Cardiovascular diseases remain the leading cause of morbidity and mortality worldwide, with acute coronary syndrome (ACS) accounting for a significant proportion of cardiovascular deaths [1]. Percutaneous coronary intervention (PCI) has emerged as the cornerstone of management for patients with ACS, providing rapid and effective coronary revascularization and improved clinical outcomes. However, the benefits of PCI are closely dependent on optimal adjunctive pharmacotherapy, particularly antiplatelet therapy, to prevent thrombotic complications such as stent thrombosis, recurrent myocardial infarction, and cardiovascular death [2].

Dual antiplatelet therapy (DAPT), consisting of aspirin and a P2Y12 receptor inhibitor, is fundamental to contemporary PCI practice. While clopidogrel was historically the most widely used P2Y12 inhibitor, its variable platelet inhibition, delayed onset of action, and reduced effectiveness in certain patient subgroups have prompted the development of more potent agents [3-4]. Prasugrel and ticagrelor are newer-generation P2Y12 inhibitors that provide faster, stronger, and more consistent platelet inhibition and are recommended over clopidogrel in international guidelines for patients with ACS undergoing PCI [5].

Prasugrel is a third-generation thienopyridine that irreversibly inhibits the P2Y12 receptor and has demonstrated superior reduction in ischemic events compared with clopidogrel in randomized trials, albeit with an increased risk of bleeding in selected high-risk populations [6]. Ticagrelor, a cyclopentyl-triazolo-pyrimidine, is a reversible P2Y12 inhibitor with rapid onset and offset of action and has been shown to reduce mortality and major adverse cardiovascular events compared with clopidogrel, without a significant increase in major bleeding [7].

In routine clinical practice, the choice between prasugrel and ticagrelor is frequently guided by physician preference, patient characteristics, bleeding risk, drug tolerability, and cost considerations. Ticagrelor-related dyspnea and prasugrel-associated bleeding concerns continue to influence prescribing patterns, underscoring the need for comparative effectiveness data from everyday practice settings [8].

In this context, the present prospective observational study was designed to compare the efficacy and safety outcomes of prasugrel versus ticagrelor in patients undergoing PCI in a real-world tertiary care setting. By evaluating ischemic events, bleeding complications, and drug-related adverse effects over one-year follow-up, this study aims to provide clinically relevant evidence to guide individualized antiplatelet therapy selection after PCI.

This was a prospective, observational, single-center study conducted at Fortis Escorts Heart Institute, New Delhi, a high-volume tertiary care cardiac center. The study period extended from July 2016 to December 2016, with clinical follow-up for all enrolled patients up to one year after the index PCI procedure. Study Population: Consecutive adult patients presenting with acute coronary syndrome (ACS) and undergoing percutaneous coronary intervention (PCI) with drug-eluting stent (DES) implantation were screened for inclusion. ACS was defined as ST-segment elevation myocardial infarction (STEMI), non–ST-segment elevation myocardial infarction (NSTEMI), or unstable angina, based on contemporary guideline criteria. Sample size: During the study period; a total of 120 patients received prasugrel and 272 patients received ticagrelor. Inclusion Criteria • ACS (STEMI, NSTEMI, or unstable angina) • PCI with DES implantation • Treatment with aspirin plus prasugrel or ticagrelor • Informed consent and willingness for follow-up Exclusion Criteria • History of hemorrhagic stroke or active pathological bleeding • Requirement for long-term oral anticoagulation • Known bleeding diathesis or platelet disorders • Severe hepatic dysfunction • Contraindication or hypersensitivity to study drugs • Pregnancy or lactation Treatment Protocol: All patients received aspirin (300 mg loading, followed by 75–150 mg daily) plus: • Prasugrel: 60 mg loading, 10 mg daily maintenance • Ticagrelor: 180 mg loading, 90 mg twice daily maintenance The choice of P2Y12 inhibitor was left to the discretion of the treating interventional cardiologist, based on clinical judgment, patient characteristics, perceived bleeding risk, and drug availability. Standard adjunctive therapies, including statins, beta-blockers, ACE inhibitors or ARBs, and proton pump inhibitors, were prescribed according to guideline recommendations. PCI Procedure: PCI was performed according to standard institutional protocols using contemporary techniques. Vascular access (radial or femoral), lesion preparation, stent selection, and use of adjunctive pharmacotherapy (including glycoprotein IIb/IIIa inhibitors) were at the operator’s discretion. All patients received drug-eluting stents. Procedural success was defined as residual stenosis <20% with TIMI grade 3 flow in the target vessel. Data Collection: Baseline demographic data, cardiovascular risk factors, clinical presentation, angiographic findings, procedural details, and in-hospital outcomes were prospectively recorded. Follow-up data were obtained through outpatient visits and telephonic interviews at regular intervals up to one year. Outcomes • Primary outcome: Major adverse cardiovascular events (MACE) • Secondary outcomes: Bleeding (BARC classification), dyspnea (NYHA), stent thrombosis, repeat revascularization, and mortality Statistical Analysis: Categorical variables were analyzed using chi-square or Fisher’s exact test using SPSS software version 25. Continuous variables were compared using Student’s t-test or Mann–Whitney U test. A p-value <0.05 was considered statistically significant.

Table 1 summarizes the baseline demographic and clinical characteristics of patients treated with prasugrel and ticagrelor. The two groups were well matched with respect to age, sex distribution, and major cardiovascular risk factors such as diabetes mellitus, hypertension, smoking status, and dyslipidemia, indicating comparability between the study groups.

Table 1: Baseline Characteristics

Table 2 outlines the clinical presentation at admission. The proportion of patients presenting with STEMI, NSTEMI, and unstable angina was similar between the two groups, suggesting that the severity and type of ACS did not influence the choice of antiplatelet agent.

Table 2: Clinical Presentation

Table 3 presents the comparison of one-year clinical outcomes between the prasugrel and ticagrelor groups. Rates of major adverse cardiovascular events, myocardial infarction, stent thrombosis, stroke, repeat revascularization, and all-cause mortality were comparable, with no statistically significant differences observed.

Table 3: Clinical Outcomes at 1 Year

Table 4 details the safety outcomes. Overall bleeding rates and BARC ≥2 bleeding events were low and comparable between groups. However, dyspnea (NYHA class II–III) was significantly more frequent in patients receiving ticagrelor, highlighting an important tolerability difference.

Table 4: Safety Outcomes

*: statistically significant

Mean age in prasugrel group was lower (57.5 years) than ticagrelor group (62.5 years) with median age of 56 years and 61 years respectively. Mean and median age is consistent with TRITON TIMI 38 trial [9] which had median age of 61 years.  Study by M yudi et al [10] also had mean age of 57 years.

Females in prasugrel and ticagrelor group comprised of around 35% of population in the respective group. TRITON TIMI 38 [9] had around 25% female patients.

Diabetes mellitus patients were equally distributed between the two groups (46.6% vs 46.3%; p=0.516). TRITON TIMI 38 [9] had 23% patients with diabetes. This difference may be caused by different geographical population and more incidence of diabetes in our country.

Hypertension was present in round 80% patients in both the groups (p=0.683) TRITON TIMI 38 [9] had around 64% of patients with hypertension. Retrospective analysis by Khayata M et al [11] (clinical outcomes of clopidogrel, prasugrel, and ticagrelor in clinical practice using the National Cardiovascular Database ACTION Registry) also showed 72% hypertensive patients.

Current smoking was present in around 39.2% vs 36.4% patients in prasugrel and ticagrelor group (p=0.601) which is consistent with TRITON TIMI 38 [9] which had 36% smokers.

Dyslipidemia was present in 82.5% vs 80.1% patients in our study which is more than in TRITON TIMI 38 [9]. This more dyslipidemia may be due to a greater number of diabetes patients in our study groups.

BARC grade 1 bleeding occurred in 12.5% vs 11% patients in prasugrel and ticagrelor group respectively (p=0.674). BARC grade 2 or more bleeding occurred in 1.1% in ticagrelor group, but there was no reported grade 2 bleeding in prasugrel group. In TRITON TIMI 38 [9] there was an increase in the rate of life-threatening bleeding with prasugrel, including a significant increase in fatal major haemorrhage. However, those reported findings conflict with other studies. Other studies concluded that there was no difference in bleeding incidence between prasugrel and clopidogrel. Other studies demonstrated that prasugrel, compared to clopidogrel, had more frequent minor/minimal bleeding events but fewer incidences of major bleeding events. Kaul U et al [12] in their study of 1000 patients also showed only 0.1% of 30-day major bleeding with prasugrel. Khayata M et al [11] in their analysis also showed less fatal bleeding with prasugrel. The lower incidence of major bleeding among the prasugrel group in our study may be explained by selection bias such that prasugrel is prescribed to patients with a low risk of bleeding and younger population comparison to ticagrelor (mean age of 57.5 years in prasugrel vs 62.5 years in ticagrelor).

Breathlessness of NYHA grade 2 or more was present in 8.3% vs 18% in the two groups (p=0.013) which was significantly more in ticagrelor group. This is consistent with PLATO trial [13] which also had more dyspnoea in ticagrelor group. Although dyspnoea improved in many cases after a week however, some patient had continued discomfort for which they had to be shifted to different antiplatelet.

Myocardial infarction incidence in the two groups was similar (p=0.647). PLATO [13] and TRITON TIMI 38 [9] showed reduced incidence of myocardial infarction in ticagrelor and prasugrel group as compared to clopidogrel. In our study when ticagrelor was compared with prasugrel, both showed similar incidence of MI. These results are comparable to the results reported by Yudi MB et al [10] where myocardial infarction did not differ significantly between ticagrelor and prasugrel groups (p=0.52).

Stent thrombosis was also found to be similar in the two groups (p=0.999). PLATO trial [13] showed reduced stent thrombosis as compared to clopidogrel while TRITON TIMI 38 [9] showed reduced stent thrombosis in prasugrel group than clopidogrel. In our study when ticagrelor is compared to prasugrel they both showed similar rates of stent thrombosis which is as per the previous results.

Stroke including both ischemic (p=0.999) and haemorrhagic (p=0.519) was found to be similar in both antiplatelet groups. In TRITON TIMI 38 [9] prasugrel did not differ in stroke incidence against clopidogrel (p=0.93).

Repeat procedure in the form of repeat PCI was done in 10% vs 7.7% in prasugrel and ticagrelor group. Although numerically higher with prasugrel it was not found to be significant (p=0.454). A larger sample size of study with longer follow up might have demonstrated the significance.

Death occurred in 6.7% vs 5.1% in prasugrel and ticagrelor (p=0.547). Although TRITON TIMI 38 [9] showed statistically significant difference in composite of cardiovascular death, nonfatal MI, stroke but no significant rates of cardiovascular death (p=0.31) or death from any cause (p=0.64) in prasugrel group was found in comparison to clopidogrel. The reduction in composite end point was primarily driven by reduction in non-fatal MI in prasugrel group. Yudi MB et al [10] also had similar rates of death in patients with prasugrel and ticagrelor (p=0.76). Therefore, taking only death in to consideration our study results are consistent with previous studies.

MACE events were reduced in ticagrelor and prasugrel group when compared with clopidogrel in PLATO [13] and TRITON TIMI 38 [9] trials. In our study when we compared ticagrelor and prasugrel there was not any significant difference in MACE events in between prasugrel and ticagrelor (p=0.432). These results were consistent with the data of Yudi MB et al [10] which also had similar rates of MACE events in patients with prasugrel and ticagrelor (p=0.57).

Limitations 

• Single center observational design
• Non randomized treatment allocation

•              Moderate sample size

Prasugrel and ticagrelor demonstrate comparable efficacy and safety following PCI in real world clinical practice. Ticagrelor is associated with a higher incidence of dyspnea, whereas major bleeding and ischemic outcomes are similar. Individualized antiplatelet selection remains essential.

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