Aaysha Cader, MD, MRCP – Page 2 – The Early Career Voice

Aaysha Cader, MD, MRCP is an Assistant Professor of Cardiology at Ibrahim Cardiac Hospital & Research Institute, Dhaka, and is currently pursuing a part-time MSc in Clinical trials at the University of Oxford. She has a special interest in interventional cardiology, acute coronary syndromes, and heart disease in women. She is a World Heart Federation Emerging Leader and a co-founder of the Global Women in Cardiology (WIC) - Early Career collaboration. You can follow her on twitter: @aayshacader

COVID-19: Looking for a silver lining

July 24, 2020July 24, 2020 Aaysha Cader, MD, MRCP

It’s July 2020, and the COVID-19 pandemic shows no signs of ending. A friend recently asked me if I ‘d ever imagined such a scenario when I decided to do medicine. The answer is no. None of us, not even our mentors had trained for a pandemic of this magnitude. Still, while this is still far from a “when life gives you lemons make lemonade” scenario, looking for those elusive positives in this global catastrophe is just one way to remain optimistic in the face of such unprecedented adversity.

So unprecedented, in fact, that as our hospital committees initially met to formulate new standards of operation, I found that as fellows in training (FIT) and (very) early-career physicians, my colleagues and I had much to contribute in terms of protocols and guidelines, even in guidance documents of national societies. With the need for rapid update of data and protocols in an extremely volatile situation, a FIT and early career COVID response team was formulated, to submit recommendations on a variety of aspects ranging from infection control, requirements for personal protective equipment (PPE), zonal divisions of hospital, allocations of responsibility and treatment protocols of infected staff, based on international guidance. It was something I had never done before, and taught me the important aspects of healthcare administration, outside of clinical work, and a renewed appreciation for what those in management do (It’s not easy to keep everyone happy!)

These testing times were also an opportunity to lead with empathy, help cultivate an essence of team spirit, and collective resilience as a team. When we had an initial outbreak of cases among our healthcare workers in April, I learnt what real leadership is – the importance of being transparent, even in the face of chaos. I learnt what it means to be present and to lead with empathy, to “be there” for junior colleagues and nurses. In the sea of misinformation, I also learnt to speak up for what was right, with authorities, rectify misconceptions especially relating to evidence-based treatment and push for the changes that were needed. Even now, everybody is still apprehensive. In more ways than one, the pandemic offered an opportunity for a much-needed change of culture within work environments, and more open discourse between peers and colleagues, a positive change that we hope will last beyond these difficult times.

While we educate ourselves on everything that isn’t cardiology, most formal training especially in terms of procedures, is still on hold as we respond to the pandemic. Locally, we have somewhat adapted to a virtual learning platform for residents. However, practising in South Asia, exposure to cutting edge technology and insights from international leaders in the field has generally been limited to the ability to be able to travel for in-person meetings overseas. Despite the chaos, the learning must not stop — while restrictions to international travel may have blocked the networking opportunities of in-person meetings, in a strange paradox, the online interactions might just have brought the world closer.

Just this week, I attended webinars from 2 different continents, without having to apply for any educational leave. Moreover, most of these virtual meetings and webinars are free of cost, and especially for fellows, the opportunity to participate and interact with world-class faculty. (Disclaimer: They are by no means a substitute for the real deal, but I’m trying hard to count the positives here!).

Like so many others I know, 2020 was supposed to be “my year” too. But tough luck. It’s not easy having to endure the stress of colleagues and family falling sick, and having to battle on, knowing fully well that it might very well be you, next. It’s important to embrace the situation and cultivate positive vibes, engage in self-care and your own wellness, however limited the options may be. By not being able to travel to see family, or even out of town for a break, it has been overwhelming to say the very least, but I can safely say that I’ve probably helped more people in the last few months, than I have on all my years as a doctor. That would probably be the biggest silver lining of them all—the opportunity to serve so many people. But in uncertain times like these, we’re all apprehensive. We don’t know when this will end. It’s a marathon, not a sprint, and we need to find the silver lining in this new normal, for the sake of our own sanity. At the same time, it’s also imperative that we consolidate the positive effects of the pandemic, the growth it has led to, and incorporate them into our practice as physicians and people.

“The views, opinions and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your personal health matters. If you think you are having a heart attack, stroke or another emergency, please call 911 immediately.”

Virtual #QCOR20 and the future of cardiology academic meetings

June 12, 2020June 12, 2020 Aaysha Cader, MD, MRCP

Much like many recent academic cardiology meetings, the American Heart Association (AHA)’s Quality of Care & Outcomes Research 2020 (#QCOR20) meeting took place virtually as well, owing to limitations posed by the COVID-19 pandemic. Having attended AHA Scientific Sessions 2019 as an international delegate, this was both my first time attending QCOR as well as my first virtual QCOR. There was a wide range of content encompassing cardiovascular outcomes research, abstract presentations, plenary sessions and also an online interactive early career session via zoom.

So, as I logged into HeartHub (https://www.hearthubs.org/qcor ) for the sessions, in the comfort of my pajamas in a time zone a dozen hours apart, I found that the platform was rather unique, convenient and user-friendly. Talks were pre-recorded in good quality, but what really stood about the #QCOR20 format was the chat function that ran simultaneously with the ongoing talks. Completely flattening all medical hierarchies, this allowed for extensive, insightful and interactive discussions in an informal manner between speakers and attendees, irrespective of where they stood in the totem pole of medicine. This also served to obviate some of the conventional barriers of Q&A sessions at large meetings, allowing for more questions as well as the active engagement of more junior delegates.

Additionally, Virtual QCOR registration came with on-demand access to recorded lectures as well as other available conference materials including handouts for until three months after sessions, allowing one to catch up on sessions that might have been missed.

This was particularly useful, because, that very weekend SCAI also hosted their annual scientific sessions virtually. In a parallel world, I wouldn’t have dreamed of testing my efficiency with two parallel meetings. But the effort to attending both was significantly less than usual, including financially, involved no flights, commutes or time off work, and conveniently, I could switch between windows to “pop in” to the sessions of my interest at either meeting.

Despite some of these conveniences, I found myself missing the buzz of in-person meetings: the anticipation of results of late-breaking clinical trials, discussions of live cases, interaction and camaraderie of meeting colleagues face to face from the around the world, seeing new technology in the exhibit calls and especially, coming to think of it, the downtime off work and the absolute joy of travel.

Basically, the nerd, the wanderlust, and the human in me didn’t quite agree entirely with this virtual format. But that’s personal. And while we can agree that the science and education will certainly find its way to clinicians, many of the other goals and expectations of such annual academic conferences hinges on in-person meetings. These include small-group practical education, meeting and networking with peers, sharing of experiences, and potential collaborations borne thereof, none of which can be effectively achieved by a virtual meeting. From the perspective of scientific associations, building agendas, policy-making, professional skills development, and interactions with industry are all far better achieved with face-to-face interactions.

With restrictions to air travel, dwindling economies, social distancing measures and the varying commitments of the global medical community facing different phases of the pandemic in their respective countries, there has been much discussion on the future of medical conferences. Given the current climate, delegates (especially international) may re-evaluate priorities, with considerations of finances and if in-person presence was in fact, absolutely necessary.

And as many more international cardiology meetings are successfully converted into virtual events, and many more physicians adapt to this convenient method of education, it begs the question if this indeed will be the default arrangement for the foreseeable future? Further, into the future, academic societies ought to consider the possibility of combining the best of both worlds, so to speak, with a “hybrid” format, offering the in-person meeting as well as the virtual format, thus giving delegates who might prefer it, the option of attending sessions live from the comfort of their homes.

Also, while large global meetings with thousands of delegates might survive the pandemic and transition into hybrid conferences, what of the smaller meetings? Some of these are dedicated to niche specialties for smaller audiences, offering opportunities for hands-on learning and more intimate networking with experts and mentors. Only time will tell if such smaller meetings will indeed prevail.

Virtual meetings may have sufficiently filled the void of medical education and academic discourse that occurred as a result of cancellations of in-person conferences. Part of this void has also been filled by increased interactions between peers on social media platforms, particularly twitter, with renewed importance of the role of social media ambassadors. In more ways than one, virtual meetings may even have brought the world closer, with many of us logging in at the same time from different time zones. But let’s be real: We can dissect a trial on twitter all we like, but it will never be the same as the standing room only attendance at late-breaking clinical trial sessions. Also, let us seriously spare a thought for the principal investigator presenting his/her pioneering research to a computer screen: that is nowhere near the real thing.

The impact of COVID-19 on the course of major professional meetings has been huge. While Science will always find a way to reach us, meetings are so much more than just science. The whole world is adapting to a new normal and it will be interesting to see how this pans out for the medical community.

COVID -19 and the clotting conundrum

May 19, 2020May 19, 2020 Aaysha Cader, MD, MRCP

Initially known as a predominantly respiratory disease, there is currently no doubt that COVID-19 is increasingly emerging as a prothrombotic condition. Observational studies, as well as published and anecdotal case reports have highlighted the thrombotic manifestations of COVID-19, with particular emphasis on the strong association between D-dimer levels and poor prognosis.^1,2 While the COVID-19 clotting narrative has been dominated by venous thromboembolism (VTE) and pulmonary embolism (PE),^3-5 macro-thrombosis of the coronary⁶ and cerebral circulations⁷ have also been reported, as have the prevalence of microthrombi arising from endotheliitis in other sites.⁸

The pathophysiology

Some authors have described this SARS-CoV-2 induced hypercoagulability as ‘thromboinflammation’, an interplay between inflammation and coagulability leading to sepsis-induced-coagulopathy (SIC) and disseminated intravascular coagulopathy in severe COVID-19 cases.⁹ The pathophysiology is still incompletely understood but may be largely explained by the three components of Virchow’s triad:

Endothelial dysfunction: SARS-CoV-2 virus enters the host using the angiotensin converting enzyme 2 (ACE2) receptor, which is widely expressed not only in the alveolar epithelium of the lungs but also vascular endothelial cells, which traverse multiple organs.⁸ Varga, et al. reported this concept of COVID-19 ‘endotheliitis’ in their paper, explaining how endothelial dysfunction, which is a principal determinant of microvascular dysfunction, shifts the vascular equilibrium towards vasoconstriction, organ ischaemia, inflammation, tissue oedema, and a procoagulant state, leading to clinical sequalae in different vascular beds.⁸ Complement-mediated endothelial injury leading to hypercoagulability has also been suggested.¹⁰

Hypercoagulability: SARS-CoV-2-induced hypercoagulability has also been attributed as a consequence of the ‘cytokine storm’ that precipitates the onset of a systemic inflammatory response syndrome, resulting in the activation of the coagulation cascade.^11,12However, whether the coagulation cascade is directly activated by the virus or whether this is the result of local or systemic inflammation is not completely understood.¹²

Stasis: Critically ill hospitalized patients, irrespective of pathophysiology are prone to vascular stasis as a result of immobilization.¹³

Currently available data: predominantly observational studies

In some of the earliest data emerging from Wuhan, Tang, et al. reported significantly higher markers of coagulation, especially prothrombin time, D-dimers and FDP levels, among non-survivors compared to survivors of SARS-COV2 novel coronavirus pneumonia (NCP), suggesting a common coagulation activation in these patients.¹

Subsequently, Zhou, et al., reported that D-dimer levels, along with high-sensitivity cardiac troponin I and IL-6 were clearly elevated in non-survivors compared with .¹⁴This was highlighted in one of the earliest CCC-ACC webinars on COVID-19 in March 2020, by Professor Cao, who drew emphasis on their data where D-Dimer >1μg/mL was an independent risk factor for in-hospital death, with an odds ratio of 18.42 (p=0.0033).^14,15

In another single centre study among 81 severe NCP patients from Wuhan, Ciu, et al., observed that D-dimer levels >1.5 μg/mL had a sensitivity of 85% and specificity of 88.5% for detecting VTE events.³ In an observational study of 343 eligible patients by Zhang, et al., the optimum cutoff value of D-dimer level on admission to predict in-hospital mortality was 2.0 µg/ml with a sensitivity of 92.3% and a specificity of 83.3%.¹⁶

With a shift in the epicenter of the pandemic, data from Europe highlighted the prevalence of both arterial and venous thrombotic manifestations among hospitalized COVID-19 patients, many of whom received at least standard doses of thromboprophylaxis.^5,13

Most recent data from an observational cohort of 2,773 hospitalized COVID-19 patients in New York, showed that in-hospital mortality was 22.5% with anticoagulation and 22.8% without anticoagulation (median survival, 14 days vs 21 days).¹⁷ Confounded by the immortal time bias, among others, these data underscore the pressing need for well-designed RCT’s to answer this burgeoning therapeutic dilemma.

Antithrombotic therapy: What is the guidance?

As physicians learn more about this clotting conundrum, there is an increasing need for evidence-based guidance in treatment protocols, especially pertaining to anticoagulation dosing and the role of D-dimers in deciding on optimum therapeutics.

International consensus-based recommendations published by Bikdeli, et al. in the Journal of American College of Cardiology on 15^th April 2020 recommend risk stratification for hospitalized COVID-19 patients for VTE prophylaxis, with high index of suspicion.¹¹ They further state that, as elevated D-dimer levels are a common finding in patients with COVID-19, it does not currently warrant routine investigation for acute VTE in absence of clinical manifestations or supporting information. For outpatients with mild COVID-19, increased mobility is encouraged with recommendations against the indiscriminate use of VTE prophylaxis, unless stratified as elevated-risk VTE.

The majority of panel members considered prophylactic anticoagulation to be reasonable for hospitalized patients of moderate to severe COVID-19 without DIC, acknowledging that there is insufficient data to consider therapeutic or intermediate dose anticoagulation; the optimal dosing however, remains unknown.¹¹ Furthermore, extended prophylaxis, with low-molecular weight heparin or direct oral anticoagulants for up to 45 days after hospital discharge, was considered reasonable for patients with low-bleeding-risk patients and elevated VTE (i.e. reduced mobility, comorbidities and, according to some members, elevated D-dimer more than twice the upper normal ).¹¹

A Dutch consensus published shortly after on the 23^rd April 2020, also recommends prophylactic anticoagulation for all hospitalized patients, irrespective of risk scores.¹²Imaging for VTE and therapeutic anticoagulation recommendations are largely guided by admission D-dimer levels and their progressive increase, based on serial testing during hospital stay, in addition to clinical suspicion. A lower threshold for imaging has been recommended if D-dimer levels increase progressively (>2,000-4,000 μg/L), particularly in presence of clinically-relevant hypercoagulability. However, in contrast to the consensus document published in JACC, the Dutch guidance recommends that, where imaging is not feasible, therapeutic-dose LMWH without imaging may be considered if D-dimer levels increase progressively (>2,000-4,000 μg/L), in settings suggestive of clinically relevant hypercoagulability and acceptable bleeding risk.¹²

The need for RCT’s

Even as we scramble to clarify the pathophysiology, the urgency to establish evidence-based standard of care in terms of anticoagulation has never been greater. Dosing is a matter of hot debate (prophylactic versus intermediate versus therapeutic), especially considering the risk of bleeding that can arise from indiscriminate anticoagulation.

Furthermore, while we have data that underscores increased coagulation activity (D-dimers in particular) as a potential risk marker of poor prognosis, D-dimers remain non-specific and there is insufficient evidence as to whether they can be used to guide decision-making on optimum anticoagulation doses among patients with COVID-19.

The existing evidence on thrombotic complications and their treatment has been primarily derived from non-randomized, relatively small and retrospective analyses. Such observational studies have been hypothesis generating at best, and in the absence of robust evidence, randomized clinical trials are imperative to address this critical gap in knowledge in an area of clinical equipoise. And there are quite a few to watch out for, as evidenced by a quick search in Clinicaltrials.gov, some of which are already recruiting.

RCT’s of therapeutic vs prophylactic anticoagulation:

Preventing COVID-19-associated Thrombosis, Coagulopathy and Mortality With Low- and High-dose Anticoagulation: a Randomized, Open-label Clinical Trial (COVID-HEP) [https://clinicaltrials.gov/ct2/show/NCT04345848]

Currently recruiting at University Hospital, Geneva, this trial randomizes 200 hospitalized adults with severe COVID-19 to therapeutic anticoagulation versus thromboprophylaxis during hospital stay. The primary endpoint is a composite outcome of arterial or venous thrombosis, DIC and all-cause mortality at 30 days.

A Randomized Trial of Anticoagulation Strategies in COVID-19 [https://clinicaltrials.gov/ct2/show/NCT04359277]

This open label RCT of hospitalized COVID-19 positive patients with a D-dimer >500 ng/ml is currently recruiting at NYU Langone Health (estimated enrolment of 1000 patients). Patients will be randomized to higher-dose versus lower-dose (e.g. prophylactic-dose) anticoagulation in 1:1 ratio. Primary endpoints include incidences of cardiac arrest, DVT, PE, MI, arterial thromboembolism or hemodynamic shock at 21 days and all-cause mortality at 1 year.

A Randomized, Open-Label Trial of Therapeutic Anticoagulation in COVID-19 Patients With an Elevated D-Dimer [https://clinicaltrials.gov/ct2/show/NCT04377997]

This randomized, open-label trial sponsored by Massachusetts General Hospital (MGH) commencing recruitment mid-May, will randomize 300 participants with elevated D-dimer > 1500 ng/ml to therapeutic versus standard of care anticoagulation in a 1:1 ratio, based on MGH COVID-19 Treatment Guidance. Designed to evaluate the efficacy and safety of anticoagulation, primary outcome measures include the composite efficacy endpoint of death, cardiac arrest, symptomatic DVT, PE, arterial thromboembolism, MI, or hemodynamic shock at 12 weeks, as well as a major bleeding event at 12 weeks.

Enoxaparin for Thromboprophylaxis in Hospitalized COVID-19 Patients: Comparison of 40 mg o.d. Versus 40 mg b.i.d. A Randomized Clinical Trial (X-COVID 19)[https://clinicaltrials.gov/ct2/show/NCT04366960]

This open-label multi-centre RCT will recruit 2712 hospitalized COVID-19 patients in Milan, Italy, randomized to subcutaneous enoxaparin 40 mg daily versus twice daily within 12 hours after hospitalization, to assess the primary outcome measure of venous thromboembolism detected by imaging at 30 days.

RCT of intermediate vs prophylactic dose anticoagulation:

Intermediate or Prophylactic-Dose Anticoagulation for Venous or Arterial Thromboembolismin Severe COVID-19: A Cluster Based Randomized Selection Trial (IMPROVE-COVID) [https://clinicaltrials.gov/ct2/show/NCT04367831]

A cluster-randomized trial of 100 participants, IMPROVE-COVID, sponsored by Columbia University will compare the efficacy of intermediate versus prophylactic doses of anticoagulation in critically ill patients with COVID-19. The primary outcome measure is the composite of being alive and without clinically-relevant venous or arterial thrombotic events at discharge from ICU or at 30 days (if ICU duration ≥30 days).

Even months later, COVID-19 continues to baffle clinicians. But what has been crystal clear right from the outset is that there is no alternative to evidence-based practice, and it stands true in the face of this clotting conundrum as well.

Image from Shutterstock

References

Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020;18(4):844-847.
Zhang L, Yan X, Fan Q, Liu H, Liu X, Liu Z, et al. D-dimer levels on admission to predict in-hospital mortality in patients with Covid-19. J Thromb Haemost. 2020 Apr 19. doi: 10.1111/jth.14859.
Cui S, Chen S, Li X, Liu S, Wang F: Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia.. J Thromb Haemost. 2020 Apr 9. doi: 10.1111/jth.14830
Poissy J, Goutay J, Caplan M, Parmentier E, Duburcq T, Lassalle F, et al. Pulmonary Embolism in COVID-19 Patients: Awareness of an Increased Prevalence. Circulation. 2020 Apr 24. doi: 10.1161/CIRCULATIONAHA.120.047430.
Lodigiani C, Iapichino G, Carenzo L, Cecconi M Ferrazzi P, Sebastian T, et al., on behalf of the Humanitas COVID-19 Task Force. Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy. Thromb Res. 2020; 191: 9–14.
Dominguez-Erquicia P, Dobarro D, Raposeiras-Roubín S, Bastos-Fernandez G, Iñiguez-Romo A. Multivessel coronary thrombosis in a patient with COVID-19 pneumonia, European Heart Journal, , ehaa393, https://doi.org/10.1093/eurheartj/ehaa393
Oxley TJ, Mocco J, Majidi S, Kellner CP, Shoirah H, Singh IP, et al. Large-Vessel Stroke as a Presenting Feature of Covid-19 in the Young. N Engl J Med. 2020 Apr 28.
Varga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R, Zinkernagel AS, et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020 May 2;395(10234):1417-1418
Connors JM, Levy JH. Thromboinflammation and the hypercoagulability of COVID-19. J Thromb Haemost. 2020 Apr 17. doi: 10.1111/jth.14849.
Magro C, Mulvey JJ, Berlin D, Nuovo G, Salvatore S, Harp J, Baxter-Stoltzfus A, et al. Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: a report of five cases [published online ahead of print, 2020 Apr 15]. Transl Res. 2020;S1931-5244(20)30070-0. doi:10.1016/j.trsl.2020.04.007
Bikdeli B, Madhavan MV, Jimenez D, Chuich T, Dreyfus I, Driggin E, et al. COVID-19 and Thrombotic or Thromboembolic Disease: Implications for Prevention, Antithrombotic Therapy, and Follow-up. J Am Coll Cardiol. 2020 Apr 15:S0735-1097(20)35008-7
Oudkerk M, Büller HR, Kuijpers D, van Es N, Oudkerk SF, McLoud TC, et al. Diagnosis, Prevention, and Treatment of Thromboembolic Complications in COVID-19: Report of the National Institute for Public Health of the Netherlands. Radiology. 2020 Apr 23:201629.
Klok FA, Kruip MJHA, van der Meer NJM, Arbous MS, Gommers DAMPJ, Kant KM, et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res. 2020 Apr 10. pii: S0049-3848(20)30120-1. doi: 10.1016/j.thromres.2020.04.013.
Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al.Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-1062.
https://www.youtube.com/watch?v=CjEhV68GcD8&feature=youtu.be
Zhang L, Yan X, Fan Q, Liu H, Liu X, Liu Z, Zhang Z. D-dimer levels on admission to predict in-hospital mortality in patients with Covid-19. J Thromb Haemost. 2020 Apr 19. doi: 10.1111/jth.14859. [Epub ahead of print]
Paranjpe I, Fuster V, Lala A, Russak A, Glicksberg BS, Levin MA, et al. Association of Treatment Dose Anticoagulation with In-Hospital Survival Among Hospitalized Patients with COVID-19 [published online ahead of print, 2020 May 6]. J Am Coll Cardiol. 2020;doi:10.1016/j.jacc.2020.05.001

The COVID-19 pandemic: In this together, a call for collective responsibility

March 23, 2020March 23, 2020 Aaysha Cader, MD, MRCP

On March 11 2020, following a 13-fold rise in COVID-19 cases outside China, the WHO declared the disease a pandemic. The novel coronavirus is now spreading in exponential proportions across the globe, crippling even some of the best healthcare systems. There are unprecedented events: there’s a sense of uncertainty, and for most of my generation, this is the “war” of our time. Times like these also call for a collective responsibility, for each of us to do our part. We are in this together, for the long haul. And I mean that in the most literal, least metaphorical way possible.

The epidemiology explained

An epidemiological study of the outbreak in China estimated the basic reproduction number (R₀) of COVID-19 to be 2.68. ¹That essentially means that early on, every COVID-19 infected person can transmit the disease to an average of 2.5 others.

The epidemic doubling time of COVID-19 is 6.4 days.¹ That means every 6-7 days, the number of cases increases by a factor of two. Exponential growth. This is the reason why the spread can be seemingly slow initially, only to lead to a sudden outbreak in a matter of days to weeks. It’s also why reducing transmission as early on in the outbreak as possible can dramatically reduce this exponential explosion of cases.

Social distancing & “flattening the curve”

Social distancing is key to slowing down rates of transmission and might very well be the most responsible act in the face of this pandemic. This includes keeping a safe distance (at least six feet) between others, avoiding social gatherings, public transport, non-essential travel/ commutes and working from home, if one can. Needless to say, these measures must be accompanied by the consistent practice of healthy hygiene.

And it works: these simulation graphics by Harry Stevens of the Washington Post are a superb demonstration of the impact of social distancing on halting disease transmissions.²

The concept of “flattening the curve” alludes to reducing the number of cases over time by slowing the rate of transmission of the disease so that healthcare systems are not overwhelmed beyond capacity. COVID -19 can be fatal in anyone, with the elderly and those with comorbidities such as diabetes, heart and lung diseases at higher risk of severe infection.³ Latest reports from the WHO now emphasize that young people are not off the hook either, with data from countries showing that people under 50 make up a significant proportion of patients requiring hospitalization.⁴

The fundamental idea of social distancing is to reduce disease transmission to EVERYONE, not just oneself. The incentive is not just preventing oneself from catching it. Even seemingly healthy individuals might develop a milder or asymptomatic form of the disease, retaining the ability to transmit it to the elderly (the worst hit) and other vulnerable groups they encounter, including young people. This leads to a rapid growth of the pandemic, overwhelming the healthcare systems beyond their capacities. An overwhelmed health care system will not be able to treat all the COVID-19 cases coming its way, and will also be limited in resources to care for someone who has a heart attack, an accident or cancer.

However, turns out staying at home is easier said than done, with some still struggling to grasp the concept. “I’ll just be a while, what can happen?” they’ll say. At a time, where testing for COVID-19 is also rationed, staying away from large gatherings is ever so much more important, especially when one shows symptoms. In the fascinating case of Patient 31 of South Korea, we see the dangerous potential of a “super-spreader” phenomenon, in a 61-year-old woman who by virtue of attending religious gatherings prior to testing positive for COVID-19, transmitted the disease in large clusters, leading to a sudden surge of cases in South Korea.⁵

Sharing information: Responsible information, not misinformation

In a pandemic such as this, there’s also a tendency for rampant misinformation, easily transmitted through social media channels. This calls for the responsible dissemination of information, and while this is applicable to everyone, the onus is more so on healthcare personnel.

Social media can be used positively and responsibly to educate the public and refute myths: platforms such as Instagram, Facebook and Twitter are proving to be a great way for healthcare personnel to reach out to communities, explain epidemiology and create awareness of healthy practices during this pandemic. The WHO website has also detailed some of the more common myth-busters: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/advice-for-public/myth-busters

Keep updated

With the volatility of the situation and the torrent of information flooding in from multiple sources, it can be difficult to sift between what’s reliable and what isn’t. These are some reliable channels you can turn to for correct information and updates. It’s also important to seek out your local source of information depending on geographic location.

The World Health Organization (WHO) Coronavirus disease (COVID-2019) situation reports (updated daily): https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports
The WHO also has an interactive Whatsapp bot: +41 79 893 18 92 (Type “hi” and send to get started)
Centers for Disease Control & Prevention (CDC) Coronavirus (COVID-19) website: Latest updates, information for healthcare professionals and resources for the community: https://www.cdc.gov/coronavirus/2019-nCoV/index.html
MedShrOpen: Coronavirus COVID-19 Daily Update at 12pm GMT: aims to provide clinicians and the public with an overview of the latest data, guidelines, key publications and policy around COVID-19: https://en.medshr.net/covid

Show solidarity

Check on your elderly friends and relatives. Refrain from hoarding essential items, thereby potentially creating a shortage, making things difficult for senior citizens and those living on a daily wage.

Donate

The economy has taken a hit, but the hit on health care is bigger. With severe shortages of essential items, those of us with the capacity to donate locally, in whatever way we can, should be doing so. The WHO also has a COVID-19 Solidarity Response Fund: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/donate

Check on your colleagues

For healthcare personnel and their families, this can be a particularly overwhelming time. Some of us may not be on the frontlines, but have friends and family who are. Just those words, “on the frontlines”, sends a chill down my spine.

But that’s exactly what this is. War. War against a common enemy. And when you’re going to war, you don’t make light of the prep.

Which brings to mind this brilliantly appropriate quote by Michael O. Leavitt, Secretary of the U.S. Department of Health and Human Services, 2007:

“Everything we do before a pandemic will seem alarmist. Everything we do after a pandemic will seem inadequate. This is the dilemma we face, but it should not stop us from doing what we can to prepare. We need to reach out to everyone with words that inform, but not inflame. We need to encourage everyone to prepare, but not panic.”

Unprecedented times call for unprecedented measures. In this global healthcare crisis and the ultimate test of our times, it is on all of us to be responsible.

References

Wu JT, Leung k, Leung GM. Nowcasting and forecasting the potential domestic and international spread of the 2019-nCoV outbreak originating in Wuhan, China: a modelling study. Lancet 2020; 395: 689–97
Stevens H. Why outbreaks like coronavirus spread exponentially, and how to “flatten the curve”. The Washington Post March 14, 2020. https://www.washingtonpost.com/graphics/2020/world/corona-simulator/?fbclid=IwAR1ALnyJWXEcBIIh1qFvz1a3JMCtAQP0_jvYIKIRqBnrKpjDKn-sEo1J39A
Centers for Disease Control & Prevention (CDC): Coronavirus Disease 2019 (COVID-19). Are You at Higher Risk for Severe Illness? https://www.cdc.gov/coronavirus/2019-ncov/specific-groups/high-risk-complications.html
WHO Director-General’s opening remarks at the media briefing on COVID-19 – 20 March 2020. https://www.who.int/dg/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19—20-march-2020
The Korean Clusters. How coronavirus cases exploded in South Korean churches and hospitals. Via Reuters Graphics. Updated March 3, 2020. https://graphics.reuters.com/CHINA-HEALTH-SOUTHKOREA-CLUSTERS/0100B5G33SB/index.html

Cardiovascular diseases in women: the heart of the matter

February 21, 2020February 21, 2020 Aaysha Cader, MD, MRCP

It was 4 am one winter night on call when I got paged:

“Youngish diabetic female, mid-thirties, chest pain for a few hours. Unremarkable ECG. Let me send troponins and see. Doesn’t seem cardiac.”

“Doesn’t seem cardiac”

Dismissed, just like that, because she was young, and because she was a woman.

A proper listen to her symptoms revealed that this could indeed, be cardiac. She was admitted, her troponins were raised, a coronary angiography done a few hours later showed an occluded principal obtuse marginal branch which was stented. She was symptom-free the same day.

Fortunately for her, a definitive culprit lesion in her coronaries could be identified, that was amenable to stenting and thus treated. For the majority of women with non-obstructive coronaries, presenting with myocardial infarction with non-obstructive coronary arteries (MINOCA)¹ or ischemia with no obstructive coronary arteries (INOCA), investigations would very likely have stopped right there, with that normal coronary angiography. Dismissed.

CVD in women

Cardiovascular disease (CVD) is the number one cause of mortality among women across the globe.²Despite improved treatment algorithms and the enormous strides made in cardiovascular care, women continue to have worse clinical outcomes than men, partly owing to them being underdiagnosed, understudied and undertreated.

One size does not fit all: A spectrum of differences

The inherent biological differences between men and women, in addition to the socio-cultural attributes of gender, mean that women have very different characteristics of ischemia in terms of symptoms, triggers, and aetiologies.³

Symptoms: While chest pain is the predominant presenting symptom in both men and women in acute coronary syndrome (ACS), historically, women have been known to present with more “atypical” symptoms such as neck pain, fatigue, dyspnea or nausea, often triggered by emotional stress but even this time-honored notion has been challenged by a recent study that found that typical symptoms were more common among women and have greater predictive value in women than in men with myocardial infarction.⁴

Co-morbidities: Women with ACS are known to be older, with a clustering of risk factors and greater prevalence of co-morbidities.³ Particularly, diabetes, smoking and a family history of ischaemic heart disease have been shown to have a stronger impact on event rates among women.³ Younger women with ACS have been found to have a worse pre-event health status (both physical and mental) in comparison to men.⁵

The age paradox: Premenopausal women are thought to be relatively protected against CVD compared to similar-aged men, owing to favorable effects of estrogen on cardiovascular function and metabolism. Intriguingly though, recent studies report an increase in hospitalization rates of ACS among young women, despite a decline among younger men. The mechanisms behind these differences remain a fairly understudied area.

Delayed presentation: Women are also known to present later, frequently attributing their symptoms to a non-cardiac-related condition such as acid reflux, stress, or anxiety.^2,3 This inaccurate symptom attribution, in addition to a lack of awareness of risk, and barriers to self-care in general, lead to a delay in seeking treatment, contributing to poorer outcomes.

Different etiologies: By virtue of an obstructed coronary artery, my patient got lucky in terms of prompt diagnosis and treatment. In about 10% of all patients, and in about a third of women, such a culprit coronary lesion cannot be identified on angiography.^2,3 Furthermore, microvascular angina affects close to a half of patients with non-obstructive coronary arteries.⁷This coronary microvascular dysfunction (CMD) is defined as the presence of symptoms and objective evidence of ischemia in absence of obstructive coronary artery disease, with blood flow reserve and/or inducible microvascular spasmAngina with no obstructive coronary arteries is twice as prevalent in women as in men,⁷ and might also contribute to the pathogenesis of heart failure with preserved ejection fraction (HFpEF), which is also more commonly observed in women.⁹

Women are still under-studied in clinical trials

In the face of such a formidable gender disparity in CVD, women continue to be under-represented in some areas of cardiovascular clinical trials, particularly in ischaemic heart disease and heart failure drug trials, the most common cardiovascular conditions affecting women. In fact, a number of pivotal cardiovascular drug trials of 2019 had less than a quarter of women enroll.^12-15 Interestingly, the PARAGON-HF trial, where 51.7% of patients were women, found a heterogeneity in treatment response: women with HFpEF responded better to valsartan-sacubitril, with a 28% reduction (rate ratio 0.73) in the primary endpoint.

In a compelling 2018 editorial, doctors Pilote and Raparelli explore the practical reasons for under-enrollment of women in cardiovascular drug trials, notably male-patterned inclusion criteria and gender-related barriers to screening and participation in trials, such as caretaking roles and low socioeconomic status. While proposing interventions to mitigate this issue (childcare and such support for women during time spent as a research participant, inclusion criteria that consider sex differences in pathophysiology, prespecified subgroup analyses, etc.), they warn that such under-representation of women could lead to sex-biased outcome measurements and missed opportunities to transfer results in clinical practice.

The issue, in essence, is not just about researching CVD in women: even within this large cohort, differences in symptoms, presentation and outcomes, heterogeneity related to age, ethnicity and geographic locations exist. Why younger women with ACS tend to have unfavorable prognoses is an as-yet unanswered question, with huge scope for research, as is microvascular dysfunction, known to be more prevalent among women.

What can be done?

With February being national heart month, and the American Heart Association’s #GoRedForWomen campaign soaring at its highest, it seems like a good time to reflect on what can (and should) be done for women with CVD. Because there is plenty left to do.

Raise awareness: It’s vital that both women and men are aware that heart disease is as big a killer in women as in men. The AHA’s signature women’s initiative Go Red for Women (https://www.goredforwomen.org/) and the sub-initiatives of Wear Red Day are great platforms dedicated to increase women’s heart health awareness. The Women’s Heart Alliance (https://www.womensheartalliance.org/) is another organization working to promote gender equity in research, prevention, awareness and treatment.

Enroll more women in clinical trials: it’s important to identify barriers accounting for the low inclusion of women in clinical trials, and actively intervene to overcome them.

Women’s Heart Health Clinic: a number of programs have successfully initiated women’s heart health clinics, exclusively catering to the diagnosis and treatment of this often-underestimated patient group.

Get more women involved: at every level, be it as clinical trialists, advocates, physicians, nurses or other health-care providers.

As physicians, perhaps the best thing we can do for our female patients is to pay more attention. Don’t dismiss a symptom, because nothing should “not seem cardiac” until proven otherwise.

So, yes:

Listen to her.

Diagnose her.

Investigate her.

Study her.

Treat her.

And don’t just #GoRedForWomen in February. #GoRedForWomen throughout the year.

References

Pasupathy S, Tavella R, Beltrame JF. Myocardial Infarction With Nonobstructive Coronary Arteries (MINOCA): The Past, Present, and Future Management. Circulation. 2017;135(16):1490-1493.
Mehta LS, Beckie TM, DeVon HA, Grines CL, Krumholz HM, Johnson Mnet al; American Heart Association Cardiovascular Disease in Women and Special Populations Committee of the Council on Clinical Cardiology, Council on Epidemiology and Prevention, Council on Cardiovascular and Stroke Nursing, and Council on Quality of Care and Outcomes Research. Acute Myocardial Infarction in Women: A Scientific Statement From the American Heart Association. Circulation. 2016;133(9):916-47.
Haider A, Bengs S, Luu J, Osto E, Siller-Matula JM, Muka T, et al. Sex and gender in cardiovascular medicine: presentation and outcomes of acute coronary syndrome. European Heart Journal (2019) 0, 1–14.
Ferry AV, Anand A, Strachan FE, Mooney L, Stewart SD, Marshall L, et al. Presenting Symptoms in Men and Women Diagnosed With Myocardial Infarction Using Sex-Specific Criteria. J Am Heart Assoc. 2019 Sep 3;8(17):e012307.
Dreyer RP, Smolderen KG, Strait KM, Beltrame JF, Lichtman JH, Lorenze NP, et al. Gender differences in prevent health status of young patients with acute myocardial infarction: a VIRGO study analysis. Eur Heart J Acute Cardiovasc Care 2016;5:43–54.
Arora S, Stouffer GA, Kucharska-Newton AM, Qamar A, Vaduganathan M, Pandey A, et al. Twenty year trends and sex differences in young adults hospitalized acute myocardial infarction: the ARIC Community Surveillance Study. Circulation. 2019;139:1047–1056.
037137Jespersen L, Hvelplund A, Abildstrom SZ, Pedersen F, Galatius S, Madsen JK, et al. Stable angina pectoris with no obstructive coronary artery disease is associated with increased risks of major adverse cardiovascular events. Eur Heart J 2012;33:734–744.
Ong P, Camici PG, Beltrame JF, Crea F, Shimokawa H, Sechtem U,et al. International standardization of diagnostic criteria for microvascular angina. Int J Cardiol 2018;250:16–20.
Srivaratharajah K1 Coutinho T, deKemp R, Liu P, Haddad H, Stadnick E, et al. Reduced Myocardial Flow in Heart Failure Patients With Preserved Ejection Fraction. Circ Heart Fail. 2016;9(7).
Scott PE, Unger EF, Jenkins MR, Southworth MR, McDowell TY, Geller RJ, et al. Participation of Women in Clinical Trials Supporting FDA Approval of Cardiovascular Drugs. J Am Coll Cardiol. 2018;71(18):1960-1969.
Pilote L, Raparelli V. Participation of Women in Clinical Trials: Not Yet Time to Rest Our Laurels. J Am Coll Cardiol. 2018;71(18):1970-1972.
Mehran R, Baber U, Sharma SK, Cohen DJ, Angiolillo DJ, Briguori C, et al. Ticagrelor with or without Aspirin in High-Risk Patients after PCI. N Engl J Med. 2019;381(21):2032-2042.
McMurray JJV, Solomon SD, Inzucchi SE, Køber L, Kosiborod MN, Martinez FA, et al; DAPA-HF Trial Committees and Investigators. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med. 2019;381(21):1995-2008.
Schüpke S, Neumann FJ, Menichelli M, Mayer K, Bernlochner I, Wöhrle J, et al; ISAR-REACT 5 Trial Investigators. Ticagrelor or Prasugrel in Patients with Acute Coronary Syndromes. N Engl J Med. 2019 ;381(16):1524-1534.
Presented by Dr Judith S. Hochman at the American Heart Association Scientific Sessions (AHA 2019), Philadelphia, PA, November 2019. https://www.ischemiatrial.org/system/files/attachments/ISCHEMIA%20MAIN%2012.03.19%20MASTER.pdf

Resolutions for 2020: Optimizing my Ikigai and the pursuit of happiness

January 14, 2020January 14, 2020 Aaysha Cader, MD, MRCP

While reflecting on an extraordinarily busy yet rewarding career year of 2019, I thought of my resolutions for 2020. I’m exceptionally bad at keeping new year resolutions, so I only made one: to be happy.

The concept of Ikigai

Happiness can mean different things to different people, and each of us, particularly medical professionals, is on a personal journey. There is a cool Japanese concept that encompasses multiple spheres of happiness, called Ikigai. Meaning “a reason for being”, it is well-depicted at the intersection of a quintessential Venn diagram that is really doing the rounds on the internet.

Image: Find your Ikigai. BODETREE, ADAPTED FROM FRANCESC MIRALLES

Fundamentally, it encompasses aligning one’s personal and career goals by combining the things one loves, is good at, what the world needs and what one is/could be paid for.¹Applied to physicians, it’s essentially the pinnacle of work-life balance.

While much is being discussed about physician wellness and work-life balance in recent times, for fellows in training and early career physicians, achieving a good work-life balance can be formidably challenging. In a formative and critical stage in your career, you want to maximize on all opportunities to learn and demonstrate competence. Given that conventional wisdom in medicine has always assumed that working harder and taking on more responsibilities is what makes one a better physician, you find yourself in a precarious position, and unable to say no, perhaps to avoid being considered “irresponsible” or “disinterested”, among others.

Thus “having it all” is way easier said than done. Thinking long and hard about this resolution, I went back to the concept of Ikigai. Seemingly, in order to discover your Ikigai, you must first find what you’re most passionate about, then find the medium through which you can express that passion.²

As cardiologists, or in fact medical professionals in general, I’d like to think that we’re already halfway there, having discovered our passion for the work we do. This got me thinking that a great part of my sense of happiness and fulfillment, my ikigai, could actually be achieved simply by getting better, more competent and efficient at my job, thus paving the way (and time) for doing the other things I also wanted to do.

While cardiology can be one of the most rewarding and emotionally fulfilling careers, it does come with significant sacrifices. In my sometimes unrealistic attempts to maintain a social life and achieve the so-called “work-life balance”, I recall doing exam revisions with my study buddy until midnight, forcibly satisfying a respectable quota of daily reading and “rewarding“ myself with a game of Settlers of Catan with my non-doctor friends late into the night, only to have to be present at rounds by eight the next morning. Especially during my initial years of training, in a pursuit to achieve work-life balance, I struggled trying to exclusively “slot out” time periods for work and leisure. As a result, my laptop became a mandatory accessory, finding a place at hangouts, parties and even vacations, where I’d squeeze in that little bit of work if I found the time.

P-squared: Matching passion with purpose

So, how do you effectively ensure time for other things in life, without compromising on expectations and quality at work? I found myself picking up handy tips from Morton T. Hansen’s fabulous book Great at Work: The hidden habits of top performers.³ One aspect that really resonated with me was the concept of P-squared, i.e. matching passion with a strong sense of purpose. He writes about how passion at work is not merely taking pleasure in the work itself, but can come from success, social interactions, learning and competence. In short, pursuing activities that are personally meaningful.

Working smarter over working harder

One way of ensuring one’s focus on meaningful activities is to prioritize and decide what work you will pour your heart and soul into.³ Naturally, each task is not guaranteed to trigger your interest to the maximum. While the “chores” that are one’s professional responsibility absolutely need to be done (and prioritized), it’s important to pick and prioritize ancillary projects, thus ensuring one’s full focus and ultimately better seeing it to fruition. Given professional hierarchy in medicine, it can sometimes be difficult to say no early on in one’s career. A piece of brilliant advice I’ve been given in such scenarios is: If it’s part of a project you happen to land but which can (and should) be done by someone else, delegate it smartly and oversee the work. The advantages are multiple: you facilitate an opportunity for someone else to gain that experience, you gain the experience of overseeing a job and most importantly, it reduces an unnecessary load on you, allowing you to make the time for the projects that matter.

Also, focusing on doing fewer things but doing them better, means that you have more time left over, which you can spend on your private life, effecting towards some degree of work-life balance.³

Share the load

A roster has a purpose and it’s important to share the load. Accepted that we all have our unique personal challenges, some more than others, I found myself chronically covering another person’s roster, stressing out and compromising on my own private time that I could very well have spent with family and friends. While mutual cooperation within a working unit is vital to good work-life balance, particularly in medicine, it should certainly not be at the expense of one’s happiness.

Take breaks

Doctor Hansen also writes about the importance of keeping one’s passion in check, and not allowing it to consume you.³ Grossly translated, it means making the time for one’s private life, be it travel, working out, reading or playing a sport. Thanks to a wonderfully supportive spouse, I might have gotten away with amalgamating work and life on most occasions, but I appreciate the necessity of making an effort to keep work passions in check, and actively make some quality time for family and friends.

“Work on how you work, not on protecting your life from work” – Morten T Hansen

All things said, I’m extremely grateful for being able to do something that I absolutely love, would hope I’m good at (!), get paid for and certainly what the world needs, neatly satisfying the central convergence of the multiple dimensions ikigai. One’s ikigai.is a deeply personal journey, and not one a mentor can spell out for you. However, actively making an effort to being efficient at work, being less stressed out and more balanced would certainly make one better at life too, translating to happier social and private lives. Achieving an Utopian level of work-life balance may not be possible, but finding happiness and fulfillment in what you do certainly is, and it’s a resolution I’m going to make an effort to keep this year. A happy new year to you all!

References

Garcia H, Miralles F. Ikigai: The Japanese Secret to a long and happy life. New York: Penguin Books; 2016.
Myers C. How To Find Your Ikigai And Transform Your Outlook On Life And Business. Feb 23, 2018. https://www.forbes.com/sites/chrismyers/2018/02/23/how-to-find-your-ikigai-and-transform-your-outlook-on-life-and-business/#6e99332a2ed4
Hansen MT. Great at Work: The Hidden Habits of Top Performers. New York: Simon and Schuster paperbacks; 2018.

The views, opinions and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your personal health matters. If you think you are having a heart attack, stroke or another emergency, please call 911 immediately.

Is Old Really Gold? The Case Against Aspirin

December 6, 2019December 6, 2019 Aaysha Cader, MD, MRCP

The recently concluded AHA Scientific Sessions provided for a myriad of sessions on antiplatelet therapy in cardiovascular disease (CVD).

The late-breaking TWILIGHT ACS trial reported a win for ticagrelor monotherapy among patients randomized after 3 months post-NSTE-ACS and PCI, in results consistent with the main TWILIGHT trial.^1-2 TWILIGHT ACS showed a reduction of clinically significant bleeding with no increased risk of ischemic adverse events at 1 year, for those randomized to ticagrelor monotherapy versus aspirin plus ticagrelor (DAPT).¹

That same day, an entire session aptly titled “Aspirin: who needs it anymore?” dedicated to the dissection of aspirin, featured a series of talks on the role for aspirin for the primary and secondary prevention of cardiovascular disease (CVD).

Questioning the potential “twilight” of aspirin therapy, Dr Roxana Mehran raised some pertinent issues particularly pertaining to bleeding risk and gastrotoxicity of aspirin, in addition to treatment failure/ “aspirin resistance” resulting from its enteric-coated preparation and potential drug-drug interactions.

Nevertheless, while aspirin may still remain in the game with respect to secondary prevention, 3 randomized clinical trials in primary prevention have ensured a “three strikes and you’re out” scenario for aspirin, culminating in a de-emphasis in the guidelines as well.

One of the best things about attending meetings is the effortless re-cap/ additional reading one does afterwards. Thus, in order to discern how such a fate befell aspirin, here’s a brief look at the “three A’s” of 2018 responsible for hitting the nail in the coffin:

The ARRIVE (Aspirin to Reduce Risks of Initial Vascular Events) trial

ARRIVE enrolled 12 546 patients (men ≥ 55 years with 2-4 risk factors and women ≥ 60 years with ≥risk factors for CVD) who were randomized to enteric-coated (EC) aspirin 100 mg/day versus placebo.^{3 ~}29·5% of participants were women. Individuals with diabetes and those at high risk of bleeding were excluded. The primary endpoint was a composite outcome of time to first occurrence of CV death, MI, unstable angina, stroke, or transient ischemic attack.

After a median follow-up of 5 years, no significant differences were observed in the primary end-point between those assigned to aspirin vs placebo (4.29% vs 4.48%; p=0.6038), although the event rate was much lower than expected, thus making the study more representative of a low-risk population. The overall incidence of adverse events was similar in both groups, however, there were significantly more gastrointestinal bleeding events (predominantly mild) in the aspirin group than placebo (0.97% vs 0.46%; p=0·0007).

The ASPREE (Aspirin in Reducing Events in the Elderly) trial

This trial enrolled 19,114 healthy community-dwelling individuals across sites in Australia and the USA aged ≥ 70 years (or ≥ 65 years if Black/ Hispanic in US) and devoid of CVD, dementia or disability who were randomized to 100 mg EC aspirin vs placebo.^4-6

The primary end-point was a composite of death, dementia or persistent physical disability while secondary end points included major hemorrhage and cardiovascular disease (defined as any ischaemic event).^4-6 At 56.4%, ASPREE enrolled the highest number of women from among the three trials.⁴ The median age of participants was 74 years.

The trial was terminated early at a median of 4.7 years of follow-up, as it was determined that no benefit would be derived with continued aspirin use in terms of primary end point. Accordingly, there were no significant differences in the primary composite outcomes (21.5 vs. 21.2 events per 1000 person-years; p = 0.79 ).⁴However, rates of major bleeding were significantly higher in the aspirin group (8.6 vs. 6.2 events per 1000 person-years; p < 0.001), with a progressive increase in the cumulative incidence of major hemorrhage across the follow-up period.⁵ The majority of these episodes were gastrointestinal bleeds, with the higher risk of upper GI bleeds being particularly more pronounced with aspirin (hazard ratio, 1.87; 95% CI, 1.32 to 2.66).⁵

There was also an increased risk of all-cause mortality in the aspirin group versus placebo (12.7 vs 11.1 events per 1000 person-years; HR, 1.14; 95% CI, 1.01 to 1.29) with cancer being the major contributor to the higher mortality seen with aspirin.⁶Thus, ASPREE concluded that the daily use of low-dose aspirin did not prolong disability-free survival among the elderly.⁶

The ASCEND (A Study of Cardiovascular Events in Diabetes) trial

A trial specifically designed to investigate the effects of aspirin in primary prevention among diabetics, ASCEND enrolled 15,480 individuals (~37. 5% women) in the United Kingdom with diabetes but no evident CVD who were randomized to 100 mg of aspirin daily versus placebo.⁷

During a mean follow-up of 7.4 years, those randomized to aspirin had a significantly lower percentage of serious vascular events in comparison to placebo (8.5% vs. 9.6%; P=0.01). However, this benefit was offset by significantly higher major bleeding events seen in the aspirin arm (4.1% vs. 3.2%, p=0.003), with no attenuation of the effect on bleeding over time. As with ARRIVE, the majority (41.3%) of major bleeding events were gastrointestinal, of which close to two thirds were in the upper GI tract. Thus, the trial concluded that the absolute benefits of aspirin in preventing CVD among diabetics were largely counterbalanced by the hazards of bleeding.

These trials formed the basis for the de-emphasis of aspirin in the 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease, which recommended against the prophylactic use of aspirin among elderly (>70 years) and those at high bleeding risk. There was also a downgrade in class of recommendation for low dose aspirin for primary prevention in select 40 to 70 year-old adults at higher ASCVD risk but lower bleeding risk (Class II b).⁸

To add to this, a comprehensive meta-analysis of 13 trials comprising of 164 225 participants without cardiovascular disease by Zheng et al., found that aspirin use was associated with a significant reduction of cardiovascular events but also an increased risk of major bleeding events compared with no aspirin.⁹

As Dr Erin Michos, one of the co-authors of the Primary Prevention guidelines pointed out in her talk at AHA 2019, this poor performance of aspirin in terms of risk-benefit could be attributed to the improved adherence to other primary prevention methods, such a reduction of smoking, better control of blood pressure and importantly more aggressive lipids control by virtue of statins.

With the much-needed emphasis on bleeding and its detrimental effects, “less is more” has been the focus in recent times, at least for antiplatelet and antithrombotic drugs, with recognition of trials that withdraw rather than add to current drug treatments. Furthermore, the appropriate prescription of drugs and increased emphasis on lifestyle modification for primary prevention cannot be understated. The onus is on physicians to keep up to date and tailor drug prescriptions to the individual patient.

Also, in keeping with the spirit of on post-conference re-caps, highly recommend the following as additional reading:

Marquis-Gravel G, Roe MT, Harrington RA, et al. Revisiting the Role of Aspirin for the Primary Prevention of Cardiovascular Disease. Circulation 2019;140(13):1115-1124.
Ridker PM. Should Aspirin Be Used for Primary Prevention in the Post-Statin Era? N Engl J Med 2018;379(16):1572-1574.
Antithrombotic Trialists’ (ATT) Collaboration, Baigent C, Blackwell L, et al. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet 2009;373:1849-60.

References:

Presented by Dr. Usman Baber at the American Heart Association Annual Scientific Sessions (AHA 2019), Philadelphia, PA, November 17, 2019.
Mehran R, Baber U, Sharma SK, et al. Ticagrelor With or Without Aspirin in High-Risk Patients After PCI. N Engl J Med2019;381:2032-42
Gaziano JM, Brotons C, Coppolecchia R, et al. Use of aspirin to reduce risk of initial vascular events in patients at moderate risk of cardiovascular disease (ARRIVE): a randomised, double-blind, placebo-controlled trial. Lancet2018;392:1036-46.
McNeil JJ, Woods RL, Nelson MR, et al. Effect of Aspirin on Disability-free Survival in the Healthy Elderly. N Engl J Med 2018;379:1499-1508.
McNeil JJ, Wolfe R, Woods RL, et al. Effect of Aspirin on Cardiovascular Events and Bleeding in the Healthy Elderly. N Engl J Med 2018;379:1509-18.
McNeil JJ, Nelson MR, Woods RL, et al. Effect of Aspirin on All-Cause Mortality in the Healthy Elderly. N Engl J Med 2018;379:1519-28.
ASCEND Study Collaborative Group, Bowman L, Mafham M, et al. Effects of Aspirin for Primary Prevention in Persons with Diabetes Mellitus. N Engl J Med 2018;379:1529-39.
Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation 2019;140(11):e596-e646.
Zheng SL, Roddick AJ. Association of Aspirin Use for Primary Prevention With Cardiovascular Events and Bleeding Events: A Systematic Review and Meta-analysis. JAMA 2019;321(3):277-287.

From across the Atlantic: making the most of your conference trip as an international delegate

November 18, 2019November 26, 2019 Aaysha Cader, MD, MRCP

Approximately 30-40% of AHA Scientific session attendees are from outside of the United States. Taking a couple (or more!) of flights, landing in a new city after a 23-hour trip from across the Atlantic and functioning at optimum levels during a meeting of such magnitude may well be a formidable task, particularly when it’s a short trip and you want to get the most of it.

While each person has their own mechanisms of adapting, here’s some derived from my relatively short experience:

Optimize the long flight hours: I personally feel that sleep makes for the finest use of flight time, particularly on long-haul flights and red-eyes. There are others, however, who might opt to use this time to fine-tune presentations and prepare points for posters. A good rest in flight also helps you adapt and combat jetlag optimally, allowing you to function at maximum efficiency.

Get the mundane things over with: Make sure you’ve sorted (and preferably pre-paid for) accommodation, figured out airport to hotel commutes, activated international roaming allowing for sufficient data/connectivity and downloaded offline maps of the city, just in case. Accommodation within walking distance to meeting location is convenient, allowing for a later wake-up (if you’re not an early riser like yours truly!) but most importantly obviating the need for figuring out taxis/ tube maps/traffic navigation when you’re very likely to be in a rush.

Pack light but pack smart: International transfers can be unpredictable; I always factor in lost/delayed bags and pack an entire day’s conference wardrobe into my hand luggage. The importance of comfortable shoes cannot be understated, especially if you’re trying to do a superspeed Flash act between meeting rooms. I also carry a large bag at meetings, one that would accommodate a fully-charged laptop and power banks, phone charger with universal adapter (absolute essential!) and a light jacket for a cold meeting room. Also, any additional space is more than welcome for journals and other print material you might pick up.

Plan your itinerary right: Basically, be in the room where it happens. Even with the most efficient meeting app, chances are you’ll have multiple overlapping sessions bookmarked. Keeping in mind the genre of sessions one might not always have access to back home, I would opt to attend late-breaking science, live cases and interactive sessions by experts, over, say, seminars and updates on more general topics.

Use social media: It’s a formidable accessory to derive the maximum conference experience. Apart from the obvious pluses of rapid access to scientific content and networking, a twitter update might even alert you to a session you intended on attending but somehow missed bookmarking.

Avail opportunities for networking: Most of conference science can now be accessed online post-conference but, one cannot put a price to the value of face-to-face networking or comparing notes with peers from across the globe, potentially even leading to collaborations. And let’s not forget the opportunities to literally pick on the brains of global experts at dedicated sessions, such as those offered at the FIT lounge.

It’s not all about the science: Make use of the additional programming. The Women in Science mentor-mentee session I had Saturday morning with Dr Noel Bairey Merz, even before I attended my first scientific session, provided a wonderful opportunity to discuss research and career with a prominent woman in cardiology (WIC).

Take breaks: Go to exhibition halls and training pavilions; If you’re super-saturated with all the scientific content, visiting booths at exhibit halls are actually a great way to take a breather, caffeinate, pick-up some new literature or check out the new tech.

Get involved: At various levels in one’s career, there are many ways international members can get involved, perhaps by joining one of the AHA’s 16 scientific councils, for a start. The Early Career Blogging program is a fantastic project: apart from the remarkable learning and networking opportunities it affords, you can’t beat the incredible perks of front row seats at the Presidential Session, including a performance by the cast of Hamilton!!

Embrace the different perspectives but apply them locally: While these meetings provide the international attendee a much-needed global perspective on a variety of aspects pertaining to cardiology, it’s also equally important to appropriately apply what you learn, taking into account local culture and tailoring it to the norms of practice back home.

Enjoy the break from work: Last but not least, even with the busiest of itineraries, international meetings offer what can sometimes be much-needed downtime and a break from work. There is no joy like that of exploring a new city, so even if it means taking an extra half day, use that “me” time to good effect. Carpe diem!