The drug sacubitril/valsartan is a new treatment for adult patients with a heart disease called heart failure, leading to insufficient blood flow to meet the body's needs. Previous studies have shown that there is a potential problem if sacubitril/valsartan is taken simultaneously with another drug group called statins which are used to lower blood cholesterol levels. If patients take both drugs there may be a risk that statins cause more adverse drug effects than if patients only take statins. The adverse drug effects feared most with this drug combination are destruction of muscles and/or liver cells, and acute inflammation of the pancreas (a gland that secretes digestive enzymes and certain hormones). As sacubitril/valsartan has only been on the market since December 2015 in the U.K., and as it is expected that it is often prescribed concomitantly with statins, it is necessary that the potential risk of concomitant use of sacubitril/valsartan and statins is further studied. This study aims to investigate whether U.K. patients who simultaneously use sacubitril/valsartan and statins are at a higher risk of the above described adverse effects than patients who only use statins.
Sacubitril/valsartan is a novel treatment for adult patients with symptomatic chronic heart failure with reduced ejection fraction. Sacubitril inhibits organic anion-transporting polypeptide (OATP) 1B1 and OATP1B3 transporters in vitro. Based on this finding, drug-drug interaction studies have been performed between sacubitril/valsartan and atorvastatin or simvastatin (substrates of these transporters). Sacubitril/valsartan increased the maximal plasma concentrations of atorvastatin and its metabolites by up to 2-fold, but did not increase the areas under the curve of atorvastatin and its metabolites. Sacubitril/valsartan had no clinically significant impact on exposures of simvastatin and its active metabolite. Given the high proportion of patients expected to be on a concomitant therapy with sacubitril/valsartan and statins, the market authorization holder of sacubitril/valsartan aims to further evaluate in the post-marketing setting this potential drug-drug interaction that may increase the risk of statin-associated myotoxicity, hepatotoxicity, or acute pancreatitis. This case-control study aims to assess the risk of myotoxicity, hepatotoxicity, and acute pancreatitis in association with concomitant use of statins and sacubitril/valsartan, compared with use of statins without sacubitril/valsartan, in adult patients with heart failure. It is part of a large, observational, multi-database post-authorization safety study using data retrieved from five different databases, including the Clinical Practice Research Datalink.
Myotoxicity; Hepatotoxicity; Acute pancreatitis.
Christoph Meier - Chief Investigator - University of Basel
Marlene Rauch - Corresponding Applicant - University of Basel
- Collaborator -
Josephina Kuiper - Collaborator - Pharmo Institute
Miriam Sturkenboom - Collaborator - University Medical Centre Utrecht
Raymond Schlienger - Collaborator - Novartis Pharma AG ( Switzerland )
Susan Jick - Collaborator - BCDSP - Boston Collaborative Drug Surveillance Program
Claudia Becker - Collaborator - University of Basel
HES Admitted Patient Care