# Detection of muscular system adverse reaction signals in sacubitril/valsartan treatment combined with statins

## TL;DR

This study identifies potential muscle-related side effects when combining sacubitril/valsartan with specific statins, using FDA data to guide safer clinical use.

## Contribution

The study introduces new evidence of drug-drug interaction signals involving sacubitril/valsartan and specific statins linked to muscular adverse effects.

## Key findings

- Combining sacubitril/valsartan with simvastatin shows significant signals for musculoskeletal muscle pain and myopathy.
- Sacubitril/valsartan with atorvastatin shows significant signals for myopathy in the multiplicative model.
- Coadministration with simvastatin increases risks for both musculoskeletal pain and myopathy.

## Abstract

To detect muscular system adverse reaction signals of sacubitril/valsartan treatment combined with statins (atorvastatin, rosuvastatin, simvastatin) to provide a reference for clinical administration.

Multiplicative and additive models were used to mine the FDA’s spontaneous reports database to detect signals of drug-drug interactions between sacubitril/valsartan and statins. SAS 9.4 software was used to conduct statistical tests for suspicious signals to determine whether the signals were statistically significant.

A total of 8,883,870 adverse reaction reports were analyzed. The combinations “sacubitril/valsartan - simvastatin - musculoskeletal muscle pain” had statistically significant correlation signals in both models (P < 0.05). The combination “sacubitril/valsartan - atorvastatin - myopathy” and “sacubitril/valsartan–simvastatin - myopathy” had statistically significant correlation signal in the multiplicative model (P < 0.05).

Compared with a single drug, coadministration of sacubitril/valsartan with atorvastatin may increase safety risks to myopathy, with simvastatin may increase safety risks to the musculoskeletal pain and myopathy, which should be closely monitored in clinical practice.