DEBATE ARTICLE
Drug-eluting stents not for all patients
F.H. de Man, P.R. Stella, P.A. Doevendans
I nterventional cardiology has made important progress in the past decades. The biggest step forward by far was the introduction of the bare metal stent. However, a major drawback introduced by the bare stent is in-stent restenosis. The drug-eluting stent was an important next step in the treatment of coronary artery disease. The results with regard to reduction of in-stent restenosis and target-vessel revascularisation are impressive. This has led to a rapid and widespread use throughout the world. In some centres, more than 90% of all stents implanted are drug-eluting. However, there has been concern about the safety profile. Long-term effects With regard to safety in the long term, data are scarce. The current trials for drug-eluting stents do not extend beyond two to three years offollow-up (and not more than 9 to 12 months in most of the major trials).'3 However, there have been several reports about late in-stent thrombosis, up to 535 days after the procedure.4'5 Other reports have described formation of coronary aneurysms and endothelial dysfunction after implantation of drug-eluting stents.67 It is therefore at least remarkable that these stents have been approved and adopted so quickly and widely without thorough long-term follow-up.
Risk of stent thrombosis The most dramatic outcome associated with stenting is stent thrombosis. Although in-stent restenosis is a relatively benign disorder from which people rarely die, stent thrombosis is associated with a high mortality rate. So, even small differences in incidence of stent thrombosis may have important implications for F.H. de Man P.R. Stella P.A. Doevendans University Medical Centre Utrecht, Utrecht, the Netherlands
Correspondence to P. Doevendans Department of Cardiology, University Medical Centre Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherands E-mail: [email protected]
174
survival and warrant our attention. The incidence of stent thrombosis with bare metal stents is reported to be 0.5 to 1.6%.810 In 2003, the Food and Drug Administration (FDA) published a web notification after receiving numerous reports of subacute stent thrombosis with the sirolimus-eluting stent."1 Theoretically, this may be expected because of the combination of delayed endothelisation of the drugeluting stent with an increased tendency to platelet aggregation on sirolimus.'2 The randomised clinical trials, however, could not confirm the raised suspicions.'"3 Iakovou conducted a prospective multicentre study to evaluate the incidence, predictors and outcome of stent thrombosis after implantation of drug-eluting stents in routine daily practice.'3 The incidence of stent thrombosis after successful implantation of drug-eluting stents at nine months was 1.3%. This is considerably higher than the reported incidence of stent thrombosis of 0.4% at one year for sirolimus, and 0.6% at nine months for pacitaxel in major clinical trials.'13 This can be explained by the observation that real-world patients and their lesions are more complex than selected patients from the major trials. The clinical consequences of stent thrombosis were death in 45% of patients and nonfatal myocardial infarction in the majority of the other cases. The strongest independent predictor of stent thrombosis was premature discontinuation of antiplatelet therapy (odds ratio 90, p
Drug-eluting stents not for all patients
F.H. de Man, P.R. Stella, P.A. Doevendans
I nterventional cardiology has made important progress in the past decades. The biggest step forward by far was the introduction of the bare metal stent. However, a major drawback introduced by the bare stent is in-stent restenosis. The drug-eluting stent was an important next step in the treatment of coronary artery disease. The results with regard to reduction of in-stent restenosis and target-vessel revascularisation are impressive. This has led to a rapid and widespread use throughout the world. In some centres, more than 90% of all stents implanted are drug-eluting. However, there has been concern about the safety profile. Long-term effects With regard to safety in the long term, data are scarce. The current trials for drug-eluting stents do not extend beyond two to three years offollow-up (and not more than 9 to 12 months in most of the major trials).'3 However, there have been several reports about late in-stent thrombosis, up to 535 days after the procedure.4'5 Other reports have described formation of coronary aneurysms and endothelial dysfunction after implantation of drug-eluting stents.67 It is therefore at least remarkable that these stents have been approved and adopted so quickly and widely without thorough long-term follow-up.
Risk of stent thrombosis The most dramatic outcome associated with stenting is stent thrombosis. Although in-stent restenosis is a relatively benign disorder from which people rarely die, stent thrombosis is associated with a high mortality rate. So, even small differences in incidence of stent thrombosis may have important implications for F.H. de Man P.R. Stella P.A. Doevendans University Medical Centre Utrecht, Utrecht, the Netherlands
Correspondence to P. Doevendans Department of Cardiology, University Medical Centre Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherands E-mail: [email protected]
174
survival and warrant our attention. The incidence of stent thrombosis with bare metal stents is reported to be 0.5 to 1.6%.810 In 2003, the Food and Drug Administration (FDA) published a web notification after receiving numerous reports of subacute stent thrombosis with the sirolimus-eluting stent."1 Theoretically, this may be expected because of the combination of delayed endothelisation of the drugeluting stent with an increased tendency to platelet aggregation on sirolimus.'2 The randomised clinical trials, however, could not confirm the raised suspicions.'"3 Iakovou conducted a prospective multicentre study to evaluate the incidence, predictors and outcome of stent thrombosis after implantation of drug-eluting stents in routine daily practice.'3 The incidence of stent thrombosis after successful implantation of drug-eluting stents at nine months was 1.3%. This is considerably higher than the reported incidence of stent thrombosis of 0.4% at one year for sirolimus, and 0.6% at nine months for pacitaxel in major clinical trials.'13 This can be explained by the observation that real-world patients and their lesions are more complex than selected patients from the major trials. The clinical consequences of stent thrombosis were death in 45% of patients and nonfatal myocardial infarction in the majority of the other cases. The strongest independent predictor of stent thrombosis was premature discontinuation of antiplatelet therapy (odds ratio 90, p
