Introduction
Acute myocardial infarction (AMI) is one of the important causes of cardiovascular death [
1]. Percutaneous coronary intervention (PCI) is crucial in reconstructing coronary arterial revascularization [
2]. Cardiac rehabilitation (CR) is a well-established and scientifically proven approach that incorporates patient education, behavior modification techniques, and exercise training to significantly improve secondary prevention outcomes in patients diagnosed with cardiovascular disease [
3]. The safety of early CR after PCI has been identified [
4]. Engagement in CR post-PCI has been linked to a noteworthy decrease in both all-cause mortality (ACM) and cardiovascular mortality [
5]. There is currently no agreement on the optimal time to begin CR following PCI in patients with AMI [
6]. An earlier study indicated that rehabilitation exercises should commence approximately 6 weeks after a cardiovascular event to allow sufficient time for medical stabilization and recovery [
7]. It is common for CR and secondary prevention programs to start no earlier than 4–6 weeks after a patient has been discharged from the hospital [
8]. According to the 2014 AHA/ACC guidelines for Non-ST-Elevation acute coronary syndrome (ACS), in patients treated with PCI, aerobic exercise training is generally recommended to commence within 1 to 2 weeks after discharge [
2].
In recent years, a growing body of research has investigated the potential advantages of starting CR at an earlier stage [
4,
9‐
11]. Patients who suffered from AMI and started engaging in progressive exercise within 1 week after undergoing PCI treatment demonstrated significantly higher left ventricular ejection fraction (LVEF) and quality of life scores compared to the control group, according to a study conducted over a 6-month period [
12]. A 6-month CR program initiated 3–7 days after PCI in AMI patients can improve LVEF and prevent ventricular remodeling [
13].
It is worth noting that some studies have also supported initiating CR in patients with AMI after PCI and discharge from the hospital. Xiao ML et al.’s study revealed that a 12-month community-based physical rehabilitation significantly reduced the risk of major adverse cardiovascular events (MACE) and improved cardiac function and physical endurance in patients who received PCI following AMI [
14]. Zhang Y et al.’s study also supported that community-based CR starting on the second week after discharge and lasting for 6 months can lead to significant improvements in cardiac ejection fraction, exercise tolerance, and cardiovascular risk factors reduction among patients with AMI [
15]. Several meta-analyses examining the effectiveness of CR have consistently demonstrated that it can help reduce the incidence of cardiovascular events [
16‐
18]. There were few studies directly exploring the impact of different initiation times or durations of CR programs on CR outcomes. Therefore, we conducted this meta-analysis to explore the impact of the time factors on CR outcomes in patients with AMI who underwent PCI.
Discussion
A total of 16 studies, including 1810 participants (774 in the rehabilitation group and 1036 in the control group), were analyzed in our meta-analysis. Among the studies we included, the CR program started as early as the second day after PCI (0.1 weeks) and as late as 1 month after PCI. The shortest intervention duration is 1 week, and the longest is 2 years. The results of the meta-regression analysis showed that there was no significant difference in the improvement of CR outcomes among AMI patients when comparing different CR starting times within 1 month after PCI or different durations of the CR programs.
PCI is considered as one of the commonly employed methods for reperfusion therapy. The benefits of early CR after PCI, particularly in patients with AMI, are increasingly recognized. It is safe to start exercising early after coronary stenting [
10]. The optimal initiation time and duration for CR following AMI has remained unclear [
37]. An earlier study suggested that rehabilitation exercise may begin around 6 weeks after a cardiovascular event to ensure adequate medical stabilization and recovery [
7]. Research in recent years has advanced the starting time for CR. A meta-analysis exploring the impact of exercise training on left ventricular remodeling after myocardial infarction suggests that early initiation time (around 1 week after AMI) and long-term exercise may confer the most significant benefits [
11]. Some studies supported the significant benefits of community or family-based CR programs after PCI treatment and discharge for improving cardiac function and quality of life in patients with AMI. In line with the 2014 AHA/ACC guidelines for Non-ST-Elevation ACS, patients are generally advised to start aerobic exercise 1–2 weeks after undergoing PCI treatment and being discharged from the hospital [
2]. A meta-analysis examining the effectiveness of home-based CR after PCI showed that it effectively enhanced cardiopulmonary function and reduced cardiovascular events [
38].
Several meta-analyses examining the effectiveness of CR have consistently demonstrated that it can help reduce the incidence of cardiovascular events [
16‐
18]. A large retrospective cohort study showed that in-hospital CR participation could significantly reduce the risk reduction of revascularisation, all-cause readmission and cardiac readmission among patients with PCI after AMI [
39]. The ETICA trial has demonstrated that engaging in long-term moderate intensity exercise training after coronary angioplasty is safe [
9]. Our study suggests that the initiation time and duration of CR had no significant impact on the occurrence of three types of cardiovascular events (arrhythmia, coronary artery restenosis and angina pectoris). Although the studies of the subgroups of all-cause mortality (ACM), MACE, and rehospitalization (RH) were not subjected to meta-regression analysis, we performed meta-analysis on the subgroups of ACM and MACE. The results showed small heterogeneity (ACM: I
2 = 0.0%,
p = 0.901; MACE: I
2 = 45.0%,
p = 0.162). Therefore, the timing of initiating CR within 1 month after PCI in AMI patients may not have a significant impact on the occurrence of cardiovascular events. According to the consensus of European Association of Cardiovascular Prevention and Rehabilitation, risk assessment is recommended for patients with ACS after PCI prior to starting physical activity. While some patients can safely start physical activity as early as the second day after PCI, those with large or complex myocardial injuries should gradually increase their physical activity level only after achieving clinical stability [
40].
Cardiac color Doppler ultrasound and 6MWT are the main methods utilized for assessing cardiac function in patients with cardiovascular disease. Typically, CR and secondary prevention programs do not begin until at least 4–6 weeks after a patient is discharged from the hospital [
8]. However, research suggests that patients who have had an uncomplicated myocardial infarction can benefit from earlier aerobic exercise training beginning as soon as 1 week after hospital discharge in order to achieve maximal anti-remodeling benefits. Additionally, it is recommended that these patients continue their aerobic exercise training for up to 6 months [
11]. This viewpoint is also supported by the research conducted by Zheng H et al. and Jiang MH et al. [
12,
13]. In our meta-regression analysis of observational studies, the starting time demonstrated a significant impact on the changes in LVEF. However, the meta-regression analysis of RCTs indicated that the initiation time and duration of CR had no significant impact on the changes in LVEF, LVEDV, and LVESV. Our main result is that during the one-month period following PCI, different initiation times and durations of CR did not have an impact on the changes in LVEF.
6MWT is a simple method for testing cardiopulmonary function. The result of meta-regression analysis did not reveal any significant association between changes in 6MWT and either initiation time or duration. 6MWT is self-paced, motivational factors could have significantly influenced performance and introduced variability across studies [
41]. Therefore, meta-regression showed significant heterogeneity in the 6MWT results.
Due to the limited number of studies within the subgroups, it was not possible to conduct a meta-regression analysis on the time factors’ effects on heart rate, blood pressure, and blood lipid levels. The forest plot only reveals certain changing trends (Fig.
5). With increasing intervention time, both heart rate and LDL-C levels significantly decreased. TC decreased more significantly as the starting time advanced. But when the starting time was earlier, a smaller reduction was observed in systolic blood pressure (SBP). These conclusions did not reach statistical significance. Lowering blood pressure after a myocardial infarction may result in impaired perfusion of target organs [
42]. The 2020 European Society of Cardiology guidelines for the management of acute coronary syndromes recommend that most individuals under 65 years of age, who are on blood pressure-lowering medications, should aim to lower their SBP to the range of 120–129 mmHg. For older patients aged 65 and above who are receiving these medications, it is generally recommended to target an SBP range of 130–139 mmHg [
37]. The earlier CR is initiated, the potential benefits for the heart may be associated with a smaller decrease in blood pressure.
The included studies all started CR within 1 month after PCI. Short-term differences in the timing of rehabilitation initiation may not have a significant impact on the improvement of cardiac function. As a result, there is no substantial difference in the incidence of cardiovascular events due to variations in rehabilitation initiation time in the short term. It is important to recognize that CR is a comprehensive and long-term process, which can vary considerably in its specific implementation across studies due to factors such as patients’ foundational treatments, lifestyle habits and socioeconomic status. These variabilities contributed to the high heterogeneity observed in continuous variable data. The conflation of time-related factors within these variables may introduce interference when evaluating the influence of time on rehabilitation outcomes.
The prognosis of AMI is also influenced by the location and number of culprit blood vessels. Lesions in the left anterior descending (LAD) and left circumflex (LCx) were associated with higher mortality rates compared to lesions in the right coronary artery (RCA) [
43]. A study demonstrated that patients with total occlusion ST-elevation myocardial infarction (STEMI) in LAD had a higher mortality rate during a 36-month follow-up period [
44]. Patients with AMI and multivessel coronary disease have a poorer prognosis compared to individuals with single-vessel disease [
45]. Only a small portion of the included studies reported the location of culprit blood vessels. Therefore, it was not possible to explore the correlation between the location of culprit blood vessels and the outcomes of CR. However, this factor should be considered as an important influencing factor in future research.
Overall, implementation of CR following PCI in patients with AMI is beneficial. However, the timing of initiating CR within 1 month after PCI in AMI patients and the duration of CR had no significant impact on the occurrence of arrhythmia, coronary artery restenosis, angina pectoris, and the changes in LVEF, LVEDV, LVESV and 6MWT. It indicates that it is feasible for patients with AMI to commence CR within 1 month after PCI and continue long-term CR, but the time factors which impact CR are intricate and further clinical research is still needed to determine the optimal initiation time and duration of CR.
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