Arq Bras CardiolArquivos Brasileiros de CardiologiaArq. Bras.
Cardiol.0066-782X1678-4170Sociedade Brasileira de CardiologiaZrg64n7XDtSnfqdfJ7RXssvS0066-782X201400210000200002S0066-782X201400504011010.5935/abc.20140110Original ArticlesEfficacy and Safety of Drug-Eluting Stents in the Real
World: 8-Year Follow-UpPellegriniDenise OliveiraGomesVitor OsórioLasevitchRicardoSmidtLuisAzeredoMarco AurélioLedurPriscilaBodaneseRodrigoSinnottLeonardoMoriguchiEmílioCaramoriPauloPUCHospital São LucasPorto AlegreRSBrazilHospital São Lucas PUC, Porto Alegre, RS,
BrazilMailing Address: Denise Machado de Oliveira Pellegrini, Avenida
Alegrete 423/1601, Petrópolis. Postal Code 90460-100, Porto Alegre, RS, Brazil.
Email: dennizmo@yahoo.com.br;
pellegrini.de@gmail.com
Potential Conflict of Interest
No potential conflict of interest relevant to this article was reported.
0108201409201410303174182211120130503201414032014This is an Open Access article distributed under the terms of the
Creative Commons Attribution Non-Commercial License which permits
unrestricted non-commercial use, distribution, and reproduction in any
medium, provided the original work is properly cited.Background:
Drug-eluting stents have been used in daily practice since 2002, with the
clear advantages of reducing the risk of target vessel revascularization and
an impressive reduction in restenosis rate by 50%-70%. However, the
occurrence of a late thrombosis can compromise long-term results,
particularly if the risks of this event were sustained. In this context, a
registry of clinical cases gains special value.
Objective:
To evaluate the efficacy and safety of drug-eluting stents in the real
world.
Methods:
We report on the clinical findings and 8-year follow-up parameters of all
patients that underwent percutaneous coronary intervention with a
drug-eluting stent from January 2002 to April 2007. Drug-eluting stents were
used in accordance with the clinical and interventional cardiologist
decision and availability of the stent.
Results:
A total of 611 patients were included, and clinical follow-up of up to 8
years was obtained for 96.2% of the patients. Total mortality was 8.7% and
nonfatal infarctions occurred in 4.3% of the cases. Target vessel
revascularization occurred in 12.4% of the cases, and target lesion
revascularization occurred in 8% of the cases. The rate of stent thrombosis
was 2.1%. There were no new episodes of stent thrombosis after the fifth
year of follow-up. Comparative subanalysis showed no outcome differences
between the different types of stents used, including Cypher®, Taxus®, and
Endeavor®.
Conclusion:
These findings indicate that drug-eluting stents remain safe and effective at
very long-term follow-up. Patients in the "real world" may benefit from
drug-eluting stenting with excellent, long-term results.
Drug-eluting stents (DES) have been used in clinical practice since 2002. Multicenter
clinical trials have clearly demonstrated the advantages of these stents in reducing
major cardiovascular outcomes, particularly target vessel revascularization (TVR),
compared with bare metal stents1. Randomized
clinical trials have not included DES, despite their increased use; thus, their
efficacy and safety in the real world has been questioned. Considerations regarding
DES safety have increased since 2006, when preliminary data indicated higher rates
of in-stent thrombosis with DES compared with bare metal stents2-5. Despite the widespread use of DES in
subsequent years, there is still a lack of long-term studies of patients who have
received these devices.
A patient registry was created within this scenario. All the patients from two
Brazilian institutions who received DES between 2002 and 2007, often with
off-label indications, were clinically followed up for 8 years.
Patient outcomes were analyzed based on the current definitions, and the efficacy
and safety of this technology were assessed.
MethodsPopulation
This study included all patients who underwent percutaneous coronary intervention
using at least 1 DES (Costar®, Cypher®, Endeavor®, Infinnium®, Janus®,
Supralimus®, and Taxus®) from January 2002 to April 2007 at the São Lucas and
Mãe de Deus hospitals in Porto Alegre (RS). Every patient that presented with
acute coronary syndrome and stable angina, with or without ST-segment elevation,
was included. The type of DES used during the procedure was left to the
discretion of the interventional cardiologist. Given the predominant use of the
Cypher®, Endeavor®, and Taxus® stents, a sub-analysis comparing the performance
of these stents was conducted.
Definitions and clinical follow-up
Data regarding the patients' clinical presentations at the time of the procedure
were collected through a detailed review of medical records. The patient groups
were defined as follows: stable angina, unstable angina, nonST elevation
myocardial infarction, ST segment elevation, and recent myocardial infarction
(MI) (<3 months before the procedure). Data regarding the procedure and
in-hospital outcomes were prospectively collected. Chronic renal failure was
defined as a glomerular filtration rate (GFR) of <60 ml/min/1.73
m26.
Clinical outcomes were defined as follows: mortality due to any cause; nonfatal
MI; CK-MB increase greater than or equal to three times the upper normal limit,
and/or electrocardiographic changes compatible with infarction (i.e., ST-segment
elevation or new inactive zone); or in patients who underwent coronary artery
bypass graft surgery, CK-MB increase greater than or equal to five times the
upper normal limit; target lesion revascularization (TLR) (i.e., percutaneous or
surgical revascularization to treat lesions in the segment of the stent or 5 mm
proximal or distal to the prior implant); and TVR (i.e., any revascularization
of the vessel treated with DES in the index procedure).
Stent thrombosis was classified according to the definition given by the Academic
Research Consortium (ARC) as follows: defined (i.e., acute coronary syndrome
with visualization of a thrombus in the segment where the DES was deployed),
probable (i.e., unexplained death within 30 days or target vessel infarction),
and possible (i.e., any unexplained death after 30 days). Based on the time of
occurrence, stent thrombosis was defined as follows: acute (i.e., within the
first 24 h), subacute (i.e., within 30 days), late (i.e., after 30 days), and
very late (i.e., after 1 year)7.
Total mortality, nonfatal MI, and TVR that occurred during the follow-up period
were defined as major adverse cardiac events (MACEs).
Angiographic success was defined as stenosis < 20% and thrombolysis in
myocardial infarction (TIMI) flow grade 3 by the end of the procedure. Clinical
success was defined as angiographic success and the absence of clinical
complications such as death, MI, urgent revascularization, and stroke during the
index hospitalization.
The first intervention was considered the index procedure for patients with more
than one intervention during the study period.
Clinical follow-up was conducted through medical appointments, phone interviews
with the patient, reviews of outpatient and in-hospital medical records, and
contact with the attending physician. All the clinical events were adjudicated
by analysis of the documentation's sources by a cardiologist who was blinded to
the other clinical data. The first clinical follow-up was performed 12 months
after the index procedure and a biannual clinical follow-up was performed
thereafter.
Quantitative coronary angiographic analysis
An experienced interventional cardiologist analyzed the baseline and
post-procedure coronary angiograms. Offline quantitative
coronary angiography of the index intervention was performed using a guiding
catheter for calibration of the image magnification (CardioNow Websend
DICOM Study Sharing Software, HeartLab, Inc., Westerly, Rhode
Island). The minimal luminal diameter and the reference vessel diameter were
measured, both before and after the intervention, from a single shot showing the
smaller luminal diameter. Coronary lesions were classified according to the
American Heart Association and the American College of Cardiology (AHA / ACC)
guidelines8.
Statistical Analysis
Statistical analysis was performed using the SPSS 19.0 software, assuming a
significance level of 5%. Quantitative variables were expressed as a mean ±
standard deviation. Categorical variables were presented as absolute and
relative frequencies and were compared by the chi-square test or Fisher's exact
test, as appropriate. Adjusted residuals greater than 1.96 (α = 0.05) were
considered statistically significant, thereby indicating a positive association
between the categories. Kaplan-Meier curves were developed for analysis of the
clinical outcomes. Cox regression analysis was used to investigate the
association between explanatory variables and outcomes. The multivariate
analysis initially included all of the variables, for which the p value was <
0.20 in the univariate analysis. Those with the highest p values were removed
one by one and only the variables with p values < 0.05 were maintained in the
final model.
Results
In total, 611 patients were included in the registry. Clinical follow-up was
available for 96.2% of the patients, with an average follow-up of 84 (±12) months
and a maximum of 96 months. The demographic characteristics and clinical
presentations of the patients are presented in Table 1.
Demographic and clinical characteristics at baseline
The mean average age was 63.7 years, and the male gender was predominant (63%).
One-third of the subjects exhibited renal failure or diabetes, more than two-thirds
had hypertension and dyslipidemia, and slightly more than one-half were smokers.
Stable angina was the most common clinical presentation.
Regarding the angiographic characteristics, most of the lesions were located in the
left anterior descending artery (in 348 patients or 56.4%). The majority of the
lesions (96.4%) were either type B2 or type C lesions (Table 2).
Qualitative characteristics of the target vessels and lesions
Patients
611
Target vessel
Left main coronary arterya
13 (1.8%)
Anterior descending artery
394 (56.4%)
Circumflex artery
128 (18.0%)
Right Coronary artery
177 (23.0%)
Treated lesions
712
Lesions per patient
1.17
Type of lesion*
Tipo A
3 (0.4%)
Type B1
22 (3.6%)
Type B2
355 (49.8%)
Type C
332 (46.6%)
Classification according to the American Heart Association and the
American College of Cardiology (AHA / ACC) guidelines.
The mean reference diameter of the target vessel before the procedure was 2.87 mm (±
0.46), with a minimal luminal diameter of 0.92 mm (± 0.51) and a mean lesion length
of 15.75 mm (± 8.37). A total of 748 DES and 83 bare metal stents were used in the
index procedure. Angiographic success was observed in 98.2% of the cases. Additional
angiographic characteristics are presented in Table
3.
Quantitative coronary angiography and procedure data
Pre-TIMI flow grade 3
n (%)
0
38 (6.20)
1
14 (2.40)
2
30 (4.90)
3
529 (86.50)
Média (DP)
Reference diameter (mm)
2.87 (0.46)
Minimal luminal diameter before the procedure (mm)
0.92 (0.51)
Lesion length (mm)
15.75 (8.37)
Maximum pressure of the DES implant (ATM)
14.88 (2.75)
Final minimal luminal diameter in the stent (mm)
2.82 (0.48)
Final minimal luminal diameter in the segment (mm)
2.41 (0.61)
Average number of stents / patient
1.3
Type of drug-eluting stent
n (%)
Costar®
25 (3.34)
Cypher®
255 (34.2)
Endeavor®
118 (15.7)
Infinium®
9 (1.20)
Janus®
6 (0.80)
Supralimus®
44 (5.80)
Taxus®
291 (38.09)
Angiographic success
600 (98.20)
Post-TIMI flow grade 3
n (%)
0
1 (0.16)
1
2 (0.32)
2
5(0.81)
3
603 (98.7)
Use of IIb/IIIa inhibitor
24 (3.90%)
Pre-dilation of the lesion
397 (65.0%)
The data represent the absolute numbers and percentages or the means and
standard deviations.
The event-free Kaplan Meier curves are shown in Figure
1. Total mortality was 8.7% at an average follow-up of 84 months (± 12).
Only 4.3% of the patients experienced a new nonfatal MI. Eight percent of the
patients required new revascularization of the target lesion; 5.4% of the procedures
were percutaneous and 2.6% were performed via bypass surgery. The incidence of
defined or probable DES thrombosis was 2.1%. Target vessel revascularization and TLR
were 12.4% and 8.0%, respectively (Table 4).
The occurrence of stent thrombosis during the follow-up period is described in Table 5. Every TVR and TLR was treated by the
same operator who performed the index procedure. Of the 13 episodes of thrombosis,
10 were admitted and treated in the same hospital where the index procedures were
performed; however the operators were not the same. All of them had a favorable
outcome. The three remaining patients were treated in other hospitals by different
operators; two of them died in the first 24 h after the rescue procedure.
The medical therapy used at the time of the final clinical follow-up is listed in
Table 6. At the first year evaluation,
95% of patients were using aspirin and 87% were using clopidogrel. At the end of
follow-up, most of the patients were using aspirin (ASA) and statins, and less than
one-quarter of the patients were using clopidogrel.
Multivariate analysis revealed that mortality was correlated with being greater than
60 years old and having a previous MI. TLR was correlated with being greater than 60
years old and the presence of calcium in the lesion. Myocardial infarction events
were positively associated with the presence of calcium in the lesion. The only
associated predictor for thrombosis was an ECC of < 60 ml/min/1.73 m2
. Previous MI was positively correlated with MACE.
An ECC of < 60 ml/min/1.73 m2 showed a significant positive correlation
with all outcomes (Table 7).
Comparative sub-analysis between the three most frequently used DES revealed that the
Taxus® device trended towards a positive association with the need
for TVR in 16.8% of the cases (p = 0.053) compared with the Cypher® and
Endeavor® stents, with 9.5% and 10.2%, respectively. This difference
was not confirmed when only TLR was evaluated (Table 8). The occurrence of MACE, stent thrombosis (defined + probable),
and infarction was not significantly different between the three stents.
The results of the registry demonstrate that the use of DES is effective long-term.
We further showed that the results of randomized trials can be replicated in
clinical practice, despite the inclusion of patients with a wide variety of clinical
and angiographic characteristics that are high risk and complex9-17.
In the present study, the low incidence of adverse events, such as new
revascularization and stent thrombosis, is similar to recent data that have
demonstrated reduced occurrence of these events with DES long-term. The mortality
rate observed during the 8 years of follow-up is similar to that demonstrated in
most randomized trials with up to 6 years of follow-up9-13.
The long-term follow-up of patients is a key differentiator of this registry. The
first report of the efficacy and safety of DES in unselected consecutive patients
with complex disease came from the RESEARCH Registry. It demonstrated that the use
of the Cypher® stent is associated with significantly lower rates of MACE and TVR
compared with bare metal stents during a 6 month follow-up12.
The reduced incidence of new revascularizations at the 8 year follow-up reported in
the present investigation also corroborates the data observed in several other
clinical studies. They observed a reduced requirement for new revascularization of
the target lesion, especially after 1 year9-20. Therefore, the hypothesis that DES would
merely delay the phenomenon of restenosis has been rejected.
The incidence of stent thrombosis associated with DES was low in our study. The low
number of patients using clopidogrel by the end of the follow-up period was expected
because dual antiplatelet therapy has been recommended for only 12 months after
DES.
The duration of dual antiplatelet therapy is a point of debate when discussing the
risk of stent thrombosis21-24. A higher incidence of thrombosis with DES
has been demonstrated when dual antiplatelet therapy is interrupted within the first
6 months after angioplasty24. Nevertheless,
the impact of long-term use of dual antiplatelet therapy is debatable. The incidence
of stent thrombosis was low in our study, despite the low number of patients using
antiplatelet drugs at the end of the follow-up period. The highest rate of stent
thrombosis was observed within the first year after the index angioplasty.
Studies comparing the incidence of stent thrombosis between DES and bare metal stents
have generated conflicting data. Clinical trials have not included stent thrombosis
as a primary outcome due to the low incidence of stent thrombosis (0.5 to 1% per
year). In a meta-analysis25,26, the incidence of stent thrombosis was
found to be similar for both DES and bare metal stents during the first year. After
1 year, the risk of thrombosis with DES was reported to be higher26. In another study, no difference in stent
thrombosis between DES and a bare metal stent was observed during a 15-month
follow-up27. In a meta-analysis of trials
limited to primary angioplasty for acute MI, the stent thrombosis rate observed with
DES and bare metal stents was similar at 1 year of follow-up27.
The frequency of various clinical outcomes of bare metal stents and DES differs
between clinical trial data and observational studies. Although clinical trials have
demonstrated similar mortality and MI rates for DES and bare metal stents,
observational real-world studies indicate a reduction in mortality in the DES
group21-25. Recent studies indicate a significant
reduction in the occurrence of stent thrombosis in second-generation DES versus bare
metal stents9,28.
The effect of different generations of DES on clinical outcomes must also be
considered. Few comparisons have been made between the Cypher®, Taxus®, and
Endeavor® stents. One study indicated that the Endeavor® stent was not inferior to
the Cypher® stent and was superior to the Taxus® stent when mortality from all
causes, MI, and TVR were assessed at 12 months29,30. In our registry, the incidence of
thrombosis, MI, and TLR was similar among those three stents. We observed a
significant difference in the incidence of TVR between the groups, with a higher
incidence in the Taxus® group.
Head-to-head comparisons between the Cypher® and Taxus® stents
indicate a lower occurrence of stent thrombosis and TLR with the Cypher®
stent31. Another head-to-head study
comparing the Endeavor® and Taxus® stents with a follow-up period of >
1 year indicated a lower incidence of stent thrombosis with the Endeavor®
stent32. Although these studies suggested
a higher incidence of thrombosis with the Taxus® stent compared with
other first-generation stents, the results were variable and inconclusive when stent
thrombosis was assessed as the primary outcome21. Recent studies comparing the second-generation stent Xience
V® versus Taxus® have demonstrated a lower incidence of stent
thrombosis with Xience V®(9,22,23), despite equal patient adherence to dual antiplatelet therapy
during the first year of follow-up. A recent meta-analysis of clinical trials
revealed a lower incidence of thrombosis with the Xience V®, compared with the
Taxus® stent30. Thus, differences in stent
thrombosis rates between the types of DES might exist, however, the magnitude of
these differences is difficult to measure34-36.
Data from studies of this nature cannot be compared with those from clinical trials
due to the nonrandomized, all-comers design. However, real world registries allow
for the assessment of outcomes in clinical scenarios that are not tested in
randomized studies.
The present study revealed adequate safety and efficacy of DES during a long-term
clinical follow-up period in the real world. It included a significant proportion of
patients at high cardiovascular risk, thereby validating the use of these stents for
routine treatment of patients with coronary artery disease.
Author contributions
Conception and design of the research: Gomes VO, Lasevitch R, Caramori P,
Pellegrini DO; Acquisition of data: Gomes VO, Lasevitch R, Ledur P, Caramori P,
Pellegrini DO; Analysis and interpretation of the data: Smidt L, Azeredo MA,
Bodanese R, Sinnott L, Caramori P, Pellegrini DO; Statistical analysis: Ledur P,
Caramori P, Pellegrini DO; Writing of the manuscript: Moriguchi E, Caramori P,
Pellegrini DO; Critical revision of the manuscript for intellectual content:
Moriguchi E, Caramori P.
Sources of Funding
There were no external funding sources for this study.
Study Association
This article is part of the thesis of master submitted by Denise Oliveira
Pellegrini, from Universidade Federal do Rio Grande do Sul.
References1. Daemen J, Serruys PW. Drug-eluting stent update 2007: part II:
Unsettled issues. Circulation. 2007;116(8):961-8.DaemenJSerruysPWDrug-eluting stent update 2007: part II: Unsettled
issuesCirculation200711689619682. Holmes DR Jr, Kereiakes DJ, Laskey WK, Colombo A, Ellis SG, Henry
TD, et al. Thrombosis and drug-eluting stents: an objective appraisal. J Am Coll
Cardiol. 2007;50(2):109-18.HolmesDRJrKereiakesDJLaskeyWKColomboAEllisSGHenryTDet alThrombosis and drug-eluting stents: an objective
appraisalJ Am Coll Cardiol20075021091183. Jensen LO, Maeng M, Kaltoft A, Thayssen P, Hansen HH, Bottcher M,
et al. Stent thrombosis, myocardial infarction, and death after drug-eluting and
bare-metal stent coronary interventions. J Am Coll Cardiol.
2007;50(5):463-70.JensenLOMaengMKaltoftAThayssenPHansenHHBottcherMet alStent thrombosis, myocardial infarction, and death
after drug-eluting and bare-metal stent coronary
interventionsJ Am Coll Cardiol20075054634704. Stettler C, Wandel S, Allemann S, Kastrati A, Morice MC, Schomig
A, et al. Outcomes associated with drug-eluting and bare-metal stents: a
collaborative network meta-analysis. Lancet.
2007;370(9591):937-48.StettlerCWandelSAllemannSKastratiAMoriceMCSchomigAet alOutcomes associated with drug-eluting and
bare-metal stents: a collaborative network meta-analysisLancet200737095919379485. Pfisterer M, Brunner-La Rocca HP, Buser PT, Rickenbacher P,
Hunziker P, Mueller C, et al; BASKET-LATE Investigators. Late clinical events
after clopidogrel discontinuation may limit the benefit of drug-eluting stents:
an observational study of drug-eluting versus bare-metal stents. J Am Coll
Cardiol. 2006;48(12):2584-91.PfistererMBrunner-La RoccaHPBuserPTRickenbacherPHunzikerPMuellerCet alBASKET-LATE InvestigatorsLate clinical events after clopidogrel
discontinuation may limit the benefit of drug-eluting stents: an
observational study of drug-eluting versus bare-metal stentsJ Am Coll Cardiol20064812258425916. Osorio Gomes V, Blaya P, Lasevitch R, Oliveira D, Hickmann P,
Smidt L, et al. Impact of chronic kidney disease on the efficacy of drug-eluting
stents: long-term follow-up study. Arq Bras Cardiol.
2011;96(5):346-51.Osorio GomesVBlayaPLasevitchROliveiraDHickmannPSmidtLet alImpact of chronic kidney disease on the efficacy of
drug-eluting stents: long-term follow-up studyArq Bras Cardiol20119653463517. Laskey WK, Yancy CW, Maisel WH. Thrombosis in coronary
drug-eluting stents: report from the meeting of the Circulatory System Medical
Devices Advisory Panel of the Food and Drug Administration Center for Devices
and Radiologic Health, December 7-8, 2006. Circulation.
2007;115(17):2352-7.LaskeyWKYancyCWMaiselWHThrombosis in coronary drug-eluting stents: report
from the meeting of the Circulatory System Medical Devices Advisory Panel of
the Food and Drug Administration Center for Devices and Radiologic Health,
December 7-8, 2006Circulation200711517235223578. Ryan TJ, Faxon DP, Gunnar RM, Kennedy JW, King SB 3rd, Loop FD,
et al. Guidelines for percutaneous transluminal coronary angioplasty. A report
of the American College of Cardiology/American Heart Association Task Force on
Assessment of Diagnostic and Therapeutic Cardiovascular Procedures (Subcommittee
on Percutaneous Transluminal Coronary Angioplasty). Circulation.
1988;78(2):486-502.RyanTJFaxonDPGunnarRMKennedyJWKingSB3rdLoopFDet alGuidelines for percutaneous transluminal coronary
angioplasty. A report of the American College of Cardiology/American Heart
Association Task Force on Assessment of Diagnostic and Therapeutic
Cardiovascular Procedures (Subcommittee on Percutaneous Transluminal
Coronary Angioplasty)Circulation19887824865029. Bangalore S, Kumar S, Fusaro M, Amoroso N, Attubato MJ, Feit F,
et al. Short- and long-term outcomes with drug-eluting and bare-metal coronary
stents: a mixed-treatment comparison analysis of 117 762 patient-years of
follow-up from randomized trials. Circulation.
2012;125(23):2873-91.BangaloreSKumarSFusaroMAmorosoNAttubatoMJFeitFet alShort- and long-term outcomes with drug-eluting and
bare-metal coronary stents: a mixed-treatment comparison analysis of 117 762
patient-years of follow-up from randomized trialsCirculation2012125232873289110. Bangalore S, Kumar S, Fusaro M, Amoroso N, Kirtane AJ, Byrne RA,
et al. Outcomes with various drug eluting or bare metal stents in patients with
diabetes mellitus: mixed treatment comparison analysis of 22,844 patient years
of follow-up from randomised trials. BMJ. 2012;345:e5170.BangaloreSKumarSFusaroMAmorosoNKirtaneAJByrneRAet alOutcomes with various drug eluting or bare metal
stents in patients with diabetes mellitus: mixed treatment comparison
analysis of 22,844 patient years of follow-up from randomised
trialsBMJ2012345e517011. Vogt A, Schoelmerich A, Pollner F, Schlitt M, Raaz U,
Maegdefessel L, et al. Comparison of outcome in 1809 patients treated with
drug-eluting stents or bare-metal stents in a real-world setting. Vasc Health
Risk Manag. 2011;7:693-9.VogtASchoelmerichAPollnerFSchlittMRaazUMaegdefesselLet alComparison of outcome in 1809 patients treated with
drug-eluting stents or bare-metal stents in a real-world
settingVasc Health Risk Manag2011769369912. Lemos PA, Hoye A, Goedhart D, Arampatzis CA, Saia F, van der
Giessen WJ, et al. Clinical, angiographic, and procedural predictors of
angiographic restenosis after sirolimus-eluting stent implantation in complex
patients: an evaluation from the Rapamycin-Eluting Stent Evaluated At Rotterdam
Cardiology Hospital (RESEARCH) study. Circulation.
2004;109(11):1366-70.LemosPAHoyeAGoedhartDArampatzisCASaiaFvan der GiessenWJet alClinical, angiographic, and procedural predictors
of angiographic restenosis after sirolimus-eluting stent implantation in
complex patients: an evaluation from the Rapamycin-Eluting Stent Evaluated
At Rotterdam Cardiology Hospital (RESEARCH) studyCirculation2004109111366137013. Costa JR Jr, Sousa A, Moreira AC, Costa RA, Cano M, Maldonado G,
et al. Incidence and predictors of very late (>or=4 years) major cardiac adverse
events in the DESIRE (Drug-Eluting Stents in the Real World)-Late registry. JACC
Cardiovasc Interv. 2010;3(1):12-8.CostaJRJrSousaAMoreiraACCostaRACanoMMaldonadoGet alIncidence and predictors of very late (>or=4
years) major cardiac adverse events in the DESIRE (Drug-Eluting Stents in
the Real World)-Late registryJACC Cardiovasc Interv201031121814. Sousa A, Costa JR Jr, Moreira AC, Cano M, Maldonado G, Costa RA,
et al. Long-term clinical outcomes of the Drug-Eluting Stents in the Real World
(DESIRE) Registry. J Interv Cardiol. 2008;21(4):307-14.SousaACostaJRJrMoreiraACCanoMMaldonadoGCostaRAet alLong-term clinical outcomes of the Drug-Eluting
Stents in the Real World (DESIRE) RegistryJ Interv Cardiol200821430731415. Saia F, Piovaccari G, Manari A, Guastaroba P, Vignali L, Varani
E, et al. Patient selection to enhance the long-term benefit of first generation
drug-eluting stents for coronary revascularisation procedures. Insights from a
large multicentre registry. EuroIntervention. 2009;5(1):57-66.SaiaFPiovaccariGManariAGuastarobaPVignaliLVaraniEet alPatient selection to enhance the long-term benefit
of first generation drug-eluting stents for coronary revascularisation
procedures. Insights from a large multicentre registryEuroIntervention200951576616. Ortolani P, Balducelli M, Marzaroli P, Piovaccari G, Menozzi A,
Guiducci V, et al. Two-year clinical outcomes with drug-eluting stents for
diabetic patients with de novo coronary lesions: results from a real-world
multicenter registry. Circulation. 2008;117(7):923-30.OrtolaniPBalducelliMMarzaroliPPiovaccariGMenozziAGuiducciVet alTwo-year clinical outcomes with drug-eluting stents
for diabetic patients with de novo coronary lesions: results from a
real-world multicenter registryCirculation2008117792393017. Marzocchi A, Saia F, Piovaccari G, Manari A, Aurier E, Benassi
A, et al. Long-term safety and efficacy of drug-eluting stents: two-year results
of the REAL (REgistro AngiopLastiche dell'Emilia Romagna) multicenter registry.
Circulation. 2007 Jun 26;115(25):3181-8.MarzocchiASaiaFPiovaccariGManariAAurierEBenassiAet alLong-term safety and efficacy of drug-eluting
stents: two-year results of the REAL (REgistro AngiopLastiche dell'Emilia
Romagna) multicenter registryCirculation26Jun2007115253181318818. Marroquin OC, Selzer F, Mulukutla SR, Williams DO, Vlachos HA,
Wilensky RL, et al. A comparison of bare-metal and drug-eluting stents for
off-label indications. N Engl J Med. 2008;358(4):342-52.MarroquinOCSelzerFMulukutlaSRWilliamsDOVlachosHAWilenskyRLet alA comparison of bare-metal and drug-eluting stents
for off-label indicationsN Engl J Med2008358434235219. Morice MC, Serruys PW, Sousa JE, Fajadet J, Ban Hayashi E, Perin
M, et al. A randomized comparison of a sirolimus-eluting stent with a standard
stent for coronary revascularization. N Engl J Med.
2002;346(23):1773-80.MoriceMCSerruysPWSousaJEFajadetJBan HayashiEPerinMet alA randomized comparison of a sirolimus-eluting
stent with a standard stent for coronary revascularizationN Engl J Med2002346231773178020. Dawkins KD, Grube E, Guagliumi G, Banning AP, Zmudka K, Colombo
A, et al. Clinical efficacy of polymer-based paclitaxel-eluting stents in the
treatment of complex, long coronary artery lesions from a multicenter,
randomized trial: support for the use of drug-eluting stents in contemporary
clinical practice. Circulation. 2005;112(21):3306-13.DawkinsKDGrubeEGuagliumiGBanningAPZmudkaKColomboAet alClinical efficacy of polymer-based
paclitaxel-eluting stents in the treatment of complex, long coronary artery
lesions from a multicenter, randomized trial: support for the use of
drug-eluting stents in contemporary clinical practiceCirculation2005112213306331321. Stone GW, Ellis SG, Cannon L, Mann JT, Greenberg JD, Spriggs D,
et al; TAXUS V Investigators. Comparison of a polymer-based paclitaxel-eluting
stent with a bare metal stent in patients with complex coronary artery disease:
a randomized controlled trial. JAMA. 2005;294(10):1215-23.StoneGWEllisSGCannonLMannJTGreenbergJDSpriggsDet alTAXUS V InvestigatorsComparison of a polymer-based paclitaxel-eluting
stent with a bare metal stent in patients with complex coronary artery
disease: a randomized controlled trialJAMA2005294101215122322. Stone GW, Moses JW, Ellis SG, Schofer J, Dawkins KD, Morice MC,
et al. Safety and efficacy of sirolimus- and paclitaxel-eluting coronary stents.
N Engl J Med. 2007;356(10):998-1008.StoneGWMosesJWEllisSGSchoferJDawkinsKDMoriceMCet alSafety and efficacy of sirolimus- and
paclitaxel-eluting coronary stentsN Engl J Med200735610998100823. Fajadet J, Wijns W, Laarman GJ, Kuck KH, Ormiston J, Baldus S,
et al. Long-term follow-up of the randomised controlled trial to evaluate the
safety and efficacy of the zotarolimus-eluting driver coronary stent in de novo
native coronary artery lesions: five year outcomes in the ENDEAVOR II study.
EuroIntervention. 2010;6(5):562-7.FajadetJWijnsWLaarmanGJKuckKHOrmistonJBaldusSet alLong-term follow-up of the randomised controlled
trial to evaluate the safety and efficacy of the zotarolimus-eluting driver
coronary stent in de novo native coronary artery lesions: five year outcomes
in the ENDEAVOR II studyEuroIntervention20106556256724. Venkitachalam L, Lei Y, Stolker JM, Mahoney EM, Amin AP, Lindsey
JB, et al. Clinical and economic outcomes of liberal versus selective
drug-eluting stent use: insights from temporal analysis of the multicenter
Evaluation of Drug Eluting Stents and Ischemic Events (EVENT) registry.
Circulation. 2011;124(9):1028-37.VenkitachalamLLeiYStolkerJMMahoneyEMAminAPLindseyJBet alClinical and economic outcomes of liberal versus
selective drug-eluting stent use: insights from temporal analysis of the
multicenter Evaluation of Drug Eluting Stents and Ischemic Events (EVENT)
registryCirculation201112491028103725. Holmes DR Jr, Kereiakes DJ, Garg S, Serruys PW, Dehmer GJ, Ellis
SG, et al. Stent thrombosis. J Am Coll Cardiol.
2010;19;56(17):1357-65.HolmesDR JrKereiakesDJGargSSerruysPWDehmerGJEllisSGet alStent thrombosisJ Am Coll Cardiol201056171357136526. Gwon HC, Hahn JY, Park KW, Song YB, Chae IH, Lim DS, et al.
Six-month versus 12-month dual antiplatelet therapy after implantation of
drug-eluting stents: the Efficacy of Xience/Promus Versus Cypher to Reduce Late
Loss After Stenting (EXCELLENT) randomized, multicenter study. Circulation.
2011;125(3):505-13.GwonHCHahnJYParkKWSongYBChaeIHLimDSet alSix-month versus 12-month dual antiplatelet therapy
after implantation of drug-eluting stents: the Efficacy of Xience/Promus
Versus Cypher to Reduce Late Loss After Stenting (EXCELLENT) randomized,
multicenter studyCirculation2011125350551327. Stefanini GG, Holmes DR Jr. Drug-eluting coronary-artery stents.
N Engl J Med. 2013;368(3):254-65.StefaniniGGHolmesDRJrDrug-eluting coronary-artery stentsN Engl J Med2013368325426528. Ko DT, Chiu M, Guo H, Austin PC, Goeree R, Cohen E, et al.
Safety and effectiveness of drug-eluting and bare-metal stents for patients with
off- and on-label indications. J Am Coll Cardiol.
2009;53(19):1773-82.KoDTChiuMGuoHAustinPCGoereeRCohenEet alSafety and effectiveness of drug-eluting and
bare-metal stents for patients with off- and on-label
indicationsJ Am Coll Cardiol200953191773178229. Roukoz H, Bavry AA, Sarkees ML, Mood GR, Kumbhani DJ, Rabbat MG,
et al. Comprehensive meta-analysis on drug-eluting stents versus bare-metal
stents during extended follow-up. Am J Med.
2009;122(6):581.e1-10.RoukozHBavryAASarkeesMLMoodGRKumbhaniDJRabbatMGet alComprehensive meta-analysis on drug-eluting stents
versus bare-metal stents during extended follow-upAm J Med20091226581.e1581.1030. Fuchs AT, Kuehnl A, Pelisek J, Rolland PH, Mekkaoui C, Netz H,
et al. Meta-analysis shows similar risk of thrombosis after drug-eluting stent,
bare-metal stent, or angioplasty. Endothelium.
2008;15(1):93-100.FuchsATKuehnlAPelisekJRollandPHMekkaouiCNetzHet alMeta-analysis shows similar risk of thrombosis
after drug-eluting stent, bare-metal stent, or angioplastyEndothelium20081519310031. Brodie B, Pokharel Y, Fleishman N, Bensimhon A, Kissling G,
Hansen C, et al. Very late stent thrombosis after primary percutaneous coronary
intervention with bare-metal and drug-eluting stents for ST-segment elevation
myocardial infarction: a 15-year single-center experience. JACC Cardiovasc
Interv. 2011;4(1):30-8.BrodieBPokharelYFleishmanNBensimhonAKisslingGHansenCet alVery late stent thrombosis after primary
percutaneous coronary intervention with bare-metal and drug-eluting stents
for ST-segment elevation myocardial infarction: a 15-year single-center
experienceJACC Cardiovasc Interv201141303832. Palmerini T, Biondi-Zoccai G, Della Riva D, Stettler C,
Sangiorgi D, D'Ascenzo F, et al. Stent thrombosis with drug-eluting and
bare-metal stents: evidence from a comprehensive network meta-analysis. Lancet.
2012;379(9824):1393-402.PalmeriniTBiondi-ZoccaiGDella RivaDStettlerCSangiorgiDD'AscenzoFet alStent thrombosis with drug-eluting and bare-metal
stents: evidence from a comprehensive network meta-analysisLancet201237998241393140233. Jaffery Z, Prasad A, Lee JH, White CJ. Drug-eluting coronary
stents - focus on improved patient outcomes. Patient Relat Outcome Meas.
2011;2:161-74.JafferyZPrasadALeeJHWhiteCJDrug-eluting coronary stents - focus on improved
patient outcomesPatient Relat Outcome Meas2011216117434. Park DW, Kim YH, Yun SC, Kang SJ, Lee SW, Lee CW, et al.
Comparison of zotarolimus-eluting stents with sirolimus- and paclitaxel-eluting
stents for coronary revascularization: the ZEST (comparison of the efficacy and
safety of zotarolimus-eluting stent with sirolimus-eluting and
paclitaxel-eluting stent for coronary lesions) randomized trial. J Am Coll
Cardiol. 2010;56(15):1187-95.ParkDWKimYHYunSCKangSJLeeSWLeeCWet alComparison of zotarolimus-eluting stents with
sirolimus- and paclitaxel-eluting stents for coronary revascularization: the
ZEST (comparison of the efficacy and safety of zotarolimus-eluting stent
with sirolimus-eluting and paclitaxel-eluting stent for coronary lesions)
randomized trialJ Am Coll Cardiol201056151187119535. Schomig A, Dibra A, Windecker S, Mehilli J, Suarez de Lezo J,
Kaiser C, et al. A meta-analysis of 16 randomized trials of sirolimus-eluting
stents versus paclitaxel-eluting stents in patients with coronary artery
disease. J Am Coll Cardiol. 2007;50(14):1373-80.SchomigADibraAWindeckerSMehilliJSuarez de LezoJKaiserCet alA meta-analysis of 16 randomized trials of
sirolimus-eluting stents versus paclitaxel-eluting stents in patients with
coronary artery diseaseJ Am Coll Cardiol200750141373138036. Leon MB, Nikolsky E, Cutlip DE, Mauri L, Liberman H, Wilson H,
et al. Improved late clinical safety with zotarolimus-eluting stents compared
with paclitaxel-eluting stents in patients with de novo coronary lesions: 3-year
follow-up from the ENDEAVOR IV (Randomized Comparison of Zotarolimus- and
Paclitaxel-Eluting Stents in Patients With Coronary Artery Disease) trial. JACC
Cardiovasc Interv. 2010;3(10):1043-50.LeonMBNikolskyECutlipDEMauriLLibermanHWilsonHet alImproved late clinical safety with
zotarolimus-eluting stents compared with paclitaxel-eluting stents in
patients with de novo coronary lesions: 3-year follow-up from the ENDEAVOR
IV (Randomized Comparison of Zotarolimus- and Paclitaxel-Eluting Stents in
Patients With Coronary Artery Disease) trialJACC Cardiovasc Interv201031010431050Eficácia e Segurança de Stents Eluidores de Drogas no
Mundo Real: Acompanhamento de 8 AnosPellegriniDenise OliveiraGomesVitor OsoérioLasevitchRicardoSmidtLuisAzeredoMarco AurélioLedurPriscilaBodaneseRodrigoSinnottLeonardoMoriguchiEmílioCaramoriPauloPUCHospital São LucasPorto AlegreRSBrasilHospital São Lucas PUC, Porto Alegre, RS,
BrasilCorrespondência: Denise Machado de Oliveira Pellegrini, Av.
Alegrete 423/1601, Petrópolis. CEP 90460-100 - Porto Alegre, RS, Brasil. Email:
dennizmo@yahoo.com.br; pellegrini.de@gmail.com
Potencial conflito de interesse
Declaro não haver conflito de interesses pertinentes.
Fundamento:
Stents eluidores de drogas têm sido utilizados na prática médica desde 2002,
e apresentam grande eficácia na redução do risco de revascularização do
vaso-alvo, e notável redução da taxa de reestenose de 50%-70%. No entanto, a
ocorrência de trombose tardia pode comprometer os resultados a longo prazo,
especialmente se o risco de trombose for mantido ao longo dos anos. Neste
contexto, o registro da prática clínica assume grande importância. Objetivo:
Avaliar a eficácia e segurança de stents eluidores de drogas no mundo
real.
Métodos:
Relatamos os resultados de todos os pacientes que foram submetidos à
intervenção coronária percutânea com stent eluidor de drogas no período
entre janeiro de 2002 a abril de 2007, e que foram acompanhados por 8 anos.
Os stents eluidores de drogas foram utilizados de acordo com as
recomendações clínicas do cardiologista intervencionista e a disponibilidade
do stent.
Resultados:
Um total de 611 pacientes foram avaliados, com acompanhamento clínico de
96,2% destes pacientes por até 8 anos. A mortalidade total foi de 8,7%.
Infarto não-fatal ocorreu em 4,3% dos casos. A taxa de revascularização do
vaso-alvo foi de 12,4% e a da lesão-alvo foi de 8,0%. A taxa de trombose de
stent foi de 2,1%. Não houve novos episódios de trombose de stent após o
quinto ano de acompanhamento. Uma subanálise comparativa indicou não haver
diferenças nos desfechos clínicos apos a utilização dos stents Cypher, Taxus
e Endeavor.
Conclusão:
Estes resultados indicam que stents eluidores de drogas são seguros e
eficazes em acompanhamentos de longo prazo, e que pacientes no mundo real
podem beneficiar destes stents, com excelentes resultados a longo prazo.
Stents Farmacológicos/tendênciasResultado do TratamentoEfetividadeEfeitos a Longo PrazoIntrodução
Stents eluidores de drogas (SEDs) têm sido usados na prática clínica desde 2002.
Estudos clínicos multicêntricos demonstraram as vantagens destes stents em
reduzir os principais desfechos clínicos cardiovasculares, principalmente a
revascularização do vaso-alvo (RVA), quando comparados com stents metálicos1. Com o aumento do uso destes dispositivos
em cenários clínicos não incluídos em ensaios clínicos randomizados, a segurança
e eficácia dos SEDs no mundo real começaram a ser questionadas. Os
questionamentos sobre a segurança dos SEDs aumentaram após 2006, quando dados
preliminares apontaram taxas mais altas de tromboses intra-stent utilizando SED,
em comparação com stents metálicos2-5.
Apesar do amplo uso de SEDs nos anos subsequentes, ainda há poucos estudos de
longo prazo de pacientes que receberam esses dispositivos.
O registro de práticas clínicas foi criado dentro deste contexto, em que todos os
pacientes provenientes de duas instituições brasileiras, que receberam SEDs
entre 2002 e 2007 - muitas vezes com indicações diferentes das preconizadas -
foram acompanhados clinicamente por 8 anos. Os desfechos clínicos destes
pacientes foram analisados com base em recomendações recentes, permitindo assim
a avaliação da eficácia e segurança desta tecnologia.
MétodosGrupo de estudo
Este estudo envolveu pacientes submetidos à intervenção coronária percutânea
usando pelo menos 1 SED (modelos Costar, Cypher, Endeavor, Infinium, Janus,
Supralimus e Taxus) de janeiro de 2002 a abril de 2007, realizada nos
hospitais São Lucas e Mãe de Deus, em Porto Alegre, Rio Grande do Sul,
Brasil. Todas as apresentações clínicas da síndrome coronariana aguda com e
sem supradesnivelamento do segmento ST e angina estável foram incluídos. O
tipo de stent utilizado durante o procedimento foi deixado aos critério do
cardiologista intervencionista. Considerando o uso predominante dos stents
Cypher(r), Endeavor(r) e Taxus(r), uma subanálise comparando o desempenho
destes 3 stents foi realizada.
Definições e acompanhamento clínico
Os dados referentes as apresentações clínicas dos pacientes no momento do
procedimento foram coletados através de uma revisão detalhada dos registros
médicos e classificados da seguinte forma: angina estável, angina instável,
infarto do miocárdio sem supradesnivelamento do segmento ST, infarto do
miocárdio com supradesnivelamento do segmento ST, e infarto do miocárdio
(IM) recente (< 3 meses antes do procedimento). Os dados dos
procedimentos e desfechos clínicos foram coletados prospectivamente.
Insuficiência renal crônica foi definida como uma taxa de filtração
glomerular (TFG) < 60 mL/min/1.73 m26 (Os resultados clínicos foram
classificados da seguinte forma: mortalidade por todas as causas, IM não
fatal, aumento da isoenzima MB da creatina quinase (CK-MB) ≥ 3 vezes o
limite superior normal, e/ou alterações eletrocardiográficas compatíveis com
infarto (e.g., supradesnivelamento do segmento ST ou nova zona inativa); ou,
em pacientes submetidos à cirurgia de revascularização do miocárdio, aumento
do CK-MB ≥ 5 vezes o limite superior normal. Revascularização da lesão-alvo
(RLA) (i.e., revascularização percutânea ou cirúrgica, tratamento de lesões
no segmento do stent ou até 5 mm da região proximal ou distal do implante
anterior), e RVA (i.e., qualquer revascularização do vaso tratado com SED no
procedimento índice).
A trombose de stent foi classificada de acordo com as definições do
Academic Research Consortium (ARC) da seguinte forma:
definida (i.e., síndrome coronária aguda com visualização do trombo no
segmento onde o SED foi implantado), provável (i.e., morte inexplicável
dentro de 30 dias ou infarto do vaso-alvo), e possível (i.e., qualquer morte
inexplicável após 30 dias). Com base no tempo de ocorrência, a trombose de
stent foi definida da seguinte forma: aguda (i.e., dentro das primeiras 24
horas), subaguda (i.e., dentro de 30 dias), tardia (i.e., após 30 dias), e
muito tardia (i.e., após 1 ano)7.
A mortalidade total, IM não fatal, e RVA que ocorreram durante o período de
acompanhamento foram considerados os principais eventos cardíacos adversos
maiores (ECAM).
O sucesso angiográfico foi considerado quando a estenose foi menor que 20% e
a trombólise em infarto do miocárdio (TIMI) apresentou fluxo de grau 3 ao
final do procedimento. O sucesso clínico foi definido como sucesso
angiográfico, conjuntamente com a ausência de complicações clínicas,
incluindo morte, IM, revascularização urgente, e acidente vascular cerebral
durante a internação índice.
Para os pacientes com mais de uma intervenção durante o período de estudo, a
primeira intervenção foi considerada procedimento índice.
O acompanhamento clínico foi realizado através de consultas médicas,
entrevistas por telefone com o paciente, consulta de registros médicos
ambulatoriais e hospitalares, e contato com o médico responsável. Todos os
eventos clínicos foram julgados através da análise dos registros por um
cardiologista que desconhecia os outros dados clínicos. O primeiro
acompanhamento clínico foi realizado 12 meses após o procedimento índice.
Posteriormente, um acompanhamento clínico bianual foi realizado.
Análise angiográfica coronariana quantitativa
As angiografias coronárias de linha de base e pós-procedimento foram
analisadas por um cardiologista intervencionista experiente. A angiografia
coronária quantitativa off-line da intervenção índice foi
realizada utilizando um cateter guia para a calibração da ampliação da
imagem, e o programa CardioNow Websend DICOM Study Sharing
(HeartLab, Inc., Westerly, Rhode Island, Estados Unidos). A análise da
medida do diâmetro luminal mínimo e do diâmetro do vaso-referência foi
realizada de uma única vez e indicou o menor diâmetro luminal antes e apos a
intervenção. As lesões coronarianas foram classificadas de acordo com as
diretrizes da American Heart Association and the American College of
Cardiology (AHA/ACC)8.
Análise estatística
A análise estatística foi realizada utilizando o programa SPSS 19.0,
considerando um nível de significância de 5%. As variáveis quantitativas
foram expressas como média ± desvio padrão. As variáveis categóricas foram
apresentadas como frequência absoluta e relativa e foram comparadas entre si
utilizando o teste do qui-quadrado ou teste exato de Fisher, conforme
apropriado. Os resíduos ajustados >1,96 (α = 0,05) foram considerados
significativos, indicando uma correlação positiva entre as categorias.
Curvas de Kaplan-Meier foram desenvolvidas para análise dos desfechos
clínicos. A análise de regressão de Cox foi utilizada para determinar a
correlação entre as variáveis explicativas e os desfechos clínicos. Todas as
variáveis onde p foi menor que 0,20 na análise univariada foram incluídas na
análise multivariada, retirando aqueles com os valores de p mais altos. As
variáveis onde p < 0,05 foram mantidas no modelo final.
Resultados
No total, 611 pacientes foram incluídos no registro. O acompanhamento clínico foi
concluído em 96,2% dos pacientes, com um acompanhamento médio de 84 (± 12) meses
e máximo de 96 meses. As características demográficas e a apresentação clínica
dos pacientes são apresentadas na Tabela
1.
Características demográficas e clínicas no início do estudo
Idade
63,7 (±11)
Sexo masculino
338 (62,4%)
TFG <60 mL/min/1.73 m2
165 (32,7%)
Diabetes
204 (34,3%)
Insulino-dependente
73 (12,4%)
Não insulino-dependente
166 (28,2%)
Hipertensão
468 (76,2%)
Dislipidemia
453 (76,8%)
Angioplastia coronária prévia
174 (28,7%)
CRM prévio
67 (11,1%)
Tabagismo
96 (15,7%)
Apresentação clínica inicial
Angina estável
363 (60,4%)
Angina instável
151 (25,1%)
IAMSST
41 (6,8%)
IAMCST
24 (4,0%)
Infarto do miocárdio recente
22 (3,7%)
TFG: taxa de filtração glomerular; CRM: cirurgia de revascularização
miocárdica; IAMSS: infarto agudo do miocárdio sem
supradesnivelamento do segmento ST; IAMCST: infarto agudo do
miocárdio com supradesnivelamento do segmento ST
A média de idade foi de 63,7 anos, e o sexo masculino foi predominante (63%). Um
terço dos pacientes apresentaram insuficiência renal ou diabetes, mais de dois
terços apresentaram hipertensão e dislipidemia, e um pouco mais da metade era
fumante. A angina estável foi a apresentação clínica mais comum.
Em relação às características angiográficas, a maioria das lesões foi localizada
na artéria descendente anterior esquerda 348 (56,4%). A maioria das lesões
(96,4%) foi do tipo B2 ou do tipo C (Tabela
2).
Características qualitativas dos vasos-alvo e lesões-alvo
Pacientes
611
Vaso-alvo
Principal artéria coronária
esquerda
13 (1,8%)
Artéria anterior descendente
394 (56,4%)
Artéria circunflexa
128 (18,0%)
Artéria coronária direita
177 (23,0%)
Lesões tratadas
712
Número de lesões por paciente
1,17
Tipo de lesão*
Tipo A
3 (0,4%)
Tipo B1
22 (3,6%)
Tipo B2
355 (49,8%)
Tipo C
332 (46,6%)
Classificação de acordo com as diretrizes da American Heart
Association and the American College of Cardiology (AHA/ACC).
A média do diâmetro-referência do vaso-alvo foi de 2,87 mm (± 0,46), com um
diâmetro luminal mínimo de 0,92 mm (± 0,51) antes do procedimento, e comprimento
médio da lesão de 15,75 mm (± 8,37). No total, 748 stents eluidores de drogas e
83 stents metálicos foram utilizados no procedimento índice. Sucesso
angiográfico foi observado em 98,2% dos casos. Outras características
angiográficas são apresentadas na Tabela
3.
Angiografia coronária quantitativa e dados de procedimento
Pré-TIMI - Fluxo grau 3
n (%)
0
38 (6,20)
1
14 (2,40)
2
30 (4,90)
3
529 (86,50)
Média (DP)
Diâmetro de referência (mm)
2.87 (0,46)
Diâmetro luminal mínimo antes do procedimento (mm)
0.92 (0,51)
Comprimento da lesão (mm)
15,75 (8,37)
Pressão máxima do implante SED (atm)
14.88 (2,75)
Diâmetro mínimo luminal final no stent (mm)
2.82 (0,48)
Diâmetro mínimo luminal final no segmento (mm)
2.41 (0,61)
Número médio de stents por paciente
1,3
Tipo de stent eluidor de drogas
n (%)
Costar
25 (3,34)
Cypher
255 (34,2)
Endeavor
118 (15,7)
Infinium
9 (1,20)
Janus
6 (0,80)
Supralimus
44 (5,80)
Taxus
291 (38,09)
Sucesso angiográfico
600 (98,20)
Pós-TIMI - Fluxo grau 3
n (%)
0
1 (0,16)
1
2 (0,32)
2
5(0,81)
3
603 (98,7)
Utilização de inibidor tipo IIB/IIIA
24 (3,90%)
Pré-dilatação da lesão
397 (65,0%)
Os dados representam valores absolutos e porcentagens, ou médias e
desvios-padrão.
As curvas Kaplan Meyer livres de eventos são mostradas na Figura 1. Considerando um acompanhamento médio de 84 meses
(± 12), observou-se uma mortalidade total de 8,7%. Apenas 4,3% dos pacientes
apresentaram um novo IM não fatal, e 8% dos pacientes necessitaram de nova
revascularização da lesão-alvo; 5,4% dos procedimentos foram percutâneos, e 2,6%
foram realizados por meio de cirurgia. A incidência de trombose de stent
definida ou provável foi de 2,1%. As revascularizações do vaso-alvo e da
lesão-alvo foram de 12,4% e 8,0%, respectivamente (Tabela 4). A ocorrência de trombose de stent durante o
acompanhamento está descrita na Tabela
5. Todas as revascularizações do vaso-alvo e da lesão-alvo foram tratadas
pelo cirurgião que realizou o procedimento índice. Dos 13 episódios de trombose,
10 necessitaram de internação e foram tratados no hospital onde os procedimentos
índice foram realizados, embora os operadores não tenham sido os mesmos. Todos
os procedimentos apresentaram uma evolução favorável. Os outros 3 pacientes
foram tratados em outros hospitais e por cirurgiões diferentes. Contudo, 2 deles
morreram nas primeiras 24 horas após o procedimento de resgate.
Resultado das curvas de Kaplan Meyer
Resultados clínicos no final do acompanhamento
n (%)
Mortalidade global
53 (8,7)
IAM não fatal
26 (4,3)
RVA
76 (12,4)
RLA
49 (8,0)
CRM
16 (2,6)
ACTP
33 (5,4)
Trombose
13 (2,1)
IAM: infarto agudo do miocárdio; RVA: revascularização do vaso alvo;
RLA: revascularização da lesão-alvo; CRM: cirurgia de
revascularização miocárdica; ACTP: angioplastia coronária
transluminal percutânea.
Ocorrência de trombose durante o acompanhamento
Ano de acompanhamento
n
Primeiro
1
Segundo
2
Terceiro
2
Quarto
3
Quinto
5
Sexto
0
Sétimo
0
Oitavo
0
A terapia médica usada no acompanhamento clínico final está mostrada na Tabela 6. No primeiro ano de
acompanhamento, 95% dos pacientes usaram aspirina e 87% usaram clopidogrel. No
final do acompanhamento, a maioria dos pacientes estava utilizando aspirina
(AAS) e estatinas, e menos de 1/4 dos pacientes estava utilizando
clopidogrel.
Medicações em uso no acompanhamento final
AAS
424 (69,6%)
Clopidogrel
147 (24,4%)
AAS + Clopidogrel
138 (22,5%)
Estatinas
420 (71,6%)
Betabloqueadores
292 (4,6%)
Inibidores da ECA
200 (33,2%)
Antagonistas do receptor AT2
94 (15,6%)
Nitratos
102 (16,9%)
AAS: ácido acetil salicílico; IECA: inibidor da enzima conversora da
angiotensina
A análise multivariada indicou que idade > 60 anos e infarto do miocárdio
prévio foram correlacionados com a mortalidade. Idade > 60 anos e a presença
de cálcio nas lesões foram correlacionadas com o desfecho clinico de RLA. Para
eventos de infarto do miocárdio, a presença de cálcio nas lesões foi
correlacionada positivamente com a mortalidade. Para o desfecho clinico de
trombose, ECC < 60 mL/min/1.73 m2 foi o único preditor associado.
Para ECAM, o preditor infarto do miocárdio prévio apresentou uma correlação
positiva.
Para todos os resultados clínicos, ECC < 60 mL/min/1.73 m2 mostrou
uma correlação positiva e significativa. Estes resultados são apresentados na
Tabela 7.
Preditores de desfechos clínicos utilizando análise
multivariada
FC (IC 95%)
P
Mortalidade
Idade > 60 anos
3,33 (1,01 - 10,97)
0,048
Infarto agudo do miocárdio prévio
5,9 (1,91 - 18,19)
0,002
TFG < 60 mL/min/1.73 m2
6,96 (2,7 - 17,95)
0
RLA
Idade > 60 anos
0,48 (0,25 - 0,90)
0,022
TFG < 60 mL/min/1.73 m2
2,73 (1,18 - 6,33)
0,019
Presença de cálcio na lesão
2,88 (1,23 - 6,72)
0,015
Infarto
TFG < 60 mL/min/1.73 m2
2,91 (0,96 - 8,83)
0,06
Presença de cálcio na lesão
4,43 (1,69 - 11,63)
0,003
Trombose de stent
TFG < 60 mL/min/1.73 m2
3,33 (0,88 - 12,63)
0,077
ECAM
Infarto agudo do miocárdio prévio
113,74 (48,14 - 268,75)
< 0,0001
TFG < 60 mL/min/1.73 m2
2,75 (1,23 - 6,16)
0,014
TFG: taxa de filtração glomerular; TLR: revascularização da lesão
alvo; ECAM: evento cardíaco adverso maior
A subanálise comparativa entre os 3 SEDs mais frequentemente utilizados revelou
que o dispositivo Taxus(c) apresentou tendência para uma correlação positiva com
a necessidade de RVA em 16,8% dos casos (p=0,053) quando comparado com os stents
Cypher e Endeavor, onde a correlação positiva foi de 9,5% e 10,2%,
respectivamente. Esta diferença não foi confirmada quando apenas RLA foi
avaliada, como mostrado na Tabela 8. A
ocorrência de ECAM, trombose de stent (definida e provável), e infarto não foram
significativamente diferentes entre os três stents.
Diferenças entre os stents com relação ao desfecho clínico
Cypher
Endeavor
Taxus
valor de p
n
255
118
291
Mortalidade
11 (4,3)
2 (1,7)
10 (3,4)
0,47
RVA
19 (9,5)
9 (10,2)
39 (16,8)
0,05
RLA
14 (7,0)
7 (8,0)
22 (9,5)
0,63
Infarto do miocárdo
24 (12,0)
12 (13,6)
41 (17,7)
0,24
Trombose de stent
3 (1,5)
1 (1,1)
7 (3,0)
0,42
ECAM
21 (8,20)
9 (7,6)
27 (9,2)
0,88
RVA: revascularização do vaso-alvo; RLA: revascularização da
lesão-alvo; ECAM: evento cardíaco adverso maior.
Discussão
Os resultados do nosso estudo demonstraram que o uso de SEDs é eficaz a longo
prazo e que os resultados de ensaios clínicos randomizados podem ser replicados
na prática clínica, apesar da inclusão de pacientes com uma ampla variedade de
características clínicas e angiográficas de alto risco e complexidade9-17.
No presente estudo, a baixa incidência de eventos clínicos tais como nova
revascularização e trombose de stent foi semelhante a dados de estudos recentes,
que demonstraram a ocorrência reduzida destes eventos com SEDs a longo prazo. A
taxa de mortalidade observada durante os 8 anos de acompanhamento foi semelhante
à reportada na maioria dos estudos randomizados com até 6 anos de
acompanhamento9-13.
A longo prazo, o acompanhamento dos pacientes foi um diferencial importante deste
registro. Os primeiros dados sobre a eficácia e segurança dos SEDs em pacientes
consecutivos não selecionados que apresentaram doenças complexas veio do
registro RESEARCH, que demonstrou que o uso do stent Cypher está associado a
taxas significativamente mais baixas de eventos cardíacos adversos maiores e à
RVA, em comparação com stents metálicos durante os 6 meses de
acompanhamento12.
A redução da incidência de novas revascularizações apos 8 anos de acompanhamento
relatado no presente estudo também corrobora os dados observados em estudos
clínicos anteriores, que indicaram a necessidade reduzida de nova
revascularização da lesão-alvo, especialmente após 1 ano9-20. Portanto, a hipótese de que SEDs
apenas adiariam o fenômeno da reestenose foi rejeitada.
Em relação ao perfil de segurança dos SEDs, observamos que a incidência de
trombose de stent foi baixa. O uso reduzido de clopidogrel ao final do período
de acompanhamento era esperado, visto que a terapia antiplaquetária dupla tem
sido recomendada por 12 meses após o uso de SEDs.
A duração da terapia antiplaquetária dupla é um tema de debate quando se discute
o risco de trombose de stent21-24. A maior incidência de trombose de
stent foi observada quando a terapia antiplaquetária dupla foi interrompida
durante os primeiros 6 meses após a angioplastia24. No entanto, o impacto do uso da terapia antiplaquetária dupla a
longo prazo é discutível. A incidência de trombose de stent foi baixa em nosso
estudo, apesar do baixo uso de medicamentos antiplaquetários ao final do período
de acompanhamento, ao passo que uma taxa de trombose de stent mais alta foi
observada no primeiro ano após a realização da angioplastia índice.
Estudos que compararam a incidência de trombose de stent utilizando SEDs e stents
metálicos não revestidos têm gerado dados conflitantes. Devido à baixa
incidência de trombose de stent (0,5% a 1,0% ao ano), os ensaios clínicos não
incluíram trombose de stent como desfecho primário. Em uma meta-análise25,26, a incidência de trombose de stent foi
semelhante após o uso de SED e stents metálicos não revestidos durante o
primeiro ano. Após um ano, o risco de trombose de stent parece ter sido mais
alto26. Em outro estudo, não houve
diferença na incidência de trombose de stent entre SEDs e stents metálicos não
revestidos durante os 15 meses de acompanhamento27. Em uma meta-análise de ensaios limitados à angioplastia primária
no infarto agudo do miocárdio, a taxa de trombose de stent observada para SEDs e
stents metálicos não revestidos foi semelhante apos 1 ano de acompanhamento27.
Dados de ensaios clínicos diferem de estudos observacionais na frequência de
desfechos clínicos após o uso de SEDs e stents metálicos não revestidos. Embora
ensaios clínicos tenham demonstrado que a mortalidade e taxas de IM foram
semelhantes para SEDs e stents metálicos não revestidos, estudos observacionais
no mundo real indicaram a redução na mortalidade, favorecendo o uso de SEDs21-25. Além disso, estudos recentes
indicaram uma redução significativa na ocorrência de trombose de stent com o uso
da segunda geração de SEDs em relação a stents metálicos não revestidos9,28.
O efeito de diferentes gerações de SEDs sobre os desfechos clínicos também deve
ser considerado. Poucas comparações foram feitas entre os stents Cypher, Taxus,
e Endeavor. Um destes estudos indicou que o stent Endeavor não é inferior ao
Cypher e é superior ao Taxus, quando a mortalidade por todas as causas, IM, e
RVA foram avaliados aos 12 meses29,30. No nosso registro, as incidências de
trombose, IM, e RLA foram semelhantes com o uso de cada um dos 3 stents.
Observou-se uma diferença significativa na incidência de RVA entre os grupos, e
uma incidência mais alta de RVA com o uso do stent Taxus.
Comparações diretas entre os stents Cypher e Taxus indicaram uma menor ocorrência
de trombose de stent e RLA com o uso do stent Cypher31. Outro estudo comparativo entre os stents Endeavor e
Taxus durante um período de acompanhamento de mais de 1 ano indicou uma menor
incidência de trombose de stent com o uso do stent Endeavor32. Embora esses estudos sugerem uma maior incidência de
trombose com o uso do stent Taxus em comparação com outros stents de primeira
geração, os resultados são variáveis e inconclusivos quando a trombose de stent
é avaliada como desfecho primário21.
Estudos recentes comparando os stents de segunda geração Xience V e Taxus
demonstraram uma menor incidência de trombose de stent com o uso do Xience
V9,22,23, apesar da adesão dos pacientes à
terapia antiplaquetária dupla ter sido semelhante durante o primeiro ano de
acompanhamento. Uma recente meta-análise de ensaios clínicos revelou uma baixa
incidência de trombose com o uso do SED Xience V em comparação com o stent
Taxus30. Assim, embora diferenças nas
taxas de trombose de stent entre os tipos de SED possam existir, a magnitude
desta diferença é difícil de avaliar34-36.
Os resultados de estudos desta natureza não podem ser comparados com os de
ensaios clínicos, devido à sua natureza não-randomizada. No entanto, os
registros do mundo real permitem avaliar os resultados em cenários clínicos não
contemplados em estudos randomizados.
Em conclusão, o presente estudo demonstrou o perfil de segurança favorável e a
eficácia dos SEDs durante um período de acompanhamento clínico de longo prazo no
mundo real, incluindo uma proporção significativa de pacientes com alto risco
cardiovascular, validando assim o uso de SEDs no tratamento de rotina de
pacientes com doença arterial coronariana.
Contribuição dos autores
Concepção e desenho da pesquisa: Gomes VO, Lasevitch R, Caramori P,
Pellegrini DO; Obtenção de dados: Gomes VO, Lasevitch R, Ledur P, Caramori
P, Pellegrini DO; Análise e interpretação dos dados: Smidt L, Azeredo MA,
Bodanese R, Sinnott L, Caramori P, Pellegrini DO; Análise estatística: Ledur
P, Caramori P, Pellegrini DO; Redação do manuscrito: Moriguchi E, Caramori
P, Pellegrini DO; Revisão crítica do manuscrito quanto ao conteúdo
intelectual importante: Moriguchi E, Caramori P.
Fontes de financiamento
O presente estudo não teve fontes de financiamento externas
Vinculação acadêmica
Este artigo é parte de Dissertação de Mestrado de Denise Oliveira Pellegrini
pela Universidade Federal do Rio Grande do Sul.