Percutaneous coronary intervention (PCI) has revolutionized the management of coronary artery disease and acute coronary syndrome (ACS). Despite advances in stent technology, thrombotic complications such as stent thrombosis and recurrent myocardial infarction remain major concerns and are closely linked to platelet activation. Dual antiplatelet therapy (DAPT), combining aspirin with a P2Y12 receptor inhibitor, forms the cornerstone of pharmacological management following PCI [1].

Clopidogrel, a second-generation thienopyridine, has been the most commonly prescribed P2Y12 inhibitor for many years. However, its clinical effectiveness is limited by delayed onset of action, interindividual variability in platelet inhibition, and genetic polymorphisms affecting hepatic metabolism. These limitations have been associated with higher rates of recurrent ischemic events and stent thrombosis in certain patient subsets [2].

Prasugrel is a third-generation thienopyridine that provides more rapid, potent, and consistent platelet inhibition than clopidogrel [3]. The TRITON–TIMI 38 trial demonstrated that prasugrel significantly reduced ischemic events and stent thrombosis compared with clopidogrel in patients with ACS undergoing PCI, albeit at the cost of increased bleeding in selected high-risk populations. Consequently, prasugrel is recommended in contemporary guidelines for ACS patients without contraindications [4].

Despite strong randomized trial evidence, real-world comparative data between prasugrel and clopidogrel remain limited, particularly from developing countries such as India, where patients often present at a younger age with a high burden of diabetes and multivessel disease. Additionally, concerns regarding bleeding risk, cost, and physician familiarity continue to influence antiplatelet selection in daily practice.

The present study was undertaken to compare the real-world efficacy and safety outcomes of prasugrel versus clopidogrel in patients undergoing PCI at a tertiary care center, with the aim of providing clinically relevant evidence to guide individualized antiplatelet therapy selection.

This prospective, observational, single-center study was conducted at a tertiary care cardiac center between July 2016 and December 2016, with follow-up extended to one year after PCI. The study protocol was approved by the institutional ethics committee, and informed consent was obtained from all participants. Study Population: Adult patients (>18 years) presenting with ACS (STEMI, NSTEMI, or unstable angina) and undergoing PCI with drug-eluting stent implantation were eligible for inclusion. Sample size: During the study period; a total of 120 patients received prasugrel and 344 patients received clopidogrel. Inclusion Criteria • Age ≥18 years • Diagnosis of ACS • PCI with drug-eluting stent implantation • Treatment with aspirin plus prasugrel or clopidogrel Exclusion Criteria • Active bleeding or bleeding diathesis • History of hemorrhagic stroke • Requirement for long-term oral anticoagulation • Severe hepatic dysfunction • Contraindication to antiplatelet therapy Antiplatelet Therapy: All patients received aspirin (300 mg loading dose followed by 75–150 mg daily). P2Y12 inhibitor therapy included: • Prasugrel: 60 mg loading dose followed by 10 mg once daily • Clopidogrel: 300–600 mg loading dose followed by 75 mg once daily The choice of agent was based on physician discretion. PCI Procedure and Adjunctive Therapy: PCI was performed according to standard institutional protocols. Procedural strategy, vascular access, and use of adjunctive pharmacotherapy were left to the operator’s discretion. 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: Continuous variables were expressed as mean ± standard deviation and compared using Student’s t-test. Categorical variables were analyzed using the chi-square or Fisher’s exact test. A p-value <0.05 was considered statistically significant.

Table 1 summarizes the baseline demographic and clinical characteristics of patients receiving prasugrel and clopidogrel. Both groups were comparable with respect to age, sex distribution, and major cardiovascular risk factors, indicating adequate baseline comparability.

Table 2 depicts the clinical presentation at admission. The proportion of STEMI, NSTEMI, and unstable angina was similar between the two groups, suggesting that initial clinical severity did not influence antiplatelet selection.

Table 1: Baseline Characteristics

Table 2: Clinical Presentation

Table 3 compares one-year ischemic outcomes between the two groups. The prasugrel group demonstrated lower rates of myocardial infarction and stent thrombosis, contributing to a reduced overall incidence of MACE compared with the clopidogrel group.

Table 3: Clinical Outcomes at 1 Year

*: statistically significant

Table 4 outlines safety outcomes. Overall bleeding rates and BARC ≥2 bleeding events were comparable between groups, indicating that prasugrel did not confer an excess bleeding risk in appropriately selected patients.

Table 4: Safety Outcomes

*: statistically significant 

Mean age in prasugrel group is lower (57.5 years) than clopidogrel group (64.19 years) with median age of 56 years and 62 years years respectively. Mean and median age is consistent with TRITON TIMI 38 [6] trial which had median age of 61 years.  Study by M yudi et al [7] also had mean age of 57 years.

Females in prasugrel and clopidogrel group comprised of around 35% of population in the respective group. TRITON TIMI 38 [6] had around 25% female patients.

Diabetes mellitus patients were equally distributed between the two groups (43.6% vs 46.3%). TRITON TIMI 38 [6] had 23% patients with diabetes. This difference may be caused by different geographical population and more incidence of diabetes in our also more number of obese patients in the study.

Hypertension was present in round 80% patients in both the groups. TRITON TIMI 38 [6] had around 64% of patients with hypertension. Retrospective analysis by Khayata M et al [8] (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 34% of the patients in prasugrel and clopidogrel group respectively which is consistent with TRITON TIMI 38 [6] which had 36% smokers.

Dyslipidemia was present in 82.5% vs 79.3% of the patients in prasugrel and clopidogrel group respectively which is more than in TRITON TIMI 38 [6]. 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 13.4% patients in prasugrel and clopidogrel group respectively (p=0.808). BARC grade 2 or more bleeding occurred in 2.9% in clopidogrel group, but there was no reported grade 2 bleeding in prasugrel group (p=0.071). In TRITON TIMI 38 [6] there was an increase in the rate of life-threatening bleeding with prasugrel, including a significant increase in fatal major hemorrhage. 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 [9] in their study of 1000 patients also showed only 0.1% of 30-day major bleeding with prasugrel. Khyata M et al [8] 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.

Breathlessness of NYHA grade 2 or more was present in 8.3% vs 11.3% in the two groups (p=0.357) which was non-significant. This is consistent with TRITON TIMI 38 trial [6] which also showed similar results.

Myocardial infarction incidence in the two groups was similar. TRITON TIMI 38 [6] showed reduced incidence of myocardial infarction in prasugrel group as compared to clopidogrel. However, our study results are comparable to results reported by Yudi MB et al [7] where myocardial infarction did not differ significantly between clopidogrel and prasugrel.

Stent thrombosis was also found to be similar in the two groups. TRITON TIMI 38 [6] showed reduced stent thrombosis in prasugrel group than clopidogrel. In our study when clopidogrel is compared to prasugrel they both showed similar rates, however there seems to be a trend towards reduced stent thrombosis in prasugrel group.

Stroke including both ischemic and haemorrhagic was found to be similar in both antiplatelet groups. This result is consistent with TRITON TIMI 38 trial [6] which also showed no difference in stroke incidence as compared to clopidogrel (p=0.93).

Repeat procedure in the form of repeat PCI was done in 10% vs 9.9% in prasugrel and clopidogrel group. Although this was not found to be significant (p=0.971).

Death occurred in 6.7% vs 7.3% in prasugrel and clopidogrel. Although TRITON TIMI 3812 showed statistically significant difference in composite of cardiovascular death, nonfatal MI, stroke but no significant difference in rates of cardiovascular death (p=0.31) or death from any cause (p=0.64) in prasugrel group was demonstrated as compared to clopidogrel. The reduction in composite end point was primarily driven by reduction in non-fatal MI in prasugrel group. Yudi MB et al [7] also had similar rates of death in patients with prasugrel and clopidogrel (p=0.76). Therefore, taking only death in to consideration our study results are consistent with previous studies.

MACE events were reduced in prasugrel group when compared with clopidogrel in TRITON TIMI 38 [6] trials. In our study when we compared clopidogrel and prasugrel, there was not any significant difference in MACE events in between clopidogrel and prasugrel (p=0.795). These results were consistent with the data of Yudi MB et al [7] which also showed similar rates of MACE events in patients with prasugrel and clopidogrel (p=0.57).

Limitations

• Observational, non-randomized design
• Single-center study

•              Moderate sample size

Prasugrel demonstrated superior efficacy compared with clopidogrel in reducing ischemic events following PCI, without a significant increase in major bleeding. Prasugrel should be considered a preferred P2Y12 inhibitor for DAPT in appropriately selected patients undergoing PCI.

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