Low dose aspirin is widely used in the primary and secondary prevention of vascular diseases. However, weight based dosing of aspirin is probably more effective in the prevention of cardiovascular diseases, especially in obese patients weighing more than 70 kgs.
Aspirin (chemical name Acetyl-salicylic acid) is a drug used in the treatment of pain, fever, inflammatory conditions like joint swelling and most importantly prevention of cardiovascular and cerebrovascular diseases.
How Aspirin works:
The major enzymes inhibited by Aspirin are cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2) and prostaglandins. COX-1 is a housekeeping enzyme. It protects to the gastric mucosa and is involved in vascular homeostasis, platelet aggregation, and kidney function. COX-2 is activated at sites of inflammation.
At low doses i.e. 75 mg to 150 mg, aspirin inhibits platelets aggregation, resulting in anti-thrombotic effects
At moderate doses of 160 mg to 325 mg per day, it has antipyretic and analgesic effects.
At high doses of 2 to 4 grams per day, it has anti-inflammatory effects and is therefore used in conditions like rheumatoid arthritis and osteoarthritis.
Aspirin in the prevention of coronary artery diseases and cerebrovascular disease
Coronary artery disease and cerebrovascular events (both ischemic and hemorrhagic strokes) are the leading causes of deaths and functional disabilities worldwide.
Aspirin in primary prevention of cardiovascular and cerebrovascular disease.
The role of Aspirin in preventing cardiovascular events in healthy individuals is debatable. Studies involving more than 100000 individuals with a mean age of 57 years have concluded that aspirin reduces the incidence of non-fatal myocardial infarction by 20%. These studies, however, have shown no net clinical benefits on overall cardiovascular mortality and incidence of stroke. The incidence of extra-cranial bleeding, however, was significantly increased in these individuals.
Most guidelines recommend an individualized approach. Some guidelines recommend that all healthy individuals and especially diabetic individuals above fifty years of age with a 10-years Framingham score of more than 10% should be started on low-dose-aspirin. Individuals with a Framingham score of 5% to 10% may be assessed for risk of gastrointestinal bleeding. Those at low risk of bleeding may be given low-dose-aspirin for primary prevention.
Role of Aspirin in secondary prevention of atherosclerotic diseases.
Evidence strongly supports the use of Aspirin in individuals who have had a prior episode of stroke, myocardial infarction or peripheral arterial disease. The major conclusions drawn from a very large trial in patients who survived a myocardial infarction, stroke or had a transient ischemic attack are as follows:
- Antiplatelet therapy, primarily aspirin, significantly reduced the risk of a subsequent vascular event. There was an absolute risk reduction in all patients (cardiovascular, cerebrovascular and vascular events)
- Low-dose-aspirin (75 mg to 150 mg) was equally effective as medium dose aspirin (160 mg to 325 mg per day) and had less adverse effects.
Weight based dosing of Aspirin in the prevention of vascular events
Till now most studies focused on comparing low-dose-aspirin and medium-dose-aspirin. As previously mentioned low dose aspirin is 75 to 150 mg per day and medium dose aspirin is 160 to 325 mg/day.
Weight based dosing of aspirin – results of a meta-analysis
A recent analysis of nine trials evaluating the role of aspirin in primary prevention of cardiovascular and cerebrovascular diseases has been published in Lancet. The study titled “Effects of aspirin on risks of vascular events and cancer according to body weight and dose: analysis of individual patient data from randomised trials” by Peter Rothwell and colleagues, have clearly stated that aspirin at low dose was effective in the primary prevention of cardiovascular and cerebrovascular events only in patients who weighed 70 kilograms or less.
Higher doses of aspirin greater than 300 mg were equally effective in the primary prevention of these disease in patients who weighed 70 kilograms or more. Low dose aspirin prevented cardiovascular outcomes by 23% in patients who were 70 kgs or less compared to only 12 % when weight was not considered.
However, the bleeding risks of low dose aspirin in patients weighing 80 to 100 kgs was significantly higher, despite the failure to prevent cardiovascular events.
Conclusion of the analysis
The authors concluded that low dose aspirin is ineffective to prevent cardiovascular events in overweight patients (>70 Kgs), smokers and those on enteric coated formulations. Weight based dosing of aspirin be incorporated into clinical practice especially in the primary prevention of cardiovascular and cerebrovascular diseases.