Effects of aspirin and clopidogrel on plasma brain natriuretic peptide in patients with heart failure receiving ACE inhibitors

Abstract

Background: By inhibiting prostaglandins, aspirin may be deleterious in heart failure (HF) and/or may counteract angiotensin-converting enzyme (ACE) inhibitor efficacy. Conversely, clopidogrel has no effect on prostaglandin metabolism. Aim: To investigate the effect of aspirin and clopidogrel on brain natriuretic peptide (BNP) levels in HF patients treated with ACE inhibitors. Methods: 36 patients with stable HF (65 ± 13 years, 24 males/12 females, NYHA class II to IV, ejection fraction < 40%, 13 with coronary disease, all treated with ACE inhibitors) were enrolled in this prospective, double-blind study and randomised to aspirin 325 mg/day or clopidogrel 75 mg/day for 14 days. BNP was determined at day 0 and day 14. Results: 19 patients were randomised to aspirin and 17 to clopidogrel. Baseline characteristics were similar in both groups. BNP levels increased in the aspirin group from day 0 to day 14 (107 ± 103 to 144 ± 149 pg/ml, p = 0.04) whereas clopidogrel had no effect (104 ± 107 and 97 ± 99 pg/ml respectively, p = 0.61). Conclusion: This study demonstrates an adverse effect of aspirin 325 mg/day on BNP plasma levels in HF patients treated with ACE inhibitors. In contrast clopidogrel 75 mg/day had no effect.

Increased Mortality Associated With Low Use of Clopidogrel in Patients With Heart Failure and Acute Myocardial Infarction Not Undergoing Percutaneous Coronary Intervention

“…For example, Serebruany et al (15) showed a significant inhibition of the increased platelet activity in patients with HF after adding clopidogrel to aspirin. Furthermore, Meune et al (25) observed that in patients with HF receiving angiotensin converting enzyme inhibitors, aspirin had an adverse effect on plasma concentrations of brain natriuretic peptides that was not found with clopidogrel. Study strengths and limitations.…”

Platelets, inflammation and anti-inflammatory effects of antiplatelet drugs in ACS and CAD

“…This may partly explain why the use of ADP-receptor antagonists like clopidogrel is superior to ASA in secondary prevention of ischaemic events in diabetic patients (119); clopidogrel may hamper the effects of increased ADP exposure. Regardless of the clinical setting, the anti-inflammatory effect of clopidogrel is dependent on the baseline inflammatory state (120). The PROCLAIM study showed, that clopidogrel treatment with 300 mg LD followed by 75 mg daily maintenance dose plus ASA 81 mg daily significantly decreased sCD40L levels 24 hours (h) after stenting, whereas ASA treatment alone did not show an effect.…”

Aspirin Use in Heart Failure

“…17 The second study showed a significant increase in BNP levels during 14 days in patients taking aspirin 325 mg daily, whereas there was no increase in BNP in those taking clopidogrel 75 mg daily. 18 By comparison to previous studies, our work reflects a more typical HF outpatient population and includes patients with atrial fibrillation and with indications for aspirin use including ischemic, vascular, and cerebrovascular disease. In our patient population, aspirin was used at a dose of 75 mg daily by 93% of patients, and clinical benefit was associated with aspirin use at 75 mg but not at higher doses.…”

“…15 Elsewhere, in the Platelet Inhibition and Patient Outcomes (PLATO) Trial of ticagrelor compared with clopidogrel in acute coronary syndrome, an interaction between higher aspirin dose (≥300 mg/d) and poorer outcome was observed. 16 Furthermore, although 2 studies have shown an adverse effect of aspirin therapy compared with clopidogrel therapy on natriuretic peptide levels in patients with HF treated with ACE inhibitors, 17,18 in both studies doses of aspirin >75 mg were used. The first of these studies showed that N-terminal pro-BNP increased in both groups but by a magnitude of 8 times greater in the aspirin-treated group.…”