Today, e-health has entered the everyday work flow in the form of a variety of healthcare providers. General practitioners (GPs) are the largest category in the public sanitary service, with about 60,000 GPs throughout Italy. Here, we present the Nu.Sa. project, operating in Italy, which has established one of the first GP healthcare information systems based on heterogeneous data sources. This system connects all providers and provides full access to clinical and health-related data. This goal is achieved through a novel technological infrastructure for data sharing based on interoperability specifications recognised at the national level for messages transmitted from GP providers to the central domain. All data standards are publicly available and subjected to continuous improvement. Currently, the system manages more than 5,000 GPs with about 5,500,000 patients in total, with 4,700,000 pharmacological e-prescriptions and 1,700,000 e-prescriptions for laboratory exams per month. Hence, the Nu.Sa. healthcare system that has the capacity to gather standardised data from 16 different form of GP software, connecting patients, GPs, healthcare organisations, and healthcare professionals across a large and heterogeneous territory through the implementation of data standards with a strong focus on cybersecurity. Results show that the application of this scenario at a national level, with novel metrics on the architecture's scalability and the software's usability, affect the sanitary system and on GPs' professional activities.