventricular arrhythmias, or cardiogenic shock. The authors concluded that during the first peak of the COVID-19 pandemic in France, there was a decrease in the number of myocardial infarction hospitalizations, associated with an increase in ischemic time, which was exclusively due to delays at the stage of seeking medical care and accompanied by an increase in the frequency of mechanical cardiovascular complications [16].

In a study led by the Chief of Cardiology at Westchester Medical Center, New York Medical College (Valhalla, New York, USA), the 2020 National Inpatient Sample database was used to identify all adult hospitalizations with a primary diagnosis of STEMI with and without concomitant COVID-19 infection. Data on 159,890 STEMI hospitalizations were included in the analysis, of which 2,210 (1.38%) had confirmed COVID-19. After correction using propensity score matching methods, patients with STEMI and COVID-19 had significantly higher in-hospital mortality compared to patients without COVID-19 (17.8% vs. 9.1%; OR 1.96). Patients with COVID-19 less frequently underwent PCI on the day of admission (63.6% vs. 70.6%), showed a trend towards a lower overall PCI rate (74.9% vs. 80.2%), and had a significantly lower rate of coronary artery bypass grafting (CABG) before discharge (3.0% vs. 6.8%). At the same time, no significant differences were found between the groups in the frequency of cardiogenic shock, need for mechanical circulatory support, extracorporeal membrane oxygenation, cardiac arrest, acute kidney injury, need for dialysis, major bleeding, or stroke.
In patients with STEMI and confirmed COVID-19 infection, performing PCI on the day of hospitalization was associated with significantly lower in-hospital mortality (adjusted odds ratio 0.42). At the same time, in the overall cohort of STEMI patients with COVID-19, there was approximately twice the in-hospital mortality, as well as a lower likelihood of PCI on the day of admission and revascularization (PCI and/or CABG) during hospitalization compared to STEMI patients without COVID-19 [17].

The COVID-19 pandemic has significantly impacted the functioning of healthcare systems worldwide. Several studies have demonstrated the adverse impact of COVID-19 on the prognosis of STEMI patients, including those admitted to cardiovascular intensive care units. In Japan, a retrospective observational study was conducted at the Tokyo Academic Medical Hospital to assess the impact of the COVID-19 pandemic on the management and outcomes of STEMI patients. Data from 398 patients hospitalized between January 1, 2018, and March 10, 2021, were sequentially included. Hospitalization rates, clinical characteristics, management strategies, and patient outcomes before and after March 11, 2020 – the date of the official pandemic declaration by the World Health Organization – were compared.
According to the data obtained, during the COVID-19 pandemic, the number of STEMI hospitalizations decreased by 10.7% compared to the previous year (117 cases vs. 131). During the pandemic, there was a significant increase in the proportion of late presentations (26.5% vs. 12.1%), as well as a significant prolongation of the time from symptom onset to first medical contact (241 min [interquartile range 70–926] vs. 128 min [66–493]) and the time from hospital arrival to balloon dilation (72 min [61–128] vs. 60 min [43–90]; p <0.001). In-hospital mortality during the pandemic was higher compared to the pre-pandemic period (9.4% vs. 5.0%), but the differences did not reach statistical significance. The authors concluded that the COVID-19 pandemic significantly impacted STEMI patients in Tokyo, leading to a moderate decrease in hospitalizations, a significant increase in the frequency of late presentations and delays in reperfusion therapy, and a trend towards increased in-hospital mortality. Under these conditions, the emergency care system for STEMI patients in Japan requires reorganization [18].

In Israel, a retrospective observational study was conducted based on the Clalit Health Services system, covering patients hospitalized for acute myocardial infarction (AMI) in several hospitals. The study was conducted by authors from the Planning and Strategy Division (Tel Aviv) and the Ruth and Bruce Rappaport Faculty of Medicine, Technion – Israel Institute of Technology (Haifa, Israel). Clinical characteristics of patients and 30-day mortality during three five-week phases of the first wave of the COVID-19 pandemic in Israel were analyzed: before quarantine (n=702), during quarantine (n=584), and after its relaxation (n=669), with comparison to the same periods in 2018 and 2019. Patients were stratified by type of myocardial infarction – ST-segment elevation (STEMI) and non-ST-segment elevation (NSTEMI). It was found that during the quarantine period, the number of AMI hospitalizations was 17% lower compared to the pre-quarantine period (rate ratio 0.83), and also 22% and 31% lower compared to the corresponding periods in 2018 and 2019, respectively. The decrease in hospitalizations was mainly due to a reduction in the number of patients with non-ST-segment elevation myocardial infarction (26% lower compared to the pre-quarantine period of 2020). In the post-quarantine period, the number of hospitalizations for STEMI and NSTEMI remained moderately reduced compared to the same periods in 2018 and 2019. Meanwhile, 30-day mortality rates did not differ between all analyzed time intervals. The authors concluded that during the first quarantine and after its completion in Israel, there was a significant reduction in the number of AMI hospitalizations, not accompanied by changes in 30-day mortality [19].

As part of a retrospective analysis, hospitalizations for AMI recorded between December 30, 2018, and May 16, 2020, in 49 hospitals of the Providence–St. Joseph Health system operating in six US states (Alaska, Washington, Montana, Oregon, California, and Texas) were studied. The study included patients ≥18 years old with a primary discharge diagnosis of AMI, including ST-segment elevation myocardial infarction (STEMI) and non-ST-egment elevation myocardial infarction (NSTEMI). Segmented regression analysis was used to assess changes in hospitalization rates. Three time periods were identified: pre-pandemic (December 30, 2018–February 22, 2020), early COVID-19 period (February 23, 2020–March 28, 2020), and late COVID-19 period (March 29, 2020–May 16, 2020). In-hospital mortality was risk-adjusted using observed-to-expected (O/E) mortality ratios and multivariate models accounting for covariates. The cohort included 15,244 AMI hospitalizations (4,955 STEMI [33%] and 10,289 NSTEMI [67%]) in 14,724 patients (mean age 68±13 years; 66% male). Starting February 23, 2020, AMI hospitalizations decreased at a rate of –19.0 cases per week for five weeks (early COVID-19 period), after which an increase of +10.5 cases per week was noted in the late period. No significant changes in demographic characteristics, comorbid cardiovascular diseases, or treatment strategies were found between periods. In the early COVID-19 period, there was an increase in the risk of in-hospital mortality (OR 1.27), disproportionately pronounced in STEMI patients (OR 1.96). In the late period, the overall O/E mortality ratio for AMI remained elevated (1.23), but the greatest contribution again came from STEMI patients: the O/E ratio consistently increased from the pre-pandemic period (1.48) to the early (1.96) and late COVID-19 periods (2.40). After adjustment for demographic and clinical factors, STEMI patients in the late period maintained an increased risk of mortality (OR 1.52). Meanwhile, for NSTEMI patients, the O/E mortality ratio remained consistently below one in all analyzed periods.
Consequently, within the Providence–St. Joseph Health system, both a significant reduction in AMI hospitalizations and a deterioration in outcomes, primarily driven by patients with ST-segment elevation myocardial infarction, were recorded during the early and late periods of the COVID-19 pandemic [20].

Thus, in patients with confirmed COVID-19 infection, the prevalence of acute myocardial injury, determined by elevated biochemical markers of myocardial damage, varies from 5% to 38% depending on clinical characteristics and disease severity. The COVID-19 pandemic has significantly impacted the provision of medical care to patients with ST-segment elevation myocardial infarction (STEMI) worldwide, including the availability and organization of reperfusion therapy. According to national and international registries, significant changes in the system of providing cardiac care to patients with acute coronary syndrome in general and STEMI in particular were recorded during the pandemic. Most studies noted a decrease in the number of hospitalizations for severe forms of coronary syndrome compared to the pre-pandemic period, with the total number of hospitalizations decreasing by approximately 20%. Analysis of available data indicates that during the early and late periods of the COVID-19 pandemic, changes were observed both in the frequency of hospitalizations for acute myocardial infarction and in clinical outcomes. Despite these changes, primary percutaneous coronary intervention maintained its status as the leading reperfusion therapy strategy, while indicators of time from symptom onset to balloon dilation in a number of studies showed no fundamental differences compared to the pre-pandemic period.

Features of Medical Care Provision and Instrumental and Medical Treatment for Hospitalized COVID-19 Patients with Acute Coronary Syndrome and Myocardial Infarction

The impact of COVID-19 infection on treatment strategies and clinical outcomes of hospitalized AMI patients has been assessed in a number of controlled observational studies. One of the largest studies was conducted by a research group from the University of Leeds (UK), aiming to assess changes in hospitalization rates, treatment strategies, and 30-day mortality of AMI patients during the COVID-19 pandemic [25].
The analysis covered data on AMI hospitalizations in 99 hospitals within the national myocardial infarction audit. Hospitalizations were classified in real time as ST-segment elevation myocardial infarction (STEMI) or non-ST-segment elevation myocardial infarction (NSTEMI) for the period from January 1, 2019, to May 22, 2020. Seven-day moving averages adjusted for seasonal variation were used to analyze temporal trends. It was found that after the introduction of a nationwide lockdown in the UK (March 23, 2020), the median number of daily hospitalizations significantly decreased, more markedly for NSTEMI (from 69 to 35 cases; IRR 0.51) than for STEMI (from 35 to 25 cases; IRR 0.74), with minimum values by April 19, 2020.
Patients hospitalized during the lockdown were slightly younger, more frequently had diabetes and cerebrovascular disease. For STEMI during the pandemic, primary percutaneous coronary intervention was performed more frequently (81.8% vs. 78.8%), with an extremely low rate of thrombolytic therapy. For NSTEMI, a significant reduction in time to coronary angiography (26.2 vs. 64.0 hours) and a reduction in hospitalization duration (from 4 to 2 days) were noted, while adherence to secondary prevention pharmacotherapy remained high (>94%). Meanwhile, 30-day mortality increased for NSTEMI (from 5.4% to 7.5%; OR 1.41) but decreased for STEMI (from 10.2% to 7.7%; OR 0.73). The authors concluded that the pandemic was accompanied by a significant decrease in AMI hospitalizations, with patients presenting later and having more severe disease, especially for NSTEMI.
Similar results were obtained in a Spanish multicenter national retrospective registry, including data from 75 specialized STEMI care centers in various regions of Spain [26]. Patients were distributed into cohorts before and during the COVID-19 pandemic with subsequent 30-day follow-up. Over 94% of patients in both groups received primary PCI. During the pandemic, a significant prolongation of total myocardial ischemic time was noted (233 [150–375] vs. 200 [140–332] minutes), with no difference in time from first medical contact to reperfusion. The number of patients with suspected STEMI decreased by 27.6%, and the number of confirmed STEMI cases decreased by 22.7%. In-hospital mortality was higher during the pandemic (7.5% vs. 5.1%), and the association persisted after multivariate adjustment (RR 1.88). The authors noted that the combination of STEMI and SARS-CoV-2 infection was relatively rare but accompanied by a twofold increase in in-hospital mortality with an unchanged reperfusion strategy.
Data from the USA, obtained by a research group from the University of Rochester School of Medicine, based on an analysis of Medicare patient hospitalizations during 2016–2020, demonstrated that the increase in COVID-19 incidence in hospitals was not associated with worsening outcomes or a decrease in revascularization rates in STEMI patients, including analysis by racial and ethnic subgroups [27]. At the same time, for NSTEMI during periods of high COVID-19 burden, an increase in in-hospital mortality and a decrease in revascularization rates were noted.
Initial data from the North American COVID-19 Myocardial Infarction Registry (NACMI), presented by Garcia S et al. [13], included STEMI patients with confirmed COVID-19 infection, suspected infection (PUI), and a comparable pre-COVID control group. The primary composite endpoint (in-hospital death, stroke, recurrent infarction, or unplanned revascularization) was recorded in 36% of COVID-19 patients, 13% in the PUI group, and 5% in the control group. COVID-19 patients more frequently had cardiogenic shock and refusal of invasive strategy; however, when coronary angiography was performed, PCI remained the dominant reperfusion strategy. The authors concluded that patients with COVID-19 and STEMI represent a high-risk group with consistently adverse clinical outcomes, while primary PCI remains technically feasible and the preferred reperfusion method, consistent with current guidelines [7].
In Turkey, researchers from the Department of Cardiology, University of Health Sciences Turkey, Şişli Hamidiye Etfal Training and Research Hospital (Istanbul, Turkey) conducted a retrospective study aimed at assessing the impact of COVID-19 infection on coronary microcirculation in ACS patients who underwent PCI [28]. The analysis included 165 ACS patients hospitalized between March 1 and June 30, 2020, of whom 26 (15.7%) had confirmed SARS-CoV-2 infection. PCR testing was performed in the presence of clinical symptoms or typical changes on computed tomography.
To assess reperfusion success, angiographic indicators of thrombolysis in myocardial infarction were used – corrected TIMI frame count (cTFC) and myocardial blush grade (MBG), which are validated markers of coronary blood flow and myocardial perfusion. The cTFC method is used as a continuous indicator of coronary flow velocity and has high reproducibility, and the MBG indicator reflects the effectiveness of microvascular perfusion and is a prognostically significant factor for mortality after primary PCI [29].
Patients with COVID-19 had higher cTFC values, indicating slower coronary blood flow, and significantly lower MBG scores (grade 0–1), indicating severe impairment of microvascular perfusion. Peak troponin I values in the COVID-19 group were significantly higher compared to patients without infection (27,335 vs. 15,959 ng/dL). Furthermore, patients with COVID-19 more frequently had reduced left ventricular ejection fraction. In-hospital mortality in the COVID-19 group was significantly higher (38.4% vs. 7.2%).
According to logistic regression analysis, cTFC values and left ventricular ejection fraction were independently associated with in-hospital mortality in COVID-19 patients with ACS. In correlation analysis, cTFC positively correlated with C-reactive protein level (r=0.340) and peak troponin I values (r=0.369). The authors concluded that COVID-19 infection is associated with slower coronary blood flow and significant impairment of microvascular perfusion in ACS patients after primary PCI.
Despite the identified adverse pathophysiological changes, professional societies, including the Society for Cardiovascular Angiography and Interventions (SCAI) and the European Association of Percutaneous Cardiovascular Interventions (EAPCI), recommended considering primary percutaneous coronary intervention as the standard reperfusion strategy for STEMI patients during the COVID-19 pandemic [30, 31].
In-hospital outcomes of STEMI patients who underwent PCI during the pandemic were further analyzed in the French national PCI France registry (Rangé G et al.) [32]. The study included 2,064 STEMI patients: 1,942 in the pre-lockdown period and 122 during lockdown restrictions. During the lockdown, a decrease in the average number of STEMI hospitalizations by 12% (139 vs. 122 cases per month) was noted. A significant increase in the time from symptom onset to first medical contact in patients self-presenting to the emergency department (238 vs. 450 minutes) was also observed.
In the lockdown group, higher rates of in-hospital major adverse cardiovascular events (MACE: death, stent thrombosis, recurrent myocardial infarction, unplanned revascularization, stroke, major bleeding) and in-hospital mortality (12.3% vs. 7.7%, and 8.2% vs. 4.9%, respectively) were noted, but the differences did not reach statistical significance. The authors concluded that the COVID-19 outbreak in France was accompanied by a decrease in STEMI hospitalizations, an increase in delays in seeking medical care, and a trend towards worsening in-hospital outcomes, despite maintaining the primary PCI strategy.
STEMI patients receiving treatment during the COVID-19 pandemic in some cases require more time to achieve reperfusion. Delayed reperfusion therapy potentially increases the risk of out-of-hospital cardiac arrest (OHCA) in this category of patients. Limited access to medical care, later seeking of medical help, and healthcare system overload during the pandemic are considered possible factors contributing to an increased risk of OHCA in STEMI.
Polish cardiologists from the Center for Invasive Cardiology, Electrotherapy, and Angiology (Nowy Sącz, Poland) conducted a retrospective study aimed at assessing the impact of the COVID-19 pandemic on the timeliness of care and periprocedural outcomes in STEMI patients complicated by out-of-hospital cardiac arrest [33]. The analysis included 5,501 STEMI patients with OHCA who underwent primary percutaneous coronary intervention with stent implantation. To minimize the influence of the non-randomized design, propensity score matching was used, resulting in the formation of 740 pairs of patients treated before and during the COVID-19 pandemic.
The authors found no significant differences in the level of in-hospital mortality and the frequency of periprocedural complications between the groups. However, patients treated during the pandemic had a statistically significant increase in the time from first medical contact to coronary angiography (101.4±109.8 min vs. 88.8±61.5 min), as well as a trend towards an increase in the interval from the onset of pain to angiography (227.9±231.4 min vs. 207.3±192.8 min). The authors concluded that, despite comparable periprocedural outcomes, treatment of STEMI patients with OHCA during the pandemic is associated with longer delays to reperfusion.
In a Chinese-American study conducted by specialists from the Department of Global Health, Peking University School of Public Health and the Department of Health Policy and Management, University of Maryland, an assessment of the impact of the COVID-19 pandemic on hospitalizations and the quality of specialized medical care for myocardial infarction patients was conducted [34]. The primary endpoint was the number of re-hospitalizations for myocardial infarction, secondary endpoints were indicators of the quality of medical care. It was found that the number of daily hospitalizations during the peak of the pandemic and after it was 53% and 38%, respectively, of the indicators for the same period in 2019. A gap between the expected and actual number of hospitalizations persisted, with some deaths associated with patients' refusal to seek medical help. Furthermore, in 2020, an increase in door-to-balloon time (from 17.5 to 34.0 min) and a decrease in the frequency of PCI (from 71.3% to 60.1%) were noted.
Data from the American Heart Association's COVID-19 Cardiovascular Disease Registry, analyzed by the TIMI Study Group (Brigham and Women's Hospital, Harvard Medical School), included information on COVID-19 patient hospitalizations from January 14 to November 30, 2020, from 105 medical centers [12]. Out of 15,621 COVID-19 hospitalizations, ST-segment elevation myocardial infarction was diagnosed in 54 patients (0.35%). In most STEMI patients, transthoracic echocardiography was performed; however, coronary angiography was performed in less than a third of patients, and 27.5% of patients did not receive any reperfusion therapy.
In STEMI patients with COVID-19, severe complications were recorded significantly more frequently compared to patients without STEMI, including shock of any etiology (47% vs. 14%), cardiac arrest (22% vs. 4.8%), acute heart failure (17% vs. 1.4%), and the need for renal replacement therapy (11% vs. 4.3%). In-hospital mortality in STEMI patients reached 41% compared to 16% in patients without STEMI. The authors concluded that STEMI in hospitalized patients with COVID-19 is relatively rare but associated with an extremely unfavorable prognosis. The low frequency of coronary angiography and primary reperfusion in this group highlights the need to adapt healthcare systems to ensure timely and modern treatment for STEMI patients during a pandemic.
In a multicenter Polish study conducted by staff from the hospital in Końskie (Poland), an analysis of 29,915 STEMI patients was performed, of whom 3,139 (10.5%) underwent aspiration thrombectomy [35]. COVID-19 infection was confirmed in 311 patients (10.8%). The study compared clinical characteristics, angiographic features, and outcomes in STEMI patients with COVID-19 (+) and without COVID-19 infection (–). Multivariate logistic regression analysis was used to identify factors associated with thrombectomy performance.
In COVID-19 (+) patients, a severe clinical status on admission was recorded significantly more frequently, including Killip class IV heart failure (12.3% vs. 5.8%), as well as a higher frequency of prehospital cardiac arrest (8.0% vs. 4.8%). Achieving TIMI-3 flow after pPCI was less frequent in COVID-19 (+) patients compared to COVID-19 (–) (80.5% vs. 87.1%). Meanwhile, periprocedural mortality did not differ statistically significantly between groups. Multivariate analysis showed that the presence of COVID-19 was an independent predictor of the need for aspiration thrombectomy (OR = 1.23). The authors concluded that STEMI patients with COVID-19 are characterized by a more severe clinical condition and high thrombotic burden, and the effectiveness of PCI in this group is lower, despite more intensive antithrombotic therapy.
Of particular interest are data from a multicenter retrospective study covering clinics in Italy, Lithuania, Spain, and Iraq, conducted by researchers from Baylor University Medical Center (Dallas, USA) [36]. The analysis included 78 patients with symptomatic COVID-19 infection and STEMI, hospitalized between February 1 and April 15, 2020. The median age of patients was 65 [58–71] years, most had significant comorbidities. During hospitalization, 10% of patients developed acute respiratory distress syndrome, 18% required invasive mechanical ventilation. Primary PCI was performed in 19 patients (24%), while 59 (76%) received fibrinolytic therapy. In patients who underwent pPCI, stent thrombosis was diagnosed in 21% of cases, and in-hospital mortality reached 26%. In the fibrinolysis group, successful reperfusion was achieved in 85% of patients, but a high frequency of hemorrhagic stroke (9%) was noted. The authors emphasized the unusually high frequency of early stent thrombosis in COVID-19 patients with STEMI, indicating the need to revise antithrombotic strategies in this category of patients.
The efficacy and safety of pPCI in STEMI patients with concomitant COVID-19 infection were also analyzed in a single-center observational study by interventional cardiologists at Barts Heart Centre (London) [37]. COVID-19 (+) patients had a significantly higher thrombotic burden, including multivessel coronary thrombosis, more frequent use of aspiration thrombectomy and glycoprotein IIb/IIIa inhibitors. Biochemically, these patients had higher levels of troponin T, D-dimer, and C-reactive protein against a background of lymphopenia. Left ventricular ejection fraction and myocardial perfusion grade were significantly lower than in patients without COVID-19. Furthermore, higher doses of heparin were required to achieve target activated partial thromboplastin time (aPTT) values. STEMI patients with COVID-19 more frequently required intensive care and had a more severe disease course. The authors concluded that COVID-19 infection is accompanied by a pronounced shift in hemostatic balance towards hypercoagulability, leading to a high thrombotic burden and worse outcomes.
The main conclusions of British interventional studies were developed in an editorial article in the Journal of the American College of Cardiology (September 2020), in which Dauerman H.L. noted that pPCI in COVID-19 patients with STEMI is a technically more complex procedure and requires increased caution [38]. It was shown that massive coronary thrombotic burden (modified thrombus score 4–5) is detected in 75% of COVID-19 (+) STEMI patients compared to 31.4% in patients without COVID-19. Multivessel thrombosis and early stent thrombosis were also significantly more common.
Despite the more pronounced thrombotic burden, in-hospital mortality in COVID-19 (+) STEMI patients in British cohorts was moderately higher than in COVID-19 (–) (17.9% vs. 6.5%), which differs from data from individual American and Italian studies where mortality reached 40–75% [40, 41]. However, approximately a quarter of COVID-19 (+) patients experienced cardiac arrest, underscoring the extreme severity of myocardial damage.
The high thrombotic burden in STEMI patients with COVID-19 is likely due to the pronounced systemic inflammatory response characteristic of SARS-CoV-2 infection. It is accompanied by activation of endothelium, platelets, leukocytes, and vascular smooth muscle cells, which is confirmed by elevated levels of C-reactive protein and D-dimer [43–45]. Previously, the association of viral infections (particularly influenza) with an increased risk of myocardial infarction has already been described [46, 47]; however, COVID-19 is characterized by a more aggressive inflammatory and thrombogenic potential, leading to thrombosis in multiple vascular beds.
The development of hypercoagulability in severe COVID-19 patients is confirmed by elastography data and clinical observations demonstrating an increase in the frequency of venous thrombosis, pulmonary embolism, ischemic strokes, and disseminated intravascular coagulation [44, 48, 49]. These data indicate the need to revise and individualize antithrombotic therapy in COVID-19 patients, especially in critical condition and when combined with acute coronary syndrome [50].
In comments by French authors from the European Georges Pompidou Hospital (Department of Cardiology, Paris, France) [51], based on data from Choudry FA et al. (2020), it is emphasized that the optimal regimen of anticoagulant therapy in STEMI patients with concomitant COVID-19 infection who have undergone PCI remains insufficiently defined. The authors note that in clinical practice, intravenous use of low molecular weight heparin (LMWH), particularly enoxaparin, may have several advantages over unfractionated heparin (UFH), including a more predictable dose-effect relationship, stable anticoagulant activity, and the absence of a need for constant laboratory monitoring and dose adjustment. This makes LMWH a potentially attractive alternative to UFH in combination with dual antiplatelet therapy, especially considering compliance with modern STEMI treatment guidelines [7, 52, 78] and the proven effectiveness of LMWH for venous thromboembolic complications in COVID-19 patients [44].
The problem of choosing a revascularization strategy and method for STEMI development against the background of COVID-19 was considered in detail in a review by American authors Yerasi C et al. (2020) [53], staff from the Division of Interventional Cardiology, MedStar Washington Hospital Center (USA). The authors noted that at the beginning of the pandemic, there were no randomized studies directly comparing different treatment strategies for STEMI in the context of COVID-19. As a guide, recommendations from Chinese specialists from Sichuan Province [54] were considered, suggesting fibrinolytic therapy for STEMI patients with symptom duration less than 12 hours and performing PCI only after receiving a negative SARS-CoV-2 test. This approach was based on an assessment of the risk of infection spread during invasive procedures and assumed conservative management of patients until respiratory status stabilized.
However, this strategy proved difficult to implement in clinical practice for several reasons. A significant proportion of patients had contraindications to fibrinolysis (history of ischemic or hemorrhagic stroke, active bleeding, elderly age, multiorgan failure, cytokine storm in COVID-19) [43]. Furthermore, in patients with signs of STEMI on ECG, alternative causes of ST-segment elevation were often identified, including takotsubo syndrome, myopericarditis, and spontaneous coronary artery dissection, which complicated clinical interpretation and choice of treatment strategy [55, 56]. The use of fibrinolytics was also accompanied by an increase in healthcare resource consumption due to longer patient hospital stays and the need for intensive monitoring.
Pre-COVID period data, obtained from the analysis of 29,190 STEMI patients from 229 hospitals participating in the Get With The Guidelines–Coronary Artery Disease (GWTG-CAD) program, showed that in-hospital mortality with fibrinolysis was higher compared to pPCI (4.6% vs. 3.3%), hospital stay duration was longer (4 vs. 3 days), and the proportion of patients with hospital stays over 4 days reached 39% vs. 28% in the pPCI group [57]. Additional concern was raised by pandemic period data indicating the development of acute respiratory distress syndrome in approximately 31% of COVID-19 patients, which may be exacerbated by an increased risk of alveolar hemorrhage with thrombolytic therapy [43, 58].
In a review by American researchers from the Georgia Heart Institute [59], it is emphasized that pPCI remains the first-line reperfusion strategy for STEMI in most countries, although the proportion of fibrinolysis-oriented strategies in modern practice varies from 2% to 13% [60]. During the COVID-19 pandemic, significant delays in reperfusion compared to the pre-COVID period were noted, due to patients' late seeking of medical help, increased infection control measures, potential risk to medical personnel, and increased time spent in emergency departments, leading to prolongation of the door-to-balloon indicator. Under these conditions, the advisability of broader use of fibrinolytic therapy in certain categories of STEMI patients was discussed [6].
Similar conclusions are presented in a review by interventional cardiologists from Manchester Heart Centre (UK) [61], which emphasizes that, despite the proven superiority of PCI over fibrinolytic therapy and its status as the gold standard for STEMI treatment in Western countries, pharmacoinvasive strategies continue to be used in some regions of the world. These approaches were studied in detail in the randomized STREAM trial [62], in which a pharmacoinvasive strategy (fibrinolysis followed by PCI within 6–24 hours) proved to be no less effective than pPCI when invasive intervention was inevitably delayed, although it was accompanied by a higher risk of intracranial hemorrhages.
Thus, during the COVID-19 pandemic, delays in STEMI patients seeking medical help, organizational limitations, increased infectious risk, and lengthening of door-to-balloon time contributed to a revision of reperfusion strategies. Despite the temporary expansion of indications for a pharmacoinvasive approach in some regions, pPCI retained its status as the preferred revascularization method. At the same time, STEMI patients with COVID-19 had a high thrombotic burden and a reduced frequency of achieving TIMI-3 flow after PCI, despite more intensive antiplatelet and anticoagulant therapy. These features underscore the need for further research aimed at optimizing antithrombotic strategy and revascularization tactics in patients with acute myocardial infarction against the background of COVID-19.

Features of Antithrombotic Therapy and Secondary Medical Prevention in Patients with COVID-19 with NSTEMI and STEMI

COVID-19 is associated with an increased tendency to develop thrombotic complications in both venous and arterial circulation. This is due to the combined effects of systemic inflammation, platelet activation, endothelial dysfunction, and venous stasis. The combination of these mechanisms creates a state of hypercoagulability, which significantly increases the risk of thromboembolic complications in COVID-19 patients [63].
An additional clinical complexity is the fact that a significant proportion of patients already receiving antithrombotic therapy for thrombotic diseases develop COVID-19, requiring a review of drug choice, dosing, and laboratory monitoring. Antithrombotic therapy and prevention of thromboembolic complications are mandatory components of managing hospitalized COVID-19 patients, as enshrined in the national clinical guidelines of the Russian Federation and the USA [7, 64]. The rationale for this approach is based on the key role of thromboinflammatory mechanisms in the pathogenesis of organ damage in SARS-CoV-2 infection.
Patients with severe forms of COVID-19 often exhibit hemostasis system disorders resembling other systemic coagulopathies associated with severe infections, including disseminated intravascular coagulation (DIC) and thrombotic microangiopathy [65]. However, coagulopathy in COVID-19 has a number of distinctive features. The combination of moderate thrombocytopenia, prolonged prothrombin time, and a significant increase in D-dimer level may indicate a DIC-like condition, but its laboratory profile differs from classic sepsis-associated DIC syndrome [66]. In sepsis, more pronounced thrombocytopenia and a less significant increase in D-dimer are typically observed than in COVID-19. It is important to note that most COVID-19 patients do not meet the International Society on Thrombosis and Haemostasis (ISTH) diagnostic criteria for DIC [67].
In some patients with severe COVID-19, clinically significant but often unrecognized venous and arterial thromboembolic complications develop [66, 67]. According to early cohort studies, the frequency of thromboembolic events in hospitalized COVID-19 patients reaches 35–45%, with the presence of coagulopathy associated with a significantly increased risk of fatal outcome [6, 9].
Many controlled studies have shown that characteristic laboratory signs of coagulopathy in COVID-19 are a significant increase in D-dimer concentration, a moderate decrease in platelet count, and prolongation of prothrombin time [69, 70]. In patients in intensive care units, the median D-dimer level was significantly higher (2.4 mg/L; IQR 0.6–14.4) than in patients outside intensive care (0.5 mg/L; IQR 0.3–0.8) [70]. An increase in D-dimer level above 1.0 mg/L was associated with an over 18-fold increase in the risk of death in COVID-19 patients [43].
Coronavirus infection is also accompanied by activation of the fibrinolytic system. Endothelial cell damage leads to massive release of tissue plasminogen activators, which may explain the extremely high levels of D-dimer and fibrin degradation products in patients with severe COVID-19 [63].
Moderate thrombocytopenia (platelet count <150 × 10⁹/L) is detected in 70–95% of patients with severe forms of COVID-19. However, thrombocytopenia is generally not an independent predictor of disease progression or adverse outcome [65, 70]. According to dynamic observations, only about 5% of patients have a platelet level decrease below 100 × 10⁹/L [69, 70].
Fibrinogen concentration in most COVID-19 patients is at the upper limit of normal or elevated, which likely reflects an acute phase inflammatory response. However, in some patients shortly before death, a sharp decrease in plasma fibrinogen level below 1.0 g/L has been described, which may indicate the development of exhaustion of coagulation potential [68].
Thrombotic microangiopathy develops as a result of pathological interaction of platelets with the vascular wall, mediated by ultra-large von Willebrand factor multimers released from damaged endothelial cells. Under normal conditions, the activity of these multimers is regulated by the metalloproteinase ADAMTS13. In systemic inflammatory conditions, including severe infections, relative deficiency of ADAMTS13 may develop. However, data on the state of the ADAMTS13 system in patients with acute coronary syndrome, myocardial infarction, and severe COVID-19 are currently limited [63].
In clinical practice, prophylactic and therapeutic use of heparins in COVID-19 patients, including when combined with acute coronary syndrome and myocardial infarction, is considered. In a retrospective study conducted in China that included 449 COVID-19 patients, it was shown that in patients with coagulopathy receiving prophylactic heparin therapy, mortality was lower compared to patients not receiving anticoagulants (40% vs. 64%) in the subgroup with severe sepsis-associated coagulopathy [68]. A particularly pronounced effect was observed in patients with D-dimer levels exceeding the upper limit of normal by more than 6 times.
There is evidence supporting the effectiveness of prophylactic use of LMWH for preventing venous thromboembolism in critically ill COVID-19 patients [71]. Given the hypercoagulable profile of the disease, thromboprophylaxis is recommended for most hospitalized COVID-19 patients in the absence of contraindications. If LMWH is unavailable, unfractionated heparin can be used, but this requires more frequent administration and laboratory monitoring. An alternative may be fondaparinux, but its potential anti-inflammatory effects, characteristic of heparins, remain insufficiently studied [63].
In patients with severe forms of COVID-19, the use of increased doses of anticoagulants compared to standard prophylaxis may be required, which is associated with a pronounced hypercoagulable state [72]. This hypothesis is currently being evaluated in a number of multicenter randomized clinical trials (NCT04372589, NCT04345848, NCT04366960).
The nature of coagulation disorders and their role in coronary thrombus formation in patients with confirmed STEMI against the background of COVID-19 infection were studied in detail in a study conducted in the Department of Cardiology, Barts Heart Centre, St Bartholomew's Hospital (London, UK) [37]. In STEMI patients with concomitant COVID-19 infection, higher levels of troponin T, pronounced lymphopenia, and a significant increase in concentrations of D-dimer and C-reactive protein were detected. Angiographically, these patients had a significantly higher thrombotic burden, frequent development of multivessel coronary thrombosis and stent thrombosis. During pPCI, aspiration thrombectomy and glycoprotein IIb/IIIa inhibitors were used more frequently, and higher doses of heparin were required to achieve therapeutic aPTT values. The authors concluded that in STEMI patients with COVID-19, there is a pronounced shift in hemostatic balance towards hypercoagulability, which is associated with greater thrombotic load and less favorable clinical outcomes. This underscores the need for routine testing for COVID-19 in all STEMI patients and conducting further research to clarify the criteria for coronary thrombosis and indications for more aggressive antithrombotic therapy in specific clinical situations.
Coronavirus disease 2019 may predispose patients to thrombotic complications in both venous and arterial circulation due to systemic inflammatory response, platelet activation, endothelial dysfunction, and blood stasis. An additional complexity is the fact that patients already receiving antithrombotic therapy for thrombotic diseases may develop COVID-19, requiring a review of drug choice, dosing, and laboratory monitoring. During the pandemic, special attention is also paid to optimizing medical care for non-COVID-19 patients suffering from thrombotic diseases, including acute coronary syndrome and acute myocardial infarction. The use of antithrombotic agents as correctors of endothelial dysfunction improves the function of damaged endothelium. It is important to consider that in combination with lopinavir + ritonavir, through inhibition of cytochrome P450 CYP3A4 enzymes, antiviral agents can affect the activity of P2Y12 inhibitors, accompanied by a decrease in the concentration of active metabolites of clopidogrel and prasugrel, and an increase in the concentration of ticagrelor. If a P2Y12 inhibitor is necessary, prasugrel is the drug of choice [77].
In a literature review by researchers from Columbia University (New York, USA), modern concepts of pathogenesis, epidemiology, and clinical outcomes of thrombotic complications in COVID-19 patients are considered, including patients with venous and arterial thrombosis, patients with pre-existing thrombotic diseases, and individuals requiring continuation of antithrombotic therapy in special clinical situations, including during pregnancy [44]. According to available data, patients with COVID-19 often exhibit hemostasis system disorders resembling disseminated intravascular coagulation, but with a distinctive laboratory profile [73]. Severe inflammatory response, critical condition, and presence of comorbid risk factors may contribute to the development of thrombotic complications, which has been noted previously with other highly virulent zoonotic coronavirus infections [74, 75]. Furthermore, the potential for drug interactions between drugs used to treat COVID-19 and antiplatelet or anticoagulant agents is emphasized [44, 78].
The influence of secondary prevention pharmacotherapy on the course of myocardial infarction in COVID-19 patients was also analyzed in a study by cardiologists from the Leeds Institute for Data Analytics and the University of Leeds (UK) [25]. The authors assessed the impact of the COVID-19 pandemic on the nature of inpatient treatment and 30-day mortality from acute myocardial infarction in 99 hospitals within the national myocardial ischemia audit. It was found that the frequency of prescribing medication therapy for secondary prevention remained stable and exceeded 94% in all analyzed subgroups. Meanwhile, 30-day mortality in patients with non-ST-segment elevation myocardial infarction (NSTEMI) increased (from 5.4% to 7.5%; OR 1.41), whereas in STEMI patients a decrease was noted (from 10.2% to 7.7%; OR 0.73). The authors concluded that during the COVID-19 pandemic, it was precisely NSTEMI patients who were characterized by a more unfavorable short-term prognosis.
It is important to remember that in patients with cardiovascular diseases, the problem of drug safety is particularly acute, as most of them have several risk factors for the development of adverse drug effects (elderly and senile age, presence of multiple pathologies, need to take ≥2 drugs, burdened allergic history) [78].
Standards for managing hospitalized patients with complicated forms of COVID-19 provide for comprehensive antiviral, antibacterial, antithrombotic, anti-inflammatory, hormonal, and symptomatic therapy. The influence of such pathogenetic and symptomatic therapy on the clinical outcomes of acute coronary syndrome and myocardial infarction has been studied to a limited extent. In a prospective observational study conducted at the Milan Regional Public Health Center, the role of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in STEMI patients hospitalized during the first wave of the pandemic was analyzed [76]. It was shown that in 2020, the time from symptom onset to hospitalization was significantly longer compared to pre-pandemic periods, and the proportion of patients with late STEMI significantly increased. At the same time, the frequency of use of ACE inhibitors and ARBs, as well as in-hospital outcomes, including mortality and hemodynamic complications, did not differ significantly from the indicators of previous years.

Conclusion

Summarized data from the presented literature review are shown in the form of a structured Table 2.
Table 2
Summary table: Tactics and features of managing patients with COVID-19 and ST-segment elevation myocardial infarction

Accordingly, managing STEMI patients against the background of COVID-19 is a complex clinical task requiring an aggressive reperfusion strategy (preferably pPCI), intensive and individualized antithrombotic therapy, and optimized organization of medical care in pandemic conditions to improve outcomes.
Thus, in patients with COVID-19, coagulation disorders mimicking systemic coagulopathies, including DIC syndrome, are often detected, but they have specific pathophysiological features. In STEMI patients with concomitant COVID-19 infection, higher levels of myocardial injury and inflammation markers, pronounced thrombotic burden, more frequent development of multivessel thrombosis and stent thrombosis, and the need for more intensive anticoagulant therapy are noted. At the same time, the principles of secondary medical prevention in myocardial infarction patients during the COVID-19 pandemic generally remain unchanged, and the use of ACE inhibitors and ARBs, according to available data, does not have a significant impact on the clinical outcomes of the disease.