Aspirin cardiovascular effects

Other adverse effects of fenoprofen include nausea, dyspepsia, peripheral edema, rash, pruritus, central nervous system and cardiovascular effects, tinnitus, and drug interactions. However, the latter effects are less common than with aspirin. 

A new compound called SH 1117 ( ) has been reported to inhibit platelet aggregation and be synergistic with aspirin similar to dipyridamole but without its cardiovascular effects. ... 

Overall Cardiovascular Effects of Aspirin in Diabetic Patients... 

Aspirin irreversibly blocks the production of thromboxane A2 by binding to cyclo-oxygenase (COX-1) in platelets, and so inhibits platelet aggregation. The beneficial cardiovascular effects are attributed to this effect. Other NSAIDs that are COX-1 inhibitors also have this effect, but it is more short-lived since they bind reversibly. These NSAIDs can therefore competitively inhibit the binding of aspirin to platelets (a fact that was shown in vitro as early as the 1980s ). When these NSAIDs are present in sufficient quantities when a daily low-dose of aspirin is given, they therefore reduce its antiplatelet effect. In vitro study confirms that COX-2 selective NSAIDs have less effect. ... 

The evidence currently available on the antagonism of antiplatelet effects is insufficient to recommend that ibuprofen is not used with low-dose aspirin. Nevertheless, some have concluded that when patients taking low-dose aspirin for cardioprotection require long-term NSAIDs for inflammatory conditions, the use of diclofenac or naproxen would seem preferable to ibuprofen.A coxib was also suggested as an alternative,but the subsequent suggestion of an increased risk of serious cardiovascular effects with the coxibs (as a class ) probably precludes this. Recently the Commission on Human Medicines (CHM) in the UK has advised that there may be a small increased risk of thrombotic events with the non-selective NSAIDs, particularly when used at high doses and for long-term treatment. ... 

The third study was the Physicians Health Study, in which 22,071 US male physicians were randomised to get either 50 mg P-carotene or 325 mg aspirin, or both, or neither, every other day for 12 years. There was no evidence of a significant beneficial or harmful effect on cancer or cardiovascular... 

Selectivity for COX-1 versus COX-2 is variable and incomplete for the older NSAIDs, but many selective COX-2 inhibitors have been synthesized. The selective COX-2 inhibitors do not affect platelet function at their usual doses. In testing using human whole blood, aspirin, ibuprofen, indomethacin, piroxicam, and sulindac are somewhat more effective in inhibiting COX-1. The efficacy of -2-selective drugs equals that of the older NSAIDs, while gastrointestinal safety may be improved. On the other hand, selective COX-2 inhibitors may increase the incidence of edema and hypertension. As of December 2008, celecoxib and the less selective meloxicam are the only COX-2 inhibitors marketed in the USA. Rofecoxib and valdecoxib, two previously marketed, selective COX-2 inhibitors, have been withdrawn from the market due to their association with increased cardiovascular thrombotic events. Celecoxib has an FDA-initiated "black box" warning concerning cardiovascular risks. It has been recommended that all NSAID product labels be revised to include cardiovascular risks. 

In view of the perceived benefit of aspirin in the secondary prevention of stroke and myocardial infarction, two large trials involving physicians as subjects were initiated to study the effect of aspirin in the primary prevention of arterial thrombosis. In the American study, 22,000 volunteers (age 40 to 84 years) were randomly assigned to take 325 mg of aspirin every other day or placebo. The trial was halted early, after a mean follow-up of 5 years, when a 45% reduction in the incidence of myocardial infarction and a 72% reduction in the incidence of fatal myocardial infarction were noted with aspirin treatment. However, total mortality was reduced only 4% in the aspirin group, a difference that was not statistically significant, and there was a trend for a greater risk of hemorrhagic stroke with aspirin. Thus, the prophylactic use of aspirin in an apparently healthy population is not recommended at this time, unless there are risk factors for cardiovascular disease. 

The current thinking concerning the role of aspirin in the prevention of cardiovascular disease is that it is beneficial in the event of myocardial infarction and stroke. It is effective because, in platelets small amounts of aspirin acetylate irreversibly bind to the active site of thromboxane A2, a potent promoter of platelet aggregation. 

In the case of aspirin, there are numerous reports of beneficial effects of low-dose aspirin in the secondary prophylaxis of cardiovascular disease (myocardial infarction and stroke). Aspirin clearly reduces the risk of myocardial infarction and stroke among patients who already have manifestations of cardiovascular disease. 

The concomitant administration of ibuprofen antagonizes the irreversible platelet inhibition induced by aspirin. Thus, treatment with ibuprofen in patients with increased cardiovascular risk may limit the cardioprotective effects of aspirin. Rare hematologic effects include agranulocytosis and aplastic anemia. Effects on the kidney (as with all NSAIDs) include acute renal failure, interstitial nephritis, and nephrotic syndrome, but these occur very rarely. Finally, hepatitis has been reported. 

The CHARISMA trial (51) enrolled 15,603 patients with either cardiovascular disease or multiple risk factors followed for a median of 28 months. Overall, the dual antiplatelet regimen (aspirin + clopidogrel) was not significantly more effective than aspirin alone in reducing the rate of death, Ml or stroke from cardiovascular causes. 

Aspirin is the most economical and effective antiplatelet drug prescribed for the treatment of cardiovascular and cerebrovascular (CV) diseases. Initially, Vane et al. (38)... 

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