The drug-eluting stents have now been observed to be superior to
bare-metal stents (BMS) in preventing recurrence of arterial stenosis.
The basic structure
consists of a metal stent covered with a polymer-coating with drug reinforced
on this coating. The drug, which is an anti-restenotic drug, is slowly released
from this stent.
There exist different drug-eluting stents which have been approved by
the U.S. FDA. While the basic mechanism of action of each of the stents remains
the same, they vary slightly in terms of deliverability, safety and efficiency.
Amongst the first-generation
are the sirolimus-eluting
and the paclitaxel-eluting
First-Generation Stents Sirolimus
is an antibiotic and anti-proliferative drug which
is released over a period of four-six weeks from the sirolimus-eluting stent.
The sirolimus drug releasing stents have been tested in various trials for
their efficacy and comparisons have been made with BMSs. It was noted in these
trials that there is a notable reduction in the cases of restenosis,
revascularization of the target lesion as well as in cases of late-lumen loss
with the use of SES. However, there was no significant difference in the rate
of reduction of the number of cases of heart attacks or deaths in these trials.
The TAXUS-II and TAXUS-IV trials have tested the efficacy of paclitaxel-eluting stents
anti-neoplastic agent commonly used in cancer chemotherapy. It inhibits the
process of mitosis or cell-proliferation and hence is used in prevention of
restenosis of the artery lumen. Its comparison with BMS in these trials found a
greater reduction in cases of restenosis and revascularization of target lesion
A comparison between SES and PES has proved that SES is slightly
superior to PES in the overall prevention of restenosis.
A disadvantage of most stents is that insertion of metal at any sites
invokes an inflammatory response. This disadvantage has led to research of
better or more bio-compatible or bio-degradable stents than the metal ones.
The second-generation stents are superior to first-generation stents in
terms of the cobalt-chromium alloy used in them. The use of this alloy allows
easier deliverability and better biocompatibility. These stents are also
thinner and more flexible than the first-generation ones.
Second-generation stents include the EES (everolimus-eluting stents)
and the zotarolimus-eluting stents (ZES).
Both everolimus and zotarolimus
are derivatives of sirolimus.
The EES have been found to stand superior and are more efficient to BMS
as supported in the SPIRIT I trial. Their efficiency over PES was also proven
in the subsequent SPIRIT-II to SPIRIT-IV trials.
Everolimus is an
derived from sirolimus. The EES release everolimus up to eighty-percent in the
first month of placement of the stent. The remaining 20% is released in next
The ZES releases
ninety percent of the drug in the first two weeks of placement. Though proven
to be superior to BMS in a few trials, the
agent is considered non-superior to PES and SES
as seen in trials like
ENDEAVOUR-III, ENDEAOUR-IV and SORT OUT-III trials.
Based on the recently and previously held trials, all these stents have
similar and comparable efficacy in their ability to prevent restenosis and
prevention of complications.
Stents and Anti-platelet Therapy
The FDA advises
of Dual-antiplatelet therapy (DAPT)
for 12 months in all cases receiving drug-eluting stents. The importance of
this is stressed and the repercussions of premature discontinuation should be
explained to both the clinicians as well as recipients of the stents.
Rethrombosis and restenosis of the coronary arteries are both common
sequels to stent placement. Coronary rethrombosis refers to clot formation in
the coronary vessels. Coronary restenosis refers to the reocclusion of the
coronary artery by the proliferation of the inner layer of the artery.
Though introduction of drug-eluting stents reduces the rise of
restenosis, it increases the risk of rethrombosis in most cases. This can lead
to serious events including heart attack and even death. Thus, an early
discontinuation of anti-platelet therapy in cases of DES can prove dangerous.
The updated guidelines (2011)
from the American College of Clinical Cardiology Foundation/American Heart
Association/Society for Cardiovascular Angiography and Intervention
(ACCF/AHA/SCAI) emphasize that DES and BMS may not be performed in patients who
seem to less likely follow the DAPT for the prescribed duration of time.
The updated guidelines emphasize on the use of 81 mg to 325 mg aspirin
prior to PCI. And those who have not received aspirin should be given 325 mg
aspirin. In addition, a second-antiplatelet agent is recommendedlike
clopidogrel, prasugel or ticagrelor.
Following PCI, indefinite use of aspirin 81mg has been recommended. The
second drug used may be clopidogrel, ticagrelor or prasugrel.
Prasugrel however is not recommended in patients above 75 years of age
and those with a history of stroke or transient ischemic attack. It could also
result in bleeding in those with a body weight less than 60kg, or on drugs that
increase the risk of bleeding such as warfarin, heparin and NSAIDS.
Use of proton-pump inhibitors in cases at a higher risk for digestive
tract bleed has also been recommended.
Drug-Eluting Stents; Manouchkathe et
al; US Pharmacist 2012.