A comparative evaluation of prasugrel and clopidogrel in patients with acute coronary syndrome undergoing percutaneous coronary intervention.
OBJECTIVE
Primary objective of this study was to compare the efficacy of Prasugrel vs. Clopidogrel in the patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI) by measuring inhibition of platelet aggregation after loading and maintenance dose of both the drugs. The patients were also assessed for safety of the drugs.


METHODS
This was a randomised, double-blind, double-dummy, comparative, multicentric clinical trial in patients with acute coronary syndrome (unstable angina, non-ST elevation MI and ST elevation MI) undergoing PCI. The patients were randomly assigned to receive prasugrel (loading dose of 60 mg followed by maintenance dose of 10-mg once daily) or clopidogrel (loading dose of 300 mg followed by maintenance dose of 75 mg once daily) for a period of 12 weeks. All the patients were co-prescribed aspirin 325 mg with both the drugs. The primary efficacy end point in this study was percentage inhibition of ADP induced platelet aggregation (IPA) at 4 +/- 1 hours after the loading dose and at 30 +/- 3 days during maintenance treatment. The platelet aggregation of both the drugs was measured by whole blood aggregometer using 10 mmol of ADP as an aggregant. Though this study was not powered to see the difference in clinical efficacy parameters, the patients were observed for the incidence of nonfatal MI, nonfatal stroke, re-hospitalization, death, or need for urgent revascularization due to a cardiac ischemic event at days 30 and 90 during the study. The safety of study drugs were evaluated by incidence of major bleeding, reported adverse drug reaction and alterations of any laboratory parameters.


RESULTS
A total of 220 patients were enrolled at 11 centres across India. Ten patients were given the loading dose of prasugrel or clopidogrel but did not underwent PCI due to change in investigator's decision to go for PCI. Out of 210 eligible patients, 21 patients were discontinued during the study. 157 patients were evaluated for platelet inhibition after loading dose at 4 hours and 150 patients at day 30 during maintenance phase of antiplalelet therapy. The investigators could not perform this test in remaining patients due to urgency and criticality of the patients. 189 patients were observed for the incidence of nonfatal MI, nonfatal stroke, rehospitalisation, urgent revascularisation or death due to a cardiac ischemic event. All eligible patients who received at least a loading dose were evalauted for safety. In prasugrel group, 85 and 77 patients were evaluated for IPA at 4 hours and day 30 respectively whereas in clopdogrel group 72 and 73 patients were tested for IPA at 4 hours and at 30 days. Patients in prasugrel group have demonstrated significantly higher inhibition of platelets as compared to clopidogrel group (82.5% vs 71.1%) at 4 hours and at 30 days (84.1% vs 67.4%). The difference in inhibition of platelets between prasugrel and clopidogrel after loading dose and maintenenace dose was statistically significant (p < or = 0.01). The patients were also evaluated for drug hyporesponsiveness to antiplatelet therapy if IPA was < 20% at day 30 from the baseline. More patients on prasugrel have shown response to antiplatlet therapy than on clopidogrel (97.4% vs 87.6%). The difference between the two groups was statistically significant (p < 0.05). There was no difference observed during the study in the incidence of nonfatal MI, nonfatal stroke, death, rehospitalisation or need for urgent revascularisation due to a cardiac event between prasugrel and clopidogrel. Both the drugs were found to be to be well tolerated and have comparable safety profile.


CONCLUSIONS
This study suggests that prasugrel is more effective than clopidogrel as an anti platelet drug as evident by inhibition of platelet aggregation. More patients on clopidogrel are likely to have poor response to therapy as compared to prasugrel. Both the drugs were well tolerated and have comparable safety profile.
Institute of Post Graduate Medical Education & Research, Cardiology Division, 244, A.J.C. Road, Kolkata - 700 020.
Arup
A
Dasbiswas
Care Hospital, Nampally, Hyderabad-500 001.
M Srinivas
MS
Rao
Dr. Ramesh Cardiac and Multispeciality Hospital Ltd., Ring Road, Near ITI College, Vijayawada- 520 008.
Pothineni Ramesh
PR
Babu
Department of Cardiology, Post Graduate Institute of Medical Education & Research, Sector-12, Chandigarh-160 012.
Rajesh
R
Vijayvergiya
Wockhardt Heart Hospitals, 14, Cunningham Road, Bangalore-560 052.
Ranganath
R
Nayak
Vikram Hospital, 71/1, Millers Road, Bangalore 560052.
Sameer
S
Dani
Life Care Institute of Medical Sciences & Research, Stadium Road, Sardar Patel Statue Corner, Naranpura, Ahmedabad- 380 014.
Sanjay
S
Tyagi
G. B. Pant Hospital & Maulana Azad Medial College, Dept. of Cardiology, J. L. Nehru Marg, New Delhi-110O 002.
Shirish
S
Hiremath
Grant Medical Foundation, Ruby Hall Clinic, 40 Sassoon Road, Pune- 411 001.
Tejas
T
Patel
SAL Hospital, Opp: Doordarshan Tower, Drive In Road, Ahmedabad-380054.
Thomas
T
Alexander
Kovai Medical Centre & Hospital Limited, P.B. No.:3209, Avanashi Road, Coimbatore-641 014.
V S
VS
Prakash
G. B. Pant Hospital & Maulana Azad Medial College, Dept. of Cardiology, J. L. Nehru Marg, New Delhi-110O 002.
Davinder Pal
DP
Singh
Department of Cardiology, Post Graduate Institute of Medical Education & Research, Sector-12, Chandigarh-160 012.
Mukesh Kumar
MK
Yadav
Department of Clinical Research, Torrent Research Center, Bhat, Gandhinagar, Gujarat.
Kashyap
K
Pathak
Department of Clinical Research, Torrent Research Center, Bhat, Gandhinagar, Gujarat.
Ambrish
A
Srivastava
D054058:Acute Coronary Syndrome / Q000628:therapy*; D000328:Adult; D000368:Aged; D001241:Aspirin / Q000627:therapeutic use; D000077144:Clopidogrel; D003131:Combined Modality Therapy; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D062645:Percutaneous Coronary Intervention; D010879:Piperazines / Q000627:therapeutic use*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D000068799:Prasugrel Hydrochloride; D058921:Purinergic P2Y Receptor Antagonists / Q000627:therapeutic use*; D013876:Thiophenes / Q000627:therapeutic use*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D013876:Thiophenes; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine; D001241:Aspirin