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