Author: Dr. Sean McAlister
64 year old male with no known PMH presents with near-syncope, bradycardia, and hypotension. Was working on his car when he felt lightheaded, so he laid down before passing out. A friend called EMS. Found to be bradycardic and hypotensive, same on arrival to the ED. Pt states this happened to him once before, about 8-9 years ago in OK, and that it resolved with some intravenous fluids in the ED.
Pt was very diaphoretic, light-headed, and pale with cool and mottled extremities. His EKG showed no ischemic changes, in particular, no evidence of an inferior myocardial infarction (MI). His initial troponin level was negative. He was given aspirin and his clinical condition improved with fluids and atropine. Repeat troponin was also negative and his repeat EKG was unchanged.
Cardiology was consulted for admission to the Cardiac ICU for further workup. This patient’s history and presentation were concerning for inferior MI, except he had no evidence of ischemia on his EKG and negative troponins. Other than anti-platelet therapy and Cardiology consultation, is there something else we should do for this patient?
Clinical Question: When there is a strong suspicion of ACS, should we start a heparin drip? Do the benefits outweigh the bleeding risks?
On day 2, while in the Cardiac ICU, his troponins elevated. He was taken to the cath lab where he was found to have a 100% RCA occlusion. A stent was placed and was eventually discharged on dual anti-platelet therapy.
Summary of Findings
Primary studies comparing heparin to placebo or aspirin alone have been lacking since the 1990s, but there have been a few systematic reviews looking at heparin use in unstable angina (UA) and non-ST segment elevated MI (nSTEMI) patients. A 2014 Cochrane review looked at eight studies from 1988-2000 on this topic, and found no mortality benefit to heparin use in UA/nSTEMI.1 There was also a non-statistically significant trend toward major bleeds with heparin. However, there was a decrease in the progression to STEMI in the heparin groups. So it sounds like heparin might not help prevent mortality, and it might hurt, but also it might help a little. Straight-forward, right?
More recently, there was a large, multi-center retrospective cohort study out of China looking at heparin use in UA/nSTEMI patients undergoing percutaneous coronary intervention (PCI).2 Just over 8,000 patients from five hospitals were enrolled over a five-year period. These patients were classified into the “parenteral anticoagulation treatment (PACT) group” if they had received PACT before PCI, or into the non-PACT group if they only received PACT during PCI, but not before or after. The incidence of both in-hospital death and all-cause death was similar between the two groups. And in keeping with our bleeding risk theme here, the incidence of major bleeds was higher in the PACT group. So heparin, in this study, seems to cause more major bleeds, without showing any mortality benefit.
But was this always the case? Surely, for heparin in ACS to become the standard of care, there must have been some studies showing its benefit, right? In 1988, Théroux et al found no mortality benefit to heparin use in UA patients over aspirin, but did show a substantial bleeding risk.3 The RISC trial in 1990 found basically the same thing in UA and non-Q wave MI patients.4 Even as far back at 1964, MacMillan and Brown found in a RCT comparing heparin versus placebo in MI patients that heparin had no mortality benefit.5 In the introduction to that study, the authors noted that heparin use in acute MI was the standard of care at the time as well, despite no RCTs showing its benefit.
Is the data supporting heparin use stronger for other conditions, or is it all this unclear? Heparin is well-studied in venous thromboembolism (VTE) prevention and treatment, and has been shown to provide a mortality benefit in these patient populations. A 2017 Cochrane review of 16 studies found no recurrences of VTEs in patients on any form of heparin (unfractionated or low-molecular weight) or route (intravenous or subcutaneous).6
Heparin does not appear to improve long-term mortality in UA/nSTEMI patients. There is also a bleeding risk with heparin. Based on the evidence above, I conclude that heparin should not be started on every suspected ACS patient. But on the other hand, I do not think we should do away with heparin all together. The decision to start heparin should be made on a case-by-case basis, ideally including both the patient and your consultants in the decision-making process.
In our case above, this patient had all the history and physical exam findings of an inferior MI, but did not initially manifest any troponin or EKG changes. Perhaps what would benefit these patients the most is prompt cardiac catheterization, but that’s a question for a different post. In this case, it was unlikely that this patient would go immediately to the cath lab until he manifested more objective changes (as was the case the following day). Therefore, starting a heparin on this patient might have been beneficial to him, given the potentially extended time to definitive treatment. In the future, if a patient appears like a textbook MI (symptomatic, like this patient), but is not manifesting trop or EKG changes, I will consider it.
Final Thoughts & Discussion
If a patient has a very symptomatic UA/nSTEMI, and does not have other major bleeding risk factors, then I will consider starting a heparin drip in conjunction with my admitting team and consultants if prompt cardiac catheterization is not possible. However, in general, the risks seem to outweigh the benefits.
What’s your practice for suspected ACS? Do you start heparin drips on patients with unstable angina or suspected ACS without EKG or enzyme evidence of ischemia? Does heparin still have a role in these patients or should we move towards prompt catheterization (also not without its own risks)? What’s your practice for nSTEMI patients? What about UA? Will high-sensitivity troponins change this discussion?
Even More FOAM Goodness!
- 1.Andrade-Castellanos C, Colunga-Lozano L, Delgado-Figueroa N, Magee K. Heparin versus placebo for non-ST elevation acute coronary syndromes. Cochrane Database Syst Rev. 2014;(6):CD003462. https://www.ncbi.nlm.nih.gov/pubmed/24972265.
- 2.Chen J, He P, Liu Y, et al. Association of Parenteral Anticoagulation Therapy With Outcomes in Chinese Patients Undergoing Percutaneous Coronary Intervention for Non-ST-Segment Elevation Acute Coronary Syndrome. JAMA Intern Med. 2019;179(2):186-194. https://www.ncbi.nlm.nih.gov/pubmed/30592483.
- 3.Théroux P, Ouimet H, McCans J, et al. Aspirin, heparin, or both to treat acute unstable angina. N Engl J Med. 1988;319(17):1105-1111. https://www.ncbi.nlm.nih.gov/pubmed/3050522.
- 4.Risk of myocardial infarction and death during treatment with low dose aspirin and intravenous heparin in men with unstable coronary artery disease. The RISC Group. Lancet. 1990;336(8719):827-830. https://www.ncbi.nlm.nih.gov/pubmed/1976875.
- 5.Brown K, MacMillan R. Initial Heparin Therapy in Acute Myocardial Infarction. Can Med Assoc J. 1964;90:1345-1348. https://www.ncbi.nlm.nih.gov/pubmed/14156828.
- 6.Robertson L, Strachan J. Subcutaneous unfractionated heparin for the initial treatment of venous thromboembolism. Cochrane Database Syst Rev. 2017;2:CD006771. https://www.ncbi.nlm.nih.gov/pubmed/28195640.