STEMI – The Early Career Voice

Anti-platelet therapy in STEMI

August 23, 2021August 17, 2021 Lina Ya'qoub, MD

ST-elevation myocardial infarction (STEMI) is considered a medical emergency globally, where the patient must seek medical help immediately. The treatment plan for this condition involves reperfusion therapy with or without stent placement, controlling the comorbidities and using specific medications to reduce the risk of recurrence and future complications.

One of the major drug categories is the antiplatelet therapy. So we will discuss briefly the different types of anti-platelet drugs used in STEMI and the different patient scenarios in STEMI. [1][2]

A-Antiplatelet Therapy to Support Primary PCI

1- Aspirin

– Loading Dose of 162 to 325 mg should be given before primary PCI, to be chewed or crushed to establish a high blood level quickly. (More rapid absorption occurs with non-enteric-coated formulations).

– After PCI, aspirin 81 -325 mg should be continued indefinitely (81 mg is the preferred dose)

2- P2Y12 receptor inhibitors

– A loading dose of a P2Y12 receptor inhibitor should be given as early as possible before or at time of primary PCI. Options include one of the following:

Clopidogrel 600 mg

US FDA has highlighted the potential impact of CYP2C19 genotype on clopidogrel pharmacokinetics and clinical response ( e.g: drug interaction with PPI ) . Nevertheless, other studies have not confirmed associations è Future studies are needed to further clarify the risk .[3]

Prasugrel 60 mg

NOT to be administered to patients with a history of stroke or transient ischemic attack and was not shown to be beneficial in patients ≥75 years of age or patients who weigh <60 kg.[4]

Ticagrelor 180 mg

** Prasugrel and Ticagrelor are preferred to clopidogrel. [5] [6]

– P2Y12 inhibitor therapy should be given for at least 1 month in patients with BMS and at least 6 months in patient with DES, using the following maintenance doses: [2]

(( This duration can be extended or reduced according to the patient specific ischemic and bleeding risks )).

Clopidogrel 75 mg daily
Prasugrel 10 mg daily
Ticagrelor 90 mg twice daily

3- GlycoProtein(GP) IIb/IIIa receptor antagonist

– these drugs are given at the time of primary PCI (with or without stenting or clopidogrel pre-treatment) in selected patients with STEMI who are receiving unfractionated heparin (UFH).

– patients who might benefit from a GP IIb/IIIa inhibitor include those who are found to have no or slow reflow, large thrombus burden, or intraprocedural bailout for distal embolization, coronary artery dissection, or hemodynamic instability.

Options include the following :

a.Abciximab:

-dose of 0.25-mg/kg IV bolus, then 0.125 mcg/kg/min (maximum 10 mcg/min)

b.high-bolus-dose Tirofiban :

– dose of 25-mcg/kg IV bolus, then 0.15 mcg/kg/min

– In patients with CrCl <30 mL/min, reduce infusion by 50%

c.Double-bolus Eptifibatide :

– dose of 180-mcg/kg IV bolus, then 2 mcg/kg/min; a second 180-mcg/kg bolus is administered 10 min after the first bolus.

– In patients with CrCl <50 mL/min, reduce infusion by 50%

– Avoid in patients on hemodialysis.

B-Antiplatelet Therapy With Fibrinolysis at a Non–PCI-Capable Hospital

1-Aspirin

– 162- to 325-mg loading dose

– should be continued indefinitely ( 81 mg is the preferred dose)

AND

2-P2Y12 receptor inhibitors

– Clopidogrel

– 300-mg loading dose for patients <= 75 years of age

– 75-mg loading dose for patients >75 years of age

– followed by: 75 mg daily should be continued for at least 14 days and up to 1 year

– prefer clopidogrel in this scenario over ticagrelor or prasugrel due to the increased risk of bleeding with the latter two. (( pretreatment with ticagrelor or prasugrel is considered a relative contraindication to fibrinolytic therapy )) [7]

C-Antiplatlet therapy when Transfer to a PCI-Capable Hospital After Fibrinolytic Therapy

1-Aspirin

– 162- to 325-mg loading dose

– 81- to 325-mg daily maintenance dose (indefinite)

– 81 mg daily is the preferred maintenance dose

2- P2Y12 receptor inhibitors

– Clopidogrel

– if the patient’s Age <= 75 years: 300-mg loading dose

– if the patient’s Age >75 years: no loading dose, give 75 mg

– Followed by 75 mg daily for at least 14 days and up to 1 year in absence of bleeding

D- Urgent CABG

1-Aspirin

– should not be withheld before urgent CABG

2- P2Y12 receptor inhibitors

– Clopidogrel or ticagrelor should be discontinued at least 24 hours before urgent on-pump CABG, if possible.

– Urgent CABG within 5 days of clopidogrel or ticagrelor administration or within 7 days of prasugrel administration might be considered, especially if the benefits of prompt revascularization outweigh the risks of bleeding.

3- GlycoProtein(GP) IIb/IIIa receptor antagonist

– Short-acting intravenous agents (eptifibatide, tirofiban) should be discontinued at least 2 to 4 hours before urgent CABG.

– Abciximab should be discontinued at least 12 hours before urgent CABG

– Urgent off-pump CABG within 24 hours of clopidogrel or ticagrelor administration might be considered, especially if the benefits of prompt revascularization outweigh the risks of bleeding.

The following table discusses some differences between P2Y12 receptor inhibitors.

P2Y12 receptor antagonist

Mechanism of binding

Loading dose

Maintenance dose

Prodrug

Comments

Clopidogrel

Irreversible

Inhibitor

300 mg

600 mg

75 mg once daily

Yes

The drug needs to be metabolized into its active form

-Warnings/Precautions:

1-Bleeding risk

2-Thienopyridine hypersensitivity

3-Thrombotic thrombocytopenic purpura (TTP) usually occurring within the first 2 weeks

– to be discontinued at least 5 days before surgery

Ticagrelor

Reversible inhibitor

180 mg

90 mg twice daily

-Warnings/Precautions:

1-Bleeding risk

2-Bradyarrhythmias and Ventricular pauses

3-Hyperuricemia

4-dyspnea

5-Thrombotic thrombocytopenic purpura (TTP) usually occurring within the first 2 weeks

– to be discontinued at ≥5 days before surgery.

Prasugrel

Irreversible inhibitor

60 mg

10 mg once daily

Yes

The drug needs to be metabolized into its active form

-Warnings/Precautions:

1-Bleeding risk

[US Boxed Warning]: Do not use prasugrel in patients with active pathological bleeding or a history of TIA or stroke.

2-Hypersensitivity

3-Thrombotic thrombocytopenic purpura (TTP) usually occurring within the first 2 weeks

– to be discontinued at least 7 days before surgery

Table (1) : Summary of P2Y12 Receptor antagonist agents dosing, pharmacokinetics and adverse effects.

A special thank you to my sister, Rawan Ya’acoub, a clinical pharmacist and assistant professor at the University of Jordan, who helped me write this blog.

Reference:

[1]- 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction

[2]- 2016 ACC/AHA Guideline: Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease

[3]-Society for Cardiovascular Angiography and Interventions; Society of Thoracic Surgeons; Writing Committee Members, Holmes DR Jr, Dehmer GJ, Kaul S, Leifer D, O’Gara PT, Stein CM. ACCF/AHA Clopidogrel clinical alert: approaches to the FDA “boxed warning”: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents and the American Heart Association. Circulation. 2010 Aug 3;122(5):537-57. doi: 10.1161/CIR.0b013e3181ee08ed. Epub 2010 Jun 28. PMID: 20585015.

[4]-Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S, Neumann FJ, Ardissino D, De Servi S, Murphy SA, Riesmeyer J, Weerakkody G, Gibson CM, Antman EM; TRITON-TIMI 38 Investigators. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007 Nov 15;357(20):2001-15. doi: 10.1056/NEJMoa0706482. Epub 2007 Nov 4. PMID: 17982182.

[5]-Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, Horrow J, Husted S, James S, Katus H, Mahaffey KW, Scirica BM, Skene A, Steg PG, Storey RF, Harrington RA; PLATO Investigators, Freij A, Thorsén M. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009 Sep 10;361(11):1045-57. doi: 10.1056/NEJMoa0904327. Epub 2009 Aug 30. PMID: 19717846.

[6]-Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S, Neumann FJ, Ardissino D, De Servi S, Murphy SA, Riesmeyer J, Weerakkody G, Gibson CM, Antman EM; TRITON-TIMI 38 Investigators. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007 Nov 15;357(20):2001-15. doi: 10.1056/NEJMoa0706482. Epub 2007 Nov 4. PMID: 17982182.

[7]- Sabatine MS, Cannon CP, Gibson CM, López-Sendón JL, Montalescot G, Theroux P, Claeys MJ, Cools F, Hill KA, Skene AM, McCabe CH, Braunwald E; CLARITY-TIMI 28 Investigators. Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation. N Engl J Med. 2005 Mar 24;352(12):1179-89. doi: 10.1056/NEJMoa050522. Epub 2005 Mar 9. PMID: 15758000.

“The views, opinions and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your personal health matters. If you think you are having a heart attack, stroke or another emergency, please call 911 immediately.”

Physicians Shouldn’t Be Heard Only During a Pandemic

April 30, 2020April 30, 2020 Adham Karim, MD

I know that COVID-19 has dominated the headlines for quite some time, and I’m sorry in advance, but yeah, this is another COVID-19 article. I’m not an infectious disease expert, and I’m not here to talk about the possible health benefits of black seed oil, vitamin C, or Alex Jones’s anti-covid toothpaste.

The anti-vaxxer movement and the virulent spread of e-cigarettes helped highlight what happens when physicians and scientists are silent on social media – pseudoscience and flat out bad advice rise to fill the void. Of course both of these movements have swung in the other direction as more knowledgeable voices found prominence, but that’s not without many unfortunate cases of measles and vape induced lung injury first causing people to second guess the misinformation.

With our current situation, there are a LOT of learning points. Chief amongst them is what happens when doctors stay out of (or get involved in) public policy. The national stockpiles were woefully understocked. The pandemic response team was dismantled (in 2018). The CDC lost huge amounts of funding. The list goes on and on. On the other hand, having an experienced physician in the room where decisions are made has had a significantly positive impact. Of course, like vaccines, statins, and social distancing, it’s difficult to quantify the impact of something when all you’re left with is the absence of a bad outcome.

What’s not difficult, is to learn from what happened with this outbreak. We’ve seen a rapid shift towards telemedicine adoption, and a lag in the deployment of testing kits. We’ve also seen that rapid adoption of a potential wonder drug treatment (hello Hydroxychloroquine) might actually result in MORE deaths, and make it difficult for people with lupus and rheumatoid arthritis to get refills on their HCQ prescriptions. Society as a whole has come to realize.

As a trainee, I’ve read heart wrenching stories about people in my position forced to work with inadequate PPE, and ultimately succumbing to this virus. I agree that medicine is a field that demands sacrifice, but I disagree that someone who signed up for this job should accept improper protection at the risk of their own life. In my own program, residents have come down with the coronavirus despite adequate PPE; so I can only imagine how those with less equipment must feel like. Having spent time on the Covid unit myself, I got a taste of what my friends in New York and Chicago were dealing with on a larger scale, and an every day basis for the past several weeks. Of course, I’m fortunate enough to work in a state that was not in the top 3 hit by coronavirus, and whose leadership includes a pro-active governor and an experienced physician.

We need to be more vocal on the policy level – and while it may not be as sexy as deploying a stent into a thrombosed LAD or as intellectually titillating as making a breakthrough in the science of atherosclerosis, it is arguably just as necessary. We don’t need to be running for office, but it certainly wouldn’t hurt to write to one’s Congress representative (https://www.house.gov/representatives/find-your-representative), and sign with your name and job title. Let them know how many people’s lives you impact, and tell them to provide you with aid. I’m not just talking about masks and gowns. I’m talking about hazard pay and disability benefits. If I suffer complications related to coronavirus, I most likely got it because of my job, not because I went to the grocery store one time last week. I want to know my family won’t get sacked with a huge bill because of that. As a physician, I’m fortunate enough to expect an increase in pay when I finish training, but I work alongside many other healthcare providers who are not so fortunate – they shouldn’t have to worry about financial calamity just for doing their job and helping their fellow countrymen.

Several iterations of coronavirus relief aid have been put out by Congress, and trillions of dollars have been disbursed. I’m glad to know that Shake Shack was able to secure 10 million dollars to pay its employees, but I’d like to know what has been done for the residents in NY who died from complications relating to Covid. What’s more is that we are now starting to see the consequences of the Covid scare – the dramatic down tick in strokes, STEMI activations and other acute illnesses doesn’t mean America suddenly got healthier – it means that a lot of these people were staying home, and our hospitals will need to be prepared to deal with the sequelae of these conditions as people start to come out of the woodwork.

In a climate where the aid given to businesses and Wallstreet far outweighs that given to the front line providers, I can only say that we physicians are not blameless. Ultimately, these are just the frustrated ramblings of another trainee who has seen so many of his colleagues impacted negatively one way or another, all while the public is more concerned with being able to mow their lawn than the wellbeing of those on the front line. As Dr. Fauci (who, by the way, might be getting nominated to be Vanity Fair’s Sexiest Man Alive) once said: “you just have a job to do. Even when somebody’s acting ridiculous, you can’t chide them for it. You’ve got to deal with them. Because if you don’t deal with them, then you’re out of the picture.”

Sources

https://www.ama-assn.org/delivering-care/public-health/residency-pandemic-how-covid-19-affecting-trainees

http://www.onlinejacc.org/content/early/2020/04/07/j.jacc.2020.04.011

https://www.medscape.com/viewarticle/928337

To Stent or not to Stent?

January 28, 2020January 28, 2020 Adham Karim, MD

In the wake of the ISCHEMIA trial results being published, and the media firestorm that ensued, I’ve run into some interesting scenarios, including STEMI patients saying they don’t want to be revascularized because they heard on the news that stents are useless (oh boy!). However, after a robust discussion with an intern, I decided to do a quick n dirty rundown of who does and does not need immediate revascularization, and which strategy to go with.

If there’s one thing you should know about the ISCHEMIA trial, it is that this study sought to answer the question of whether or not STABLE ischemic heart disease would benefit from an aggressive revascularization strategy vs a conservative strategy of goal-directed medical therapy. This had nothing to do with patients who had ACS. I will also add that with long-term followup, the results might change, nobody knows for certain. The reason I say this is because the PCI arm had a signal towards harm in the first 6 months after revascularization, but as they approached 4 years, the mortality curves started to separate in favor of the aggressive revascularization arm. As it stands, their conclusions were not in favor of an aggressive strategy over a conservative one. Interestingly, these results didn’t differ very much from the COURAGE trial, where they found no significant difference between optimal medical therapy vs PCI for stable ischemic heart disease. Differences to note include the fact that COURAGE did NOT use FFR, and did not have routine use of DES.

Keep in mind, patients with left main stenosis > 50% were excluded from both of these trials, as were those who had recent revascularization within the past 6 to 12 months (PCI or CABG). The reason I mention this is because some people thought these results contradicted the findings of the COMPLETE trials – but no, these trials looked at different sets of patients altogether!

A few big wins for the ISCHEMIA trial:

CT-angiography was shown to be very reliable
FFR-guided PCI is becoming more routinely accepted as the preferred method of PCI
Optimal medical therapy really helps…even if there turns out to be a mortality benefit in favor of early-PCI, the fact that it takes several years to emerge is a statement about how helpful these medications truly are.

With regards to stable ischemic heart disease, clear indications for revascularization include left main stenosis > 50%, proximal LAD with >50% stenosis, or multi-vessel disease with signs of impaired ventricular function. Typically, cardiologists will employ the SYNTAX score, which is a validated system used to grade the severity and complexity of lesions. Typically, SYNTAX scores < 23 are amenable to PCI and non-inferior to CABG. The typical scenario for PCI is when you have isolated disease in only 1 or 2 vessels, and this is amenable to stenting.

Once you have significant left main disease, especially in conjunction with 2-3 vessel disease, the SYNTAX score is > 32, and CABG is superior.

Until very recently, it was generally accepted that isolated left main disease could be treated by PCI or CABG. However, some controversy has erupted recently after the results of the EXCEL trial were published. Specifically, the EXCEL trial had a composite endpoint of stroke, MI, or death, and there was no statistically significant differences between the two groups. Surgeons will tell you that the higher rates of the composite endpoint were driven by excess all-cause mortality in the PCI arm, as compared to peri-procedural MI in the CABG arm…in other words, while the composite endpoints were similar in both groups, the individual endpoint of mortality was higher with PCI, whereas peri-procedural MI was higher with CABG. This can certainly be a bit contentious, especially if you wonder what the clinical significance of a troponin elevation is after CABG. Nonetheless, the trial was powered to detect differences in the COMPOSITE endpoint, not in the individual endpoint of mortality.

The STICH trial demonstrated a significant benefit (albeit 10 years out) in favor of revascularization (this study only looked at CABG) for patients with ischemic heart failure. The FREEDOM trial took it one step further and tried to compare DES to CABG for mutli-vessel CAD in diabetics. The findings were strongly in favor of CABG over PCI, and this has become the accepted paradigm.

When you’re not sure, if they have funky looking anatomy AND they’re diabetic, you can make a safe gamble and ask your attending if they think this patient is a CABG candidate. 9 times out of 10, you’ll look like a genius.

In Conclusion:Stable ischemic heart disease has some controversy surrounding the role of revascularization, but ALL patients should be on optimal medical therapy

Patients with significantly reduced EF, Left main, proximal LAD disease, all should warrant a closer look at whether or not they would benefit from revascularization

Always try to involve a multi-disciplinary team when thinking about revascularization, at the end of the day, we are in the business of do no harm, so a second set of eyes can be beneficial.

The views, opinions and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your personal health matters. If you think you are having a heart attack, stroke or another emergency, please call 911 immediately.

References:

https://www.ischemiatrial.org/

Boden, W. E., O’rourke, R. A., Teo, K. K., Hartigan, P. M., Maron, D. J., Kostuk, W. J., … & Chaitman, B. R. (2007). Title LM, Gau G, Blaustein AS, Booth DC, Bates ER, Spertus JA, Berman DS, Mancini GB, Weintraub WS; COURAGE Trial Research Group. Optimal medical therapy with or without PCI for stable coronary disease. N Engl J Med, 356(15), 1503-16.

Campos, C. M., van Klaveren, D., Farooq, V., Simonton, C. A., Kappetein, A. P., Sabik III, J. F., … & Serruys, P. W. (2015). Long-term forecasting and comparison of mortality in the Evaluation of the Xience Everolimus Eluting Stent vs. Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL) trial: prospective validation of the SYNTAX Score II. European heart journal, 36(20), 1231-1241.

Stone, G. W., Kappetein, A. P., Sabik, J. F., Pocock, S. J., Morice, M. C., Puskas, J., … & Banning, A. (2019). Five-year outcomes after PCI or CABG for left main coronary disease. New England Journal of Medicine, 381(19), 1820

Heart Attack and Stroke: Same Disease, Different Organs?

June 18, 2019June 20, 2019 John Chen, MD

I’m spending the last month of internal medicine residency on a neurology rotation. I suppose that’s fair; my wife, a neurology resident, had to do a whole year of medicine. To me, the most interesting part of neurology is the parallel between stroke and acute myocardial infarction (AMI). Conceptually these are two manifestations of a common underlying disease process. Yet, there are glaring differences in their management, and I can’t help but wonder why.

For instance, neurologists and cardiologists use different protocols for anticoagulation and thrombolysis. Tissue plasminogen activator (tPA) is a first line therapy for ischemic stroke unless there are contraindications, including recent use of anticoagulation. Thrombolytic therapy is also used to treat STEMI when percutaneous coronary intervention (PCI) is not immediately available. In contrast to stroke, STEMI thrombolysis calls for higher doses of tPA as well as concurrent infusion of heparin to prevent recurrent thrombosis.¹ Perhaps thrombolysis after stroke is a more cautious affair due to the risk of reperfusion injury and hemorrhagic conversion.

For decades STEMI PCI has largely replaced tPA, yet endovascular therapy for stroke is a relatively recent innovation and its utility is limited to proximal large vessel occlusions. While PCI relies on balloon expandable stents designed to prevent restenosis, stenting is perhaps a less attractive option in stroke due to the tortuous anatomy of intracranial vessels and the bleeding risk associated with dual antiplatelet therapy.² Instead, neurologists perform mechanical thrombectomy using stent retrievers and aspiration catheters. While routine thrombectomy during STEMI PCI is generally not beneficial,³ aspiration and rheolytic catheters can be used selectively in the event of large thrombus burden.

Finally, evidence does not support facilitated PCI (i.e. pretreatment with tPA prior to PCI).^4-5 Interestingly, it is common practice among neurologists to pretreat with tPA prior to mechanical thrombectomy. Theoretically pretreatment may facilitate clot extraction, but does this strategy outweigh the additional bleeding risk?⁶

Heart attack and stroke are similar diseases occurring in different organs. With widespread adoption of mechanical thrombectomy for acute stroke, the fields of neurology and cardiology increasingly share similar practices. Still, there are striking differences in stroke and AMI management—no doubt a constant source of cognitive dissonance as I complete my neurology rotation and start cardiology fellowship.

References:

Kijpaisalratana N, Chutinet A, Suwanwela N. Hyperacute simultaneous cardiocerebral infarction: Rescuing the brain or the heart first? Frontiers in Neurology 2017;8:664.
Gralla J, Brekenfeld C, Mordasini P, Schroth G. Mechanical thrombolysis and stenting in acute ischemic stroke. Stroke 2012;43:280-285.
Jolly SS, James S, Dzavik V, et al. Thrombus aspiration in ST-segment elevation myocardial infarction. An Individual Patient Meta-Analysis: Thrombectomy Trialists Collaboration. Circulation. 2016;135:143–152.
The ASSENT-4 PCI Investigators. Primary versus tenecteplase-facilitated percutaneous coronary intervention in patients with ST-segment elevation acute myocardial infarction (ASSENT-4 PCI). Lancet. 2006;367:569–578.
Ellis SG, Tendera M, de Belder MA, et al. Facilitated PCI in patients with ST-elevation myocardial infarction. N Engl J Med. 2008;358:2205–17.
Kasemacher J, Mordasini P, Arnold M, et al. Direct mechanical thrombectomy in tPA-ineligible and -eligible patients versus the bridging approach: a meta-analysis. J Neurointerv Surg. 2019;11:20-27.