Using 3D to test personalised cancer treatments in five days

29th May 2019

Why doesn’t the same treatment work in the same way for every patient? How can a drug’s performance be optimised without causing side effects due to an excessive dosage?

In an attempt to answer these questions, researchers at the University of Geneva (UNIGE), Switzerland, have devised a cell co-culture platform that reproduces a patient’s tumour structure in 3D. The scientists can use it to test several drugs or their combinations at different stages of the tumour’s development. They now need only five days to identify which treatment will be most effective for a particular case, and the combination can then be translated for clinical practice. The results have been published in Scientific Reports.¹

Colorectal cancer is the third most common form of cancer diagnosed today and the fourth most deadly in the world: 1.4 million people are affected each year, with 700,000 fatalities. A range of treatments is available, including chemotherapy, but the high dosages cause numerous side effects and patients commonly develop resistance. These treatments are currently tested on 2D tumour cell cultures before being administered to patients. “But that doesn’t correspond to reality,” explains Patrycja Nowak-Sliwinska, a professor at the School of Pharmaceutical Sciences at the UNIGE’s Faculty of Science. “Not only does a tumour develop in 3D, but it also contains other types of cells, such as fibroblasts (tissues) and endothelial cells (blood vessels).” As a result, the Geneva-based scientists have built a new platform that uses a patient’s tumour cell lines to recreate the tumour in 3D. It also keeps it alive, so that the impact of the treatments can be analysed during the different stages of its development.

The team headed by Professor Nowak-Sliwinska, in collaboration with groups led by Didier Colin (HUG) and Olivier Dormond (CHUV), selected six cell lines derived from six different patients. The cells were stabilised in a hollow, U-shaped culture plate so that they stayed agglomerated and floated in a cell culture medium optimised to feed the tumour. “The structure can then be organised by itself in 3D and continue its development,” says Professor Nowak-Sliwinska. “The three types of cells that make up the tumour carry on interacting with each other, as though they were in the patient’s body.”  

Three drugs better than one
The researchers then tested several different combinations of three approved drugs at different developmental stages of the cultured tumours. “Our first observation was that each patient responded differently to the same combination, demonstrating that it’s impossible to reach similar efficacy for each patient with the same treatment. It needs to be considered on a case-by-case basis,” says Professor Nowak-Sliwinska. The scientists also found that a low-dose combination of three drugs was much more effective than a high-dose of one drug alone. “Treatment resistance and side effects occur when the dose is too high. Combining several drugs at low doses helps to circumvent this problem and improve treatment responses,” says the professor.

Personalised treatments in five days
The new platform opens the door to personalised medicine. “By extracting a cell line from the patient’s tumour, we can recreate the tumour in 3D on our platform and test the different drug combinations directly on that specific tumour. We can then select the optimal treatment for that particular patient,” continues Professor Nowak-Sliwinska. This meticulous work takes five days on average, a short enough time to act quickly against the cancer. “In this instance, we’re interested in colorectal cancer but this platform, which is easy to reproduce, can obviously be used for all kinds of tumours at a relatively low cost,” says Nowak-Sliwinska by way of conclusion.

Reference

1.     Zoetemelk M et al. Short-term 3D culture systems of various complexity for treatment optimization of colorectal carcinoma. Sci Rep 2019;9(1)DOI: 10.1038/s41598-019-42836-0

Skin patch shows promise for children with milk-induced eosinophilic oesophagitis

A study from Children’s Hospital of Philadelphia (CHOP) finds that a skin patch may be useful in treating children with a painful, chronic condition called eosinophilic oesophagitis (EoE) triggered by milk.¹

Among 20 children with EoE who wore Viaskin Milk – a skin patch measuring just over an inch long containing trace amounts of milk protein – nine (47%) saw an improvement in their symptoms and normalization of their biopsies after 11 months. This is the first study to examine how this treatment, called epicutaneous immunotherapy, may help children with milk-induced EoE.

The pilot study followed 20 children aged 4 to 17 with EoE. The patients followed a milk-free diet for nine months, then re-introduced milk into their diet for the next two months. After 11 months, almost half of those wearing the Viaskin Milk patch had fewer EoE symptoms, including less inflammation when they underwent an endoscopy compared to none in the placebo group.

“This study shows great promise for an immunotherapy that aims to desensitise children to milk,” said study leader Jonathan Spergel, MD, PhD, Chief of the Allergy Program at CHOP. “Our next step would be to launch a much larger study to confirm our results. Currently, there’s no cure for EoE, so this would be the first strategy to treat the underlying cause of the disease.”

EoE is a food-based disease that causes redness, swelling and itching in the oesophagus when a patient eats a food that triggers their reaction. Traditional allergy testing is not helpful. Patients may experience nausea, vomiting, or a burning sensation in the throat. If left untreated, the oesophagus may narrow due to scarring. Currently, the only ways to manage EoE is to treat the symptoms with off-label topical steroids which may cause growth retardation, or to follow a restrictive diet which may be difficult for patients to follow. Children with EoE often have other allergic disorders such as asthma, seasonal allergies or eczema.

Reference

1.     Spergel J et al. Efficacy of Epicutaneous Immunotherapy in Children with Milk-Induced Eosinophilic Esophagitis. Clin Gastroenterol Hepatic 2019;DOI: 10.1016/j.cgh.2019.05.014

Stem cell differences could explain why women are more likely to develop adrenal cancer

Scientists have discovered a potential biological reason why women are more likely to develop adrenal disorders, including cancer. According to the researchers, the answer could lie in the increased turnover of hormone-producing cells found in the adrenal glands of females.

The adrenal gland is a hormone producing organ that sits on top of the kidneys. The outer part, or cortex, is responsible for the production of several hormones, including the stress-related hormone cortisol and the blood pressure controlling aldosterone. Adrenal cancer is relatively rare but occurs approximately three times more in women than in men. The cellular basis for this difference has not been investigated in detail but uncovering it might lead to sex-specific treatments and has huge implications for many areas of research.

Dr Andreas Schedl, from INSERM, France, who led the study said: “To our surprise we found that adrenal cells in female mice show a much more rapid turnover compared to males, which we could trace back to a different behaviour of adrenal stem cells between the two sexes. Furthermore, we could show that the observed differences are due to hormones that are produced by testes that suppress cell division, thus slowing down renewal in the male adrenal.”

The scientists studied the adrenal cortex of male and female adult mice and found that female mice replace their entire set of hormone-producing cells within three months, while it takes male mice an entire nine months. Using different techniques to label cells within the adrenal cortex, they established that females not only have a higher proliferation rate of cells, but also recruit stem cells from a different part of the adrenal gland.¹

The research has wide reaching implications, as it demonstrates the basic mechanism underlying the increased turnover of cells within the adrenal gland, providing a possible explanation for the increased incidence of adrenal disorders in women.

Dr Schedl explained: “It is early days and many more experiments will need to be performed before our research can directly benefit patients. However, we believe that our study teaches a number of important lessons that are of immediate relevance to scientists, pharmacologists and clinicians.”

This research might lead to sex-specific treatment options for diseases like adrenal cancer and, according to Dr Schedl, could have implications on a far wider field of disorders: “Importantly, while our study concentrated on the adrenals, we are convinced that similar differences may also be found in other organ systems.”

Dr Helen Rippon, Chief Executive of the charity Worldwide Cancer Research, whose supporters helped fund the study, said: “Sex differences are not necessarily the first thing that comes to mind when thinking about cancer research or treatments. But this study has shown that it is crucial to consider potential differences between male and female when trying to understand the basis of cancer biology. Most importantly, these findings could have implications for treatment options further down the line and highlight the importance of early-stage, discovery research. We are delighted to fund this kind of research, as we believe that these innovative approaches are ultimately going to lead to a world where no life is cut short by cancer.”

Reference

1.     Grabek A et al. The Adult Adrenal Cortex Undergoes Rapid Tissue Renewal in a Sex-Specific Manner. Cell Stem Cell 2019;DOI: 10.1016/j.stem.2019.04.012

Pollen allergies occur more frequently in anxiety sufferers

Led by Claudia Traidl-Hoffmann, Director of the University Center for Health Sciences at University Hospital Augsburg (UNIKA-T) and Professor of Environmental Medicine at the Technical University of Munich, the team has differentiated between perennial or non-seasonal allergies and study participants also answered questions about their psychological health.

The focus here was on depression, generalised anxiety disorders, and acute mental stress. “There are studies that focus on the psychological components of skin diseases or allergic asthma. For the first time, we are now able to show a connection with seasonal allergies,” explains Katharina Harter, the publication’s lead author. Around a quarter of those surveyed (27.4%) stated that they suffered from allergies, with 7.7% reporting perennial, 6.1% seasonal, and 13.6% other forms of allergic reactions.

People with generalised anxiety disorders also suffered more often from pollen allergies, but not from year-round allergies. Statistically, these were actually less frequent in the group of anxiety sufferers. A possible explanation for this might be that people with persistent allergies develop different coping strategies to deal with stress, which protect them from anxiety disorders.

By contrast, there was a positive correlation between perennial allergies and depression or depressive episodes. However, the structure of the study did not allow for clarification of whether allergies increase susceptibility to depression or whether depression itself is a risk factor for allergies. What surprised the research team was the fact that psychological factors had little – if any – influence on the occurrence of food and drug allergies.

Possible mitigating factors that could compromise causal relationships were statistically excluded in this study. These included age, smoking/non-smoking status, gender, and family predispositions (for example, to allergic asthma). However, Harter also outlines the study’s weaknesses: “We have a relatively high average age of 61 years, so younger people are rather underrepresented here. The findings are also based on personal reports rather than official allergy diagnoses. But we have blood samples from all participants and intend to scientifically verify this point,” she confirms. According to Prof.Traidl-Hoffmann, what this study particularly underscores is the importance of devoting sufficient time to patients. This is the only way to complement clinical evaluations with psychosocial aspects to support an integrated therapeutic approach, such as that practised by the University Outpatient Clinic for Environmental Medicine at UNIKA-T.

Reference

1. Harter K et al. Different Psychosocial Factors Are Associated with Seasonal and Perennial Allergies in Adults: Cross-Sectional Results of the KORA FF4 Study. Int Arch Allergy Immunol 2019;DOI: 10.1159/000499042

Weekly pharmacy visits boost drug adherence and quality of life in heart failure patients

Elderly patients with heart failure who see a pharmacist once a week are more likely to take their tablets and be active in daily life, according to late breaking results from the PHARM-CHF randomised controlled trial presented at Heart Failure 2019.¹

“Adhering to a complex medication regimen is a huge challenge for elderly patients with heart failure,” said co-principal investigator Professor Martin Schulz, of the Department of Clinical Pharmacy, Freie Universitaet Berlin, Germany. “It is estimated that 30% to 50% of patients in Europe are non-adherent to heart failure medications, which results in increased frequency and severity of symptoms such as breathlessness, worsening heart failure and consequent hospitalisations, and higher mortality.”

Non-adherence includes not collecting a prescription, taking a lower dose or less pills than prescribed, drug holidays (during weekends or holidays, or when feeling better), or completely stopping one or more drugs.

The PHARM-CHF trial investigated whether regularly seeing a pharmacist improves adherence to heart failure medications.² A total of 237 ambulatory chronic heart failure patients aged 60 years and older were randomly allocated to usual care or a pharmacy intervention and followed-up for a median of two years. The average age was 74 years, 62% were male, and the median number of different drugs was nine.

The intervention started with a medication review. Patients brought their drugs to a pharmacist who made a medication plan, checked for drug interactions and double medications, and contacted the physician about any risks. Patients then visited the pharmacy every 8-10 days to discuss adherence and symptoms, and have blood pressure and pulse rate measurements. Drugs were provided in a pillbox with compartments for morning, noon, evening, and night on each day. The pharmacist updated the medication plan if needed and contacted the doctor with new drug-related problems or significant changes in vital signs.

The primary efficacy endpoint was the proportion of days three heart failure medications were collected (using pharmacy claims data) in the year after randomisation. The drugs were beta blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and mineralocorticoid receptor antagonists. Compared to usual care, the intervention resulted in a significant 5.7% absolute increase in collection.

The researchers also calculated the proportion of patients who collected the three drugs at least 80% of the days under study (defined as adherent) compared to baseline. The proportion of adherent patients increased from 44% to 86% in the pharmacy group and from 42% to 68% in the usual care group – a significant 18%-points difference between groups. Patients in the pharmacy group were three times more likely to become adherent compared to the usual care group. Six patients would need to receive the intervention to achieve at least 80% adherence in one patient.

There was no difference between groups in the primary composite safety endpoint of days lost in the year following randomisation due to unplanned cardiovascular hospitalisations or all-cause death.

Improvement in quality of life was more pronounced in the pharmacy group after one year and significantly better compared to the usual care group after two years. This meant patients in the pharmacy group were less limited in their daily activities and less worried about their disease.

Professor Schulz, who is also director of the Department of Medicine at ABDA – Federal Union of German Associations of Pharmacists, said patients would need to see the pharmacist every week lifelong for the benefits to continue: “The key point is that pharmacy visits need to be used as an opportunity to provide structured care.”

Co-principal investigator Professor Ulrich Laufs, director of the Department of Cardiology, Leipzig University, Germany, said: “Cardiologists and general practitioners would welcome this type of intervention since it does not change the medication that is prescribed but helps patients to follow the treatment strategy.”

References

1. The abstract ‘Pharmacy-based interdisciplinary intervention for patients with chronic heart failure: results of the PHARM-CHF randomized controlled trial’ was presented during the session Late breaking trial II – Chronic heart failure on Sunday 26 May.
2. Laufs U et al. PHARMacy-based interdisciplinary program for patients with Chronic Heart Failure (PHARM-CHF): rationale and design of a randomized controlled trial, and results of the pilot study. Eur J Heart Fail 2018;20:1350-9.

Inhaled combination treatment shows significant improvements over current standard-of-care

23rd May 2019

1. Watz H et al. The Combination of Indacaterol/Glycopyrronium/Mometasone Furoate is Superior to High-Dose Salmeterol/Fluticasone Propionate in Improving Lung Function in Patients with Asthma. ATS abstract 2019
2. Beier J et al. The Efficacy of the Combination Indacaterol/Glycopyrronium/Mometasone Furoate is Independent of Time of Dosing in Patients with Asthma. ATS abstract 2019

NICE issues final guidance for inotersen for hATTR amyloidosis

Akcea Therapeutics UK Ltd has announced that the National Institute for Health and Care Excellence (NICE) has published its final Highly Specialised Technologies (HST) Guidance for Tegsedi^® (inotersen) for the treatment of stage 1 or stage 2 polyneuropathy in adult patients with hereditary transthyretin amyloidosis (hATTR).^1,2

This follows the positive Final Evaluation Document (FED)³ recommending that patients in England with this rare, inherited, severely debilitating and fatal disease, can access the treatment on the NHS.

hATTR amyloidosis is a severe, progressive, and life-threatening disease caused by the abnormal formation of the TTR protein and aggregation of TTR amyloid deposits in various tissues and organs throughout the body, including in peripheral nerves, the heart and intestinal tract.⁴ The progressive accumulation of TTR amyloid deposits in these organs often leads to intractable peripheral sensorimotor neuropathy, autonomic neuropathy, and/or cardiomyopathy, as well as other disease manifestations.² hATTR amyloidosis causes significant morbidity and progressive decline in quality of life, severely impacting activities of daily living.2 The disease often progresses rapidly and can lead to premature death.² The median survival is 4.7 years from diagnosis.⁵

Inotersen is an antisense oligonucleotide (ASO) inhibitor of human transthyretin (TTR) production. It is the first and only subcutaneous RNA-targeting drug designed to reduce the production of human transthyretin (TTR) protein.⁶

This HST Guidance is the final recommendation from NICE regarding how this treatment should be used in the NHS in England. Now that the final guidance has been published, the NHS mandate requires that inotersen is available for routine use within 90 days for patients in England. The NHS in Wales has committed to have funding available earlier, 60 days post-FED.

“This is a great milestone for inotersen and marks the successful conclusion of this health technology assessment for inotersen,” commented Dr. Richard A. Jones, SVP Head of Europe for Akcea Therapeutics. “Patients in the UK with hATTR amyloidosis have to date had very limited treatment options to date, so this news will be well received among the amyloidosis community. Akcea are committed to advancing and making accessible transformative treatments for patients living with serious and rare diseases.”

This follows a similar recommendation by the Committee for Medicinal Products for Human Use of the European Medicines Agency in 2018.

References

1. National Institute for Health and Care Excellence (NICE). Tegsedi (inotersen) Highly Specialised Technology Guidance (HST9) Available at: https://www.nice.org.uk/guidance/hst9. Accessed 22 May 2019.
2. National Institute for Health and Care Excellence (NICE). Tegsedi (inotersen) Highly Specialised Technology Guidance (HST9). Final Guidance Document Available at https://www.nice.org.uk/guidance/hst9/resources/inotersen-for-treating-h… Accessed 22 May 2019.
3. National Institute for Health and Care Excellence (NICE). Tegsedi (inotersen) Final Evaluation Document. Available at: https://www.nice.org.uk/guidance/hst9/documents/final-evaluation-determi… . Last accessed May 2019.
4. Damy T et al. (2015) Cardiac Findings and Events Observed in an Open-Label Clinical Trial of Tafamidis in Patients with non-Val30Met and non-Val122Ile Hereditary Transthyretin Amyloidosis. J Cardiovasc Transl Res. 8(2):117-127.
5. Swiecicki PL et al. Hereditary ATTR amyloidosis: a single-institution experience with 266 patients. Amyloid 2015;22(2):123-3.
6. eMC. Tegsedi Summary of Product Characteristics. Available at: www.medicines.org.uk/emc/product/10011/smpc. Last accessed May 2019.

Lupus characteristics and progression differ among racial/ethnic groups

1. Maningding E et al. Racial/Ethnic Differences in Prevalence of and Time to Onset of SLE Manifestations: The California Lupus Surveillance Project (CLSP). Arthritis Care Res 2019;doi: 10.1002/acr.23887

Expert consensus published on use of imaging to guide heart attack treatment

22nd May 2019

Imaging provides a more precise diagnosis of a heart attack that can be used to individualise treatment. That is the main message of an expert consensus paper published in the European Heart Journal,¹ and presented at EuroPCR 2019 in Paris.²

Heart attacks are diagnosed and treated using coronary angiography, an invasive procedure which provides an X-ray outline of the arteries supplying blood to the heart. Invasive imaging of the arteries gives more detail but there has been controversy over when to use it.

This document seeks to resolve that debate. It promotes the adoption of intracoronary imaging in two major areas: 1) acute coronary syndromes including heart attack and 2) when diagnostic information from angiography is unclear.

Which patients and lesions merit imaging? For acute coronary syndromes, advice is given on atypical presentation, complex lesions, and non-obstructive coronary artery disease. The paper provides criteria for assessment of the arteries, interpretation of images, choice of treatment, and guidance during stent insertion (percutaneous coronary intervention; PCI). In the past it was thought that most acute coronary syndromes were caused by ruptured plaque. Intracoronary imaging has identified plaque erosion and eruptive calcified nodules as other causes which may benefit from different treatment. In addition, intracoronary imaging clearly shows thrombus, which angiography may miss or misidentify.

“Imaging is more accurate, helps guide decisions and facilitates tailored therapy, especially in younger heart attack patients who more frequently have plaque erosion or non-atherosclerotic coronary artery disease,” said senior author Dr Giulio Guagliumi, of the Ospedale Papa Giovanni XXIII, Bergamo, Italy.

Coronary angiography is often ambiguous during heart attacks which lack an identifiable culprit lesion or have multiple culprit lesions. Intracoronary imaging provides clarity before and during PCI. An ageing population and rising levels of diabetes mean that more lesions causing heart attacks are calcified, which is difficult to detect using angiography and more challenging for PCI. In addition, angiography may be hazy for certain anatomies such as tortuous vessels and aneurysms.

Patients referred for PCI increasingly have comorbidities and complex coronary artery disease. Dr Guagliumi said: “Intracoronary imaging is particularly useful in complex patient and lesion scenarios and the paper states settings where it would provide maximum benefit – for instance patients with non-ST elevation acute coronary syndromes, calcified vessels, long lesions or in-stent restenosis. This ties in with the realities of healthcare, where there is no appetite to spend time and money imaging simple lesions.”

Dr Guagliumi noted that imaging companies have mainly focused on improving image quality. “More attention should be devoted to making imaging systems more user friendly for clinicians, with automated analysis and classification. There is more to gain clinically through developments in these areas.”

He concluded: “The role of intravascular imaging to diagnose acute coronary syndromes, select treatment, and guide PCI will continue to grow. With it we expect to achieve superior long-term outcomes.”

The document was written by a panel organised by the European Association of Percutaneous Cardiovascular Interventions (EAPCI) and is part 2 of a series on the clinical use of intracoronary imaging. Part 1 focused on stent selection and optimisation criteria.³ Both documents discuss intravascular ultrasound (IVUS) and optical coherence tomography (OCT).

References

1. Johnson TW et al. Clinical use of intracoronary imaging. Part 2: acute coronary syndromes, ambiguous coronary angiography findings, and guiding interventional decision-making: an expert consensus document of the European Association of Percutaneous Cardiovascular Interventions. Eur Heart J 2019;doi:10.1093/eurheartj/ehz332.
2. Paper presented on Tuesday 21 May at 16:45 CEST during the lecture “Clinical use of intracoronary imaging – EAPCI expert consensus”. The lecture is in the session “Continuous LIVE demonstration from Hospital Universitario Clínico San Carlos – Madrid, Spain”, held 13:15 to 17:00 CEST in the Main Area / Level 1 of the Palais des Congrès in Paris.
3. Räber L et al. Clinical use of intracoronary imaging. Part 1: guidance and optimization of coronary interventions. An expert consensus document of the European Association of Percutaneous Cardiovascular Interventions. Eur Heart J 2018;39:3281-3300. doi:10.1093/eurheartj/ehy285.

Women less likely to be resuscitated and survive a cardiac arrest than men

Women who have a cardiac arrest outside the hospital setting are less likely to receive resuscitation from bystanders and more likely to die than men, according to new research published in the European Heart Journal.¹

The researchers, led by Hanno Tan MD, PhD, at the University of Amsterdam found that men and women did not receive equal treatment when suffering a cardiac arrest in the community. An important factor in this was that people did not recognise that women who collapsed were having a cardiac arrest, leading to delays in calling the emergency services and delays in providing resuscitation treatment. Cardiac arrest occurs when the heart goes into an irregular rhythm and then stops beating completely. It is different to a heart attack (or myocardial infarction).

Dr Tan said: “We found that the worse outcome in women is largely attributable to the fact that women had about half the chance of having a shockable initial rhythm compared to men.”

Shockable initial rhythm is the heart rhythm recorded when someone with cardiac arrest is connected to an electrocardiogram machine; it is very fast (often more than 300 beats a minute) and chaotic. This fast and irregular rhythm prevents the heart from beating in a coordinated way so that there is no effective pump function, and blood can no longer circulate round the body and to the heart, leading to cardiac arrest. Death occurs within minutes unless the heart can be shocked back to a normal rhythm by means of an electrical current from a defibrillator. If this does not happen, then the shockable initial rhythm dissolves into a “flat line”, which indicates the absence of any electrical activity from the heart. At this point it is too late for defibrillation to work and the only remaining option is chest compression to try to restore circulation sufficiently for the heart to regain its electrical and mechanical activity. The ability to recognise and treat a cardiac arrest within minutes is, therefore, crucial to being able to treat patients while they still have a shockable initial rhythm and before their heart stops.

Dr Tan and his team analysed data from all resuscitation attempts made by emergency services between 2006 to 2012 in one province in The Netherlands. They identified 5717 out-of-hospital cardiac arrests treated during this period, 28% of which occurred in women.

They found that women were less likely than men to receive a resuscitation attempt by a bystander (68% versus 73%), even when there was someone there to witness the collapse (69% versus 74%). Survival from the time of the cardiac arrest to admission to hospital was lower in women (34% versus 37%), and women were less likely to survive from admission to discharge (37% versus 55%). Overall, the chances of women surviving to be discharged from hospital was about half that of men (12.5% versus 20%). The researchers believe this is largely explained by the lower rate of shockable initial rhythm in women – 33% versus 52% – and found several reasons that might explain this difference.

“Even when we adjusted our results to take account of pre-existing diseases and factors relating to the way in which resuscitation was provided by professionals, for example how long it took for the ambulance to arrive or time to defibrillation after cardiac arrest, we still found that women were half as likely as men to have shockable initial rhythm,” said Dr Tan. “This suggests that the lower proportion of women with shockable initial rhythm is not fully explained by women being more likely to have pre-existing diseases or by different resuscitation factors, and that other, as yet undiscovered, factors also play a role. However, when we looked only at cardiac arrest victims who did have a shockable initial rhythm, we found there was no difference in overall survival rates between men and women.”

The researchers also found differences in the way women were treated in hospital. They were less likely to be diagnosed with an acute myocardial infarction, and less likely to undergo coronary angiography or percutaneous coronary intervention.

The researchers say that a possible reason why fewer women have shockable initial rhythm by the time the emergency services reach them may be because fewer women than men tended to have a cardiac arrest when there were other people around to see it happen (for demographic reasons, there are more elderly women living on their own than men), and because the symptoms of a heart attack (one of the most common causes of cardiac arrest) may not be recognised so quickly in women.

“People may be less aware that cardiac arrest can occur as often in women as in men, and the women themselves may not recognise the urgency of their symptoms,” said Dr Tan. “Women may have symptoms of an impending heart attack that are less easy to interpret, such as fatigue, fainting, vomiting and neck or jaw pain, whereas men are more likely to report typical complaints such as chest pain.”

The researchers call for a range of measures to tackle the problem of survival differences between men and women, ranging from public awareness campaigns about heart attack and cardiac arrest in women to reorganisation of health care systems in order to provide faster resuscitation to women, particularly those living on their own, for instance, by wearable devices that monitor heart rate and circulation and that can send alerts to monitoring systems.

“As cardiac arrests occur most often outside the hospital setting in the general population, much can probably be gained by raising awareness in society that cardiac arrest is as common in women as in men but may have different symptoms. Given the short window available to save the life of the patient, every minute in this early phase counts; help, if only a call to the emergency number by a lay person, is crucial. So, raising awareness through public campaigns could make a big impact on women’s survival. The fact that in-hospital treatment also seems to be different is a finding that can be acted on now and may be easier to implement,” he concluded.

Limitations to the study include the fact that 181 surviving patients were not included because they did not consent, and data on pre-existing diseases in 27.5% of heart attack patients were missing, although in both cases the missing data were distributed evenly between the sexes. The researchers had no information on symptoms patients may have reported before their heart attacks, which may have influenced how quickly witnesses might make an emergency call.

Reference

1. Blom M et al. Women have lower chances than men to be resuscitated and survive out-of-hospital cardiac arrest. Eur Heart J 2019;doi:10.1093/eurheartj/ehz297