Restenosis is the recurrence of stenosis, a narrowing of a blood
vessel, leading to restricted blood flow.
Restenosis usually pertains
to an artery or other large blood vessel that has become narrowed,
received treatment to clear the blockage and subsequently become
renarrowed. This is usually restenosis of an artery, or other blood
vessel, or possibly a vessel within an organ.
Restenosis is a common adverse event of endovascular procedures.
Procedures frequently used to treat the vascular damage from
atherosclerosis and related narrowing and renarrowing (restenosis) of
blood vessels include vascular surgery, cardiac surgery, and
The phenomenon of vessel restenosis, an immune response to damaged
tissue, is known to be a common adverse event and the Achilles heel of
angioplasty and stenting. Reducing restenosis is one of the highest
priorities in research and the development of new endovascular
Restenosis rates of drug-eluting stents appear to be
significantly lower than bare-metal stents, and research is underway
to determine if drug-eluting balloons also improve restenosis
When a stent is used and restenosis occurs, this is called in-stent
restenosis or ISR. If it occurs following balloon angioplasty, this
is called post-angioplasty restenosis or PARS. The diagnostic
threshold for restenosis in both ISR or PARS is ≥50% stenosis.
If restenosis occurs after a procedure, follow-up imaging is not the
only way to initially detect compromised blood flow. Symptoms may also
suggest or signal restenosis, but this should be confirmed by imaging.
For instance, a coronary stent patient who develops restenosis may
experience recurrent chest pain (angina) or suffer from a minor or
major heart attack (myocardial infarction), though they may not report
it. This is why it is important that a patient comply with follow-up
screenings and the clinician follows through with a thorough clinical
assessment. But it is also important to note that not all cases of
restenosis lead to clinical symptoms, nor are they asymptomatic.
1.1 Rates in cardiac procedures
1.2 Rates in peripheral procedures
2.2 As "late loss"
2.3 Percent diameter restenosis
2.4 Binary restenosis
7 See also
9 External links
Rates of restenosis differ between devices (e.g., stent-grafts,
balloon angioplasty, etc.) and location of procedure (i.e., centrally
located in the heart, such as the coronary artery, or in peripheral
vessels such as the popliteal artery in the leg, the pudendal artery
in the pelvis, or the carotid artery in the neck).
Rates in cardiac procedures
In cardiac procedures, balloon angioplasty has been associated with a
high incidence of restenosis, with rates ranging from 25% to 50%, and
the majority of these patients need further angioplasty within 6
A 2010 study in India comparing coronary drug-eluting stents (DES)
with coronary bare-metal stents (BMS) reported that restenosis
developed in 23.1% of DES patients vs 48.8% in BMS patients, and
female sex was found to be a statistically significant risk factor for
Rates in peripheral procedures
In peripheral procedures, rates are still high. A 2003 study of
selective and systematic stenting for limb-threatening ischemia
reported restenosis rates at 1 year follow-up in 32.3% of selective
stenting patients and 34.7% of systematic stenting patients.
The 2006 SIROCCO trial compared the sirolimus drug-eluting stent with
a bare nitinol stent for atherosclerotic lesions of the superficial
femoral artery, reporting restenosis at 2 year follow-up was 22.9% and
A 2009 study compared bare nitinol stents with percutaneous
transluminal angioplasty (PTA) in superficial femoral artery disease.
At 1 year follow-up, restenosis was reported in 34.4% of stented
patients versus 61.1% of PTA patients.
Vessel restenosis is typically detected by angiography, but can also
be detected by duplex ultrasound and other imaging techniques.
As "late loss"
Conceptual schematic illustrating effectiveness of endovascular
interventions on lumen diameter to improve blood flow as represented
by acute gain, late loss (restenosis), and net gain.
Late loss is synonymous with restenosis, and literally means loss of
the lumen after a procedure intended to open the vessel. It measures
either the percent (relative) or absolute change in minimum luminal
diameter (MLD) over the months following a vascular procedure, such as
the implantation of a stent-graft. Late loss is one metric that is
useful in determining the effectiveness of vascular interventions in
clinical trials for either an individual patient or a group of
But late loss is only part of the terminology in describing the
outcomes of vascular interventions. For instance, the implantation of
a stent-graft will first provide an acute gain in lumen diameter. In
other words, there is an immediate gain in lumen size because the
implanted stent opens up the vessel. However, over time, the body's
inflammatory immune response (described below in the "Causes" section)
reacts to the stent-graft via smooth muscle proliferation, etc., which
literally pushes the stent-graft back, narrowing the vessel and losing
at least a percentage of what was previously gained, or late loss.
The net gain of lumen diameter is the difference between acute gain
and late loss, and is a measure of stent-graft effectiveness.
Percent diameter restenosis
Percent diameter restenosis (or just percent diameter stenosis) is a
measure observed in individual patients and is typically calculated as
the difference between the minimal (or minimum) luminal diameter (MLD)
from the target reference vessel diameter (RVD), divided by the RVD,
and multiplied by 100 to get the percentage of stenosis. It is an
important measure needed to calculate binary restenosis (see Binary
Restenosis section below). The RVD is typically calculated by
averaging the MLD of the healthy part of the vessel both proximal and
distal to the vessel lesion.
There is some controversy of the accuracy of observing the lesion MLD
itself, since many atherosclerotic lesions may create uneven "hills
and valleys" within the lumen, making a true MLD difficult to obtain
or estimate. Some research indicates calculating "area stenosis" is
also a valid measure of actual vessel stenosis compared to diameter
stenosis alone, but this requires additional analysis because a
tracing of the lumen border must be performed. However, there are
computer programs available to automatically perform this function. It
may be helpful to obtain both percent diameter and area percent
stenosis, especially since the two percentages may not always
correlate with each other.
An occlusion, or the blocking of all blood flow through a vessel, is
considered 100% percent diameter stenosis.
Binary restenosis is traditionally defined as a reduction in the
percent diameter stenosis of 50% or more (≥50%). It is also known as
just "binary stenosis". The term "binary" means that patients are
placed in 2 groups, those who have ≥50% stenosis and those who have
<50% stenosis. Binary restenosis is an epidemiological method of
analyzing percent diameter stenosis for observing not only an
individual patient, but also performing statistical techniques on
group of patients to determine averages (descriptive measures of
central tendency) or as a predictive variable.
Surgery to widen or unblock a blood vessel usually has a long-lasting
beneficial effect for the patient. However, in some cases, the
procedure itself can cause further narrowing of the vessel, or
restenosis. Angioplasty, also called percutaneous transluminal
coronary angioplasty (PTCA), is commonly used to treat blockages of
the coronary or peripheral arteries (such as in the limbs). The
balloon inserted into the narrowing ‘smashes’ the cholesterol
plaques (atherosclerosis) against the artery walls, thus widening the
size of the lumen and increasing blood flow. However the action
damages the artery walls, and they respond by using physiological
mechanisms to repair the damage. (See physiology below.) 
A stent is a mesh, tube-like structure often used in conjunction with
angioplasty to permanently hold open an artery, allowing for
unrestricted blood flow, or to support a weakness in the artery wall
called an aneurysm. The artery can react to the stent, perceive it as
a foreign body, and respond by mounting an immune system response
which leads to further narrowing near or inside the stent.
Damage to the blood vessel wall by angioplasty triggers physiological
response that can be divided into two stages. The first stage that
occurs immediately after tissue trauma, is thrombosis. A blood clot
forms at the site of damage and further hinders blood flow. This is
accompanied by an inflammatory immune response.
The second stage tends to occur 3–6 months after surgery and is the
result of proliferation of cells in the media, a smooth muscle wall in
the vessel. This is also known as
Neointimal Hyperplasia (NIHA).
In the first stage of restenosis, administering anti-platelet drugs
(called IIb/IIIa inhibitors) immediately after surgery greatly reduces
the chance of a thrombosis occurring.
Drug-eluting stents are now being trialled in Europe, Canada and the
USA, as well as in Asia-Pacific. These stents are coated with
pharmaceuticals that inhibit tissue growth and thus reduce the risk of
restenosis from scar-tissue and cell proliferation.  There has been
some success with these new stents in reducing the occurrence of
restenosis, with clinical studies showing an incidence rate of 5% or
If restenosis occurs without a stent, it is usually treated with more
angioplasty. Once restenosis has occurred and been
treated by angioplasty, the chances of restenosis occurring again are
increased by a factor of 2. This treatment is also
used if restenosis occurs at either the proximal or distal end of the
If restenosis occurs within a stent (also known as in-stent stenosis),
it may be treated with repeated angioplasty and insertion of another
stent inside the original, sometimes with a drug-eluting
Over the past 5 years, ISR is preferentially treated with a drug
eluting balloon, which is a balloon coated with the same anticancer
drugs that prevent restenosis. The Balloon avoids the need for a
double layer of metal which is used when an in-stent restenosis is
treated with another stent within the original stent
Alternative treatments include brachytherapy, or intracoronary
radiation. The radiation kills cells and inhibits tissue growth
(similar to a patient undergoing cancer therapy).
Images of restenosis with bare-metal stents and drug-eluting stents
are here .
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British Heart Foundation-
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Treatment Of In-