If you are diagnosed with significant narrowing of the major heart arteries, it is more likely that you will undergo percutaneous coronary intervention (PCI) rather than open heart bypass graft surgery.
PCI is a procedure performed under local anaesthesia through the wrist or groin artery where a minute plastic catheter is passed through the limb arteries to the heart arteries and the narrowed heart artery is usually opened with a cylindrical mesh (stent) mounted on a balloon catheter. The stent is expanded by inflation of the balloon and the balloon catheter is then removed. The stent provides mechanical support to the expanded arterial segment and prevents spontaneous “collapse” of the arterial segment that may result from elastic recoil.
Following the opening of blocked heart arteries with stents, patients are routinely given blood thinning medications such as aspirin in combination with another blood thinning agent to prevent the clumping and aggregation of platelets. This dual anti-platelet therapy (DAPT) is given to prevent the platelets from “sticking” to the exposed surface of the stent strut within the lumen of the heart artery and causing the formation of a blood clot.
Duration of blood-thinning medications
The question on the minds of most patients is “Is it safe to stop the blood thinning medication?”. Mr A asked this question to his family doctor. He had stents placed into all his 3 major heart arteries using the first generation metallic stent that was coated with a polymer which contained drugs which gradually elute from the polymer into the surface of the arterial wall to prevent scar tissue formation (Drug Eluting Stent).
He had been well for 4 years and had asked his family physician whether it was possible for him to stop his blood thinning medication. His doctor had advised him that since he has been well for 4 years, he could stop his blood thinning medication.
Two weeks later, he was seen at the hospital’s emergency department for chest pain. He was found to have an evolving acute heart attack as a result of occlusion of the stents in his 3 major heart arteries by blood clots. An emergency PCI was performed to remove the blood clots and to open his heart arteries. This risk of occlusion of the stents with blood clots is a real risk with potentially dire consequences.
Upon implantation of a stent in the heart artery, the artery will form a layer of new cells in the arterial lumen to cover the exposed stent strut surface. If the stent surface is completely covered by the new layer of cells, platelet deposition will not occur. However, many of the earlier generation stents cannot be completely covered by the new layer of cells as the stent struts are much thicker, make coverage incomplete.
This incomplete coverage can also occur in the following events:
1) Distortion of the stent struts with protrusion of stent struts into the arterial lumen;
2) Failure of the stent to be in direct contact with the arterial wall during deployment; and
3) Remodelling of the arterial wall following stent deployment resulting in dilatation of the arterial wall with failure of the arterial wall to be in contact with the stent struts.
Simply put, these situations result in some of the stent struts remaining exposed and not covered by a layer of cells. With cessation of DAPT in these situations, there is an increased risk of platelet deposition on the walls of the stents triggering a biological reaction which results in the formation of blood clots and occlusion of the stent.
Current guidelines from professional cardiology organisations in the United States (American College of Cardiology, American Heart Association, and Society for Coronary Angiography and Intervention) recommend that for those with an acute heart attack who require emergency PCI, DAPT should be continued for at least 12 months after PCI. However if the PCI is performed electively in a non-emergency situation, a shorter period can be considered although the period is not specified. This shorter period of DAPT can also be considered for those with a high risk of bleeding.
The current guidelines from the European Society of Cardiology recommend DAPT for 12 months after PCI for an acute heart attack. However, for those with stable heart disease who undergo non-emergency PCI, the European Society of Cardiology recommends DAPT for 6 months after PCI. A shorter duration can be considered for those with a high risk of bleeding. Conversely, the duration can be longer if the bleeding risk is lower and the patients still has residual significant blockage of the heart arteries despite PCI.
Beyond blood thinning
The question is that whether the other non-aspirin anti-platelet agents (such as clopidogrel) have any additional benefits beyond thinning the blood and preventing the formation of a blood clot. Experimental studies show that clopidogrel can reduce the level of certain blood factors that have both the ability to cause inflammation and to facilitate the deposition of cholesterol into damaged lining of the lumen of the blood vessel. In addition when compared to those given placebo, those on clopidogrel had reduction in the size of the plaque and the plaque was more stable with more fibrous component (less likely for the plaque lining to tear and cause a heart attack). In the CASCADE trial published in 2014 in the Circulation journal, those on DAPT for 1 year after bypass heart surgery were less likely to have progression of existing heart artery disease and less likely to develop new occlusions.
Choice of stents
In an observational study published in 2007 in the Journal of the American Medical Association by researchers led by Eisenstein, patients with drug eluting stent implanted in their heart arteries who were well at 6 months, and had continued DAPT for 2 years had significantly less death (2% versus 5.3%) and heart attacks compared to those who were on aspirin only. Other observational studies show a similar trend. In one study on diabetics who had PCI, the incidence of death and heart attacks was as high as 16.5% for those who had less than 6 months of DAPT.
There are 9 randomised studies comparing DAPT for at least 12 months compared to a shorter duration of DAPT. The results are mixed with 7 studies showing no significant difference, 1 showing better outcomes with longer DAPT and 1 showing worse outcomes with longer DAPT.
The data generally show that prolonged DAPT carries an increased of bleeding. While many of the observational studies were based on data from early generation stents, most of the randomised studies were based on second generation stents. There is increasing evidence that with the use of second generation stents, the likelihood of late occlusion of stents by the formation of blood clots has almost been completely eliminated.
To stop or not to stop
The current data tells the following:
• For those with first generation stents, DAPT should be continued for at least 12 months.
• For those who had a heart attack and had stents put in the heart arteries, DAPT should at least be continued for 12 months.
• For those who had elective PCI procedures and have had second generation stents, it is reasonable to discontinue DAPT at 6 months if there is no residual significant narrowing of the heart arteries.
• For those who have a high risk of bleeding, second generation stents are preferred as some state in their “Instructions For Use” (IFU) that it is possible to interrupt the DAPT treatment after one month should the need arise (e.g. emergency surgery, bleeding stomach ulcer.)
The next question on most patient’s mind is whether after the period of DAPT treatment, can they stop the anti-platelet treatment completely or do they need to continue with one single anti-platelet agent? For those with first generation stents, they should continue with a single anti-platelet agent and this also applies for those with a heart attack. However for those who have no heart attacks, no residual heart artery disease and have second generation stents placed in their heart arteries, it may be possible to discontinue the antiplatelet agent completely provided that the risk factors for heart disease are well controlled and there is no other significant blockage of arteries in the body.
There is currently no consensus in this area. However, studies that have utilised special imaging methods to study the completeness of coverage of second generation stents by a new layer of cells in the arterial lumen provide supporting evidence that these newer generation stents achieved near complete coverage of the stents within weeks to months.
With the advent of newer generation of polymer stents that are absorbed by the body, the risk of stent occlusion by blood clots is zero when the polymer stent is completely absorbed in 2 to 3 years. Hence, theoretically the patient does not require any other anti-platelet medication after the stent is completely absorbed. However, if the patient has residual significant heart artery disease or uncontrolled risk factors, a single anti-platelet agent should be continued. The reason is that although the risk of stent occlusion by blood clots can be eliminated, the risk of subsequent heart attacks can be reduced by the consumption of an anti-platelet agent.