Benefits of AstraZeneca overwhelmingly high despite increased clotting risk

Anastasia Tsirtsakis

28/04/2021 4:49:03 PM

New European research has found the risk of a rare blood clotting syndrome associated with the vaccine is double what has been previously reported.

AstraZeneca vaccine.
European estimates for the risk of the rare blood clotting syndrome associated with AstraZeneca are around double that indicated in EU data.


Risk versus benefit.
That is the debate that has taken centre stage as global concerns have continued to mount over a rare blood clotting syndrome associated with the AstraZeneca vaccine.
But a new analysis conducted by the European Medicines Agency’s (EMA) human medicines committee is helping to clarify just how rare that risk is, and how effective the vaccine could be in preventing hospital and intensive care unit (ICU) submissions, as well as death.  
According to the findings, the incidence of thrombosis with thrombocytopenia syndrome (TTS) following the AstraZeneca vaccine for people aged 20–49 is 20 per million.
That risk then halves to 10 per million for people aged in their 50s and 60s, and drops to about five per million for those 70 and over.
The analysis also breaks down the benefits by infection rate scenario – ranging from high, medium and low – based on an assumption of vaccine effectiveness of 80% over a period of four months.
If infection rates are medium – akin to Victoria’s second wave – the vaccine could prevent up to 1967.5 hospitalisations, 258.5 ICU admissions and 530 deaths per million, compared to a risk of 8.5 cases of TTS, for people over 50 in Australia.
The benefits for over-50s can also be seen when infection rates are low, with the potential to prevent up to 373 hospitalisations, 41 ICU admissions and 151.5 deaths per million.
The findings have added further weight to Australian Technical Advisory Group on Immunisation (ATAGI) advice for people under the age of 50 to receive Pfizer’s mRNA vaccine rather than AstraZeneca.
To date, GPs in Australia have delivered more than one million doses of AstraZeneca, out of which six cases of TTS have been recorded, including one fatality.
In line with global reports, the cases have been in people aged under 50, with the exception of an 80-year-old Victorian man.
While the European analysis has confirmed the blood-clot risks following AstraZeneca are low, the estimates are double what has been indicated in UK data that has been used to inform Australia’s updated vaccination strategy.
But according to ATAGI’s Co-Chair, Victoria’s Deputy Chief Health Officer Professor Allen Cheng, the risk is still ‘pretty small’ and while the group is considering the evidence, he says it is unlikely to impact advice for Australians over 50.
‘Obviously we’re looking at all data as it comes in, so if anything changes we might have to change our advice, but not at this stage,’ he said
Chair of RACGP NSW&ACT Associate Professor Charlotte Hespe this week told the Senate Select Committee on COVID-19 that GPs had faced challenges since ATAGI changed its advice, giving rise to vaccine hesitancy. She said consistent messaging is needed to help patients understand the small risk associated with the vaccine.
‘We’ve got large numbers around the world that have demonstrated what a good vaccine it is,’ Associate Professor Hespe said.
‘What would be really nice is having consistent messaging from across the states, as well as [from a] Federal [level].
‘We do know that AstraZeneca is safe and has a really good outcome for the vast majority of people that it is indicated for … and we just need to be able to get on with doing that and have some clearer communication lines about Pfizer versus AstraZeneca for people as they plan going forwards.’
The Sydney-based GP empathised with patients, saying it can be difficult for some to understand what was at stake if vaccine uptake remained low, given the low numbers of community transmission in Australia.
‘It’s hard for people to understand what that risk means to them when we just otherwise really seem to have a normal life,’ Associate Professor Hespe said.
‘Whereas we know medically that what we’re trying to do is prevent the awfulness that is happening overseas.
‘I think some more conversation around “this is why we’re doing it as a community” [would be helpful]. Whereas it’s a no brainer when you’re actually amongst the pandemic infection numbers.’
The EMA used data reported to the European database for side effects to calculate the risk of TTS, but acknowledges that, as with many population-based analyses, there are some uncertainties.
‘These uncertainties stem from the lack of uniform data across the EU, possible delays in reporting side effects, possible unreported side effects, and limited data from observational studies. As more data become available, the estimates of benefits and risks can be updated,’ the EMA said.
While previous overseas data has indicated TTS is most common in younger females, the EMA’s analysis concluded that there is ‘insufficient data available’ from across the EU to provide further context on benefits and risks with regard to gender.
Associate Professor Hespe said changes to the vaccine strategy have further cemented the importance of people getting vaccinated by their GP. She also reiterated the ongoing need for practices to secure larger vaccine supplies.
‘There does seem to be a rather bizarre way that the vaccine numbers have been allocated around the country so that increased numbers have gone sometimes to practices that don’t have large numbers of their own patients, but are seen as being a “vaccine hub”,’ Associate Professor Hespe said.
‘For instance, my own practice, we’ve got well over 8000 patients waiting for vaccine [and] we get 50 doses a week.
‘Whereas a GP down the road from me has been complaining because he gets 400 doses a week but actually is a solo GP with far more limited patients of his own, and it’s because he’s designated as a respiratory clinic that he’s been doing the rollout of the vaccine.
‘While we’ve still got a lot of the older patients and people with medical conditions [waiting to be vaccinated], I would just beg that the numbers of vaccines to those “standard practices” actually have increased numbers so they can actually just roll it out smoothly.’

Correction: This article previously stated that during a period of medium infection rates, vaccines could prevent up to 9070 hospitalisations, 1110 ICU admissions and 3170 deaths per million people, for people over 50 in Australia, while resulting in 30 cases of TTS.

It also stated that during a period of low infection rates, vaccines could prevent up to 2150 hospitalisations, 230 ICU admissions and 1080 deaths per million people. It has since been updated to better reflect the risks based on the Australian population.

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Dr Robert William Micallef   29/04/2021 7:30:27 AM

The risk benefit analysis was done on the basis of having a covid infection rate of one in every 250 people. This means we would not see this risk benefit until 100,000 people in Australia are infected with covid. In Australia I can see no reason to recommend the AZ vaccine in anyone under the age of 70. If we are honest the only reason the government is still recommending it’s use in over 50s is because of political expediency.

Dr Robert William Micallef   29/04/2021 8:24:18 AM

Looking at the analysis the EMA has done.: For a low infection rate of 55 per 100,000 they found in 50-59 for every covid death prevented there was 1.1 deaths from blood clots with low platelets. For 60-69 it was 3 covid deaths prevented for every 1 clot death. The real benefits only are apparent from 70 onwards. In terms of clot deaths the risk outweighs the benefit for those under 60 and is marginal for those under 70 assuming a low infection rate the equivalent of 13,750 people in the Australian population.

Dr Emad Mikhael Hanna   29/04/2021 8:24:30 AM

well if there is safer vaccines, why put our young people through this?
If any young person dies, the family is going to remember me or you who gave him the deadly needle not ATAGI.

Dr Wakinyjan Catherine Tabart   29/04/2021 12:05:32 PM

We need to realise that we cant predict when infections might get our of control in the community again. Over the long term, unless the new strains are not adequately covered by the current vaccines, the benefits should still be enough in over 50s, especially if we want to start travelling or work in higher risk professions for contact with potential SARS-CoV-2. Living in the NT I am a bit nervous that infection could escape from the Howard springs facility and then spread rapidly. I've had my first AZ vaccine but will not be fully vaccinated until late June.

Dr Wendelin Ikarus Dietrich Fischer   29/04/2021 2:21:12 PM

I think after actually reading the study esp. the last part of their comparison- you quickly get get the point only old people should have this vaccine if you don‘t want to kill young people.....and that is without knowing any of the potential longterm problems of those new vaccines in the years to come ( risk of autoimmune disease, risk of ADE, no genotoxicity or cancerogenicity studie)

Dr Ruth Appleby   29/04/2021 4:07:52 PM

Dr Micallef is mistaken when he quotes the analysis as comparing deaths from blood clots with deaths from COVID-19. In every table, the comparison is CASES of blood clots with low platelets (TTS, thrombosis with thrombocytopenia symdrome) versus the COVID-19 metric of interest. This is accurately reflected in the text of article. So far the Australian experience has been one death out of 6 cases of TTS. With increased awareness, early detection and improved treatment for individuals with post-vaccine TTS, we would expect the survival rate to further improve, especially if ICUs are not overwhelmed with active COVID cases.

Dr Ruth Susan Appleby   29/04/2021 4:18:14 PM

Dr Tabart's point is also very important to take into consideration. No-one can tell when community infections will get out of control. I am based in Cambodia and this country was virtually unscathed by COVID-19 until two months ago. Now community transmission is skyrocketing, and I am looking forward to getting vaccinated with one of the Chinese vaccines, since that is what is available here.
Australia's unvaccinated population remains naive and vulnerable to SARS-CoV-2 infection. With the pandemic rampaging around the world, it is inevitable that sooner or later pretty much every Australian will be exposed to it. We cannot keep it at bay forever. That is a prospect that needs to be part of every risk analysis, regardless of the momentarily current state of transmission in Australia.