Resistance to RAAS Inhibitors Not Easily Improved
Patients who show a poor response to a certain dose and medication also show a poor response to higher doses and other RAAS inhibitors, meta-analysis shows.
Individual resistance to renin-angiotensin-aldosterone system inhibitors (RAASi) is not surmounted by some specific adjustments in therapy, according to a new study.
The finding is based on a meta-analysis of 11 randomized crossover trials involving 395 albuminuric patients treated with RAASi, nonsteroidal anti-inflammatory drugs (NSAIDs), or a complementary low sodium diet (24 treatments in total). They specifically compared daily losartan 50 mg versus enalapril 10 mg; losartan 100 mg versus enalapril 20 mg; and aliskiren 300 mg versus irbesartan 300 mg.
“Individuals who show a poor response to one dose or type of RAASi also show a poor response to higher doses, other types of RAASi or NSAIDs, or a reduction in dietary salt intake,” Sergei Petrykiv, MD, University Medical Center Groningen in Groningen, The Netherlands, and collaborators concluded in an online report published in the Clinical Journal of the American Society of Nephrology.
The team found that individual albuminuria responses correlated despite 2 different doses of the same RAASi or NSAID. Individual albuminuria also did not decline markedly when the current RAASi or NSAID was switched to another drug in the same class (e.g., an angiotensin-converting enzyme inhibitor to an angiotensin receptor blocker) or in an alternate class. Reducing dietary sodium intake likewise did not result in substantial improvement. Therapy resistance persisted regardless of systolic blood pressure, potassium level, or diabetes status.
“Whether other drugs or drug combinations targeting pathways beyond the renin-angiotensin-aldosterone system and prostaglandins would improve the individual poor response requires further study,” according to Dr Petrykiv and his collaborators. The team also suggested genetic or molecular profiling to understand what drives response.
Petrykiv SI, Laverman GD, Persson F, Vogt L, et al. Renin-angiotensin-aldosterone system intervention. Clin J Am Soc Nephrol 2017;12. doi: 10.2215/CJN.00390117