ABSTRACT
BACKGROUND: The treatment of acute coronary syndromes involves a combination of antiplatelet therapies. Proton pump inhibitors are frequently recommended for patients receiving clopidogrel in addition to aspirin, to minimise the risk of bleeding. Several studies have shown that proton pump inhibitors can affect the platelet inhibitory effects of clopidogrel. However, the data on whether this has an effect on clinical outcomes are conflicting and a definitive answer is still awaited. AIM: To provide an overview of the evidence for the pharmacological interaction between proton pump inhibitors and clopidogrel and to discuss whether this interaction translates into adverse clinical outcomes. Despite recent developments, clear consensus is lacking. METHODS: A search of the published literature combined with the authors' knowledge of the field. RESULTS: There is evidence to show that proton pump inhibitors can influence the pharmacodynamics of clopidogrel, but the data suggesting clinical effects are weak and conflicting. Supporting a clinically important interaction are four retrospective studies including over 11,000 patients prescribed both clopidogrel and a proton pump inhibitor. Evidence against a clinically important interaction is derived from over 18,000 patients from seven studies, including the only prospective trial to examine the potential interaction. Confounding variables are relevant and prospective clinical evidence is lacking. CONCLUSIONS: Proton pump inhibitors offer clear protection and the concern over clinically relevant interactions with clopidogrel is biologically plausible, but not yet proven.
Subject(s)
Acute Coronary Syndrome/drug therapy , Aspirin/pharmacology , Platelet Aggregation Inhibitors/pharmacology , Proton Pump Inhibitors/pharmacology , Ticlopidine/analogs & derivatives , Aspirin/therapeutic use , Clopidogrel , Drug Interactions , Drug Therapy, Combination , Humans , Platelet Aggregation Inhibitors/therapeutic use , Proton Pump Inhibitors/therapeutic use , Risk , Ticlopidine/pharmacology , Ticlopidine/therapeutic useSubject(s)
Angioplasty, Balloon, Coronary/standards , Antibodies, Monoclonal/therapeutic use , Coronary Disease/surgery , Immunoglobulin Fab Fragments/therapeutic use , Platelet Aggregation Inhibitors/therapeutic use , Practice Guidelines as Topic/standards , Abciximab , Antibodies, Monoclonal/adverse effects , Cohort Studies , Female , Hospitals, Teaching , Humans , Immunoglobulin Fab Fragments/adverse effects , Male , Middle Aged , Platelet Aggregation Inhibitors/adverse effects , Risk FactorsABSTRACT
INTRODUCTION: Spironolactone is increasingly being used in the treatment of heart failure. However, it has been associated with cases of hyperkalaemia. The common use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin-2 receptor (AT2) antagonists in heart failure increases the risk of hyperkalaemia. OBJECTIVE: To identify the risk of spironolactone withdrawal, hyperkalaemia and severe hyperkalaemia in patients prescribed spironolactone together with either an ACE inhibitor or an AT2 antagonist. METHODS: Retrospective identification and analysis of patients co-prescribed an ACE inhibitor or an AT2 antagonist with spironolactone. Patients' records were linked to their biochemical results and the doses of spironolactone, ACE inhibitor and AT2 antagonists received by them. RESULTS: We found that a higher proportion of patients in our cohort stopped taking spironolactone compared with the Randomised Aldactone Evaluation Study and a higher proportion developed hyperkalaemia, a predicted adverse effect of spironolactone combination with an ACE inhibitor or an AT2 antagonist. Patients with diabetes mellitus and those with a haematocrit below 0.36, were more likely to develop hyperkalaemia than those without these traits. CONCLUSIONS: Spironolactone is a common cause of hyperkalaemia when used in combination with either an ACE inhibitor or an AT2 antagonist. This reinforces the need for care when extrapolating the results of clinical trials to daily clinical practice.
