Warfarin or Aspirin | Which Is a Better Drug for Prevention of Myocardial Infarction?

Introduction:

Warfarin or Aspirin | Which Is a Better Drug for Prevention of Myocardial Infarction? | MediUpdates article – Noncommunicable illnesses, particularly cardiovascular diseases (CVD), is becoming a worldwide health issue, particularly in low- and middle-income nations. Noncommunicable diseases account for around 71 percent of worldwide fatalities, with 78 percent of NCD deaths occurring in poor and medium-income nations. Cardiovascular illnesses are responsible for 44 percent of NCD deaths worldwide (CVD). For more than a decade, ischemic heart disease and stroke have been identified as the main causes of CVD-related fatalities. Furthermore, in low and medium-income countries, this two CVD-related mortality accounted for 15.2 million deaths in 2016.. (WHO, 2018). While the numbers above paint a bleak picture, they also show that there is a significant possibility to reduce NCD-related morbidity if ischemic heart disease and stroke are prioritized and treated with promptness and efficiency.

Ischemic heart disease and strokes, as previously mentioned, are two primary causes of CVD-related fatalities and are classified as Coronary Artery Disease (CAD). CAD is the most prevalent kind of CVD, in which plaque deposits restrict the circumference of circulatory arteries delivering oxygenated blood to the heart.  When the plaque ruptures, blood clots form in the arteries, obstructing blood flow to the heart muscles. This adversity increases the likelihood of myocardial cell damage, which raises the risk of myocardial infarction, also known as a heart attack. Patients with cardiovascular disease (CVD) who have had a previous myocardial infarction (MI) or ischemic stroke are more likely to have another MI. A common consequence of acute myocardial infarction is atrial fibrillation (AF) (AMI). Atrial fibrillation, commonly known as arrhythmia or irregular heartbeat, is seen in 6–21% of MI patients, potentially raising the risk of MI in CVD patients. Poor blood flow is caused by a fast, irregular heart rhythm, which can lead to blood clots, strokes, heart failure, and other heart-related illnesses.

Anticoagulant medicines and platelet inhibitors are the medications of choice for long-term thrombosis (blood clotting) and MI therapy. Despite the fact that its use for CVD prophylaxis is controversial, aspirin is a common choice for platelet inhibition in order to lower the risk of CVD mortality and future occurrences of MI. Within 2-5 years after a previous MI, 15-20% of patients are at risk of dying from a re-infarction. Warfarin is the most often administered oral anticoagulant to individuals with AF all over the world. Warfarin is a blood thinner that works by blocking vitamin K-dependent coagulation factors (prothrombin). Prothrombin inhibits the synthesis of thrombin, a protein that controls the formation of blood clots. In addition to anticoagulation, lowering thrombin levels lowers thrombogenicity.

Aspirin, also known as acetylsalicylic acid, works by acetylating platelet-dependent enzyme cyclooxygenase (COX)-1 and suppressing the production of thromboxane A2, resulting in an anti-platelet action. It also slows the development of atherosclerosis by reducing inflammatory responses in CAD. Aspirin improves endothelial dysfunction in atherosclerosis, increases vasodilation, and decreases thrombosis by blocking the production of COX-dependent vasoconstrictors.  Aspirin is given as a secondary preventative treatment in CVD patients because it has an immediate and long-term effect on platelets.

Although the results were not statistically significant, an American comparative analysis of MI and AF found that patients with both MI and AF had a greater risk of death than those with AF alone. When compared to non-Warfarin users, the use of Warfarin resulted in a substantial reduction in MI.

Although there have been debates over the short- and long-term benefits and drawbacks of anticoagulant and antiplatelet combination therapy, their intrinsic and extrinsic effects may be therapeutically beneficial in the treatment of acute ischemic heart disease. Aspirin is often favored over Warfarin due to its ease of use, low cost, comparability, and efficacy. Warfarin has been shown in previous studies to be more effective than a placebo in preventing new MI occurrences. Furthermore, Warfarin is recognized to offer greater advantages to aspirin, despite the fact that aspirin is now the most commonly used medication.

Three randomized studies of aspirin and warfarin in various doses and combinations assisted in the understanding of the usage of two medicines in patients with MI.

The first research, published in 1997, was a randomized, double-blind comparison study in the United States comparing fixed low-dose Warfarin plus Aspirin against Aspirin alone after a heart attack. Based on a random allocation, 8803 MI patients between the ages of 21 and 85 who had a MI and had increased myocardial enzyme concentrations, chest pain, or abnormalities in electrocardiography were given a daily dosage of 160 mg aspirin, 1 mg Warfarin + 80 mg aspirin, or 3 mg Warfarin + 80 mg aspirin.  All of the medicines, including the placebo, had the same look. An independent data and safety monitoring board conducted an interim analysis to verify safety, effectiveness, and futility.

Second, a 2002 research hypothesized that combining aspirin and warfarin was more beneficial than taking aspirin alone. A randomised open label controlled research was conducted at 78 Department of Veterans Affairs medical centres across the United States with a 2.7-year follow-up. 5059 patients with an acute MI (median age 62 years, 98 percent males) were given Warfarin (goal international normalised ratio [INR] 1.5 to 2.5 IU) Plus Aspirin (81 mg/dl) or Aspirin (162 mg/dl) alone on a daily basis.

An open-label, multi-centric, randomized controlled trial comparing the effectiveness of Aspirin (160 mg daily), Warfarin with a combination of doses of Aspirin (75 mg daily), and Warfarin after a MI. The research comprised patients of both genders under the age of 75 who had an acute myocardial infarction as defined by the World Health Organization: chest discomfort, change in electrocardiograph, creatine kinase 250 U/litre, and aspartate aminotransferase 50 U/litre. There were no intermediate analyses and treatment continued until a specified number of incidents occurred.

Results

The daily doses of 160 mg aspirin, 1 mg warfarin + 80 mg aspirin (1 mg W+ 80 mg A), and 3 mg warfarin + 80 mg aspirin (3 mg W+ 80 mg A) all demonstrated equal effectiveness, with less than 1% difference between the three regimens. The following was the relative risk of a main incident in each of the three groups:

Group Therapy

Compared to (3mg W+ 80mg A): 160 mg A

In comparison to (1mg W+ 80mg A), 160 mg A

Compared to (3 mg W + 80 mg A), (1 mg W plus 80 mg A)

Primary Event Relative Risk

0.95 (95 percent confidence interval: 0.81-1.12, p=0.57)

0.87-1.22, p=0.74; 1.03 (0.87-1.22, p=0.74)

0.93 (p=0.41) (0.78-1.11)

In the Warfarin+ Aspirin vs. Aspirin trial, there was a 15% reduction in yearly mortality in the combined dosage of Warfarin + Aspirin vs. Aspirin alone, as well as severe bleeding (1.28 vs. 0.72 incidents per 100 person-years of follow-up, P 0.001). However, both groups had the same rate of cerebral bleeding (14 patients each).

There was no significant difference in overall mortality rate between the three groups (Aspirin (160 mg daily) and Warfarin in combination dosage with Aspirin (75 mg daily) and Warfarin) in the effectiveness trial of Warfarin, Aspirin, or both. When compared to aspirin, however, warfarin in combination with aspirin and alone had a greater effect on reinfarction. The total number of incidents, including repeated occurrences, was greatest in the Aspirin group (24.5%), followed by Warfarin (19.4%), and the Aspirin + Warfarin group (19.4%). (17.4 percent ). 11 of the 14 hemorrhagic fatalities happened while the patient was on medicine, with 5 of them using Warfarin and 6 taking a combination of Warfarin and Aspirin.

In the patients under therapy, 0.17 percent received aspirin, 0.68 percent received warfarin, and 0.75 percent received a combination of aspirin and warfarin every year for non-fatal severe bleeding episodes. Minor bleeding events occurred at a rate of 0.84 percent, 2.14 percent, and 2.70 percent per year in the three arms (aspirin, warfarin, and combination).

Discussion

In individuals with myocardial infarction, low-dose fixed-dose warfarin (1 mg or 3 mg) in conjunction with low-dose aspirin (80 mg) or 160 mg aspirin alone had no extra therapeutic advantages. The combination of Warfarin (at a mean international normalized ratio of 1.8) with low-dose Aspirin had no additional benefit.

Warfarin, on the other hand, was a more effective medication whether used alone or in conjunction with aspirin than aspirin alone. After an acute myocardial infarction, there was a decrease in the frequency of various occurrences, although it was linked with a greater risk of bleeding. Patients taking Warfarin were shown to withdraw in large numbers owing to hemorrhage, percutaneous coronary intervention, or coronary artery bypass grafting, all of which might have compromised Warfarin’s effect.

Conclusion

When compared to Aspirin or Warfarin alone, the combination dosage of Warfarin and Aspirin was the most effective medication for preventing events after myocardial infarction. Major bleeding, on the other hand, was more common with the combined dosage.