Drug-eluting stents in real life

Background key features

• DES for the treatment of coronary artery disease are widely used by interventional cardiologists for the treatment of obstructive coronary stenosis. Current guidelines gathering state-of-the-art knowledge recommend prolonged dual antiplatelet therapy mandatory after DES implant. However, dual antiplatelet therapy can lead to serious bleeding complications, especially among complex patients, and makes it difficult to perform elective surgeries if needed during this period.
• The rising number of complex patients and complex coronary lesions treated increases the number of patients in which difficult clinical decisions have to be taken.
• Both interventional and clinical cardiologists may participate in the decision on which should be the best treatment option for complex patients with high risks of both bleeding and thromboembolic complications.

1 ) The clinical dilemma

The addition of antimitotic drugs released from polymer coatings into coronary stents has achieved a significant decrease of in-stent restenosis and a corresponding decrease in the subsequent need for new revascularisations. Furthermore, drug-eluting stents (DES) significantly reduce major adverse cardiac events. These beneficial results have lead to a widespread use of these devices in patients with increasing degrees of lesion complexity and comorbidities.

After the initial experience with DES, researchers and clinicians have been faced with a new unfrequent but critical complication: DES thrombosis, accounting for 0,35-3,1%/year in patients receiving DES.

The use of DES call for prolonged dual antiplatelet therapy in order to avoid thrombus formation within the stent during the endothelisation period. Thus, many patients benefiting from less neointimal proliferation in order to prevent restenosis and susequent revascularisations, carry the risk of delayed or incomplete endothelisation, particularly after discontinuation of antiplatelet therapy (hazard ratio: 57 95% CI: 15-220). The problem increases with the dramatic drop in adherence to medication after 3 months of therapy, due to lack of medical information, reimbursement policies and many other factors.

Additionally, patients undergoing percutaneous coronary revascularisation are older, with a significant degree of comorbidities which complicate medical decisions and require special attention (multiple drug regimens, reduced mobility, risk of falling, risk of urgent trauma surgeries, gastrointestinal complications).

2) DES vs. BMS in real life

Clinical cardiologists consider percutaneous revascularisation for their patients to achieve longer survival and better symptom relief. In some clinical scenarios, complex patients undergo coronary revascularisation with one or more stents which are placed by an interventional cardiologist that decides which stent is suitable for the patient.

The decision whether to implant a BMS or a DES is taken in most instances exclusively by the interventional cardiologist, who usually does not assume patient follow-up and does not tackle the possible complications.

There are some accepted situations in which DES have demonstrated in clinical trials to be clearly superior to BMS (“on-label indications”): stable/unstable angina, single de novo lesions in native vessels, diameter 2,5-3,75 mm and length up to 28 mm and coronary arteries supplying a large area of jeopardised myocardium (proximal anterior descending artery or total chronic occlusion).

Despite these indications, some interventional cardiologists also accept DES use in other situations, for instance myocardial infarction, high-risk acute coronary syndromes, systolic dysfunction, bifurcations, chronic total occlusions, saphenous venous grafts, multi-vessel disease, diabetics and left main stenoses, based on their experience or on non-evidence based anatomical or clinical reasons (the so-called “off-label indications”). BMS are currently widely used in simple or short lesions involving vessels above than 3mm in diameter.

3) The basis for the decision

The decision regarding stent implantation and the corresponding oral anticoagulant/antiplatelet treatment in different clinical scenarios should be based on a stepped approach (see Figure 1).

First of all, we should consider the risk of bleeding inherent to that particular patient. This risk can be classified as low, medium or high according to some patient characteristics and the likelihood of some planned/unplanned future surgeries. Table 1 lists some of the frequently performed procedures in which there exist a high risk of bleeding and, as a result, a conflict can arise between the need for intensive antithrombotic therapy and the surgical risk of bleeding. In the low-risk category, among others, can be included dermatologic, dental (perhaps with the exception of wisdom tooth extraction), ophthalmologic, and arthroscopic interventions. Evidence exists that significant bleeding complications are very unusual in those procedures in which blood loss is scarce or is easy to control by local haemostatic measures. Therefore, these procedures can be performed safely on dual antiplatelet therapy.

The second consideration is the risk of thromboembolic complications, including coronary events and specifically in-stent thrombosis. In patients with a high thromboembolic risk (Table 2), especially if bleeding risk is also significant, DES implantation should be carefully evaluated and comprehensive decision made by both clinical and interventional cardiologists.

4) Unanswered questions

There are some remaining questions that will be answered in future studies:

• Which patients should undergo dual antiplatelet therapy beyond usual 6-12 months because of a permanent stent thrombosis risk?
• Which scores better predict further benefits in real-life from DES? Do scores obtained from clinical studies represent real-life patients?

Future techniques analysing antiplatelets' effect, safer DES, better antiplatelet regimens and better medical knowledge will help reduce thrombotic and bleeding complications resulting from coronary artery revascularisation.

Figure 1 summarises the general approach in terms of oral antiplatelet and anticoagulant treatment in patients receiving DES and BMS:

Figure 1: Algorythm for the management of anticoagulant-antiplatelet therapy in patients receiving coronary stents.



ASA: acetyl salicylic acid; OAC: oral anticoagulant treatment; BMS: bare metal
stents; DES: drug eluting stents; CABG: coronary bypass surgery.
* 1 year after an acute coronary syndrome
** Clopi + OAC also possible
*** Avoid DES if possible.

Conclusion:

Practical guidelines are the following :

• Any patient receiving either a BMS or a DES should receive dual antiplatelet therapy with clopidogrel and aspirin during a variable period, depending on the type of stent. After that period, aspirin should be continued indefinitely.
• Patients receiving chronic anticoagulant treatment can receive a DES, preferably if bleeding risk is low (< 3 %).
• DES should be avoided in patients with a high risk of bleeding, in whom BMS are preferable in order to reduce the likelihood of short-term and chronic bleeding complications.
• Comorbidities, age, and concomitant drug therapies should be taken into account when deciding if a DES should be implanted or not in a given patient, with an equal if not higher level of importance as pure anatomical considerations. In this decision-making process the clinician in charge of the patient must play a major role.