COVID management remains most expensive intervention while Aspirin remains ill-studied, underutilized and ignored by HCPs in the profit motivated world - Javed Akram

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Proceedings of Webinar on Aspirin and Covid19
COVID management remains most expensive
intervention while Aspirin remains ill-studied,
underutilized and ignored by HCPs in the
profit motivated world - Javed Akram
Aspirin use is associated with improved outcomes
in hospitalized Covid19 patients, there was 47%
decrease in patients going on Ventilator
Hypoxia & coagulopathy remains the most
important modifiable risk factors

By Shaukat Ali Jawaid

LAHORE: Covid19 pandemic is likely to remain endemic hence we need to develop local new normal guidelines in the light of best global practices. So far no evidence based guidelines for the management of Covid19 are available. We need to identify critical ill patients early. Hypoxia and Coagulopathy remains the most important modifiable risk factors. Studies have proved that Aspirin use is associated with improved outcomes in hospitalized Covid19 patients but unfortunately in this profit motivated world, this most economically priced antiplatelet and anti-inflammatory drug remains ill-studied, underutilized and ignored by the healthcare professionals all over the world since there is no money in it. This was stated by Prof. Javed Akram Vice Chancellor of University of Health Sciences Lahore who is also President of Pakistan Society of Internal Medicine (PSIM). He was making a presentation on “Aspirin and Covid19” at a Webinar organized by Pakistan Aspirin Foundation in collaboration with University of Health Sciences and PSIM on May 9th 2021.


Prof. Javed Akram

This academic activity was moderated by Dr. Fawad Farooq Consultant cardiologist at NICVD Karachi while members of the Experts Panel included Prof. Abdus Samad and Prof. Ejaz Ahmad Vohra from Karachi and Prof. Shahbaz Kureshi from Islamabad who is also current President of Pakistan Aspirin Foundation.

Continuing Prof. Javed Akram said that some old drugs which are economically priced including Aspirin and Vitamin-D are being ignored in the treatment of Covid19. Our objective, he pointed out, should be to support these drugs if there is any evidence. It is reported that both these drugs work very well in Covid19 as well. We should highlight their advantages for the benefit of poor patients. He hastened to add that he had no financial interest in any of the pharmaceutical companies marketing these preparations Aspirin and Vitamin-D and his views was based on his personal clinical experience and supported by numerous studies which he quoted during the presentation.


Some of the issues which he discussed in detail during his presentation included virus vs. host mechanism, severity index, critically ill Covid19 patients and role of platelets in Covid19, Covid management and the role of Aspirin. Prof. Javed Akram further stated that we have so far seen over 39, 0000 mutants of this disease and we are looking at various mutants. So far mutants like UK, South Africa have been identified but we have not seen Indian mutant in Pakistan so far. Speaking about the transmission of Covid19, Prof .Javed Akram opined that we have always believed that it is not a droplet infection but Aerosol infection. Investigators have measured the particle sizes of infection aerosols and shown that pathogens are most commonly found in small particles aerosols which are airborne and breathable. A recent study published in Lancet from Wuhan China has confirmed that it is an aerosol infection. Hence it is more dangerous, we have to shut the Air-conditioning, and we must work in more ventilated areas. Cytokine storm results in liver lung injury and it is increased in patients with heart failure. Damage of airway epithelial and endothelial cells were also discussed in detail.


Prof. Ejaz Ahmed Vohra

Talking about the drivers of mortality in Covid19 he mentioned virus quantity, co morbidity, age, host response, virus binding, Vitamin-D status, Lymphocyte depletion, Cytokine storm, Metabolic disorders, secondary infection, hypoxia, coagulopathy, ASA as a guarantor drug, Ventilator Acquired Pneumonia. Fibrosis in lungs is very dangerous. Aspirin taken before the Covid19 infection is much better than taken after the patients gets infection. A study conducted in New York City which enrolled 5,700 patients showed that most of the patients were suffering from hypertension, diabetes mellitus, obesity, cardiovascular diseases, congestive heart failure, COPD, Cancer and chronic kidney disease, chronic respiratory disease. Almost 88% of patients had more than one co-morbidity. He was of the view that all high risk patients must be put on low dose Aspirin therapy. Case fatality is very high in heart failure, cardiovascular disease, cancer and diabetes mellitus. He also talked about host factors which predict severity of the disease. Patients who are deficient in Vitamin –D, D-Dimer levels were lower in that study. Vitamin D helps reduce the mortality as supplementation of Vitamin-D shows improvement in LDH levels of Covid patients. The second most common endocrine abnormality seen in short stature patients is Vitamin-D deficiency (63%), he added.


Speaking about the proposed cascade in Covid coagulopathy he mentioned altered circulating dynamic, epithelial injury, endothelial mediated alveolar injury, T cell infiltration, neo angiogenesis, fibrin dynamics, platelet aggregation, activation of pro coagulant pathways, vascular inflammation. Then intravascular clotting starts, leading to embolism and then infarct in multiple beds takes place. Studies have shown that almost 71.4% of Covid19 infection patients die due to coagulopathy. He then talked about SP elicited inflammatory response. Platelets, he opined are the central players in Covid19 in the process of thrombo inflammation in Covid 19 infection. In this condition half-life of platelets is reduced from ten days to just one day. Hence increased platelet destruction is seen in Covid. Thrombocytopenia also increases. Though due to thrombocytopenia the quantity of platelets decreases a little bit but their function improves. That is why we think that Aspirin should be used even in thrombocytopenia. Even low platelet count will function very well. Covid19 serum induces platelet activation. The patients then suffer from ARDS, coagulopathy leads to clot formation followed by cytokine storm. Athero thrombosis in Covid is due to endothelial damage, retinal, embolic, VTE, micro vascular, hepatic, cerebrovascular diseases, cardiovascular diseases, renal disorders and peripheral vascular diseases.


Management of Covid

Management of Covid includes patient monitoring, enhanced electrolytes balance, protection from DVT, caloric intake. ECMO is very helpful in managing critical patients. Gastric protection, oxygen therapy, protective effect of ASA platelet inhibition. Anti-inflammatory, endothelial protection, micro and macro vascular diseases protection, and decrease in lung injury. He then shared the details of a recently published study from USA in which 75% of enrolled patients were not taking Aspirin while only 25% were taking Aspirin. It showed that Aspirin had a huge protective effect in reducing mortality. This study was undertaken by Veterans Health Administration.

Discussing association of mortality and Aspirin prescription for Covid19, Prof. Javed Akram said that this study findings were that if platelets are between twenty five to fifty thousand, one must start antiplatelet therapy but if their number is below that, then stop Aspirin. Use of Aspirin significantly reduced hospitalization and mortality. Aspirin prescription was discovered to be strongly associated with decreased mortality rates for Covid19 positive patients enrolled in this VA study. ECMO was used in very critically ill patients. We used it in late Prof. Mustafa Kamal former VC of Nishtar Medical University while he was critically ill.


Prof. Abdus Samad

Currently we are looking at SAS2 vaccine induced thrombotic thrombocytopenia. I feel why we should not use Aspirin in these patients though we are not recommending its use in this condition at present. Recurrence with Covid19 infection can occur, Protect yourself, use oral anticoagulation,, antiplatelet, Statins, domestic oxygen, respiratory rehabilitation, stem cells, these patients also need psychological support, take care of co morbidities and use Aspirin .He emphasized that platelet activation occurs early hence Aspirin can be used in high risk patients. Unfortunately at present Aspirin is underutilized and ignored, these are orphan drugs which can save lot of lives. It has been shown that in patients taking Aspirin; there was 47% decrease in going on Ventilator which is a major advantage of Aspirin therapy, he remarked. However, more prospective studies are required; we must promote the rational use of Aspirin and produce our own data based on local studies. Critically ill patients need to be identified early, all experimental therapies should be used in local context after obtaining informed consent from the patients, Aspirin may be used in high risk patients during Covid19 pandemic and let us all join hands to promote the rational use of Aspirin in Covid prevention and treatment, he concluded.


Discussion

Responding to a question during the discussion, Prof. Javed Akram said that in the management of moderate to severe disease, along with the use of Rivaroxaban, oral anticoagulation drugs should be used. All patients with COVID 19 moderate to severe disease must be put on Aspirin therapy. We must use it for primary prevention and use Aspirin in patients over forty years of age. In my practice Prof. Javed Akram stated, I use low dose Aspirin in all my patients unless there is some contra indication. There is no harm in giving it to all most of whom have some risk factors unless there is some contra indication. He made it clear that giving Aspirin to patients when Covid19 infection has already occurred will not be of much help but putting them on Aspirin before they get infected is very helpful.

Prof. Shahbaz Kureshi suggested use of Enoxaban for four to twelve weeks. Most of the Covid19 patients, he said, die due to myocardial infarction and stroke. Prof. Javed Akram said he has treated a large number of patients in ICU but have seen just one patient who had bleeding due to Aspirin who had large duodenal ulcer. Patient died due to thrombocytopenia and not because of bleeding.

 


 Prof. Shabaz Kureshi

Asked about the dose of Aspirin, Prof Javed Akram said he used 75mg but in patients with comorbid, he used 150mg daily. Warfarin, he said, can be used but it requires strict monitoring since it has lot of interactions and we must remember that most of the Covid19 patients are already taking more than a dozen drugs. Prof. Shahbaz Kureshi remarked that Aspirin will prevent coagulopathy but should not be used as prophylaxis in such patients. The mere fact that 47% of Covid19 patients on Aspirin Prof. Javed Akram said were spared from going on to the Ventilators is a very strong evidence for its use in these patients .He further stated that most of the Covid19 patients are being treated by pulmonologist but unfortunately they are not aware of the benefits of Aspirin. It is our responsibility to become active and generate local data through local studies.

Prof. Abdus Samad participating in the discussion supported the use of Aspirin in Covid19 patients with mild to server diseases. Studies, he said, have now shown that pre-Covid Aspirin therapy has significantly reduced the morbidity and mortality. Speaking in his typical style Prof. Samad remarked that let us not wait for the enemy to attack us first, we must attack before the infection occurs and that is with the use of Aspirin and other effective medications unless there is some specific contra indication for the use of Aspirin. Let us not wait for the guidelines. During the 1965 Indo Pakistan War had we waited for the guidelines, Indian army would have entered Lahore. However, we did the right thing and attacked them beyond the BRB canal, did not allow them to cross this BRB, though it resulted in precious loss of lives of Pakistan Army as many got martyred in this attack but it proved to be an effective strategy, he added.


Recent surveys have also shown that almost 50% of the population in Mardan was tested proved to the Covid positive hence they all should be put on Aspirin therapy. I myself will put everyone covid19 positive patient and those with high risk on low dose Aspirin therapy unless there is some contra indication. India and Pakistan, he further stated, must learn lessons from each other in managing Covid19 pandemic. Our habits are similar and we have similar socioeconomic conditions. We should not allow Covid19 infection to play havoc. Let us follow the SOP, for primary prevention use mask and observe social distancing. In all those cities where covid19 infection is high, all Covid19 positive cases must be put on Aspirin therapy. It is a safe, effective and most economically prices antiplatelet drug. Bleeding incidence is very low as pointed out by Prof Javed Akram; he has seen just one patient in his practice while managing hundreds of patients in ICU. Almost 90% of our patients have two to three comorbid conditions hence the use of low dose Aspirin therapy is valid, he remarked.

DR. Fawad Farooq

It was also pointed out that thrombocytopenic purpura was first reported in a patient on Heparin. Hence one must use Heparin very carefully. Majority of the diabetes mellitus patients die from myocardial infarction and many patients with Covid19 infection died due to embolism. On a suggestion from Prof. Shahbaz Kureshi, Prof. Javed Akram said that we will develop a protocol for a study enrolling outcome of patients with Covid19 infection those who were taking Aspirin and those who were not on Aspirin. We can collect data from all over the country involving various people. Prof. Shahbaz Kureshi also suggested that let us from the platforms of Pakistan Aspirin Foundation start campaign for primary prevention of Covid. It should include following SOPs, use of mask, social distancing and all other non-pharmacological interventions and then those found positive, use low dose Aspirin as well.

Prof. Ejaz Ahmad Vohra emphasized the importance of generating local data by doing local studies. He was of the view that we must ensure rational use of Aspirin and don’t take any step which brings disrepute to this most safe, effective economically priced antiplatelet agent. So far there have been just a few studies hence we should advice use of Aspirin only in Covid19 positive cases.


Mr. Shaukat Ali Jawaid General Secretary of Pakistan Aspirin Foundation thanked Prof Javed Akram for the excellent presentation and highlighting the beneficial effects of use of Aspirin in Covid19 infection. The most impotent point in his presentation, he said, was that almost 47% Covid19 patients who were already on Aspirin therapy were saved from going on the Ventilators. It is very heartening news and will encourage the healthcare professionals to use low dose Aspirin in all Covid19 positive patients. Prof. Abdus Samad’s aggressive management strategy of attacking the enemy before infection occurs also needs to be highlighted as it has shown drastic reduction in morbidity and mortality.

Earlier in his introductory remarks, Dr. Fawad Farooq stated that every day we come to know something new about COVID19 pandemic. New information is coming up as regards its diagnosis, management strategies, treatment plans. Today’s webinar is devoted to one aspect of Role of Aspirin in management of Covid19. It is evident from other manifestations that blood thinning is a big issue. A good thing about our guest speaker today Prof. Javed Akram VC UHS is that he always presents his original local data which is extremely important and it will enlighten all of us on the management of Covid19 pandemic.


Later Mr. Akhtar Director Marketing and Sales in Atco Laboratories who had sponsored the Webinar thanked Prof. Javed Akram for his very elaborate presentation and also thanked the other distinguished panelists for their useful input and valuable remarks. He also thanked Dr. Fawad Farooq for moderating the Webinar and Mr. Shaukat Ali Jawaid Chief Editor Pulse International for joining the session.