Homem de 39 anos com angina pós-infarto. Coronariografia demonstrou: obstrução total proximal da artéria coronária direita (ACD), lesões obstrutivas de 95% na artéria descendente anterior (ADA), 80% no 2° ramo marginal esquerdo (ME) e 95% na artéria circunflexa (ACX). O paciente foi submetido a implante de stent TAXUS 3,0 x 24 mm e stent EXPRESS 2,75 x 24 mm nos terços proximal e distal da ACD, respectivamente, e stent INFINNIUM 3,0 x 24 mm na ADA com sucesso. Após 7 meses, apresentou IAM anterior por trombose do stent INFINNIUM e reestenose do stent TAXUS, sem perda de resultado nos stents convencionais.
Hospital Stella Maris - Guarulhos, SP
Homem de 39 anos com angina pós-infarto. Coronariografia demonstrou: obstrução total proximal da artéria coronária direita (ACD), lesões obstrutivas de 95% na artéria descendente anterior (ADA), 80% no 2° ramo marginal esquerdo (ME) e 95% na artéria circunflexa (ACX). O paciente foi submetido a implante de
Os estudos multicêntricos randomizados comparativos entre os
O relato de caso de um paciente submetido a múltiplos implantes de
Trata-se de um homem de 39 anos de idade admitido com o diagnóstico de IAM inferior, com duas horas de evolução. Foi medicado com estreptoquinase intravenosa, apresentando sinais de reperfusão. A pressão arterial foi 140/90 mmHg e a freqüência cardíaca 80 bpm. A ausculta cardiopulmonar era normal. Apresentava como fatores de risco para doença arterial coronariana: tabagismo, obesidade, dislipidemia e hipertensão arterial.
Durante a hospitalização, evoluiu com angina pós-infarto. A coronariografia mostrou oclusão proximal da ACD, lesões obstrutivas de 95% no terço médio da ADA, 90% no terço proximal da ACX e de 80% no início do 2° ramo marginal esquerdo (ME2). A circulação colateral estava presente da ACD para a ACD ++/4+. A ventriculografia esquerda mostrou hipocontratilidade nas paredes inferior e anterior, de moderada intensidade, com fração de ejeção de 50%.
O paciente foi medicado com clopidogrel 300 mg via oral, no dia anterior ao procedimento e estava em uso de ácido acetilsalicílico (AAS) 200 mg via oral ao dia. Foi iniciada a infusão de cloridrato de tirofibana (AGASTRAT®) intravenoso 12 horas pré-implante e mantida por mais 12 horas pós-implante. Após a recanalização mecânica da ACD com a guia Shinobi® 0,014", foi realizada a pré-dilatação das lesões proximal e distal com cateter-balão Wordpass® 2,0 x 20 mm, seguido do implante de
Após dois meses da primeira internação, foi realizado o implante dos
Após sete meses da primeira internação, o paciente foi admitido com o diagnóstico de IAM anterior com mais de 12 horas de evolução, tratado com atenolol, aspirina, sinvastatina, enoxaparina e captopril. A coronariografia mostrou obstrução subtotal do
Trata-se do primeiro relato na literatura médica da trombose tardia pós-implante de
Iakovou e cols.5 descreveram o padrão angiográfico de reestenose pós-implante de
No presente caso, a reestenose ocorrida no TAXUS foi focal na borda proximal, portanto, dentro dos padrões de reestenose relatados para esse tipo de
Em relação ao INFINNIUM o quadro clínico e angiográfico caracterizam uma trombose intra-
Pesquisa recente realizada no banco de dados do
A reação de hipersensibilidade pós-implante de
As reações de hipersensibilidade a metais pesados (molibdênio e níquel) têm sido relatadas em 8% dos pacientes submetidos a implante de
O paclitaxel tem sido relacionado com reações de hipersensibilidade, mas a maioria dessas reações foram atribuídas ao veículo óleo de castor, não utilizado nos
Os polímeros biodegradáveis e não biodegradáveis, quando aplicados aos
Virmani e cols.9, em relato de óbito por trombose coronariana 18 meses pós-implante de
Portanto, podemos concluir que ocorreu uma trombose tardia do
Declaro não haver conflitos de interesses pertinentes.
Luciano Maurício de Abreu Rua Arminda de Lima, 480/171 07095-010 – Guarulhos, SP E-mail:
Artigo recebido em 08/08/06; revisado recebido em 08/08/06; aceito em 05/10/06.
A male 39 year-old patient with post-infarction angina. The coronary angiography showed total proximal obstruction of right coronary artery (RCA), obstructive lesions of 95% of the anterior descending artery (ADA), 80% of the second left marginal branch (LM2), and 95% of the circumflex artery (CXA). The patient was successfully implanted with a Taxus 3.0 x 24 mm stent and an Express 2.75 x 24 mm stent in the proximal and distal thirds of the RCA, respectively, and with an Infinnium 3.0 x 24 mm stent in the ADA. After seven months, the patient had an anterior acute myocardial infarct (AMI) due to thrombosis of the Infinnium stent and restenosis of the Taxus stent, with no loss of results in the conventional stents.
Hospital Stella Maris - Guarulhos, SP - Brazil
A male 39 year-old patient with post-infarction angina. The coronary angiography showed total proximal obstruction of right coronary artery (RCA), obstructive lesions of 95% of the anterior descending artery (ADA), 80% of the second left marginal branch (LM2), and 95% of the circumflex artery (CXA). The patient was successfully implanted with a Taxus 3.0 x 24 mm stent and an Express 2.75 x 24 mm stent in the proximal and distal thirds of the RCA, respectively, and with an Infinnium 3.0 x 24 mm stent in the ADA. After seven months, the patient had an anterior acute myocardial infarct (AMI) due to thrombosis of the Infinnium stent and restenosis of the Taxus stent, with no loss of results in the conventional stents.
Randomized multicentric studies comparing drug-eluting stents and conventional stents showed superiority of medicated stents in reducing the rate of restenosis1. Nevertheless, late safety results of these stents have not been completely established. Late in-stent thrombosis (after 30 post-implantation days), which was not observed in the first series of studies, has recently been reported2-4.
This case report of a patient who underwent multiple stent implants in whom late thrombosis occurred in the Infinnium stent associated with the restenosis of the Taxus stent, without restenosis of the conventional stents, raises an interesting discussion on the reasons for this event.
The patient is a 39-year-old man admitted with a diagnosis of inferior AMI for two hours. He was medicated with intravenous streptokinase and showed signs of reperfusion. Arterial pressure was 140/90 mmHg and heart rate was 80 bpm. Cardiopulmonary auscultation was normal. Risk factors for coronary artery disease were smoking, obesity, dyslipidemia, and arterial hypertension.
During hospitalization, the patient progressed with post-infarction angina. Coronary angiography showed proximal occlusion of the RCA, obstructive lesions of 95% of the mid third of the ADA, 90% of the proximal third of the CXA, and 80% at the beginning of the second left marginal branch (LM2). Collateral circulation was present from RCA to RCA ++/4+. Left ventriculography showed moderate hypocontractility of the inferior and anterior walls with an ejection fraction of 50%.
The patient was treated with 300 mg oral clopidogrel on the day before the procedure, and was using 200 mg oral aspirin, once a day. An intravenous infusion of tirofiban hydrochloride (AggastratTM) was initiated 12 hours pre-implant and maintained for an additional 12 hours post-implant. After mechanical recanalization of the RCA with the ShinobiTM 0.014" guidewire, pre-dilation of the proximal and distal lesions was performed with a WordpassTM 2.0 x 20 mm balloon catheter followed by the successful implantation of an ExpressTM 2.75 x 24 mm stent at the distal lesion and a Taxus ExpressTM 3.0 x 24 mm stent at the proximal lesion, both of them inflated to 12 atmospheres (
Two months after the first hospitalization, a BeStentTM 4.0 x 12 mm was implanted at the CXA lesion and an AVETM 3.5 x 9 mm stent was implanted at the LM2 lesion, both successfully. On pre-implant control coronary angiography it was noted that the Infinnium stent placed in the ADA maintained the initial result (
Seven months after the first hospital stay, the patient was admitted with a diagnosis of anterior AMI for over 12 hours, treated with atenolol, aspirin, simvastatin, enoxaparin, and captopril. The coronary angiography showed a subtotal obstruction of the Infinnium stent with TIMI grade I flow and a 90% focal obstructive lesion on the upper border of the Taxus stent. Conventional stents implanted in the CXA and LM branch showed no loss of results (
This is the first report in medical literature on late post-implant thrombosis of the Infinnium stent and it has the unique feature of a restenosis of the Taxus stent with no restenosis of the conventional stents.
Iakovou et al.5 described the angiographic pattern of post-implant restenosis of the Taxus stent and observed the prevalence of restenosis location in the body portion and borders of the stent (72%), followed by location in the borders (16%) and the body (11%) of the stent. When located in the borders, a proximal predominance was noted that was attributed to a more intense flow in this region of the stent that resulted in "washing" of the drug, leaving the stent more vulnerable to restenosis. The patterns of restenosis observed were focal (50%), diffuse in-stent (4%), proliferative (25%), and total obstruction (21%)5,6.
In our case, the Taxus restenosis location was focal in the proximal border, and therefore within the patterns of restenosis reported for this type of stent.
As to the Infinnium stent, the clinical and angiographic pictures were typical of late in-stent thrombosis, seven months after implant. The patient received clopidogrel for six months and thrombosis occurred 30 days after interruption of the medication; hence, it does not seem to us that the discontinuation of the drug, per se, was responsible for the thrombotic event. Recent publications have shown that late in-stent thrombosis occurred in 0.35 to 0.72% of the patients who underwent drug-eluting stent implants, most of them after discontinuation of clopidogrel, with a 4-day to 26-month interval between drug interruption and thrombosis, suggesting that an additional mechanism is responsible for this phenomenon, possibly late hypersensitivity to one of the stent components2-4.
A recent investigation carried out in the database of the Food & Drug Administration (FDA) and the Research on Adverse Drug/Device Events and Reports (RADAR) found 5,783 reports related to adverse events with drug-eluting stent implantations, and 262 reports of hypersensitivity, 13 of which were classified as probable and 4 of them confirmed by autopsies of patients with deaths associated with late in-stent coronary thrombosis7.
Post-implant hypersensitivity reactions of drug-eluting stents may occur due to antiplatelet treatments or stent components (polymer, drug, or metal portion).
Hypersensitivity reactions to heavy metals (molybdenum and nickel) were reported in 8% of patients who underwent stainless steel stent implants8. Hypersensitivity to these metals were associated with restenosis but not with thrombosis, and eosinophilic infiltrate was not observed upon histologic examination of human coronary arteries after implantation of stainless steel stents9. In our case, it is unlikely that this mechanism was responsible, since three conventional stents were implanted and none of them presented restenosis, and one of them was the Express stent platform for the Taxus stent.
Paclitaxel has been associated with hypersensitivity events, but most of these reactions were attributed to the castor oil vehicle, which is not used in drug-eluting stents9. The occurrence of a late hypersensitivity reaction to paclitaxel in this case report is unlikely, since the drug used in the Taxus and Infinnium stents is completely released within 30 and 48 days post-implant, respectively.
When applied to conventional stents, biodegradable and non-biodegradable polymers trigger local and systemic post-implantation hypersensitivity reactions in coronary arteries of pigs10. The Taxus Express stent uses the poly (styrene-b-isobutylene-b-styrene) polymer, and the Infinnium stent uses three polymers (poly-DL-lactide-co-glycolide, poly vinyl pyrrolidone, and poly lactide l-co-caprolactone), all of them biodegradable.
In a report on a death by coronary thrombosis 18 months post-implantation of a Cypher™ stent, Virmani et al9, upon histologic examination, observed giant cells surrounding a polymer fragment that had detached from the stent and numerous eosinophils in the artery wall.
Therefore, we may conclude that this is a case of a late thrombosis of the Infinnium stent 30 days after discontinuation of clopidogrel use, probably related to a late hypersensitivity reaction to the stent polymer. As to restenosis of the Taxus stent, it seems to be a local phenomenon not related to allergic reactions.
No potential conflict of interest relevant to this article was reported.
Luciano Maurício de Abreu Rua Arminda de Lima, 480/171 07095-010 – Guarulhos, SP - Brazil E-mail:
Manuscript received August 8, 2006; revised manuscript received August 8, 2006; accepted October 5, 2006.