The researchers conducted a prospective observational animal experiment using pigs for 8 weeks to determine the relationship between nicotine and microstructural changes within the stent.5) The results revealed that nicotine promoted neointimal formation, inhibited re-endothelialization, and induced an inflammatory reaction after DES implantation. These findings suggest that nicotine influences microstructural changes such as neointimal proliferation post-DES, indicating that while DES may reduce the risk of in-stent restenosis (ISR), continuous smoking over decades can contribute to ISR and exacerbate inflammatory reaction, potentially leading to clinical events.

This study is notably the first prospective observational study in the field. The method used to administer nicotine via an osmotic pump was crucial, as it allowed the nicotine concentration to stabilize, mimicking habitual smoking. In this study, the nicotine was released at sustained blood concentrations of approximately <5 ng/mL. These concentrations are much lower than those produced by cigarette smoking or nicotine gum and are similar to or lower than those produced by electronic cigarettes (vaping).6) In other words, emphasizing that even very low concentrations of nicotine exposure can worsen neointima formation and inflammatory reactions is important. Considering that exposure to very low concentrations of secondhand smoke also promotes systemic inflammatory reactions, the results of this study convey an important message from a public health perspective.7)

This study has certain limitations. First, this study was conducted on healthy coronary arteries from non-smokers without arteriosclerosis. In addition, stent over-dilation injury is induced in rare intimal cells with normal elastic artery. If the experiment had been conducted on arteries exposed to smoking or disease for a prolonged period (6 months or more), worse outcomes could have been expected. Second, while nicotine use alone allows the separation of its biological effects from those of other active components such as carbon monoxide, tar, and ammonia, but the impact of nicotine modifies on re-endothelialization and inflammation can be changed by the other active components in tobacco. Third, experiments on systemic inflammatory markers and coagulation-related factors, including plasminogen activator inhibitor-1, were not conducted, making assessing the effect on stent thrombosis difficult. Furthermore, including a group that discontinues nicotine use to determine whether doing so can reduce NIH is necessary. Admittedly, this may be too ambitious.

This study provides new insights into the consequences and mechanisms by which nicotine exacerbates NIH. The question is not whether smoking negatively affects the neointima formation after percutaneous coronary intervention—It undoubtedly does. The message is simple: you must quit smoking immediately.