Drug-eluting Stents Flashcards
What is coronary heart disease?
How common is CHD?
What are the other names for CHD?
Heart’s blood supply is blocked or interrupted by a build-up of plaque (fatty deposits (cholesterol), white blood cells, calcium, and other substances) in the coronary arteries.
UK’s biggest killer (82K deaths/year)
Also called coronary artery disease + atherosclerotic heart disease
How do we treat CHD?
2 treatment approaches
Coronary artery bypass graft (CABG)
- In the operation, your surgeon uses a blood vessel from your leg, arm or chest to divert blood around narrowed or clogged parts of the major arteries, to improve blood flow and oxygen supply to the heart
Angioplasty
- Balloon procedure to open an obstruction or narrowing of a blood vessel. Also known as Percutaneous Transluminal Coronary Angioplasty (PTCA)
What is the main problem/risk of angioplasty?
Restenosis
Recurrence of stenosis (narrowing of blood vessel).
It is defined as a decrease in the luminal diameter by greater than 50% in the stented area of the vessel (post-angioplasty restenosis, PARS).
Describe the 2 main mechanisms of restenosis following angioplasty
Elastic recoil
Depends on the presence of elastin in the arterial wall. It is a passive process that occurs in seconds to minutes as a result of the elastic laminae applying opposing force to the overstretch caused by balloon inflation. This reduces the lumen by up to 40%
Neointimal and smooth muscle hyperplasia
Immune system’s reaction to the intrusion of angioplasty following the damage incurred on the endothelial barrier at the site of balloon inflation. Proliferation and migration of vascular smooth muscle cells primarily in the tunica intima, resulting in the thickening of arterial walls and decreased arterial lumen space.
What is a stent?
A stent is a small mesh tube that is used to treat narrow or weak arteries
Stents eliminated the concern for POBA’s elastic recoil effect.
What do we consider when designing a bare metal stent?
- Composition
- Stainless steel
- Cobalt chromium alloy
- Nickel chromium alloy
- Architectural design
- Delivery system (ie, the balloon catheter that delivers the stent)
What are the advantages + disadvantages of BMS?
+ No elastic recoil
- in-stent restenosis surfaced within 3-6 months after surgery due to excessive neointima stent coverage
Discuss the role of drug-eluting stent structural components
Minimise neointimal and smooth muscle hyperplasia
They work very well. Restenosis rate, mortality rate of procedure + emergency CABG rate is lower than in BMS + balloon angioplasty.
What are the advantages + disadvantages of DES?
+ Significantly reduce the risk of restenosis
- expensive
- the requirement for prolonged dual antiplatelet therapy after DES implantation.
What was the 1st generation drug-eluting stent?
Sirolimus-eluting stent (2003-2011)
- Sirolimus drug has potent antiproliferative and immunosuppressive effects and blocks the cell cycle mainly of the smooth-muscle cell from the G1 to S phase.
- Due to the polymer, 75% of the drug is released over the first 10 days. Nevertheless, the antirestenotic properties of the Cypher proved to persist for much longer.
Paclitaxel-eluting stent
- Paclitaxel drug stabilises microtubules and thereby inhibits cell division in the G0/G1 and G2/M phases
Definition of Stent Thrombosis
Rare condition (it occurs in less than one in 200 patients) that occurs when a blood clot forms on the surface of a stent, raising the risk of blood flow in an artery being reduced or cut off.
Complications can be serious - recurrent chest pain or heart attack.
Occurs with both bare metal and drug-eluting stent (for which late stent thrombosis is prevalent).
How do we treat stent thrombosis?
What is the duration of antiplatelet therapy?
Therapy include dual antiplatelet therapy
Aspirin + either clopidogrel (Plavix) or prasugrel (Effient) to prevent clots from forming.
Duration:
BMS: aspirin and Plavix or Effient for at least one month after procedure
DES: aspirin and Plavix or Effient for at least a year after procedure.
What was the aim of 2nd generation DES?
What are the ways to modify this?
Decrease in neointimal response and more rapid re-endothelialisation
- Thinner strut stent backbones,*
- Less inflammatory*
- More biocompatible polymers*
- Lower drug dosing*
e. g. Zotarolimus-eluting stent (2005-present)
What is biolinx polymer system made up of?
. The hydrophobic C10 polymer is based on hydrophobic butyl methacrylate to provide adequate hydrophobicity for zotarolimus
The hydrophilic C19 polymer is manufactured from a mixture of hydrophobic hexyl methacrylate, and hydrophilic vinyl pyrrolidi-none and vinyl acetate monomers, to provide enhanced biocompatibility
The hydrophilic polyvinyl pyrrolidinone increases the initial drug burst and enhances biocompat-ibility.
Discuss differences between 1st and 2nd generation DES
Clinical studies showed metal thinner strut platforms achieving less angiographic restenosis when compared to thick strut DES platforms
Thickness: 1st DES > 2<span>nd</span> DES
Stainless steel vs. Cobalt-Chromium
Discuss challenges of biodegradable stents
Name an example od biodegradeable DES
Made of polymers or metal alloys with or without a drug coating, that have the potential to scaffold the artery to allow natural healing to take place, and then biodegrade.
3 major hurdles
1) lack of radio-opacity, which necessitates radio-opaque stent markers;
2) reduced radial force as compared with stainless steel, necessitating thicker stent struts;
3) Reduced ability of the stents to be deformed.
When should BMS be considered?
