Basics of Antiplatelets

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# Basics of Antiplatelets
## Cath Conference
### Anish Sanjay Shah, MD<br><span style="font-size: 70%;">Cardiology Fellow<br>University of Illinois at Chicago</span>
### November 16, 2021

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# Objectives

1. Pathophysiology of atherosclerotic lesions

1. Role of antiplatelet agents in coronary artery disease

1. Types of antiplatelet agents and their mechanism

1. Use cases for antiplatelet agents

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# Pathophysiology

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.footnote[
NEJM 2007
]

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background-image: url("atherosclerosis.jpg")
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.footnote[
Mackman et al 2018
]

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### Atherosclerosis

- Leads to narrowing of the arterial lumen, allowing for tissue ischemia to occur with increased metabolic demands (e.g. coronary ischemia with angina)

- Increases risk for plaque rupture or erosion `\(\rightarrow\)` intravascular thrombi

- Arterial thrombi are _white clots_ which are primarily platelets, stabilized by fibrin and tissue factor (that triggers coagulation cascade)

- Both platelet activation and coagulation cascade occur in parallel

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# Mechanisms

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.footnote[
Nature 2007
]

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.footnote[
Patrono et al 2017 (JACC)
]

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### Pharmacology

There are three general, non-redundant pathways for platelet activation.

1. `\(TXA_{2}\)` (thromboxane) pathway

1. `\(ADP\)` (adenosine diphosphate) pathway

1. Thrombin-activated pathways

All transduce __independent__ signals for platelet activation, and are thus __additive__.

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### Pathways

| Pathway | Description |
|:--- |:--- |
| Cyclooxygenase-1 inhibitors | `\(COX1\)` suppresses `\(TXA_{2}\)` |
| `\(P2Y_{12}\)` inhibitors | `\(ADP\)` receptor blockade |
| Protease-activated receptor inhibitors | `\(PAR1\)` and `\(PAR4\)` ligand blockade (normally activated by thrombin-catalyzed proteolysis) |

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### Agents

| Mechanism | Subtypes | Drugs |
| --- | --- | --- |
| `\(COX\)` inhibitors | type 1 | aspirin | 
| `\(COX\)` inhibitors | type 2 | NSAIDs | 
| `\(P_{2}Y_{12}\)` receptor blockers | irreversible | ticlopidine, clopidogrel, prasugrel |
| `\(P_{2}Y_{12}\)` receptor blockers | reversible | ticagrelor, cangrelor |
| `\(GPII_{a}III_{b}\)` inhibitors | monoclonal Ab | abciximab |
| `\(GPII_{a}III_{b}\)` inhibitors | synthetic | eptifibatide, tirofiban |
| `\(PDE\)` inhibitors | | dipyridamole, cilostazol | 
| `\(PAR\)` inhibitors | type 1 | vorapaxar |

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# Secondary Prevention

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### Secondary Prevention

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#### Stable Coronary Artery Disease

With no intervention:

- SAPT with low-dose aspirin
- SAPT with clopidogrel as an _alternative_

With PCI (DES):

- DAPT for 6 months

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#### Acute Coronary Syndrome

With PCI (DES):

- DAPT for 12 months (and then SAPT)
- Can decrease to 6 months based on bleeding risk

_However, data is increasing for reducing the duration of DAPT._

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Even with antiplatelet therapy, __2-5%__ of CAD/PAD patients have __MACE__.

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### Dual Antiplatelet Therapy

.footnote[
Patrono et al 2017 (JACC)
]

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# Thank You