Implanting stents is the most efficient and minimally invasive technique for treating coronary artery diseases, but the risks of stent thrombosis (ST) and in-stent restenosis (IRS) hamper the healing process. There have been a variety of stents in market but dominated by ad hoc design motifs. A systematic design method that can enhance deliverability, safety and efficacy is still in demand. Most existing designs are focused on patient and biological factors, while the mechanical failures related to stenting architectures, e.g., inadequate stent expansion, stent fracture, stent malapposition and foreshortening, are often underestimated. With regard to these issues, the self-expanding (SE) stents may perform better than balloon-expandable (BE) stents, but the SE stents are not popular in clinic practice due to poor deliverability, placement accuracy, and precise match of the stent size and shape to the vessel. This paper addresses the importance between stent structures and clinic outcomes in the treatment of coronary artery disease. First, a concurrent topological optimization method will be developed to systematically find the best material distribution within the design domain. An extended parametric level set method with shell elements is proposed in the topology optimization to ensure the accuracy and efficiency of computations. Second, the auxetic metamaterial with negative Poisson’s ratio is introduced into the self-expanding stents. Auxetics can enhance mechanical properties of structures, e.g., fracture toughness, indentation and shear resistance and vibration energy absorption, which will help resolve the drawbacks due to the mechanical failures. Final, the optimized SE stent is numerically validated with the commercial software ANSYS and then prototyped using additive manufacturing techniques. Topological optimization gives a rare opportunity to exploiting the unique advantages of additive manufacturing. Hence, the topologically optimized auxetic architectures will provide a new solution for developing novel stenting structures, especially conductive to self-expanding SE stents. The new design will overcome the limitations of conventional SE stents associated with mechanical structures while maintain their valuable features, to help reduce the occurrence of ST and ISR and benefit the clinic practice in treating coronary heart disease.