The drug sacubitril/valsartan is a novel treatment for adult patients with heart failure, a heart disease leading to insufficient blood flow to meet the body's needs. Before sacubitril/valsartan became available to the public (December 2015 in the United Kingdom), it was tested in a limited number of humans in pre-marketing studies. These studies showed that sacubitril/valsartan intake sometimes led to swelling in different areas of the body of study participants, such as the face, tongue, arms, or legs. Also, in some study participants, the drug could cause low blood pressure, increase in potassium levels (a vital substance for the body that can however become dangerous if its blood levels are too high), liver damage, and decreasing kidney function. The same adverse effects have already been observed in patients treated with other medications that have been available to the public to treat heart failure for a long time before sacubitril/valsartan. Now that sacubitril/valsartan has become available to the public, this study aims to quantify the risk of above named adverse effects associated with use of sacubitril/valsartan compared with use of other drugs that have already been on the market for treating heart failure among a large population of patients.
Sacubitril/valsartan is a novel treatment for adult patients with symptomatic chronic heart failure. In the double-blind phase of a large pre-marketing trial, a higher proportion of patients randomized to sacubitril/valsartan had angioedema as compared to the angiotensin-converting enzyme inhibitor (ACEI) enalapril (0.45% vs. 0.24%). Also, hypotension was reported more often in sacubitril/valsartan users compared with enalapril users (17.6% vs. 11.9%). Hyperkalemia or serum potassium concentrations >5.4 mmol/l were reported slightly less often in sacubitril-valsartan users compared with enalapril users (11.6% and 19.7% vs. 14.0% and 21.1%, respectively). The risk of hepatotoxicity or renal impairment did not differ considerably between the two patient groups. Nevertheless, hyperkalemia, hepatotoxicity, and renal impairment are listed as potential or identified risks in the risk management plan of sacubitril/valsartan. Real-world data to quantify the above outlined adverse events associated with sacubitril/valsartan use and the relative risk of these in new users of sacubitril/valsartan compared with new users of ACEIs, are missing. This large post-authorization cohort study based on data from five European databases (including the Clinical Practice Research Datalink) will assess the risk of angioedema and other outlined adverse events in association with sacubitril/valsartan use versus ACEI use in adult patients with heart failure.
Angioedema; Hepatotoxicity; Hypotension; Renal impairment; Hyperkalemia.
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