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Warfarin or Aspirin Which Is a Better Drug in Myocardial Infarction Prevention?
Non-communicable diseases, especially Cardio-Vascular Diseases (CVD) are emerging as a global health concern especially among low and middle-income countries. About 71% of deaths worldwide are due to non-communicable diseases and 78% of global NCD deaths occur in low and middle-income countries. 44% of NCD deaths at the global level are attributed to cardiovascular diseases (CVD). Ischemic heart disease and stroke have been recognized as major causes of CVD-related deaths for more than a decade. To add to it, two CVD-related deaths accounted for 15.2 million deaths in 2016 in low- and middle-income countries. (WHO, 2018). While the figures mentioned above show a very grim picture, they also show a great opportunity to reduce NCD-related morbidity if ischemic heart disease and stroke are taken seriously and treated with a quick and efficient response. extreme.
As we already know, cardiovascular diseases and Ischemic strokes are the two main causes of CVD-related deaths and can be classified as Coronary Artery Disease (CAD). CAD is the most common type of CVD which reduces the circulation of blood vessels supplying oxygenated blood to the heart due to the deposition of plaque. When the plaque breaks, it is replaced by blood clots in the arteries that block the blood supply to the heart muscles. This stress increases the risk of damage to myocardial cells, which in turn increases the risk of myocardial infarction known as heart attack. Cardiovascular disease (CVD) patients with a previous episode of myocardial infarction (MI) or ischemic stroke are more likely to experience a subsequent MI. Atrial fibrillation (AF) is a known complication of acute myocardial infarction (AMI). Atrial fibrillation also known as arrhythmia or irregular heartbeat is common in 6-21% of MI patients which may increase the risk of MI in CVD patients. A fast, irregular heart rate causes poor blood flow leading to blood clots, stroke, heart failure and heart-related heart diseases.
Anticoagulant agents and platelet inhibitors are the drugs of choice for long-term management of thrombosis (blood clots) and MI. Aspirin is a popular choice administered for platelet inhibition in order to reduce the chances of CVD death and subsequent cases of MI as well, although its use for CVD prevention is subject to controversy. 15-20% of patients are at risk of death due to re-infarction within 2-5 years of previous MI. The most commonly prescribed anticoagulant for patients worldwide with AF is Warfarin. Warfarin is a blood thinner that inhibits vitamin K-dependent coagulation factors (prothrombin). Prothrombin reduces the production of thrombin which is important in altering the formation of blood clots. Reduction in thrombin levels, reduces thrombogenicity in addition to anticoagulation.
Aspirin, also known as Acetylsalicylic acid, acts as an acetylating agent, which neutralizes the enzyme-dependent cyclooxygenase (COX)-1 and reduces the generation of thromboxane A2 that creates an anti-platelet effect. Furthermore, it reduces the inflammatory responses in CAD and prevents the progression of atherosclerosis. Aspirin inhibits the formation of COX-dependent vasoconstrictors by improving endothelial dysfunction in atherosclerosis, increasing vasodilation and reducing thrombosis. As Aspirin has an immediate and long-term effect on platelets, Aspirin is prescribed as a secondary prevention measure in CVD patients.
An American comparative study of MI and AF showed a higher risk of death in patients with both MI and AF and in contrast to AF alone, by results not statistically significant. Warfarin use showed a significant reduction in MI when compared to non-Warfarin.
Although, there have been controversies on the short-term and long-term merits and demerits of the combined treatment of anticoagulant and antiplatelet, their intrinsic and synergistic effect may be of clinical benefit in the treatment of acute ischemic heart diseases. Aspirin is generally preferred over Warfarin due to ease of administration, low cost, comparability and efficacy. Previous studies have established the beneficial effects of warfarin compared to placebo in preventing new episodes of MI. In addition, Warfarin is known to have higher benefits than Aspirin, while Aspirin is currently the most widely used drug.
Three randomized trials of Aspirin and Warfarin in different doses and combinations help in the knowledge of the use of the two drugs in the case of patients with MI.
The first study of 1997, was a randomized, double-blind study in the USA on low-dose Warfarin and Aspirin with Aspirin alone after MI. 8803 MI patients, in the age group of 21-85 years, sent an episode of MI, with a high myocardial enzyme concentration, with chest pain or changes in the electrocardiograph were treated with a daily dose of 160 mg Aspirin or 1mg Warfarin + 80mg Aspirin. or 3 mg Warfarin + 80 mg Aspirin based on randomization. All drugs are identical in appearance with placebo. There is an interim analysis by an independent data and safety monitoring committee to ensure safety, effectiveness and efficacy.
Second, is a 2002 comparative study, hypothesized the combination of Aspirin and Warfarin is more effective than Aspirin alone. A randomized controlled trial with 2.7 years of follow-up across 78 United States Department of Veterans Affairs medical centers. 5059 patients (median age 62 y, 98% men) who had an acute MI were is administered daily with Warfarin (the international equivalent of the target [INR] 1.5 to 2.5 IU) + Aspirin (81 mg/dl) or Aspirin (162 mg/dl) alone.
A comparative efficacy study of Aspirin (160 mg daily), Warfarin with a combined dose of Aspirin (75 mg daily) and Warfarin as an open-label, multi-centric, randomized controlled trial sent MI. Patients of both sexes, younger than 75 years, with severe myocardial insufficiency according to the recommendations of the World Health Organization: chest pain, changes in the electrocardiograph, creatine kinase < 250 U/liter, aspartate aminotransferase < 50 U/liter in it is in the study. Treatment continued until a predetermined number of events occurred and no interim analyzes were performed.
The daily dose of 160 mg Aspirin or 1mg Warfarin + 80mg Aspirin (1mg W+ 80mg A) or 3 mg Warfarin + 80 mg Aspirin (3mg W+ 80mg A) showed the same effect with less than 1% variation between the three treatments. The relative risk of a primary event across the three groups was:
160 mg A compared with (3mg W+ 80mg A)
160 mg A compared with (1mg W+ 80mg A)
(1 mg W plus 80 mg A) compared with (3 mg W + 80 mg A)
Relative risk of the first event
0·95 (95% CI 0·81–1·12, p=0·57)
1·03 (0·87-1·22, p=0·74)
0·93 (0·78-1·11, p=0·41)
In the Warfarin + Aspirin versus Aspirin study, a 15% reduction in annual mortality was observed in the combined Warfarin + Aspirin as opposed to Aspirin alone, including major bleeding (1.28 vs 0.72 events per 100-year follow-up. , P < 0.001). However, the rates of internal bleeding were the same in both groups (14 patients each).
In the study of the effect of Warfarin, Aspirin or both, statistically, there was no difference in the overall mortality rate between the three groups (Aspirin (160 mg daily) and Warfarin in a combined dose with Aspirin (75 mg daily) and Warfarin). However, Warfarin in combination with aspirin and only showed a better effect on recovery when compared with Aspirin. The total number of events or events including events was also higher in the Aspirin group (24.5%) as compared to Warfarin (19.4%) and Aspirin + Warfarin (17.4%). Of the 14 hemorrhagic deaths, 11 occurred while on medication of which 5 were on Warfarin medication and 6 on a combined dose of Warfarin and Aspirin.
Overall adverse events of non-fatal major bleeding events in patients under treatment, 0.17% received Aspirin, 0.68% received Warfarin and 0.75% received a combination of Aspirin and Warfarin per year. Minor bleeding events observed in the three arms- Aspirin, Warfarin and combined were 0.84%, 2.14% and 2.70% per year respectively.
In patients with an episode of Myocardial Infarction, no additional clinical benefits were observed in low, fixed-dose warfarin (1 mg or 3 mg) in combination with low-dose aspirin (80 mg). aspirin 160 mg only. Neither the average dose of Warfarin (at an average global standard of 1.8) nor the low dose of Aspirin had any added clinical benefits.
Meanwhile, Warfarin, is an effective drug when administered alone or combined with aspirin, compared to aspirin alone. There is a reduced incidence of multiple events after acute myocardial infarction but is associated with a higher bleeding risk. A large number of patient withdrawals were observed in patients on Warfarin due to bleeding, coronary artery disease or coronary artery disease, which may have affected the effect of Warfarin.
Therefore, the combined dose of Warfarin and Aspirin is the most effective drug for the prevention of events after myocardial infarction when compared with Aspirin or Warfarin alone. However, severe bleeding occurs frequently with the combined dose.
Services referred to:
1. Karunathilake SP, Ganegoda GU. Secondary Prevention of Cardiovascular Diseases and Application of Technology for Early Warning. Biomed Res Int. Year 2018; 2018. doi: 10.1155/2018/5767864
2. World Health Organization. Top 10 causes of death. World Health Organization.
3. Gelbenegger G, Postula M, Pecen L, et al. Aspirin for primary prevention of cardiovascular disease: A meta-analysis with specific focus on subgroups. BMC Med. 2019;17(1):198. doi:10.1186/s12916-019-1428-0
4. Ittaman SV, Vanwormer JJ, Rezkalla SH. The Role of Aspirin in the Prevention of Cardiovascular Disease. Clin Med Res. 12:3-4. doi:10.3121/cmr.2013.1197
5. Mekaj YH, Daci FT, Mekaj AY. Therapy and Clinical Risk Management Dovepress New insights into the mechanisms of action of aspirin and its use in the prevention and treatment of thrombosis and thromboembolism. Ther Clin Risk Manag. 2015:11-1449. doi: 10.2147/TCRM.S92222
6. Dai Y, Ge J. Clinical Use of Aspirin in the Treatment and Prevention of Cardiovascular Disease. Year 2012; 2012. doi: 10.1155/2012/245037
7. Paez Espinosa EV, Murad JP, Khasawneh FT. Aspirin: Pharmacology and Clinical Applications. 2012;2012:15. doi: 10.1155/2012/173124
8. Krumholz HM, Radford MJ, Ellerbeck EF, et al. Aspirin in the Treatment of Acute Myocardial Infarction in the Elderly Benefits. Cycle. 1995;92(10):2841-2847. doi: 10.1161/01.CIR.92.10.2841
9. Fiore LD, Ezekowitz MD, Brophy MT, Lu D, Sacco J, Peduzzi P. Department of Veterans Affairs Cooperative Studies Program Clinical Trial Comparing Combined Warfarin and Aspirin With Aspirin Alone in Survivors of Acute Myocardial Infarction. Cycle. 2002;105(5):557-563. doi:10.1161/hc0502.103329
10. Dear VM. Warfarin combined with low-dose aspirin in MI does not provide a clinical benefit over aspirin alone. ACP J Club. 2002;137(2):47. doi:10.7326/ACPJC-2002-137-2-047
11. Fuster V. A randomized double-blind trial of fixed low-dose warfarin plus aspirin after myocardial infarction. Lancet. 1997;350(9075):389-396. doi:10.1016/S0140-6736(97)01180-X
12. Hurlen M, Abdelnoor M, Smith P, Erikssen J, Arnesen H. Warfarin, Aspirin, or Both after Myocardial Transplantation. N Engl J Med. 2002;347(13):969-974. doi:10.1056/NEJMoa020496
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