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Katsoularis I, Fonseca-Rodriguez O, Farrington P, et al. Risk of acute myocardial infarction and ischaemic stroke following COVID-19 in Sweden: a self-controlled case series and matched cohort study. Lancet. 2021 Aug 14;398(10300):599-607. doi: 10.1016/S0140-6736(21)00896-5. Epub 2021 Jul 29. (Original study)
Abstract

BACKGROUND: COVID-19 is a complex disease targeting many organs. Previous studies highlight COVID-19 as a probable risk factor for acute cardiovascular complications. We aimed to quantify the risk of acute myocardial infarction and ischaemic stroke associated with COVID-19 by analysing all COVID-19 cases in Sweden.

METHODS: This self-controlled case series (SCCS) and matched cohort study was done in Sweden. The personal identification numbers of all patients with COVID-19 in Sweden from Feb 1 to Sept 14, 2020, were identified and cross-linked with national inpatient, outpatient, cancer, and cause of death registers. The controls were matched on age, sex, and county of residence in Sweden. International Classification of Diseases codes for acute myocardial infarction or ischaemic stroke were identified in causes of hospital admission for all patients with COVID-19 in the SCCS and all patients with COVID-19 and the matched control individuals in the matched cohort study. The SCCS method was used to calculate the incidence rate ratio (IRR) for first acute myocardial infarction or ischaemic stroke following COVID-19 compared with a control period. The matched cohort study was used to determine the increased risk that COVID-19 confers compared with the background population of increased acute myocardial infarction or ischaemic stroke in the first 2 weeks following COVID-19.

FINDINGS: 86 742 patients with COVID-19 were included in the SCCS study, and 348 481 matched control individuals were also included in the matched cohort study. When day of exposure was excluded from the risk period in the SCCS, the IRR for acute myocardial infarction was 2·89 (95% CI 1·51-5·55) for the first week, 2·53 (1·29-4·94) for the second week, and 1·60 (0·84-3·04) in weeks 3 and 4 following COVID-19. When day of exposure was included in the risk period, IRR was 8·44 (5·45-13·08) for the first week, 2·56 (1·31-5·01) for the second week, and 1·62 (0·85-3·09) for weeks 3 and 4 following COVID-19. The corresponding IRRs for ischaemic stroke when day of exposure was excluded from the risk period were 2·97 (1·71-5·15) in the first week, 2·80 (1·60-4·88) in the second week, and 2·10 (1·33-3·32) in weeks 3 and 4 following COVID-19; when day of exposure was included in the risk period, the IRRs were 6·18 (4·06-9·42) for the first week, 2·85 (1·64-4·97) for the second week, and 2·14 (1·36-3·38) for weeks 3 and 4 following COVID-19. In the matched cohort analysis excluding day 0, the odds ratio (OR) for acute myocardial infarction was 3·41 (1·58-7·36) and for stroke was 3·63 (1·69-7·80) in the 2 weeks following COVID-19. When day 0 was included in the matched cohort study, the OR for acute myocardial infarction was 6·61 (3·56-12·20) and for ischaemic stroke was 6·74 (3·71-12·20) in the 2 weeks following COVID-19.

INTERPRETATION: Our findings suggest that COVID-19 is a risk factor for acute myocardial infarction and ischaemic stroke. This indicates that acute myocardial infarction and ischaemic stroke represent a part of the clinical picture of COVID-19, and highlights the need for vaccination against COVID-19.

FUNDING: Central ALF-funding and Base Unit ALF-Funding, Region Västerbotten, Sweden; Strategic funding during 2020 from the Department of Clinical Microbiology, Umeå University, Sweden; Stroke Research in Northern Sweden; The Laboratory for Molecular Infection Medicine Sweden.

Ratings
Discipline Area Score
Public Health 7 / 7
Infectious Disease 6 / 7
Emergency Medicine 6 / 7
Cardiology 6 / 7
Hospital Doctor/Hospitalists 6 / 7
Internal Medicine 6 / 7
Neurology 6 / 7
Comments from MORE raters

Emergency Medicine rater

This is a self-controlled case series (SCCS) and matched cohort study (MCS) of the effect of COVID-19 on the incidence of myocardial infarction (MI) and stroke (CVA) in Sweden. The number of enrolled patients was large (>400,000). The reliability of the results depend on having chosen appropriate controls. The methods are very complex although described in detail. The results are reported as incident rate ratio (IRR) for the SCCS and odds ratios for the MCS. For both MI and CVA and both SCCS and MCS, the IRRs were markedly elevated for the first week following COVID-19, with the effect lessening in the subsequent 2 weeks. For example, the IRRs for MI and CVA for the first week were 8.44 and 6.18, respectively. These findings suggest that COVID-19 is a risk factor for MI and CVA, that MI and CVA represent a part of the clinical picture of COVID-19, and highlights the need for vaccination against COVID-19.

Emergency Medicine rater

This is an excellent cohort study looking at the outcome of AMI or CVA in patients diagnosed with COVID. Although anecdotally we have all noticed the same pattern, this provides relative risks with confidence intervals to guide our decision-making process.

Hospital Doctor/Hospitalists rater

As the authors point out, early in the pandemic there was confusion over "missing" heart attacks and strokes (e.g. the NYT's "where have all the heart attacks gone?") that may have diminished concern initially about the connection between COVID-19 and vascular events. I think most hospitalists are now aware that COVID-19 can cause both venous and arterial events. That said, it's nice to have more evidence and this is a well-designed observational study that includes data on almost every patient with COVID-19 in Sweden, and outcomes data from databases that have been previously validated.

Internal Medicine rater

I think we recognize clot as a possible complication / presentation of COVID, but it's nice to have this confirmation that arterial as well as venous clot risk is quite elevated for at least a short period of time.

Public Health rater

This is a large study confirming prior studies which showed that COVID-19 is an independent risk factor for future ischemic events.

Public Health rater

This is definitely worth a detailed and critical read.
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