1. Coronary artery disease is caused by a buildup of plaque in the coronary arteries known as atherosclerosis. This plaque can rupture, causing a blood clot (thrombus) known as atherothrombosis. 2. Atherothrombosis can lead to acute coronary syndromes including unstable angina, NSTEMI, or STEMI depending on the severity of the blockage. 3. Platelets play a key role in atherothrombosis by adhering to plaque and activating the clotting cascade, forming a thrombus. This thrombus can partially or completely block blood flow, causing symptoms ranging from chest pain to heart attack.

1. CORONARY ARTERY DISEASE
What is coronary artery disease?
Coronary artery disease is an atherosclerotic disease of coronary artery (ies).
Atherosclerosis is a hardening & narrowing of lumen of coronary artery. This is usually
caused by the buildup of plaque (deposits of cholesterol, smooth muscle cells, fibrous
cap etc.), a process called atherosclerosis. The plaque may burst, tear or rupture,
leading to formation of a blood clot. This process is called atherothrombosis.
CAD: alternative names
 CHD: Coronary heart disease
 IHD : Ischemic heart disease
 Atherosclerotic Heart Disease
 Atherosclerotic cardiovascular disease
How is CAD manifested?
CAD is manifested as one of the following clinical entities:
o Chronic stable angina
o Acute coronary syndrome
o Sudden cardiac death
What are the symptoms of CAD?
 Chest discomfort:
o Most heart attacks involve discomfort in the center of the chest that lasts
more than a few minutes, or that goes away and comes back.
o It can feel like uncomfortable pressure, squeezing, fullness or pain.
 Discomfort in other areas of the upper body:
o Symptoms can include pain or discomfort in one or both arms, the back,
neck, jaw or stomach.
 Shortness of breath:
 With or without chest discomfort.
 Other signs may include:
 Breaking out in a cold sweat, nausea or lightheadedness
Chronic stable angina
 Angina is chest pain resulting from myocardial ischemia.

2.  It results because of imbalance between myocardial oxygen supply and oxygen
demand.
 The underlying pathophysiology is coronary atherosclerosis.
 The chest discomfort lasts for few minutes. It is relived by taking rest or nitrates.
Acute coronary syndrome (ACS):
ACS is one of the clinical conditions categorized under coronary artery disease. Patient
with ACS may have one of the following presentations:
 Unstable angina
 NSTEMI (Non-ST segment Elevation Myocardial infarction)
 STEMI (ST segment Elevation Myocardial Infarction)
How does atherosclerosis occur?
 Age
 Hypercholesterolemia,
 Smoking,
 Hypertension,
 Diabetes, and
 Other coronary risk factors
 Initiate damage to endothelial cells & endothelial cells undergo dysfunction and
initiate the atherosclerotic process.
Plaque Formation:
 Intima: Intimal layer of coronary artery contains few resident smooth muscle cells
(SMCs) & a layer of extracellular matrix
 Media: In medial layer, SMCs embedded in an elastin-rich extracellular matrix.
 Note: There are three layers of coronary artery: 1. Tunica intima- it is the innermost
layer, 2. Tunica media-middle layer, and 3. Tunica externa- outermost layer
 Expression of adhesion molecules for leucocytes & chemoattractants occurs in
response to endothelial damage.

3.  Leaking of LDL-C occurs through endothelium into intimal layer after endothelial
damage.
 Macrophages bind to endothelial adhesion molecules and infiltrate the endothelial
cell.
 Macrophages imbibe ox-LDL through scavenger receptors to form foam cells. This
process is known as Phagocytosis.
 Migration of SMCs occurs from medial layer into intimal layer.
 SMCs secrete collagen & elastin
Maturation of Plaque
 SMCs surround the foam cell
 Fibrous cap containing collagen & elastin is formed on SMCs.
 So, the mature plaque contains the fibrous cap, SMCs & lipid core containing many
macrophages, dead cells and lipids.

4. Plaque formation: Summary
What is the fate of atherosclerotic plaque?
 The atherosclerotic plaque may become stable or unstable depending upon various
factors.
 Unstable plaque gets ruptured and lead to thrombus (clot) formation, a process
called as atherothrombosis.
What are the differences between stable & unstable plaque?
No. Stable plaque Unstable plaque
1 Thick fibrous cap Thin fibrous cap
2
More smooth muscle
cells
Less smooth muscle cells
3 Less lipid content More lipid content
1.
•When the endothelium is dysfunctional, monocytes and leucocytes bind to
endothelial adhesion molecules and can infiltrate the endothelial cell
2. •Low density –lipoprotein (LDL) molecules are able to penetrate the vessel wall.
3.
•The macrophages (monocytes in tissues) digest the LDL, becoming foam cells,
which thereby create a lipid-filled atherosclerotic plaque - A central lipid Core
4.
•Foam cell is surrounded by SMCs migrated from medial layer into intimal layer -
Middle SMCs Layer
5.
•A collagen & elastin fibers are release from nearby fibroblasts by growth factors
stimulation - Thus, a Outer fibrous cap is formed on SMCs.
6. •Thus , a mature plaque is formed.
Atherothrombosis: Thrombus
Superimposed on Atherosclerotic
Plaque
Adapted with permission from Falk E, et al. Circulation. 1998;92:657-671. Slide reproduced with permission
from Cannon CP. Atherothrombosis slide compendium. Available at: www.theheart.org.

5. ATHEROTHROMBOSIS:
Atherothrombosis is process, wherein a thrombus (blood clot) is formed on a ruptured
atherosclerotic plaque.
 Multiple factors contribute to plaque rupture, including
o Endothelial dysfunction,
o Plaque lipid content,
o Local inflammation causing breakdown of the shoulder of the plaque,
o Coronary vasoconstriction,
o Local shear stress forces,
o Platelet activation, and
o Status of the coagulation system
- All of this culminates in the formation of a platelet rich thrombus on the
disrupted plaques.
 Types of Plaque Ruptures :
o Through & through rupture of plaque’s fibrous cap
o Superficial erosion of the endothelial cell
 Thrombosis comprises two dynamically interrelated stages:
o Primary hemostasis - initiated by platelets as they adhere to damaged
vessels and forms a platelet plug.
o Secondary hemostasis - involves activation of coagulation system.
 Activated platelets can provide a surface for coagulation enzymes, & the ultimate
enzyme of coagulation, thrombin, is a potent platelet activator.
How are platelets involved in atherothrombosis?

6. Platelet adhesion, activation and aggregation with resultant arterial thrombus formation,
are pivotal in the pathophysiology of acute coronary syndrome.
Platelet pathophysiology
 Platelet adhesion:
o Normally platelets are moving freely in blood stream.
o Once, the plaque gets ruptured, platelet adhesion (sticking together) starts.
o vWF (von Willebrand factor), released from sub-endothelium is responsible to
initiate platelet adhesion.
 Platelet activation:
o Platelet adhesion is followed by platelet activation.
o Substances like ADP, thromboxane A2 etc. are released from the activated
platelets.
 Platelet aggregation:
o Platelet aggregation is followed by formation of platelet plug. The final pathway in
platelet aggregation is mediated through the glycoprotein (GpIIb/IIIa) receptor
pathway.
How clotting system is involved in atherothrombosis?
o Under physiological conditions, clotting factors are in inactivated state.
o Simultaneously with formation of the platelet plug, the plasma clotting system is
activated. The extrinsic system is activated by the release of tissue factor.
o Tissue factor activates VII factor and forms a TF:VIIa complex
o Ultimately, factor X is activated and leads to formation of thrombin by activating
prothrombin (II a).Thrombin in turn cleaves fibrinogen to fibrin.
o Fibrin, which is formed from the activation of clotting system gets entangled in the
platelet plug and forms a mesh-like structure.

7. Thrombus formation
o Thus, a thrombus is formed as a result of platelet adhesion, activation & aggregation
on one side and activation of clotting system on other side.
How is ACS diagnosed?
ACS is diagnosed based on clinical features, ECG presentation & cardiac markers.
Unstable angina (UA):
o Rest angina or angina with minimal exertion usually lasting at least 20 min.
Fibrin
TF + VII TF:VIIa
VIIa
XIa
Aa
XI
IXa IX
VIII
VIIIa
X Xa
V Va
Thrombin (IIa)
Fibrinogen
Prothrombin (II)
Ca2
+

8. o New-onset severe angina usually defined as within the last month.
o Crescendo angina-defined as previously diagnosed angina that has become
distinctly more frequent, longer in duration, or more severe in nature.
It can result from
o Non-occlusive thrombus,
o Dynamic obstruction ( vasoconstriction ) or
o Increased myocardial oxygen demand in the face of fixed oxygen supply.
o The mortality ranges from 2% to 5.5% at 30 days and 4% to 15.5% at 1 year.
o Those with normal ECG have better prognosis while those with ST depression or
T wave inversion have worst prognosis.
Non ST segment Elevation Myocardial infarction:
o Clinical presentation is similar to unstable angina and prognosis is similar to STEMI.
o Typically, chest pain lasts up-to 1 hour because of transient occlusive thrombus.
o Myocardial necrosis (evidenced by cardiac markers in blood) without acute ST-
segment elevation or Q waves.
o ECG changes such as ST-segment depression, T-wave inversion, or both may be
present.
o Mortality ranges from 5.5% to 9.5% at 30 days and 11% to at 20 % at 1 year.
ST Segment Elevation Myocardial Infarction:
o In this type, chest discomfort lasts more than 1 hour.
o There is complete occlusion coronary artery with trans-mural thrombus.
o This is the most severe and life threatening condition.
o Myocardial necrosis with ECG changes showing ST-segment elevation that is not
quickly reversed by nitroglycerine or showing new left bundle branch block.
o Q waves may be present.
o The mortality ranges from:
o 4.5 % to 9.6% at 30 days and
o 6.7% to 25.6% at 1 yr depending upon the infarct size.

9. CAD Management: Medical
Anti-thrombotic drugs:
Anti-platelets:
o Examples: aspirin, clopidogrel, tirofiban etc.
o Antiplatelet drugs inhibit platelet aggregation by virtue of their actions at different
target sites.
o Aspirin inhibits Tx A2 ( thromboxane A2)
o Clopidogrel inhibits ADP ( adenosine diphosphate ) receptors
o Tirofiban inhibits GpIIb/IIIa receptors ( glycoprotein receptor)
Anti-coagulants:
o Examples: heparin, LMWHs (Low molecular weight heparin) etc.
o Anticoagulants work at clotting system by inhibiting activation of different clotting
factors.
o Like, LMWH inhibits activation of X (predominantly) and II factor.
Fibrinolytics:
o Examples: streptokinase, urokinase, alteplase etc.
o Fibrinolytic drugs breakdown thrombus and helps to dissolve thrombus.
o They are mainly effective maximum upto 12 hours from the onset of chest in acute
coronary syndrome patients.
Nitrates:
o Examples: nitroglycerine, isosorbide mononitrate & dinitrate
o Nitrates provide an exogenous source of vasodilator nitric oxide, thereby inducing
coronary vasodilatation even when endogenous production of nitric oxide is impaired
by coronary artery disease.

10. o Sublingual nitroglycerine is very well established in the initial therapy of angina of
effort.
o Isosorbide dinitrate may be given sublingually to abort an anginal attack and then
exerts antianginal effects for about 1 hour.
o Long acting nitrates like isosorbide dinitarate are frequently given for the prophylaxis
of angina.
o Nitrate tolerance, likewise, a potential problem can be prevented or minimized when
sustained -release preparations are given.
o Using sustained release preparations of mononitrate, the dosage range 30 to 240 mg
once daily was evaluated now extensively.
Antihypertensives
o Examples: beta blockers like metoprolol, ACE inhibitors like ramipril, angiotensin
receptor blockers like losartan etc.
o Hypertension has a consistent, linear and independent relationship with risk of CAD.
o The efficacy of antihypertensive drugs depend not only on controlling blood pressure
but also controlling co-existing risk factors, especially those for coronary artery
disease, which is the major cause of mortality in hypertensive patients.
o Antihypertensive drugs are useful in reducing mortality in patients with CAD.
Lipid lowering
o Hypercholesterolemia is one of the important risk factors for development as well as
recurrence of CAD.
o The currently available lipid lowering drugs can be divided into the statins, the bile
acid sequestrants, the fenofibrates, the cholesterol absorption inhibitors and nicotinic
acid.
o Of these, statins have proven benefits with a few side effects.
o The new class of drug i.e. cholesterol absorption inhibitors are also promising for
reducing LDL-Cholesterol.
o Lipid lowering drugs like statins, ezetimibe, and fenofibrate are used routinely in
management of CAD.
CAD Management: interventions/surgery
 Percutaneous coronary interventions
o Balloon angioplasty
o Stenting
 Surgical procedure: CABG (coronary artery bypass grafting)
Coronary angioplasty
 Coronary angioplasty also referred to as percutaneous coronary intervention
(PCI), is a procedure used to open clogged heart arteries.
 Angioplasty involves temporarily inserting and expanding a tiny balloon at the site
of blockage in coronary artery to help widen a narrowed artery.

11. Stenting
 Angioplasty is usually combined with implantation of a small metal coil called a
stent in the clogged artery to help prop it open and decrease the chance of it narrowing
again (re-stenosis)
 Types of stents: bare metal stents (BMS) & drug-eluting stents (DES)
CLAVIX
(Clopidogrel 75, 150, 300mg tab.)
PLATELET PATHOPHYSIOLOGY

12. Platelet adhesion: Normally platelets are moving freely in blood stream. Once, the
plaque gets ruptured, platelet adhesion (sticking together) starts. vWF (von Willebrand
factor ),released from sub-endothelium , is responsible to initiate platelet adhesion.
Platelet activation: Platelet adhesion is followed by platelet activation.Substances like
ADP, thromboxane A2 etc. are released from the activated platelets.
Platelet aggregation: Platelet aggregation is followed by formation of platelet plug. The
final pathway in platelet aggregation is mediated through the glycoprotein (Gp II b/IIIa )
receptor pathway.
Profile of Clopidogrel
Clopidogrel is an anti-platelet drug. It is an ADP receptor antagonist. It gets metabolized
to an active compound. The active metabolite irreversibly binds to the P2Y12 (ADP )
receptor on the surface of platelet.
Pharmacokinetics:
Absorption (oral): rapid, not affected by food or antacids
Metabolism: rapid and extensive hepatic metabolism

13. Half-life: 8 hours (but has an irreversible effect on platelets, with a lifespan of
approximately 7–10 days)
Excretion: 50% in urine and 46% in feces, after 5 days
Benefits
Clopidogrel is found to be very effective in a secondary prophylaxis of ischemic events
like myocardial infarction, stroke & peripheral arterial disease. Clopidogrel has been
shown to reduce rates of adverse cardiac events and mortality when given in a loading
dose before PCI and in a maintenance dose thereafter in ACS patients.
Clavix AS: Profile
Clavix AS 75: Each tablet contains Clopidogrel 75 mg +aspirin 75 mg
Clavix AS 150: Each tablet contains clopidogrel 75 + aspirin 150 mg
Aspirin in low doses (75-325 mg) works as an antiplatelet drug. Aspirin's actions are
mediated by irreversibly acetylating the enzyme cyclooxygenase (COX). COX has two
isoforms: COX-1 and COX-2. Aspirin selectively inhibits COX-1 over COX-2 by 166-fold.
The anti-thrombotic action of aspirin is mainly due to inhibition of platelet COX-1, which
prevents the synthesis of thromboxane A2. COX-2 remains essentially unaffected at
aspirin doses of less than or equal to 300 mg. Clopidogrel inhibits ADP receptor and
subsequently inhibits glycoprotein (Gp IIb/IIIa) receptors and thereby inhibits platelet
aggregation. Thus both drugs work synergistically on the targets of platelet aggregation.
Clopidogrel with aspirin reduces the risk of vascular diseases*. The combination is better
than aspirin monotherapy. Tolerability of the combination is as good as that of aspirin.
(*European Society of Cardiology on CHARISMA trial)
Indications: specialty wise
Cardiologist & Consultant Physician
1. Prevention of vascular events (ischemic complications) in patients with
Ischemic heart disease (IHD):
Patients with recent ischemic heart disease, recent stroke and peripheral arterial disease
are at increased risk of recurrence of vascular events like myocardial infarction, stroke
etc. Platelets play a central role in the patho-physiology of arterial thrombosis. Anti-
platelets are indicated in the secondary prevention of vascular events.
 CAPRIE Trial (Lancet 1991;337:459-460)
Patients (n=19185) of atherosclerotic vascular disease divided in to two groups:
Clopidogrel 75mg & Aspirin 325mg OD. Results showed an 8.7% reduction in the
composite endpoint of ischemic stroke, myocardial infarction, or vascular death with
clopidogrel.
 CURE ( New England Journal of Medicine Aug 16,2001)
(The Clopidogrel Unstable angina to prevent Recurrent Events) trial

14. Patients (n=12562) with NTEMI ACS randomized to receive either a bolus dose of
Clopidogrel 300 mg followed by 75 mg/day for 3-12 months + Aspirin 75-325 mg
compared with Aspirin 75-325mg alone. Result showed that composite end point of CVS
death, myocardial infarction or stroke were significantly reduced (20% over an average
9-month follow-up period) in the clopidogrel group as compared to the other group.
2. Prevention of vascular events (ischemic complications) in patients with
ACS (Medically managed)
The final event leading to acute coronary syndromes (ACS) is spontaneous
atherosclerotic plaque rupture. This event is analogous to the plaque rupture caused by
percutaneous coronary intervention (PCI). Both events initiate a platelet response that
starts with the adhesion of platelets to the vessel wall, followed by the activation and
then aggregation of platelets. Clopidogrel reduces risk of vascular events in ACS
patients.
Rationale of loading dose of clopidogrel: Optimal platelet inhibition is a key
therapeutic goal for patients undergoing percutaneous coronary intervention. Initiating
therapy with clopidogrel 75 mg daily induces inhibition of ADP-induced platelet
aggregation as early as 2 h after the first dose, but requires 3–7 days to achieve
maximal inhibition of platelet aggregation. Adding a 300 mg loading dose to clopidogrel
shortens the time to maximal platelet inhibition significantly. Recent data suggest that
further increasing the loading dose to 600 mg provides an even shorter time to maximal
platelet inhibition.
3. Prevention of vascular events in patients with ACS undergoing PCI
The PCI-CURE study (Lancet 2001; 358:527-533)
In the PCI-CURE trial of 2658 patients, pretreatment with clopidogrel for a median of 10
days prior to PCI reduced the combined 30-day incidence of death, non-fatal myocardial
infarction, and urgent target vessel revascularization by 30%.
CREDO Trial (JAMA 2002; 288: 2411-2420)
Long term benefit of clopidogrel plus aspirin after PCI was shown in the CREDO trial. At
one year, the composite end point of death, myocardial infarction or stroke was reduced
by 27% in the clopidogrel
Efficacy of Clopidogrel Reloading in Patients With Acute Coronary
Syndrome Undergoing Percutaneous Coronary Intervention During
Chronic Clopidogrel Therapy (ARMYDA-8 RELOAD-ACS Trial) [Am J Cardiol 2013;
112:162-8].

15. Key secondary endpoints:
 Non significant risk of major or minor bleeding.
 Greater platelet inhibition with Clopidogrel reload arm than the placebo arm at
PCI and at both post-PCI determinations.
Conclusion:
 An additional 600 mg clopidogrel load given 6 hours before PCI is associated
with a lower incidence of MACE (around 70 % reduction) at 1 month in patients
receiving chronic clopidogrel therapy admitted for ACS without risk of bleeding
complications.
CURRENT/OASIS 7: (NEJM 2010; 363:930-942)

16. Clopidogrel Optimal Loading Dose Usage to Reduce Recurrent EveNTs/Optimal
Antiplatelet Strategy for InterventionS
Primary outcome measures was first occurrence of cardiovascular death, myocardial
infarction and stroke (Time Frame: 30 days) & Secondary Outcome Measures was major
bleeding (Time Frame: 30 days)
Study results showed that doubling the loading and maintenance doses of clopidogrel in
ACS patients undergoing planned PCI significantly reduces stent thrombosis and
cardiovascular events, largely driven by reductions in MI, without a significant increase in
major bleeding.
Double maintenance dose study: (European Heart Journal 2007 28(15):1814-1819)
Objective was to test whether an increase in the clopidogrel maintenance dose results in
increased inhibition of platelet aggregation. Pre-treatment with 600 mg of clopidogrel and
within 12 h after successful PCI.
A double-blind, randomized study on platelet aggregation in patients (n=60) treated with
a daily dose of 150 or 75 mg of clopidogrel for 30 days. Platelet function was evaluated
30 days after the intervention with optical aggregometry and a new point-of-care test
(VerifyNowTM P2Y12 assay).
Maximal 5 µM ADP-induced platelet aggregation 30 days after PCI in Group treated with
150 mg/day showed 45.1 ± 20.9% & Group treated with 75 mg/day showed
65.3±12.1%;P < 0.001. The VerifyNowTM P2Y12 assay also indicated a higher degree
of platelet function inhibition in the group treated with 150 mg/day (60.0 ± 72.0 P2Y12
Reaction Units) than in the group treated with 75 mg/day (117.0± 64.3 P2Y12 Reaction
Units; P = 0.004.
Administration of a 150 mg oral maintenance dose of clopidogrel results in more intense
inhibition of platelet aggregation than administration of the currently recommended 75
mg maintenance dose.
Diabetologist: Secondary prevention of vascular events in diabetes patients
Risk of vascular events in diabetic patients:
Type 2 diabetic patients are at higher risk of cardiovascular events than non-diabetics.
80% of patients with diabetes die due a thrombotic death*. 75% of these deaths are due
to cardiovascular complications, and the rest is due to cerebro-vascular events and
peripheral vascular complications*.
(* J Diabetes Complications. 2001 Jan-Feb;15(1):44-54)
Rationale of clopidogrel

17.  Patients with type 2 diabetes mellitus (T2DM) are characterized by enhanced
platelet reactivity and reduced in vitro responsiveness to anti-platelet agents. The P2Y12
receptor plays a pivotal role in platelet aggregation. This role is emphasized by the
results of clinical trials that demonstrate improvement of long-term clinical outcomes in
patients treated with clopidogrel.
OPTIMUS study: (Circulation. 2007; 115:708-716.)
Randomized Comparison of a High Clopidogrel Maintenance Dose in Patients
With Diabetes Mellitus and Coronary Artery Disease.
Figure: Flow diagram of the study
Maximal adenosine diphosphate–induced (20 mol/L) platelet aggregation was
significantly reduced in the 150-mg group compared with the 75-mg group. All other
platelet function parameters showed enhanced clopidogrel-induced antiplatelet effects
with 150 mg, which returned to baseline values after resumption of standard dosing. A
150-mg maintenance dose of clopidogrel is associated with enhanced antiplatelet effects
compared with 75 mg in high-risk T2DM patients.
Nephrologist: Secondary prevention of vascular events in CKD patients.
 Percutaneous Coronary Intervention High Clopidogrel Dose in Patients With
Chronic Kidney Disease Having Clopidogrel Resistance (CR) After PCI.
Key Results:
 Patients in the 150 mg group had 65 % lower rates MACE.
 There was no significant difference in major or minor bleeding.
 Patients in the 150 mg group had greater inhibition of platelet aggregation.

18. Cumulative Stent thrombosis-free survival was better in the 150 mg/d group than in the
75 mg/d group (P < 0.028).
 Conclusion: One-month administration of 150 mg/d of clopidogrel decreases the rate of
ST and MACE without increasing bleeding in patients with CKD after PCI.
Neurologist: Secondary prevention of stroke or TIA
 Clopidogrel Plus Aspirin Prevents Early Neurologic Deterioration and Improves 6-
Month Outcome in Patients With Acute Large Artery Atherosclerosis Stroke.
 Clin Appl Thromb Hemost. 2014 Sep 23.
 Randomized active control study
 Sample Size: 574
 Study Participants : large artery atherosclerosis (LAA) stroke patients
 Groups :
o Clopidogrel plus aspirin (dual therapy; n = 286) or
o Aspirin alone (monotherapy; n = 288).
 Follow up : 6 months
 Outcomes :
o Primary : Early neurological deterioration (END)
o Secondary : Recurrent ischemic stroke (RIS)
 Results :
o The prevalence of END and RIS was lower in patients on dual therapy than in
those on monotherapy during the 30 days.
o At 6 months, dual therapy improved outcomes among older patients and those
with symptomatic stenosis in the posterior circulation and basilar artery.
 Conclusion :
o Clopidogrel plus aspirin is superior to aspirin alone for reducing END and RIS
within 30 days and improves outcomes in certain subgroups at 6 months.
10 Must Know Points
1. Clopidogrel selectively and irreversibly inhibits ADP-induced platelet aggregation.
2. Absorption of clopidogrel is rapid, not affected by food or antacids.

19. 3. Clopidogrel is indicated for secondary prevention in patients with recent myocardial
infarction, recent stroke and established peripheral arterial disease.
4. It is also indicated for ACS patients and those patients who are undergoing
percutaneous coronary intervention.
5. Loading dose of clopidogrel leads to rapid & higher level of platelet inhibition in ACS
patients & patients undergoing PCI.
6. Higher maintenance dose (150 mg/day) is found to be more effective in high risk
patients like diabetes.
7. Clopidogrel 600-mg double bolus achieves greater platelet inhibition than
conventional single loading doses, according the PREPARE study.
8. In low clopidogrel responders, increasing maintenance dose to 150 mg/day reduces
platelet reactivity.
9. Extensive clinical trial database is available on clopidogrel.
10. It is well tolerated.