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therapy. The composite risk reduction was 20% for patients taking aspirin and 29% for those not taking aspirin, a difference that did not reach statistical significance48.

A second retrospective review subsequently also reported no adverse effect of concomitant aspirin use with ACEIs on long-term survival49.

Given these retrospective results, many physicians believe the data justify prescribing aspirin and ACEIs together when there is an indication for use of aspirin.

On the other hand, other physicians would consider not combining aspirin with an ACEI because there are no data to indicate that it can reduce the risk of ischemic events in patients with HF50, or they might consider the use of an alternative antiplatelet agent such as clopidogrel, which does not interact with ACEIs and which may have superior effects in preventing ischemic events. However, clopidogrel does not have an indication for the primary prevention of ischemic events and is approximately 50 times more expensive than aspirin. In conclusion, there may be an important interaction between aspirin and ACEIs, but there is controversy regarding this point, and it requires further study.

Finally, clinical experience in patients who are hemodynamically or clinically unstable suggests that the hypotensive effects of ACE inhibition may attenuate the natriuretic response to diuretics51. As a result, in patients who are responding poorly to diuretic drugs, it may be prudent to interrupt treatment with the ACE inhibitor temporarily until the clinical status of the patient stabilizes.

Risks of treatment

Most of the adverse reactions of ACE inhibitors can be attributed to the 2 principal pharmacological actions of these drugs, namely angiotensin suppression and kinin potentiation. However, other types of side effects, unrelated to either pharmacological effects, may also occur (e.g., rash and taste disturbances).

Adverse Effects Related to Angiotensin Suppression

The most common adverse effects of ACE inhibition in patients with HF are hypotension and dizziness. Blood pressure declines without symptoms in nearly every patient treated

48 Teo KK, Yusuf S, Pfeffer M, et al. Effects of long-term treatment with angiotensin-converting-enzyme inhibitors in the presence or absence of aspirin: a systematic review. Lancet 2002;360:1037-43.

49 Harjai KJ, Solis S, Prasad A, Loupe J. Use of aspirin in conjunction with angiotensin-converting enzyme inhibitors does not worsen long-term survival in heart failure. Int J Cardiol 2003;88:207-14.

50 Antiplatelet Trialists’ Collaboration. Collaborative overview of randomised trials of antiplatelet therapy, I: prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients [published erratum appears in BMJ 1994;308:1540]. BMJ 1994;308:81-106.

51 Flapan AD, Davies E, Waugh C, Williams BC, Shaw TR, Edwards CR. Acute administration of captopril lowers the natriuretic and diuretic response to a loop diuretic in patients with chronic cardiac failure. Eur Heart J 1991;12:924-7.

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