Safety of Enteric-Coated and Buffered Aspirin Questioned
ABSTRACT & COMMENTARY
Source: Kelly JP, et al. Risk of aspirin-associated major upper-gastrointestinal bleeding with enteric-coated or buffered product. Lancet 1996;348:1413-1416.
Enteric-coated aspirin (ECASA) resists disintegration in the stomach and dissolves in the duodenum. Several endoscopic studies in healthy volunteers have confirmed the greater safety of ECASA compared with plain ASA. There was less gastric erosion and bleeding in those who used ECASA (Hoftiegen JW, et al. Lancet 1980;2:609-612). Endoscopic studies, however, have not confirmed that buffered ASA (BASA) produces less gastric damage (Lanza FL, et al. N Engl J Med 1980;303:136-138).
In a case-controlled study based on data collected between 1987 and 1994, Kelly et al tested the assumption that ECASA and BASA are less likely to cause major upper gastrointestinal (UGI) bleeding than plain ASA.
Patients (n = 550) admitted to 28 Massachusetts hospitals with a first episode of endoscopy-proven UGI bleeding and controls (n = 1202) matched for age, sex, date, marital status, education, cigarette smoking, and use of alcohol and nonsteroidal anti-inflammatory drugs (NSAID) were interviewed about ASA use during the week before bleeding (cases) or interview (controls).
The relative risks of UGI bleeding at average daily doses of 325 mg or less compared to controls were: 2.6 for plain ASA, 2.7 for ECASA, and 3.1 for BASA. At doses greater than 325 mg the relative risk was 5.8 for plain ASA and 7.0 for BASA. (See Table.) The data for ECASA were insufficient for evaluation. There were no important differences in risk among the three forms of ASA according to site of bleeding, gastric or duodenal, or when users of NSAIDs were excluded. Therefore, the authors conclude that the use of even low doses of ECASA or BASA carries a three-fold increase in the risk of major UGI bleeding compared to controls, and there is no substantial difference in the risk of major UGI bleeding according to the type of ASA preparation used.
Table
Relative risk of UGI bleeding with regular* use of ASA formulations
| ASA Type and Dose | Cases (n) | Relative Risk (95% CI) | |
| Plain ASA<325mg/d | 45 | 2.6 (1.7-4.0) | |
| Plain ASA>325mg/d | 81 | 5.8 (3.9-8.6) | |
| ECASA<325mg/d | 17 | 2.7 (1.4-5.3) | |
| ECASA>325mg/d | 2 | n/a | |
| BASA<325mg/d | 10 | 3.1 (1.3-7.6) | |
| BASA>325mg/d | 18 | 7.0 (3.0-16) | |
| * used at least every other day for at least one week. | |||
COMMENTARY
The benefits of regular ASA use in the secondary prevention of heart attack, stroke, and death are well established (Neuro Alert 1992;7:45-46) and ASA's possible value in reducing the risk of colorectal cancer and preventing the progression of vascular dementia is under investigation. Many physicians, therefore, recommend ASA prophylaxis for healthy adults even though its value for the primary prevention of heart attack and stroke is not proven. Because in some studies of ASA in secondary stroke prevention (Bornstein NM, et al. Stroke 1994; 25:275-277), maximal stroke prevention effects of ASA were not achieved at lower doses of ASA, namely those below 500 mg/d, physicians are likely to recommend that patients take higher doses of ASA but in coated or buffered preparations. Physicians and patients alike assume that ECASA and BASA are not harmful to the GI tract because these formulations are usually better tolerated than plain ASA. The present study refutes this assumption. Therefore, in patients who need ASA prophylaxis, the minimum effective dose of 81 mg or less daily should be recommended since recent data indicate that differences between ASA dosage and stroke risk reduction are insignificant (Algra A, van Gjin J. J Neurol Neurosurg Psychiatry 1996;60:197-199; Neuro Alert 1996;14:71).
The authors state that their findings should discourage the indiscriminate use of ASA for primary prevention of heart attack and stroke. This seems like a very large statement, given the small sample of patients and the lack of precise data on duration of dosing. Nevertheless, it is worthwhile to be reminded that ASA is a powerful therapeutic agent and that the same effects on platelets and prostaglandin synthesis that make it therapeutically useful also make it liable to cause serious bleeding complications.
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