Abstract Background Atherosclerosis and coronary artery disease (CAD) are potentially preventable through lifestyle modifications and the use of medical cholesterol-lowering drugs in individuals at risk. However, guidelines for optimal use of statins are debated, and not enough is known about the real-world barriers to effective CAD-prevention. Understanding the mechanisms of prophylactic treatment failure in patients who undergo PCI for their first atherosclerotic event could help improve primary prevention strategies. Purpose To 1) examine the relative contribution of failure mechanisms of medical prophylaxis in patients undergoing PCI for their first atherosclerotic event, 2) examine how clinical characteristics differ between patients with different failure mechanisms, and 3) examine whether long-term outcomes after PCI differ depending on the mechanism of prophylactic failure. Methods A retrospective study was conducted to study electronic healthcare records for all patients ≥18 years treated with PCI at Gentofte Hospital, Denmark in 2019. Data was extracted from electronic health care records. Patients with first atherosclerotic event were divided into cardiovascular risk groups based on the ESC/EAS guidelines and further into four different prophylactic failure mechanism groups based on cardiovascular risk, statin indication, statin use and whether the risk-based LDL-C treatment goals were reached. Results 507 patients were treated with PCI for their first atherosclerotic event. 54% were categorized as low-moderate cardiovascular risk. 41% were not on statin and did not have class I indication for statin treatment (strategy failure). 26% were not on statin treatment despite class I indication for statin treatment (implementation failure). 18% were on statin treatment but had not reached their LDL-C target (efficiency failure), and 16% were on statin treatment, and had reached the LDL-C target (efficacy failure). Patients with strategy failure, were more likely to be younger, mostly males, and often had a smoking history. Patients with implementation failure, were typically elderly, with relatively few comorbidities. The frequency of death, myocardial infarction, stroke, or repeat revascularization over 4 years was 15.3%, with no statistically difference between the groups (p =0.3). Conclusion In this cohort study, patients treated with PCI for first atherosclerotic event were often classified as low or intermediate risk, and a majority had not been on statin treatment before. Improved primary prevention should focus on at-risk groups that are either not included in current recommendation for statin treatment, especially young smokers, or patients not receiving treatment despite recommendations, especially older patients with few medical contacts.Cardiovascular risk & failure mechanismKaplan-Meier MACE