Thromboembolic events observed with AstraZeneca COVID-19 vaccine; absolute risk small
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An analysis of data registries from three countries showed the AstraZeneca vaccine was associated with small but increased rates of hospital contacts for thromboembolic coagulation disorders, especially for thrombocytopenia.
A post hoc analysis demonstrated that while the RR for those conditions was increased, the absolute risk was low.
In the self-controlled analysis that included more than 5.3 million patients, researchers also observed statistically significant increases in risk for hospital contacts for thrombocytopenic and thromboembolic events after the BNT162b2 (Comirnaty, Pfizer-BioNTech) and mRNA-1273 (Spikevax, Moderna) vaccines; however, the risk was small compared with those observed after receiving the AZD1222 (Vaxzeyria, AstraZeneca) vaccine.
“The adenovirus vector vaccine Vaxzevria is associated with rare but severe complications such as thrombocytopenia and sinus venous thrombosis,” Jacob Dag Berild, MD, MPH, medical officer in the department of infection control and vaccines at the Norwegian Institute of Public Health in Oslo, Norway, told Healio. “Reassuringly, no consistent association was observed between the mRNA vaccines Spikevax and Comirnaty and these rare complications.”
Risk by vaccine type
Berild and colleagues analyzed individual-level data from national registries in Denmark, Finland and Norway for patients who received the AstraZeneca, Pfizer or Moderna vaccine. Researchers assessed the relative rate of hospital contacts for CAD, coagulation disorders or cerebrovascular disease in a 28-day period after vaccination compared with the control period before vaccination. Secondary outcomes were individual diseases within the main outcome groups of coagulation disorders, such as venous or arterial thrombosis, and cerebrovascular disease, such as intracranial hemorrhage or cerebral thromboembolic events. The researchers conducted self-controlled case series (SCCS) analyses for each country to estimate relative incidences of study outcomes for patients vaccinated during the study in the 28 days after vaccination compared with the pre-vaccination (control) period for each vaccine.
“In the SCCS method, each individual acts as their own control, and as such, the model implicitly controls for time-invariant confounders, such as sex, genetics and chronic underlying health conditions,” the researchers wrote.
During the study period, more than 5.3 million people across the three counties received the AstraZeneca (12%), Pfizer (80%) or Moderna (8%) vaccines. Researchers observed 265,339 incident events after vaccination, of which 44% were for CAD, 21% were for coagulation disorders and 35% were for cerebrovascular disease. Most incident events (93%) occurred in patients born in 1971 or earlier; 44% were women.
In the 28-day period after vaccination, researchers observed an increased rate of CAD after the Moderna vaccine (RR = 1.13; 95% CI, 1.02-1.25) but not after the AstraZeneca vaccine (RR = 0.92; 95% CI, 0.82-1.03) or Pfizer vaccine (RR = 0.96; 95% CI, 0.92-0.99).
There was an observed increased rate of coagulation disorders seen after all three vaccines, with an RR of 2.01 for the AstraZeneca vaccine (95% CI, 1.75-2.31), 1.12 for the Pfizer vaccine (95% CI, 1.07-1.19) and 1.26 for the Moderna vaccine (95% CI, 1.07-1.47). Researchers also observed an observed increased rate of cerebrovascular disease after all three vaccines, with an RR of 1.32 for the AstraZeneca vaccine (95% CI, 1.16-1.52), 1.09 for the Pfizer vaccine (95% CI, 1.05-1.13) and 1.21 for the Moderna vaccine (95% CI, 1.09-1.35).
Excess risk after vaccination remains low
In a post hoc analysis on absolute risk, the researchers estimated excess events per 100,000 doses for each outcome, demonstrating that although the RR was significantly increased, the absolute risk was low.
Researchers estimated the excess number of thrombocytopenic and cerebral venous thrombosis events after the AstraZeneca vaccine were 4.9 (95% CI, 2.9-6.9) and 1.6 (95% CI, 0.6-2.6) per 100,000 doses, respectively.
“The absolute risk calculated in our study also indicates the rarity of these events,” the researchers wrote. “The mechanism is still under investigation, and it has been suggested that it could be a rare vaccine-related variant of heparin-induced thrombocytopenia because of the presence of antibodies to platelet factor.”
The researchers noted the risk-benefit ratio of the vaccine depends on the risk for contracting COVID-19 and the risk for a severe outcome from COVID-19 weighted against the risk for an adverse event after vaccination.
“Clinicians need to be aware that the rare but serious syndrome called vaccine-induced immune thrombotic thrombocytopenia, or VITT, that can develop in the weeks after vaccination with an adenovector vaccine,” Berild told Healio. “The Nordic countries no longer use the adenovirus vector vaccines, since we have alternative vaccines. We did observe increased rates of several thromboembolic and thrombocytopenic outcomes after the two mRNA vaccines, but the rates were not consistent in sensitivity analysis checking the underlying assumptions. More research on these findings, with another design, is warranted.”
For more information:
Jacob Dag Berild, MD, MPH, can be reached at jacobdag.berild@fhi.no.
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