|
| The Drama of Drug-eluting Stent Thrombosis: Dr. Jekyll and Mr. Hyde |
| Wail Nammas |
| Assistant Professor of Cardiology, Ain Shams University, Egypt |
| *Corresponding author: |
Dr. Wail Nammas, MD
Cardiology Department
Ain Shams
University Hospitals
Faculty of Medicine
Ain Shams University
Abbassia, Cairo,
Egypt
Tel: +2 012 4063718
Fax: +2 02 24820416
E-mail: wnammas@hotmail.com |
|
| |
| Received July 22, 2011; Accepted August 10, 2011; Published August 12, 2011 |
| |
| Citation: Nammas W (2011) The Drama of Drug-eluting Stent Thrombosis: Dr.
Jekyll and Mr. Hyde. Translational Medic 1:102e. doi:10.4172/2161-1025.1000102e |
| |
| Copyright: © Nammas W. This is an open-access article distributed under the
terms of the Creative Commons Attribution License, which permits unrestricted
use, distribution, and reproduction in any medium, provided the original author and
source are credited. |
| |
| Long as the introduction of percutaneous coronary intervention
(PCI), restenosis has always been the stumbling stone of this innovative
therapeutic technology [1-3]. As such, the arrival of drug-eluting stents
(DES) in scene has offered what initially seemed to be the long-waited
solution to this troublesome sequel of everyday practice. Indeed, very
early following FDA approval of first-generation DES in 2003, these
devices have convincingly reshaped the landscape of interventional
cardiology that the Healthcare Systems took a bold initiative of assigning
impressively high reimbursements to account for their extraordinary
cost. It was a short halcyon period during which interventional
cardiologists were anxious of being deemed guilty if they did not offer
their patients the so-called 'smart' stent whenever technically feasible.
Then, with the fall of 2006, the winds began to shift with alarming
reports raising concerns about disturbingly higher rates of very late
(after one year) stent thrombosis associated with the use of DES as
compared with bare-metal stents (BMS). The media flashed the red
light particularly with some evidence suggesting that relative to other
acute coronary syndrome events, DES thrombosis was associated with
substantially higher mortality and morbidity. Albeit infrequent, almost
all cases developed a myocardial infarction, and one-tenth to one-third
of cases died [4]. Soon the FDA assigned an expert panel to review
evidence available from an array of sources, and in December 2006,
the panel expectedly announced that there was an evidence for a small
- though insignificant - increase in stent thrombosis events following
DES [5]. However, evidence was far from clear, and intuitively, further
evidence was still needed especially given the rare nature of the event
that made all the available reports statistically underpowered. |
| |
| Attempts to quantify such a rare-by-nature event would reasonably
require increasing the number of patients, and/or protracting the
length of follow-up. Hence, meta-analyses were called into action. One
of these, performed by Stone et al, pooled data from 9 randomized trials
(5261 patients) comparing DES versus BMS [6]. They demonstrated
the incidence of stent thrombosis to be almost identical between the
two stent types during the first year of follow-up (0.6%), nevertheless,
between 1 and 4 years, that incidence was much higher with DES (0.5%
versus 0.1%). Published in the same year 2007, Mauri et al provided a
meta-analysis of 8 of these same trials; this time adjudication of events
from patient-level data was based on the newly introduced Academic
Research Consortium classification of stent thrombosis [7]. Ultimately,
they concluded that the 4-year incidence of definite or probable stent
thrombosis was similar for sirolimus-eluting stents as compared with
BMS (1.5% versus 1.7% respectively) as well as for paclitaxel-eluting
stents versus BMS (1.8% versus 1.4% respectively). Interestingly, almost
one-half of these events occurred very late with DES in comparison with
around one-third such events following BMS. Yet, evidence of the
aforementioned meta-analyses stems from randomized controlled
trials performed under the heavy constraint of long lists of exclusion
criteria which might have not actually reflected real-life practice. In this
regard, registry data would work well. Daemen et al reported a largescale
real-world registry from two high-volume centers with an average
follow-up of 1.7 years [8]. In this, the cumulative rate of definite stent
thrombosis was 1.1% early following the procedure (within one
month), whereas thereafter, it occurred at a constant annual rate of
0.6% per year. |
| |
| On the other frontier, the key advantage of DES is significant
reduction of restenosis, translated clinically into major reduction of target vessel revascularization (TVR). Weighted evidence from
randomized trials demonstrated TVR rates to be cut-off by one-half
to two-thirds with DES as compared with BMS at 5 years follow-up,
amounting to roughly 10-15% need for TVR following DES at longterm
[6,9]. Whether one can accept the trade of extra non-fatal TVR
for a much smaller risk of stent thrombosis that could result in death
of myocardial infarction was the theme of a decision-analytic model by
Garg et al. [10] comparing DES with BMS in terms of quality-adjusted
life expectancy. Eventually, they concluded that the threshold excess
risk of very late stent thrombosis with DES versus BMS, above which
BMS would be the preferred strategy, is only 0.14% per year (over 4
years follow-up). However, two important parameters stand out as
chief determinants of the outcome of their model: the incidence of
TVR following BMS and the length of time over which DES continues
to pose an excess risk of stent thrombosis. Therefore, one should be
more ready to accept higher levels of risk of very late stent thrombosis
offended by DES in patients with a higher risk of restenosis and
subsequent TVR. Conversely, the longer we believe that the risk of
very late stent thrombosis will persist, the higher the impetus to favor
the use of BMS. It is noteworthy that this model did not consider
the possibility that extended use of dual anti-platelet therapy beyond
one year after PCI might help protect against the excess risk of stent
thrombosis associate with DES, albeit at the cost of extra major
bleeding events [11]. Obviously, this latter has 'pushed' the world's
foremost authorities of guidelines to extend the duration of dual antiplatelet
therapy following the implantation of first-generation DES up
to one year, and might ultimately 'push' the guidelines' committees to
recommend continuing the 'drug-dependant' state, indefinitely. Under
these circumstances, surgery needing discontinuation of this therapy
would pose an imminent risk of a 'hard endpoint'. Do patients then
comply with extended prescriptions of dual anti-platelet therapy?
A recently reported randomized study employing DES has shown
that the proportion of patients receiving dual anti-platelet therapy at
24-months follow-up was 59.4% and 63.9%, for everolimus eluting and
paclitaxel eluting stents, respectively [12]. |
| |
| At the end of the day, the patient, the ultimate 'client' of this
market, should be actively indulged in the decision-making process.
Do we honestly supply our patients with comprehensive and up-todate
information about our 'product', DES? Do all patients who receive
DES on elective basis have a clear background on the small but longlasting
risk of stent thrombosis, and probability of having a 'serious
event' as a result? Are they regularly made aware of the pros and cons
of what they will 'hold inside'? And what about the safety and efficacy
profile of new-generation DES already 'in duty'? Make no mistake, arguments of clinical equipoise between the available drug-devices will
remain, and undoubtedly, will continue to provide a potential venue
for future research. |
| |
|
| References |
| |
- Al Suwaidi J, Berger PB, Holmes DR Jr (2000) Coronary artery stents. JAMA
284: 1828-1836.
- Peterson ED, Cowper PA, DeLong ER, Zidar JP, Stack RS, et al. (1999) Acute
and long-term cost implications of coronary stenting. J Am Coll Cardiol 33:
1610-1618.
- Kastrati A, Hall D, Schömig A (2000) Long-term outcome after coronary
stenting. Curr Control Trials Cardiovasc Med 1: 48-54.
- Garg P, Mauri L (2007) The conundrum of late and very late stent thrombosis
following drug-eluting stent implantation. Curr Opin Cardiol 22: 565-571.
- Food and Drug Administration. Circulatory Systems Device Advisory Panel
transcript for December 8, 2006, meeting. 2007.
- Stone GW, Moses JW, Ellis SG, Schofer J, Dawkins KD, et al. (2007) Safety
and efficacy of sirolimus- and paclitaxel-eluting coronary stents. N Engl J Med
356: 998-1008.
- Mauri L, Hsieh WH, Massaro JM, Ho KK, D'Agostino R, et al. (2007) Stent
thrombosis in randomized clinical trials of drug-eluting stents. N Engl J Med
356: 1020-1029.
- Daemen J, Wenaweser P, Tsuchida K, Abrecht L, Vaina S, et al. (2007) Early
and late coronary stent thrombosis of sirolimus-eluting and paclitaxel-eluting
stents in routine clinical practice: data from a large two-institutional cohort
study. Lancet 369: 667-678.
- Morice MC, Serruys PW, Barragan P, Bode C, Van Es GA, et al. (2007) Longterm
clinical outcomes with sirolimus-eluting coronary stents: five-year results
of the RAVEL trial. J Am Coll Cardiol 50: 1299-304.
- Garg P, Cohen DJ, Gaziano T, Mauri L (2008) Balancing the risks of restenosis
and stent thrombosis in bare-metal versus drug-eluting stents: results of a
decision analytic model. J Am Coll Cardiol 51: 1844-1853.
- Eisenstein EL, Anstrom KJ, Kong DF, Shaw LK, Tuttle RH, et al. (2007)
Clopidogrel use and long-term clinical outcomes after drug-eluting stent
implantation. JAMA 297: 159-68.
- Stone GW, Midei M, Newman W, Sanz M, Hermiller JB, et al. (2009)
Randomized comparison of everolimus-eluting and paclitaxel-eluting stents:
two-year clinical follow-up from the Clinical Evaluation of the Xience V
Everolimus Eluting Coronary Stent System in the Treatment of Patients with
de novo Native Coronary Artery Lesions (SPIRIT) III trial. Circulation 119: 680-
686.
|
| |
| |
|
|
|
This article |
DOWNLOAD |
|
CONTRIBUTE |
|
SHARE |
|
EXPLORE |
|
 |
 |
| |
|
| |
| |
| |
|
Untitled Document
|
|
|
|
|
