Regular exercise is known to be effective for the primary and secondary preventions of cardiovascular disease.1,2 Studies have reported that a systematic cardiac rehabilitation combined with regular exercise improved cardiopulmonary function, psychosocial state, and quality of life of the patient, decreased the all-cause and cardiovascular mortality by 20-30%,3-5 and delayed the progression or reduced the severity of artherosclerosis.6,7 Primary percutaneous coronary intervention (PCI) was effective for long- and short-term treatment of patients with acute myocardial infarction,8 though considerable recurrence and restenosis were reported.9 Although the rate of stent thrombosis occurrence within 12 months after PCI was reported to be approximately 1% because of a new dual-antiplatelet therapy regimen, the mortality due to stent thrombosis was 20-40%.1 As such, to reduce the incidence of restenosis in the stented coronary area, a drug-eluting stent (DES) was introduced, and studies have reported that the rate of restenosis was significantly lower in the DES group than in the bare metal stent group.10,11 In the DES, however, late stent thrombosis occurred 1-12 months after the intervention due to delayed strut endothelialization and potential prothrombotic characteristics.1 Thus, safety continues to be a problem.12

Coronary sclerosis and its risk factors interrupt the vasolidation produced by the vascular endothelial cells, and change the relationship between the vascular wall, inflammatory cells, and platelets.13 The growth of tunica intima is related to the late luminal loss after the implantation of the stent,14 and with the inflammatory reaction caused by persistent shear stress15 and the vascular damage that accompanies increased c-reactive protein (CRP).16 The endothelial dysfunction that occurs after the implantation of the stent is an independent predictor of initial restenosis.17

Based on these findings, studies have revealed that 6 months of regular exercise after the insertion of the stent reduced the late luminal loss in the stented area.18 In addition, an increased peak VO₂ could improve exercise capability and regular exercise improved endothelium-dependent vasodilatation through the activation of endothelial nitric oxide synthase.18 In another study examining patients with stable coronary artery stenosis (≤75% diameter stenosis), regular exercise without coronary artery intervention increased the maximum oxygen consumption (VO₂max) and thus, reduced the inflammatory reaction. This is unlike coronary intervention without regular exercise. In the two-year follow-up period of the patients, there were fewer cardiac events in the regular-exercise-without-coronary intervention group.19

It is known that in patients with coronary artery diseases, the implantation of a DES reduces the rate of restenosis, compared with the insertion of a bare metal stent. However, there have not been any controlled studies that compared the extent of restenosis after the implantation of the DES in the cardiac rehabilitation group and in the non-cardiac rehabilitation group. There are also no published studies that have compared the extent of the restenosis of different types of DESs based on the findings that cardiac rehabilitation reduced the rate of restenosis after the insertion of a stent. As such, this study compared the extents of the in-stent restenosis between the cardiac rehabilitation group and the control group of patients who had received various types of DESs.

Although advances in medical technology have gradually reduced mortality due to coronary artery disease, the prevalence of the disease continues to rise each year.23,24 It was reported that for patients who had survived, particularly those who had experienced myocardial infarction, their quality of life would decrease due to their decreased ability to be active in daily life.25 As hospital stay has shortened due to advances in coronary artery intervention and the development of novel drugs,26 the need to control possible complications and risk factors of recurrence has emerged.

Cardiac rehabilitation is considered particularly important because it is known to improve the exercise capability of patients with coronary artery disease and in the secondary prevention of the disease through a comprehensive program that consists of an individualized exercise program based on the exercise prescription, nutrition consultation, a smoking cessation program, drug therapy, and weight control.27

Post-coronary artery intervention restenosis has a high medical cost and an increased risk of revascularization.18 Both the bare metal stent and the DES have the possible issue of stent thrombosis and restenosis, and thus, may result in the recurrence of myocardial infarction and death.28 In particular, it was reported that a DES could result in hypersensitivity to polymers and delayed endothelialization in the stented area,28 and that DM, among the predictors of thrombosis, decreased the effect of antiplatelet agents, such as aspirin and clopidogrel.29 In this study, of the eight patients with restenosis in the control group, three had DM. In addition, a study had reported that regular exercise reduced the inflammatory reaction related to the in-stent restenosis in patients with heart failure or CAD.18 Thus, it is believed that various relevant factors that may induce restenosis should be controlled with an active cardiac rehabilitation program for patients who had undergone coronary artery intervention. This study was performed with patients who had a DES implanted, and we investigated the influence of cardiac rehabilitation-based regular exercise on post-stent implantation restenosis in patients who had a DES implant. A study that compared two types of first-generation DESs, a SES (sirolimus-eluting stent) and a PES (paclitaxel-eluting stent), showed that SES was superior to PES in reducing late loss10 and another study reported that there was no difference between SES and PES with regard to late loss.26 This study compared the late restenoses of first-, second-, and third-generation stents, and found no difference in the restenoses of the three generations in the cardiac rehabilitation and control groups.

Recently, however, it was reported that the risk of very late thrombosis increased by 0.1-0.6% each year in the DES-implanted group (unlike in the bare-metal-stent-implanted group)30 and that interest in DES-related mortality and late stent thrombosis is increasing.26,30 As such, studies are underway to compare mortality and the recurrence of myocardial infarction in relation to DES. Therefore, a study that compares the diameter restenoses after a short- and long-term follow-up is needed. One study that has demonstrated the relationship between a high level of activity and the proportion of cardiovascular diseases has shown that 3-6 months of high-intensity exercise reduced in-stent restenosis in patients who had undergone coronary artery intervention. The high-intensity exercise was related to the activation of nitric oxide (NO) synthase (due to the improved vascular endothelial cells), the decreased CRP that promotes arteriosclerosis, and the reduced endothelin-1 production that exacerbates the endothelial cell function.18 Likewise, in this study, late luminal loss and late loss were significantly lower in the cardiac rehabilitation group than in the control group, and the number of patients with in-stent restenosis significantly differed between the two groups (n=1 and 8, respectively). Steady cardiac rehabilitation-based exercise capability measurement can assist in the early detection of coronary artery restenosis31 and the assessment of the exercise capability through regular measurement of the VO₂ consumption can be the most robust and independent predictor of cardiovascular disease mortality.18 Thus, regular cardiac rehabilitation and exercise capability measurements are considered important for patients who had undergone coronary artery intervention. The limitations of this study are: first, the decision to participate in the cardiac rehabilitation program was left to the patients to decide, and those with a high risk of cardiac crisis were not assigned to the community setting exercise group. Thus, it was impossible to perform a random selection comparative analysis. Second, the difference in the management of various risk factors, such as hypertension, diabetes, hyperlipidemia, obesity, and smoking between the two groups was not clearly identified. Third, as the study period was nine months, follow-up time was short. Further studies with long-term comparison of the restenosis of the cardiac rehabilitation group with that of the control group and between different-generation DESs are needed, as are studies on the mortality and morbidity of coronary artery disease. Fourth, this study did not have a large sample, which was also a limitation in the other studies that compared restenosis after the insertion of DESs. In particular, interpreting the results of the studies that compared the diameter restenosis of different generations of DESs is still debatable. Thus, it is believed that randomized controlled studies with more subjects will achieve more objective outcomes.

Cardiac rehabilitation significantly reduced in-stent late luminal loss, late loss, and percent diameter stenosis, regardless of the type of the ever-advancing DESs. This indicates that cardiac rehabilitation can significantly delay the progression of in-stent restenosis.

Therefore, we expect that adequate exercise through cardiac rehabilitation can reduce the rate of intervention repetition and mortality in patients with cardiovascular disease or who had undergone a coronary artery intervention.