A Significant Consequence Of Gene Flow Is That It Warfarin or Aspirin Which Is a Better Drug in Myocardial Infarction Prevention?

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Warfarin or Aspirin Which Is a Better Drug in Myocardial Infarction Prevention?


Noncommunicable diseases, particularly cardiovascular disease (CVD), are emerging as a global health concern, particularly in low- and middle-income countries. About 71% of deaths globally are caused by noncommunicable diseases, and 78% of global NCD deaths occur in low- and middle-income countries. Cardiovascular disease (CVD) accounts for 44% of NCD deaths globally. Ischemic heart disease and stroke have been recognized as the leading causes of CVD-related mortality for more than a decade. In addition, these two CVD-related deaths accounted for 15.2 million deaths in low- and middle-income countries in 2016. (WHO, 2018). Although the figures mentioned above paint a grim picture, they also present a significant opportunity to reduce NCD-related morbidity if ischemic heart disease and stroke are prioritized and treated promptly and efficiently.

As previously recognized, ischemic heart disease and stroke are the two leading causes of CVD-related death and can be classified as coronary artery disease (CAD). CAD is the most common type of CVD caused by plaque buildup that narrows the blood vessels that supply oxygenated blood to the heart. When the plaque ruptures, it is replaced by blood clots in the arteries that block the blood supply to the heart muscle. This adversity increases the likelihood of myocardial cell damage, which increases the risk of a heart attack. Patients with a previous episode of cardiovascular disease (CVD) 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 and may increase the risk of MI in CVD patients. A fast, irregular heart rate impairs blood flow, leading to blood clots, strokes, heart failure and other heart-related diseases.

Anticoagulant agents and platelet inhibitors are the drugs of choice for the long-term management of thrombosis (blood clotting) and MI. Aspirin is a popular choice administered for platelet inhibition that reduces the likelihood of CVD death and subsequent cases of MI, although its use for CVD prevention is subject to controversy. 15-20% of patients are at risk of death from re-infarction within 2-5 years prior to MI. Warfarin is the most common oral anticoagulant prescribed to patients worldwide with AF. Warfarin is a blood thinner that inhibits vitamin K-dependent coagulation factors (prothrombin). Prothrombin reduces the production of thrombin which mainly controls the formation of blood clots. A decrease in thrombin levels, in addition to anticoagulation, reduces thrombogenicity.

Aspirin acts as an acetylating agent known as acetylsalicylic acid, which irreversibly inactivates the platelet-dependent enzyme cyclooxygenase (COX)-1 and suppresses the formation of thromboxane A2 leading to an anti-platelet effect. This, in turn, reduces the inflammatory response in CAD and prevents the progression of atherosclerosis. Aspirin inhibits the production of COX-dependent vasoconstrictors in atherosclerosis by improving endothelial dysfunction, increasing vasodilation, and reducing thrombosis. Because of the immediate and long-term effects of aspirin 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 as opposed to AF alone, the results were not statistically significant. A significant reduction in MI was observed with the use of warfarin compared to non-warfarin.


Although the short-term and long-term merits and harms of anticoagulant and antiplatelet combination therapy have been debated, their intrinsic and extrinsic effects may be clinically beneficial in the treatment of acute ischemic heart disease. Aspirin is generally preferred over warfarin because of ease of administration, low cost, comparability, and efficacy. Previous studies have established the beneficial effects of warfarin compared with placebo in preventing new episodes of MI. Further, warfarin is known to have superior benefits over aspirin, while aspirin is currently the most commonly used drug.


Three randomized studies of different doses and combinations of aspirin and warfarin contributed to the knowledge of the use of the two drugs in patients with MI.

The first study, from 1997, is a randomized, double-blind comparative study in the USA of fixed low-dose warfarin and aspirin with aspirin alone after MI. 8803 MI patients, aged 21–85 years, were treated with a daily dose of 160 mg aspirin or 1 mg warfarin + 80 mg aspirin after an MI event, with elevated myocardial enzyme concentrations, chest pain, or electrocardiograph changes. or 3 mg warfarin + 80 mg aspirin based on random allocation. All drugs, including placebo, were visually identical. Interim analysis was performed by an independent data and safety monitoring board to ensure safety, efficacy, and futility.

Second, according to a 2002 comparative study, the combination of aspirin and warfarin was more effective than aspirin alone. A randomized open-label controlled study with 2.7 years of follow-up at 78 Department of Veterans Affairs medical centers in the United States. 5059 patients (median age 62 years, 98% male) with acute MI were administered daily warfarin (target international normalized ratio). [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 aspirin (75 mg daily) and warfarin as an open-label, multi-centered, randomized controlled trial after MI. Patients of both sexes aged less than 75 years with acute myocardial infarction were included according to World Health Organization recommendations: chest pain, electrocardiograph changes, creatine kinase <250 U/litre, aspartate aminotransferase <50 U/litre. Treatment continued until the predetermined number of study events and no interim analysis was performed.


A 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 similar efficacy with less than 1% of the difference between the three treatments. The relative risk of the primary event in the three groups was:

treatment group

160 mg A compared to (3mg W+ 80mg A).

160 mg A compared to (1mg W+ 80mg A).

(1 mg W with 80 mg A) compared to (3 mg W + 80 mg A).

Relative risk of primary 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 a study of warfarin + aspirin versus aspirin, the combined dose of warfarin + aspirin showed a 15% reduction in annual mortality, compared with aspirin alone, with major bleeding (1.28 vs 0.72 events per 100 person-years of follow-up. , P < 0.001). However, intracranial hemorrhage rates were similar in both groups (14 patients each).

In a study of the efficacy of warfarin, aspirin, or both, there was no statistically significant difference in overall mortality between the three groups (aspirin (160 mg daily) and warfarin (75 mg daily) and the combined dose of warfarin). Shown. The overall number or incidence of recurrent events was highest in the aspirin group (24.5%) compared with the warfarin (19.4%) and aspirin + warfarin groups (17.4%). Of the 14 hemorrhagic deaths, 11 occurred while on active medication, 5 of which occurred in the warfarin regimen and 6 were on combined doses of warfarin and aspirin.

Of the total adverse events of nonfatal major bleeding episodes in treated patients, 0.17% received aspirin, 0.68% received warfarin, and 0.75% received a combination of aspirin and warfarin per year. Minor bleeding episodes observed in the three aspirin, warfarin, and combination arms were 0.84%, 2.14%, and 2.70% per year, respectively.


In patients with an episode of myocardial infarction, the combination of low, fixed-dose warfarin (1 mg or 3 mg) with low-dose aspirin (80 mg) with 160 mg aspirin showed no additional clinical benefit. The combined dose of warfarin with low-dose aspirin (international normalized ratio 1.8) showed no additional clinical benefit.

Thus, warfarin, compared to aspirin alone, was an effective drug when administered alone or in combination with aspirin. Acute myocardial infarction has a reduced incidence of multiple events but is associated with a higher risk of rebleeding. A higher rate of patient withdrawal was observed in warfarin patients due to bleeding, percutaneous coronary intervention, or coronary-artery bypass grafting, which may have affected the effect of warfarin.


Thus, the combined dose of warfarin and aspirin was the most effective drug in preventing post-myocardial infarction events compared to aspirin or warfarin alone. However, heavy bleeding occurs with the combination dose.

Works Cited:

1. Karunathilake SP, Ganegoda GU. Use of technology for secondary prevention and early diagnosis of cardiovascular diseases. Biomed Res Int. 2018; 2018. doi:10.1155/2018/5767864

2. World Health Organization. Top 10 Causes of Death. World Health Organization.

3. Gelbenegger G, Postula M, Paysen L, et al. Aspirin for primary prevention of cardiovascular disease: a meta-analysis with special 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. Therapeutics and Clinical Risk Management Dovpress Aspirin’s mechanism of action and new insights into its use in the prevention and treatment of arterial and venous thromboembolism. Ther Clin Risk Manage. 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. 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 elderly Medicare beneficiaries. Circulation. 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 warfarin and aspirin alone with aspirin alone in survivors of acute myocardial infarction. Circulation. 2002;105(5):557-563. doi:10.1161/hc0502.103329

10. Hey VM. The combination of warfarin with low-dose aspirin in MI does not offer clinical benefits beyond 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 with aspirin after myocardial infarction. The 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 Infarction. N Engl J Med. 2002;347(13):969-974. doi:10.1056/NEJMoa020496

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