Impact of Tirofiban and Cilostazol on Cardiac Recovery in Elderly Patients with Acute Coronary Syndrome

Introduction

Coronary heart disease (CHD) occurs when the coronary arteries become occluded or stenotic, leading to ischemia in the heart muscle [1]. The prevalence of coronary artery disease is rising in China, making it one of the most common heart conditions. As of 2022, approximately 11.39 million individuals in China were diagnosed with coronary heart disease, a major component of CAD. Additionally, cardiovascular diseases (CVDs) accounted for 45.86% and 48.00% of all deaths in urban and rural areas, respectively, underscoring the significant impact of CAD on public health in China [2]. One of the primary treatments for CHD is percutaneous coronary intervention (PCI) [3]. PCI offers significant advantages over thrombolytic therapy in treating acute CHD by reducing infarct size and clinical adverse events, ultimately leading to better clinical outcomes for patients. However, clinical studies have shown that even when PCI successfully opens the infarct-related blood vessels, myocardial tissue in some patients fails to achieve effective reperfusion [4,5]. This phenomenon, known as the “no-reflow” or “slow-flow” phenomenon, occurs when platelet activity increases, leading to the formation of microthrombi caused by the rupture and compression of atherosclerotic plaques during PCI. These microthrombi can obstruct myocardial microvasculature in the distal coronary artery. Intraoperative mechanical manipulation and ischemia-reperfusion injury further exacerbate endothelial damage, triggering local vessel inflammation, microvascular spasm, and platelet activation, which prevents adequate coronary blood flow. Studies have reported that the incidence of the slow-flow phenomenon during emergency PCI ranges from 10% to 30%, leading to severe myocardial ischemia and impaired cardiac function recovery, and significantly affecting the prognosis of CHD patients [6]. Additionally, inflammatory factors and myocardial markers after PCI can exacerbate the local inflammatory response in the coronary arteries, increasing levels of myocardial markers (indicating myocardial injury and serum enzyme elevation) in some patients, thereby affecting their clinical prognosis [7]. Therefore, identifying an optimal PCI treatment approach to reduce the incidence of no-reflow or slow-reflow, minimize postoperative inflammatory reactions, and lower myocardial marker levels is clinically crucial. Platelet activation plays a critical role in the pathogenesis of coronary artery disease and in the absence or slow return of flow after PCI. Adequate anti-platelet therapy can significantly improve reperfusion of the myocardial microcirculation after PCI. Currently, clopidogrel in combination with aspirin is the standard anti-platelet regimen following PCI and is effective in reducing the risk of in-stent thrombosis [8]. However, some patients have low or no response to clopidogrel, a condition known as clopidogrel resistance [9], highlighting the need for more effective and relatively safe anti-platelet strategies.

Recent studies have confirmed that tirofiban, a platelet glycoprotein IIb/IIIa (GP IIb/IIIa) receptor antagonist, is a potent anti-platelet agent that effectively inhibits platelet adhesion and aggregation. It has been widely used in the treatment of PCI for high-risk patients with acute coronary syndromes (ACS) [10]. Furthermore, research and long-term clinical application have demonstrated that tirofiban not only exerts anti-platelet effects but also plays a role in reducing inflammation, protecting endothelial function, and lowering myocardial marker levels after surgery [11–12].

Moreover, cilostazol has been investigated for its potential role in preventing no-reflow and slow-flow phenomena during PCI [13]. By increasing intracellular cAMP levels, cilostazol not only inhibits platelet aggregation but also promotes vasodilation, which can enhance coronary microcirculation and reduce distal embolization. Additionally, its anti-inflammatory effects can mitigate endothelial dysfunction and lower microvascular resistance, thereby improving myocardial reperfusion. Some studies suggest that cilostazol administration prior to PCI can significantly reduce the incidence of slow-flow and no-reflow events, ultimately leading to better cardiac outcomes [13–15].

Cilostazol, a newer anti-platelet drug, selectively inhibits cyclic adenosine monophosphate (cAMP) phosphodiesterase, increasing intracellular cAMP levels, inhibiting the production of thromboxane (TXA2) in membrane phospholipids, and thereby reducing platelet release of adenosine diphosphate (ADP) and serotonin. This action contributes to its anti-platelet and vasodilatory effects. Additionally, cilostazol inhibits smooth muscle cell proliferation, a key factor in in-stent thrombosis [16–18]. Although a few studies have explored the effects of combining tirofiban and cilostazol on cardiac function and prognosis in elderly ACS patients after PCI, further investigation is needed. This case-control study provides new insights into the clinical management of post-PCI patients.

Material and Methods

GENERAL INFORMATION:

From April 2020 to April 2022, 80 elderly patients with acute coronary syndrome (ACS) treated at our hospital were randomly assigned to either the control group (n=40) or the observation group (n=40). All patients received percutaneous coronary intervention (PCI). The control group was treated with aspirin and clopidogrel as per routine practice, while the observation group received a combination of tirofiban and cilostazol.

To minimize selection bias, randomization was performed using a computer-generated random number sequence, ensuring equal allocation to both groups (1: 1 ratio). Allocation concealment was maintained using sealed opaque envelopes. Blinding was partially implemented with outcome assessors analyzing laboratory biomarkers, and clinical endpoints were blinded to group allocation. However, treating physicians were not blinded due to the nature of the intervention. All patients provided informed consent, and the study was approved by the Research Ethics Committee of Taizhou Jiangyan Hospital of Traditional Chinese Medicine, Taizhou, Jiangsu Province, China (Reference number: TJH/CR/073/20). A flow chart of the study is presented in Figure 1.

INCLUSION CRITERIA:

The inclusion criteria were: (1) age ≥60 years (this criterion was selected due to the increased prevalence of ACS and higher risk of PCI-related complications in this age group, and elderly patients often have a higher incidence of clopidogrel resistance, which can influence treatment outcomes); (2) diagnosis of acute coronary syndrome (ACS) based on established diagnostic criteria [19] and indications for PCI treatment, included a confirmed diagnosis of cardiovascular disease such as ACS, absence of hemorrhagic diseasing no known allergy to contrast medium, target vessel diameter <2.25 mm, hemodynamic stability, and no high-mortality comorbidities; (3) patients needed to have clear consciousness with no cognitive impairment, ensuring their ability to cooperate with treatment; (4) onset of symptoms within 12 hours, accompanied by progressive myocardial ischemia and an unstable ECG; and (5) provided voluntary informed consent before enrolment.

EXCLUSION CRITERIA:

The exclusion criteria were: (1) contraindications for PCI; (2) a history of anemia or thrombocytopenia; (3) previous PCI or coronary artery bypass grafting (CABG); (4) active hemorrhage at the time of enrolment; (5) a history of major surgery or gastrointestinal/cerebral hemorrhage within the past 3 months; (6) diagnosed with infectious diseases of the central nervous system, mental illnesses, hematological disorders, or significant organ dysfunction; and (7) known allergies to any of the drugs used in this study.

Calculation formula of sample size:

Where n1 is required sample size per group, Zα/2 is standard normal deviate corresponding to the significance level (α=0.05, Z=1.96 for a two-tailed test), Zβ is standard normal deviate corresponding to the desired power (β=0.20, Z=0.84 for 80% power), p is estimated proportion of success (effect size), c is allocation ratio between groups (c=1 for equal allocation), P1 is expected total effective rate in the treatment group (0.97), and P2 is expected total effective rate in the control group (0.76). Each group had 36 cases, and the expected dropout rate was 10%, according to calculations. The 2 groups each included 40 patients, for a total of 80 patients. The expected treatment effect size was informed by prior clinical studies and meta-analyses evaluating similar interventions in acute coronary syndrome (ACS) patients. Notably, a meta-analysis by Rout et al demonstrated that an invasive strategy in older patients with non–ST-segment-elevation ACS significantly reduced the risk of a composite of death and myocardial infarction (MI), MI alone, and subsequent revascularization compared with a conservative strategy [20]. This previous study by Rout et al supports the effective rate in the treatment group (P1=0.97) compared to the control group (P2=0.76) [20].

TREATMENT METHODS:

According to interventional therapy guidelines, all patients were initially treated with 300 mg of aspirin enteric-coated tablets (German Bayer Vital GmbH, H20120236) and 600 mg of clopidogrel sulfate (French Sanofi Pharma Bristol-Myers Squibb SNC, BH20080268) prior to interventional therapy. The control group received 100 mg of aspirin enteric-coated tablets once daily, in addition to conventional drug treatments, including nitrates, statins, angiotensin-converting enzyme inhibitors, and β-receptor blockers. Clopidogrel hydrosulfate tablets (75 mg) were administered orally once daily.

In the observation group, tirofiban hydrochloride (H20041165) was intravenously administered at a dose of 10 μg/(kg·min) after the guide wire passed through the diseased artery, followed by a continuous intravenous infusion at a dose of 0.1 μg/(kg·min) for 24 hours after the operation. Cilostazol tablets (Zhejiang Dier Pharmaceutical Co., Ltd., Chinese Medicine H20058054) were administered orally at a dose of 200 mg once daily. Patients in the observation group received continuous treatment for 1 month.

OBSERVATION INDEX:

(1) Criteria for determining the curative effect.

The patient’s symptoms are considered resolved when both their own reported symptoms and the results of clinical examinations are normal. Improvement in the patient’s symptoms with near-normal clinical examination results is considered partial improvement. Lack of improvement or worsening of the patient’s symptoms is considered a treatment failure. The total effective rate=(markedly effective + effective)/the total number of cases ×100%, and the clinical efficacy was evaluated after 1 month of treatment.

(2) Before and 1 month after surgery, LVEDD, LVESD, and LVEF were monitored by two-dimensional echocardiography.

(3) Blood sample collection and biomarker analysis.

Before PCI and 1 month after PCI, venous blood samples (5 mL and 3 mL) were collected after a 12-hour fast. Serum was separated by centrifugation at 3000 rpm for 10 minutes and analyzed using ELISA for hs-CRP, TNF-α, and IL-6. CK-MB and hs-cTnT levels were measured using a Cobas h232 analyzer, while platelet aggregation rate and PLT levels were assessed via thromboelastography and an automated blood analyzer. Platelet function tests were conducted before PCI and 24 hours after PCI to evaluate changes in platelet activity.

(4) Quality-of-life score.

Prior to and 1 month after surgery, the health status questionnaire (SF-36) was used to assess quality of life [21]. The scale included 5 parts, including social function, physiological function, health status, mental health, and somatic diseases (20 points/part, a total of 100). Quality of life was proportional to the score.

(5) Adverse cardiovascular events.

The occurrence of MACE, such as vascular restenosis, heart failure, malignant arrhythmia, revascularization, and death, was monitored during the treatment period. The total incidence of MACE=the sum of all kinds of cardiovascular events/the total number of cases ×100%. Restenosis is defined as a “healing” response to the treatment of local coronary artery injury after successful PCI has been performed resulting in local restenosis. Heart failure is a clinical syndrome characterized by impaired cardiac circulation, which results from the dysfunction of the heart’s systolic and/or diastolic functions. This leads to incomplete drainage of venous blood from the heart and stagnation of blood in the venous system, which ultimately leads to inadequate perfusion of blood in the arterial system. An attack of malignant arrhythmia can cause a drop in blood pressure, which can lead to syncope and even sudden death. Revascularization refers to the reconstruction of blood vessels and restoration of blood supply.

SUCCESS CRITERIA FOR PCI:

The procedural success of PCI was defined by achieving TIMI-3 flow after the intervention, a TIMI frame count within the normal range, and residual stenosis <20% as assessed by quantitative coronary angiography.

STATISTICAL ANALYSIS:

The data were analyzed using SPSS 21.0 statistical software. Prior to analysis, the normality of data distribution was assessed using the Shapiro-Wilk test, and homogeneity of variance was evaluated using Levene’s test. Continuous variables following a normal or approximately normal distribution are presented as mean±standard deviation (χ̄±s), while those not following a normal distribution are expressed as median (interquartile range, IQR). Normally distributed data were analyzed using an independent sample t test for between-group comparisons and a paired t test for within-group comparisons. Non-normally distributed data were analyzed using the Mann-Whitney U test for between-group comparisons and the Wilcoxon signed-rank test for within-group comparisons. Categorical data are presented as frequencies (n,%), and differences between groups were assessed using the χ̄² test or Fisher’s exact test, where appropriate. A P value of <0.05 was considered statistically significant.

Results

GENERAL CHARACTERISTICS OF THE PATIENTS:

The study included 80 elderly patients diagnosed with acute coronary syndrome (ACS), who were randomly assigned to either the observation group (n=40) or the control group (n=40). In the observation group, there were 28 men and 12 women, with an age range of 60 to 85 years and a mean age of 69.03±9.51 years. The distribution of lesion types included 10 cases of unstable angina pectoris, 17 cases of ST-segment elevation myocardial infarction (STEMI), and 13 cases of non-ST-segment elevation myocardial infarction (NSTEMI). Regarding coronary artery involvement, 11 patients had single-vessel disease, 13 had two-vessel disease, and 6 had three-vessel disease. The Genisi score for coronary stenosis ranged from 55.00 to 92.00, with a mean score of 74.32±4.55. In the control group, there were 25 men and 15 women, with an age range of 61 to 88 years and a mean age of 68.93±9.61 years. The distribution of lesion types included 12 cases of unstable angina pectoris, 16 cases of STEMI, and 12 cases of NSTEMI. Coronary artery disease involvement included 10 cases of single-vessel disease, 12 cases of two-vessel disease, and 8 cases of three-vessel disease. The Genisi score for coronary stenosis ranged from 57.00 to 93.00, with a mean score of 74.10±4.36 (Table 1). No statistically significant differences were observed between the 2 groups in terms of baseline clinical characteristics (P=0.25), indicating that the groups were comparable for subsequent analysis.

PROCEDURAL SUCCESS AND THERAPEUTIC EFFECTS:

Procedural success was defined as achieving TIMI-3 flow, a TIMI frame count within normal limits, and residual stenosis <20% following intervention. Both the observation and control groups achieved high procedural success rates, consistent with the literature. Specifically, procedural success was achieved in 39 patients (97.5%) in the observation group and 38 patients (95%) in the control group, with no statistically significant difference between the groups (P=0.64). The treatment outcomes in the observation group were classified as remarkably effective in 26 patients, effective in 13 patients, and ineffective in 1 patient, yielding a total effective rate of 97.50%. In contrast, the control group demonstrated remarkably effective outcomes in 12 patients, effective outcomes in 20 patients, and ineffective outcomes in 8 patients, resulting in a total effective rate of 80.00%. The observation group exhibited a significantly higher effective rate compared to the control group (P=0.001). The results are illustrated in Figure 2.

CARDIAC FUNCTION INDICES BEFORE AND AFTER SURGERY:

Prior to surgery, no significant differences were observed between the groups in left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), or left ventricular ejection fraction (LVEF). One month after surgery, LVEDD and LVESD decreased, while LVEF increased in both groups. The observation group showed significantly lower LVEDD (P=0.00) and LVESD (P=0.028) values and higher LVEF (P=0.043) compared to the control group. Detailed results are presented in Table 2.

SERUM INFLAMMATORY FACTORS:

Before surgery, no significant differences were observed in serum levels of IL-6 (P=0.061), hs-CRP, (P=0.210), or TNF-α (P=0.340). One month after surgery, all 3 markers decreased significantly, with the observation group showing significantly lower levels of IL-6 (P= 0.001), hs-CRP (P=0.002), and TNF-α (P=0.021) compared to the control group. Detailed results are presented in Table 3.

MYOCARDIAL MARKERS:

Before surgery, there were no significant differences in serum creatine kinase-MB (CK-MB) (P=0.639) and high-sensitivity cardiac troponin T (hs-cTnT) levels (P=0.547). At 24 hours postoperatively, both CK-MB (P=0.001) and hs-cTnT (P=0.002) increased significantly in both groups, with the observation group showing significantly lower levels compared to the control group (P<0.05). Detailed results are presented in Table 4.

PLATELET AGGREGATION RATE AND PLATELET COUNT (PLT):

Before surgery, no significant differences were observed in platelet aggregation rate or PLT levels between the groups. One month after surgery, platelet aggregation rates decreased significantly in both groups, with the observation group showing a significantly lower rate compared to the control group (P=0.004). No significant differences in PLT levels were observed between the groups (P= 0.73). Detailed results are presented in Table 5.

QUALITY-OF-LIFE SCORES:

Prior to treatment, no significant differences were observed in quality-of-life scores between the groups. One month after treatment, scores for physiological function (P=0.046), health status (P=0.004), social function (P=0.001), mental health (P=0.001), and somatic disease (P=0.031) improved significantly in both groups, with the observation group showing significantly higher scores compared to the control group (P<0.05). Detailed results are presented in Table 6

INCIDENCE OF MAJOR ADVERSE CARDIAC EVENTS (MACE):

The incidence of MACE in the observation group was significantly lower (2.50%) compared to the control group (22.50%) (P=0.007). Detailed results are presented in Table 7.

Discussion

The pathological basis of ACS is coronary atherosclerosis and intraluminal thrombosis. Therefore, percutaneous coronary intervention (PCI) is an effective therapeutic strategy for ACS patients. However, the mechanical stress exerted on the coronary artery wall by balloon expansion and stenting during PCI can cause plaque rupture and intimal injury, leading to platelet activation and subsequent platelet adhesion and aggregation [22]. This platelet aggregation releases vasoactive substances and inflammatory mediators into the bloodstream, further exacerbating endothelial damage [23,24]. In ACS patients undergoing PCI, these events can result in slow blood flow and even no-reflow phenomena after the procedure [25,26]. Consequently, antithrombotic therapy is essential during and after PCI. However, complications may also contribute to various postoperative risk events, necessitating careful consideration of comorbidities when formulating intraoperative and postoperative treatment plans. Since PCI involves cardiac catheterization to reopen occluded and stenotic coronary arteries, it effectively restores vascular patency and alleviates coronary artery stenosis [27]. However, the placement of stents inevitably causes endothelial injury, which can trigger thrombosis, thereby worsening the patient’s condition and compromising PCI outcomes [28,29]. After PCI, anti-platelet aggregation therapy is routinely administered, but complications such as embolic events and even mortality can still occur.

This study evaluated the impact of combining tirofiban with cilostazol on cardiac function recovery and prognosis in elderly ACS patients after PCI. The control group received standard antithrombotic therapy, whereas the experimental group received an additional combination of tirofiban and cilostazol. The results demonstrated a total effective rate of 80.0% in the control group and 97.5% in the observation group, indicating that the combination therapy significantly enhanced treatment efficacy. Moreover, both groups had a reduction in LVEDD and LVESD and an increase in LVEF 1 month postoperatively. Notably, these improvements were more pronounced in the observation group, suggesting that tirofiban combined with cilostazol significantly promotes cardiac function recovery in elderly ACS patients after PCI.

The efficacy of cilostazol in preventing intimal hyperplasia and reducing cardiovascular events has been supported by multiple clinical trials. The Sufficient Treatment of Peripheral Intervention by Cilostazol (STOP-IC) study demonstrated that cilostazol significantly reduced angiographic restenosis rates after endovascular therapy in femoropopliteal lesions, supporting its potential role in preventing neointimal hyperplasia [30]. Additionally, Soga et al found that cilostazol improved long-term outcomes after endovascular therapy in patients with intermittent claudication, reinforcing its anti-restenotic and vasodilatory properties [31]. Moreover, an experimental study showed that cilostazol was non-inferior to paclitaxel in inhibiting intimal hyperplasia in a balloon angioplasty model, further validating its therapeutic benefits in vascular interventions [32]. A meta-analysis by Chen et al confirmed that triple anti-platelet therapy with cilostazol, aspirin, and clopidogrel significantly reduced thrombotic complications without increasing major bleeding events compared to dual anti-platelet therapy (DAPT) in PCI patients [33]. These findings align with our study, where cilostazol addition improved anti-platelet efficacy and reduced post-PCI inflammatory response, thereby enhancing cardiovascular protection.

Regarding tirofiban, clinical evidence has shown its potent GP IIb/IIIa inhibition reduces thrombotic events and improves PCI outcomes in ACS patients. A study by Guo et al found that tirofiban combined with standard DAPT led to superior clinical efficacy and reduced MACE in ACS patients undergoing PCI [34]. Similarly, the TARGET trial demonstrated that triple anti-platelet therapy including tirofiban resulted in improved survival and reduced ischemic events at 1-year follow-up [35]. Moreover, Lakkis et al revisited tirofiban dosing strategies, confirming its strong platelet inhibition and favorable safety profile during PCI [36]. These large-scale studies support our findings that the combination of cilostazol and tirofiban enhances antithrombotic protection and improves post-PCI outcomes compared to standard DAPT alone.

Emerging evidence suggests that PCI can transiently exacerbate the local coronary inflammatory response [32,33]. Emergency PCI can stimulate the endothelium, leading to increased expression of adhesion molecules, chemokines, and inflammatory cytokines. High-sensitivity C-reactive protein (hs-CRP) is a key inflammatory marker that directly activates the coagulation cascade, upregulates adhesion molecules, reduces nitric oxide (NO) production, disrupts antioxidant defense mechanisms, and contributes to endothelial dysfunction. Additionally, hs-CRP serves as a marker of post-PCI inflammatory response and correlates positively with the severity of intimal injury. One month after surgery, serum levels of hs-CRP, TNF-α, and IL-6 were significantly lower in the observation group, indicating that tirofiban combined with cilostazol effectively reduces systemic inflammation and improves patient prognosis. Additionally, recent research has emphasized the role of the platelet-to-hemoglobin ratio (PHR) as a predictor of in-hospital mortality in STEMI patients undergoing PCI, indicating that hematological indices can further refine risk stratification in these patients [37]. Hs-CRP, synthesized primarily by the liver, plays a crucial role in acute inflammation by activating monocytes and granulocytes, promoting the release of inflammatory cytokines, chemokine-1, and adhesion molecules, thereby exacerbating endothelial injury and thrombogenesis [38]. Additionally, PCI-induced vascular injury promotes TNF-α release, which disrupts endothelial integrity, induces endothelial proliferation and vascular stenosis, promotes neutrophil aggregation, and enhances oxidative stress, further exacerbating endothelial dysfunction and thrombosis formation [39]. Thus, serum levels of hs-CRP and TNF-α can serve as prognostic indicators after PCI [40]. IL-6, another pro-inflammatory cytokine, induces CRP synthesis, upregulates intercellular adhesion molecule-1 expression, exacerbates inflammatory injury, promotes fibrinogen production, and contributes to thrombogenesis [41]. Studies have reported a strong association between IL-6 levels and myocardial infarction progression [42,43]. Although IL-6, TNF-α, and hs-CRP have short half-lives, their levels can remain elevated due to persistent inflammation in ACS patients after PCI. Studies have shown that IL-6 correlates with disease severity in ACS [44], while CRP serves as a predictor of adverse cardiovascular outcomes [45]. Additionally, prolonged CRP elevation has been linked to worse long-term prognosis in ACS patients [46]. Moreover, TNF-α, a key mediator of inflammation, contributes to endothelial injury, plaque instability, and myocardial dysfunction, and its sustained elevation has been associated with increased mortality and worse outcomes in coronary artery disease [47]. These findings suggest that measuring these markers even after 1 month provides valuable prognostic insights.

Creatine kinase-MB (CK-MB) is a myocardial isoenzyme involved in intracellular energy transport and muscle contraction, while high-sensitivity cardiac troponin T (hs-cTnT) is a regulatory protein that mediates actin-myosin interactions [39,42]. Both CK-MB and hs-cTnT are specific cardiac biomarkers, typically present at low serum levels under normal physiological conditions. However, after myocardial infarction, cardiomyocyte injury leads to the release of CK-MB and hs-cTnT into circulation, resulting in elevated serum concentrations [39–41]. Studies suggest that CK-MB and hs-cTnT levels correlate with myocardial injury severity [48–50]. The present study observed that serum CK-MB and hs-cTnT levels peaked 24 hours after PCI but were significantly lower in the observation group thereafter, suggesting that tirofiban combined with cilostazol mitigates myocardial injury and reduces the incidence of MACE. Additionally, the platelet aggregation rate was significantly lower in the observation group, indicating a superior anti-platelet aggregation effect of tirofiban combined with cilostazol compared to aspirin and clopidogrel monotherapy. These findings align with previous studies [51]. Although cilostazol, aspirin, and clopidogrel all exert anti-platelet effects through distinct mechanisms, cilostazol uniquely inhibits platelet function through multiple pathways, preventing thrombosis while mitigating aspirin and clopidogrel resistance [52]. Notably, no significant difference in platelet count (PLT) was observed between groups, suggesting that cilostazol does not induce excessive platelet depletion or increase bleeding risk. Postoperative quality of life and MACE incidence were also analyzed. One month after PCI, patients in the observation group had significantly higher scores in physical functioning, health status, social functioning, mental well-being, and overall physical condition. Furthermore, the incidence of MACE was markedly lower in the observation group (2.5%) than in the control group (22.5%), indicating that tirofiban combined with cilostazol improves long-term prognosis following PCI. Additionally, both agents were well tolerated, with a low incidence of cardiovascular adverse events. Studies have shown that prolonged emergency department delay time significantly impacts all-cause mortality in STEMI patients undergoing PCI, highlighting the critical role of early intervention in improving survival outcomes [53].

Despite these promising findings, this study has several limitations. The sample size calculation was based on estimated effect sizes from prior studies. However, a formal G-Power analysis was not incorporated at the study’s inception, which may have affected the statistical power of the findings. Additionally, this study focused exclusively on elderly ACS patients, limiting generalizability to younger populations. While elderly patients have a higher thrombotic risk and distinct hemodynamic responses, excluding younger individuals may have introduced selection bias. Future studies should include broader age groups to validate these findings. Another limitation is the choice of clopidogrel as the standard anti-platelet agent in the control group, despite ESC and AHA guidelines favoring ticagrelor or prasugrel for stronger platelet inhibition. This may have influenced the study results, as ticagrelor or prasugrel may provide superior protection against thrombotic events. Moreover, the study only evaluated outcomes at 1 month after PCI, limiting insights into the long-term durability of the observed clinical benefits. Future research should include longer follow-up periods to assess sustained cardiovascular protection. Although randomization and allocation concealment were implemented, potential biases in patient selection and treatment allocation cannot be fully excluded. A multicenter study with a larger sample size would help mitigate center-specific biases.

Conclusions

The combination of tirofiban and cilostazol is a safe and effective therapeutic strategy for elderly ACS patients undergoing PCI, significantly enhancing cardiac function recovery and improving long-term prognosis. Future research should focus on large-scale, multicenter, and multiregional studies to further validate these findings.