Episode #228 The Journey of Drug-Eluting Stents and Anesthesia Patient Safety

Hello and welcome back to the Anesthesia Patient Safety Podcast. My name is Alli Bechtel, and I am your host. Thank you for joining us for another show. Let’s take a quick quiz. Question: How long do patients need to continue dual-antiplatelet therapy following placement of a drug eluding stent?

Before we dive into the episode today, we’d like to recognize Vertex Pharmaceuticals, a major corporate supporter of APSF. Vertex Pharmaceuticals has generously provided unrestricted support to further our vision that “no one shall be harmed by anesthesia care”. Thank you, Vertex Pharmaceuticals – we wouldn’t be able to do all that we do without you!”

Don’t worry. We will reveal the answer to our question on the show today as we discuss our featured article from the October 2024 APSF Newsletter. It is “New Drug-Eluting Cardiac Stents and Dual Antiplatelet Therapy: How Short is Too Short?” by Janak Chandrasoma, Abigail Song, Joseph Szokol, and Antreas Hindoyan. This article has it all, history, a literature review, and guidelines. Plus, we have exclusive content from the authors. To follow along with us, head over to APSF.org and click on the Newsletter heading. First one down is the current issue, October 2024. Then, scroll down until you get to our featured article today. I will include a link in the show notes as well.

To help kick off the show today, we are going to be hearing from one of the authors. Let’s take a listen now.

[Szokol] “I am Joseph Szokol, a professor of clinical anesthesiology at the Keck School of Medicine of USC in Los Angeles, California. The reason we wrote this article was due to the significant knowledge gap on the subject of the duration of dual anti platelet therapy after the placement of a drug eluting cardiac stent.

The outdated and probably prevalent view is that patients received a drug eluting stent would have to be on dual anti platelet drugs for anywhere between six and twelve months. The obvious concern is the fear of early and late stent thrombosis. However, there has been a revolution and technology behind drug eluting stents.

While most drug eluting stents are based on durable polymers such as cobalt chromium, platinum chromium, and other metals, they’re increasing use of biodegradable polymer-based drug eluting stents, which allows for an even shorter period of time with dual entry. platelet therapy, which has a potential for a decreasing inflammatory response and to prove drug elution kinetics and low rates of early and late stent thrombosis.

Additionally, there are a new generation of anti-proliferative agents, which have allowed the early discontinuation of dual antelope platelet therapy. With over 600, 000 cardiac stents placed a year, it will not be unusual for an anesthesia professional to be faced with these newer generation stents.”

[Bechtel] Thank you so much to Szokol for helping to introduce this important topic. Have you provided anesthesia care for a patient who had one of these newer generation cardiac stents place? And now, it’s time to get into the article.

First, we are going to review some history going back to the Spring 2009 APSF Newsletter and the article, “Perioperative Coronary Stent Thrombosis: A Continuing Safety Concern” by Greenberg and colleagues. This article from our archives highlighted the risk of late thrombosis after drug-eluting stent placement. When an in-stent thrombosis occurred, there was a 60% myocardial infarction rate with a mortality rate of almost 50%. These events were rare, but devastating when they occurred. Animal studies of bare metal stents revealed complete endothelialisation in 28 days and for the first generation drug-eluting stents there was incomplete healing at 180 days. The recommendations in 2008 from the American College of Chest Physicians included delaying elective surgery for 12 months after placement of a drug-eluting stent. As we know, many surgeries are not purely elective and the recommendations did not address patients requiring urgent surgery. The 2009 APSF article recognized this threat to anesthesia patient safety. There was a call to action for collaboration between the patient, internist, surgeon, anesthesia professional, and cardiologist to consider the type and timing of stent placed, the nature and urgency of the surgery, the management of perioperative antiplatelet therapy, and the choice of facility to perform the surgery. Patients with recent stent placement who required urgent surgery would ideally have their surgery performed at a facility with 24 hour interventional cardiology available to perform emergent percutaneous coronary intervention if required to treat the dreaded in-stent thrombosis. I will include a link to the 2009 APSF Newsletter article in the show notes as well.

Over the past 15 years, there has been some technological advancements when it comes to cardiac stents. The first-generation stents were made of a standard bare metallic stent and a coated polymer mixed with an anti-restenotic drug such as sirolimus or paclitaxel. Newer-generation drug-eluting stents include biodegradable polymer stents or bioresorbable scaffolds. These have a lower rate of in-stent thrombosis and may need a shorter duration of dual antiplatelet therapy without compromising patient safety.

An important consideration with every type of cardiac stent when deciding on the optimal duration of dual antiplatelet therapy is balancing the risks. On one hand, there is the risk of in-stent thrombosis and on the other, there is the risk of bleeding complications. Prolonged dual antiplatelet therapy is associated with an increased risk of bleeding complications and elderly patients and those with multiple comorbidities are at higher risk as well. When bleeding complications occur, this increases the risk of morbidity and mortality. We can calculate the bleeding risk associated with dual antiplatelet therapy with the PRECISE-DAPT Score and the Academic Research Consortium for High-Risk Bleeding, the ARC-HBR Criteria. To calculate the PRECISE-DAPT score, you can head over to precisedaptscore.com and use their web calculator. There, you will need to input the hemoglobin level, age, white blood cell count, creatinine clearance, and if there was a prior bleeding event to get the patient’s score and their calculated bleeding risk. Check out the link in the show notes.

The ARC-HBR includes 20 clinical criteria that were determined based on consensus and published evidence. The good news is that you don’t have to calculate a score. Patients are high bleeding risk if they have at least one major criteria or two minor criteria present or they are not high bleeding risk. Here are the major criteria:

1. Long-term oral anticoagulation
2. Severe or end-stage chronic kidney disease (CKD) (estimated glomerular filtration rate [eGFR] <30 ml/min)
3. Hemoglobin <11 g/dl
4. Spontaneous bleeding requiring hospitalization and transfusion in the past 6 months
5. Moderate to severe baseline thrombocytopenia (platelet count <100 x 109/L)
6. Chronic bleeding diathesis
7. Liver cirrhosis with portal hypertension
8. Active cancer in the past 12 months
9. Previous spontaneous ICH (at any time)
10. Previous traumatic ICH within the past 12 months
11. Presence of known brain arteriovenous malformations
12. Moderate to severe ischemic stroke within the past 6 months
13. Nondeferrable major surgery on dual antiplatelet therapy
14. Recent major surgery or trauma within 30 days before PCI

And the minor criteria:

1. Age >75 years
2. Moderate CKD (eGFR 30-59 ml/min)
3. Hemoglobin 11-12.9 g/dl for men and 11-11.9 g/dl for women
4. Spontaneous bleeding requiring hospitalization or transfusion within the past 12 months not meeting major criterion
5. Long-term use of oral nonsteroidal anti-inflammatory drugs or steroids
6. Any ischemic stroke at any time not meeting major criterion

Check out Table 1 in the article for a list of the High Bleeding Risk Criteria. Remember, high bleeding risk is defined as the presence of at least one from the list of high bleeding risk criteria.

Let’s continue our literature review with some of the evidence that supports a shorter duration for dual antiplatelet therapy. There are two early studies that evaluated high-risk patients who underwent PCI and then completed a short duration of dual antiplatelet therapy with either ticagrelor monotherapy or ticagrelor with aspirin. Ticagrelor is a reversible and direct-acting oral P2Y 12 receptor antagonist that provides faster, greater, and more consistent platelet inhibition when compared to Clopidogrel. The first study published in the Lancet in 2018 reported improved outcomes after PCI for patients who received Ticagrelor and Aspirin for one month followed by Ticagrelor alone for 23 months compared to standard antiplatelet therapies with clopidogrel or ticagrelor with aspirin for 12 months followed by aspirin for 12 months. The second study, published in the New England Journal of Medicine in 2019 evaluated high-risk patients who underwent PCI and completed 3 months of dual antiplatelet therapy. The results revealed that Ticagrelor monotherapy was associated with a lower incidence of clinically relevant bleeding compared to ticagrelor and aspirin therapy. There was no higher risk of death, MI, or stroke with Ticagrelor monotherapy.

If you want to continue the literature review, check out Table 2 in the article for a list of recent studies that looked at shorter duration dual antiplatelet therapy regimens. Overall, these studies highlight the safety and efficacy of shorter duration dual antiplatelet therapy. Another important consideration is that the newer coronary stents may be a good choice for patients at higher risk for bleeding. The results from these studies reveal lower rates of ischemia which means shorter duration dual antiplatelet therapy which means lower bleeding risk and less complications from bleeding. Multiple studies have shown that the newer stents are comparable to bare metal stents in terms of all-cause mortality, myocardial infarction, stroke, and ischemia-driven target lesion revascularization.

We will be back next week to continue the literature review and discuss the societal recommendations in more detail. Before we wrap up for today, we are going to turn our attention to Table 3 in the article. There are three societies that have provided recommendations. Let’s go through them now.

• First, the ACC/AHA guidelines are level of recommendation 2a with level of evidence A and the recommendation is that a shortened dual antiplatelet therapy of 1-3 months is reasonable.
• Next, the European society of cardiology guidelines have level 2a recommendations with level of evidence B. Their recommendation is that in patients with high risk of bleeding, discontinuation of P2Y12 receptor inhibitor therapy after 3 months should be considered.
• Finally, the American College of Chest Physicians provdes a conditional recommendation with very low-level certainty of evidence for the following: In patients receiving aspirin and a P2Y12 inhibitor who had coronary stents placed within the last 3 to 12 months and are undergoing elective surgery/procedure, we suggest stopping the P2Y12 inhibitor prior to surgery over continuation of the P2Y12 inhibitor.

Don’t worry, we will be back next week to talk about the evidence and recommendations in more detail. Plus, we will have more exclusive content from one of the authors.

If you have any questions or comments from today’s show, please email us at [email protected]. Please keep in mind that the information in this show is provided for informational purposes only and does not constitute medical or legal advice. We hope that you will visit APSF.org for detailed information and check out the show notes for links to all the topics we discussed today.

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Until next time, stay vigilant so that no one shall be harmed by anesthesia care.

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