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Warfarin or Aspirin Which Is a Better Drug in Myocardial Infarction Prevention?
Non-communicable diseases, especially cardiovascular diseases (CVDs), are becoming a global health problem, especially in low- and middle-income countries. About 71% of global deaths are caused by NCDs and 78% of NCD deaths occur in low- and middle-income countries. 44% of deaths from noncommunicable diseases globally are attributed to cardiovascular disease (CVD). Ischemic heart disease and stroke have been identified as the leading causes of CVD death for more than a decade. In addition, these two cardiovascular-related deaths accounted for 15.2 million deaths in low- and middle-income countries in 2016. (WHO, 2018). While the figures mentioned above paint a very grim picture, they also represent a huge opportunity to reduce the morbidity associated with non-communicable diseases if ischemic heart disease and stroke are prioritized and treated with a rapid response and maximum efficiency.
As previously mentioned, ischemic heart disease and stroke are the two leading causes of CVD-related death and can be categorized as coronary artery disease (CAD). CAD is the most common type of CVD, which narrows the blood vessels that supply the heart with oxygenated blood due to plaque deposition. When the plaque ruptures, it is replaced by blood clots in the arteries, which block the flow of blood to the heart muscles. This problem increases the likelihood of myocardial cell damage, which in turn increases the risk of myocardial infarction, commonly known as a heart attack. Cardiovascular disease (CVD) patients with a previous myocardial infarction (MI) or ischemic stroke event are highly 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 heartbeat causes poor blood flow, leading to blood clots, stroke, heart failure and other heart-related diseases.
Anticoagulants and platelet inhibitors are the drugs of choice for the long-term management of thrombosis (blood clotting) and MI. Aspirin is a popular choice used to inhibit platelets to reduce the chance of CVD mortality and subsequent MI, although its use for CVD prevention is controversial. 15-20% of patients are at risk of death from a re-infarction within 2-5 years after a previous MI. The most common oral anticoagulant prescribed to patients with AF worldwide is warfarin. Warfarin are blood thinners that inhibit vitamin K-dependent coagulation factors (prothrombin). Prothrombin reduces the generation of thrombin, which mainly regulates the formation of blood clots. Decreasing thrombin levels in addition to anticoagulation reduces thrombogenicity.
Aspirin, also known as acetylsalicylic acid, acts as an acetylating agent that irreversibly inactivates the platelet-dependent enzyme cyclooxygenase (COX)-1 and inhibits the formation of thromboxane A2, creating an antiplatelet effect. In addition, it reduces inflammatory responses in CAD and inhibits the progression of atherosclerosis. Aspirin blocks the formation of COX-dependent vasoconstrictors by improving endothelial dysfunction in atherosclerosis, increasing vasodilation and reducing thrombosis. Because Aspirin has an immediate and long-term effect on platelets, Aspirin is prescribed as a secondary prevention in CVD patients.
A US comparative study of MI and AF showed a higher risk of mortality in patients with MI and AF as opposed to AF alone, as the results were not statistically significant. The use of warfarin showed a significant reduction in MI compared to the use without warfarin.
Although there are controversies about the short- and long-term advantages and disadvantages of combined anticoagulant and antiplatelet therapy, their intrinsic and extrinsic effects may be of clinical benefit in the treatment of acute ischemic heart disease. In general, aspirin is preferred over warfarin because of ease of administration, low cost, comparability, and efficacy. Previous studies have shown beneficial effects of warfarin compared with placebo in preventing new MI events. In addition, warfarin is known to have better benefits than aspirin, while aspirin is currently the most widely used drug.
Three randomized trials of aspirin and warfarin in different doses and combinations have helped inform the use of the two drugs in patients with MI.
The first study, from 1997, is a randomized, double-blind, comparison study in the US of fixed low-dose warfarin plus aspirin versus aspirin alone after MI. 8803 MI patients, aged 21-85 years, post-MI, with elevated myocardial enzymes, accompanied by chest pain or electrocardiographic changes, were treated with a daily dose of 160 mg aspirin or 1 mg warfarin + 80 mg aspirin . or 3 mg warfarin + 80 mg aspirin based on random assignment. All drugs were identical in appearance, including the placebo. An independent data and safety monitoring committee performed an interim analysis to ensure safety, efficacy and futility.
Second, a comparative study from 2002 hypothesizes that the combination of aspirin and warfarin is 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% men) who had an acute MI received daily warfarin (target international normalized ratio [INR] 1.5 to 2.5 IU) + aspirin (81 mg/dl) or aspirin alone (162 mg/dl).
A comparative study of the efficacy of aspirin (160 mg daily), warfarin with a dose combination of aspirin (75 mg daily), and warfarin as an open-label, multicenter, randomized controlled trial after MI. The study included patients of both sexes, younger than 75 years, with acute myocardial infarction according to the recommendations of the World Health Organization: chest pain, change on the electrocardiograph, creatine kinase <250 U/liter, aspartate aminotransferase <50 U/liter. study. Treatment continued until a predetermined number of events occurred and no interim analyzes were performed.
A daily dose of 160 mg aspirin or 1 mg warfarin + 80 mg aspirin (1 mg W + 80 mg A) or 3 mg warfarin + 80 mg aspirin (3 mg W + 80 mg A) showed similar efficacy with less than a 1% change differences between the three treatments. The relative risk of the primary event in the three groups was:
160 mg A vs. (3 mg W + 80 mg A)
160 mg A vs. (1 mg W + 80 mg A)
(1 mg W with 80 mg A) vs. (3 mg W + 80 mg A)
Relative risk of the 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 the warfarin + aspirin versus aspirin study, a 15% reduction in annual mortality was observed with the combined dose of warfarin + aspirin compared with aspirin alone, along with major bleeding (1.28 vs. 0.72 events per 100 person-years of follow-up). , P <0.001). However, the rate of intracranial hemorrhage was 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 the overall death rate between the three groups (aspirin (160 mg daily) and warfarin combined with aspirin (75 mg daily) and warfarin). However, warfarin in combination with aspirin alone showed a better effect on reinfarction compared to aspirin alone. The total number of events, including recurrent events, was highest in the aspirin group (24.5%) compared to the warfarin group (19.4%) and the aspirin + warfarin group (17.4%). Of the 14 hemorrhagic deaths, 11 occurred during active drug use, of which 5 were on warfarin and 6 were on combined doses of warfarin and aspirin.
Of the total number of nonfatal major bleeding adverse events in treated patients, 0.17% received aspirin, 0.68% warfarin, and 0.75% a combination of aspirin and warfarin per year. Minor bleeding episodes observed in the three groups – aspirin, warfarin and combination were 0.84%, 2.14% and 2.70% per year, respectively.
In patients with an episode of myocardial infarction, no additional clinical benefit was observed when combining low-dose fixed-dose warfarin (1 mg or 3 mg) with low-dose aspirin (80 mg) 160 mg of aspirin alone. Likewise, the combination of warfarin dose (at a mean international normalized ratio of 1.8) with low-dose aspirin had no additional clinical benefit.
While warfarin was an effective drug when given alone or in combination with aspirin, compared to aspirin alone. The incidence of multiple events after acute myocardial infarction was reduced, but was associated with a higher risk of bleeding. A high number of withdrawals due to bleeding, percutaneous coronary intervention or coronary artery bypass grafting, which may have affected the effect of warfarin, have been observed in patients taking warfarin.
Thus, the combined dose of warfarin and aspirin was the most effective drug for preventing events after myocardial infarction compared with aspirin or warfarin alone. However, major bleeding occurred more frequently with the combined dose.
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