Aims: To compare the anti thrombocyte effects of locally manufactured clopidogrel with the anti thrombocyte consequence of clopidogrel manufactured by transnational pharmaceutical abroad.
Methodology: A sum of 118 topics were enrolled, 18 to 65 old ages of age, who presented with suspected ischaemic bosom disease and were indiscriminately assigned to have either drug A ( Pidogrel ) or drug B ( Plavix ) in a dual blind mode for 7 yearss. Platelet collection was measured in both the groups at baseline and at concluding visit.
Consequences: Base line thrombocyte aggregability in both drug groups was non significantly different ( p=0.317 ) Mean decrease in thrombocyte collection by drug-A was 8.47+/- 0.45 ohms ( p & A ; lt ; 0.001 ) and average decrease in thrombocyte collection by drug-B was 8.62+/- 0.46 ( P & A ; lt ; 0.001 ) . The difference in thrombocyte aggregability at twenty-four hours 7 ( follow up ) between the two groups was non statistically important i.e. , was the same.
Decision: Locally manufactured clopidogrel is every bit effectual as that manufactured by the transnational company abroad giving us the added advantage of cost effectivity.
Platelet activation and collection significantly contributes to the development of cardiovascular events. The initial measure in this procedure is the adhesion of thrombocytes, with the aid of its receptors, to the disrupted endothelium.1,2,3 This is followed by thrombocyte activation, synthesis and release of different go-betweens including Thromboxane A2 and ADP, which farther amplify the process.4, 5 Subsequently thrombocyte collection occur which consequences in stopper formation.4, 6 Inhibition of this procedure plays of import function in the bar of cardiovascular disease.7,8 Aspirin merely partly inhibit thrombocyte collection by barricading thromboxane mediated collection pathways.9,10 Clopidogrel blocks P2Y12 ADP receptor and therefore ADP induced platelet collection is inhibited.11,12 Patients holding least sensitiveness to the effects of acetylsalicylic acid on Arachidonic acid tract were found to be extremely sensitive to the ADP receptor adversary clopidogrel.13 Clopidogrel is now the recommended intervention in patients with acute coronary syndromes and in those undergoing PCI.14,15 Compared with aspirin alone combination of clopidogrel and acetylsalicylic acid cut down the hazard of ischaemic events in patients undergoing PCI and non STEMI. 16, 17
Clopidogrel is manufactured by a transnational pharmaceutical company with the trade name name of Plavix. In developing states like Pakistan, many patients with ACS or Post PCI can non afford it for long, because of its high cost. Many local companies with different generic names have launched it. The efficaciousness of most of these locally manufactured clopidogrel is non known. Present survey was performed to compare the anti thrombocyte effects of locally manufactured clopidogrel with the anti thrombocyte consequence of clopidogrel manufactured by transnational pharmaceutical as measured by suppression of thrombocyte collection utilizing whole blood aggregometry.
MATERIAL AND METHODS
This dual blind randomized clinical test was conducted in the out patients section of Cardiology, Post Graduate Medical Institute Lady Reading Hospital Peshawar, from 24th October 2007 to 28th Jan 2008. Patients aged 18-65 old ages, irrespective of gender, with suspected IHD showing to cardiology OPD were included in the survey. Those patients holding established IHD, undergoing PCI or CABG utilizing other antiplatelet or anticoagulant drugs, holding known hypersensitivity to clopidogrel, history of shed blooding upset, or deranged RBC, WBC or thrombocyte counts were excluded from the survey. Pregnant and breastfeeding females were besides excluded. Thus a sum of 118 patients were included in the survey. All patients gave written informed consent to take part in the survey.
Platelet collection survey was performed with whole blood aggregometry. The machine used was Chronolog Whole Blood Aggregometer ( 591 ) , which was supplied by the patronizing company. All other instruments like cuvettes ; micropipettes, saline, reagents, vacuette tubing etc were besides supplied by the patron.
On twenty-four hours one, 5 milliliter blood was drawn by direct veni puncture utilizing vacuette tubings. After roll uping the blood tubings were gently inverted several times to guarantee complete commixture in the Na citrate, decoagulant, nowadays in the vacuette tubings.
Patients were so randomized and given prefilled bottles incorporating either drug A ( 75mg tablets of generic Pidogrel ) or drug B ( 75mg of branded Plavix ) . Patients were asked to take day-to-day one tablet of their several drug orally and describe back on twenty-four hours seven.
Attendant medicines needed, were continued, with the exclusion of other antiplatelet and anticoagulant drugs.
From the whole blood, already drained out ; 0.5 milliliter was diluted with an tantamount volume of isosmotic saline and incubated for 5 proceedingss at 37oC. The electric resistance of each sample was monitored at consecutive 1-minute interval until a stable baseline was established. The agonist ADP ( 20 micromole/l ) was so added to the sample and collection was monitored for 6 proceedingss. The collection consequences expressed as ohms ( & A ; acirc ; „¦ ) over the period was noted as pre-drug baseline reading. Graphic printout of each reading was obtained. Out of 118 patients who were enrolled in this survey, 105 patients completed the follow-up on twenty-four hours 7 while 12 were lost to followup and 1 withdrew her consent. Each patient was asked about conformity and 5 milliliter of blood was once more drained from each patient and the process repeated. To find the anti thrombocyte consequence of the survey drug, the concluding reading of thrombocyte collection ( in ohms ) was recorded.
Before originating the survey, it was approved by ethical commission of Lady Reading Hospital Peshawar. This survey was performed in conformity with ICH ( International Conference on Harmonisation ) and GCP ( Good Clinical Practices ) guidelines.
Data was analyzed utilizing SPSS version 11. Paired T trial was used to observe difference between the suppression of aggregability for both drugs.
Consequence: -A sum of 105 patients with ischemic bosom disease, 60 ( 57.1 % ) males and 45 ( 42.9 % ) females. Fifty five patients ( 52.4 % ) received drug A ( Pidogrel ) and 50 ( 47.6 % ) patients received drug B ( Plavix ) . Base line thrombocyte aggregability in both drug groups was non significantly different ( p=0.317 ) . Average decrease in thrombocyte collection by drug-A was 8.47+/- 0.45 ohms ( p & A ; lt ; 0.001 ) and average decrease in thrombocyte collection by drug-B was 8.62+/- 0.46 ( P & A ; lt ; 0.001 ) . The difference in thrombocyte aggregability at twenty-four hours 7 ( follow up ) between the two groups was non statistically important i.e. , was the same.
Like in the western states ischaemic bosom disease is besides on the rise in our state. 18, 19 The good effects of antiplatelet drug Clopidogrel in patients with ischaemic bosom disease have been investigated extensively, but bulk of landmark surveies were conducted in western population.20,21 Maximum benefits of clopidogrel can be achieved when it is used on a regular basis for a drawn-out period.14 Sing the socioeconomic position of bulk of our local population, good conformity can be achieved merely when low cost drugs are available. With the handiness of locally manufactured clopidogrel, it is indispensable to prove their effectivity. In this respect really limited work has been done so far. 22, 23
In old surveies local clopidogrel was compared with branded clopidogrel, but high lading dosage of 600mg was used. The follow-up reading in these surveies was taken at 24 hours or less than 24 hours continuance. With high lading dosage of clopidogrel, rapid oncoming of action can be achieved.24
In present survey, we used low dosage ( 75mg ) of clopidogrel taken daily and follow-up reading was taken at twenty-four hours 7, because low dosage clopidogrel has slow oncoming of action and ranges steady province suppression after 4-7 yearss. 25 Of the presently available trials to asses the suppression of thrombocyte collection, LTA ( Light Transmission Aggregometry ) is considered to be the gilded criterion, but its usage is chiefly limited to specialise laboratories.26
In our survey we used whole blood aggregometry to buttockss platelet collection suppression because it needs short clip, is reliable,27 and is FDA approved.28,29 WBA measures electrical electric resistance between two electrodes, immersed in whole blood, after add-on of a thrombocyte agonist utilizing a chronolog aggregometer.30,31
In our survey we compared the effects of two trade names of clopidogrel in suppressing thrombocyte collection in patients with suspected CAD in our local population. Both drugs were found to hold equal anti thrombocyte consequence. Our consequences correlate with the consequences of a old local survey, in which another trade name of clopidogrel was used.22 In both these surveies patients with suspected ishemic bosom disease were included. On other manus another local survey concluded that different trade names of clopidogrel were non every bit effective.23 Unlike our survey, in that survey, patients with documented CAD, admitted either for ACS or undergoing PCI, were included. The dissension in harmony between our consequences and the consequences of this survey may be due to the different populations selected. It is possible that there patients were holding a different haemostatic/coagulation profile and might hold a higher thrombocyte aggregability which could non be inhibited by barricading the ADP receptor with Clopidogrel.
Our survey has certain restrictions. It was a individual Centre survey. Persons selected for survey were holding suspected ischaemic bosom disease, which can non truly stand for the patients in which guidelines recommend usage of clopidogrel i.e. patients with ACS and station PCI. Alternatively of clinical events, thrombocyte collection was taken as the foster terminal point. As drugs were non taken straight in forepart of physician, conformity may be another prejudice in the survey.
Clopidogrel is an of import drug used in the life endangering state of affairss. Studies done so far in local apparatus include different populations, different doses and different trade names of clopidogrel.
A big multicentre two-base hit blinded test further demands to be conducted in Pakistan ; at the same time comparing efficaciousness of all normally used local Clopidogrel in the same population.
In the given fortunes our findings suggest that the locally manufactured clopidogrel is every bit effectual as that manufactured by transnational pharmaceutical abroad giving the added advantage of cost effectivity.