Heparin or Not? An Evidence-Based Treatment for NSTEMI Patients with a History of Bleeding

Case Report:

A 77-year-old male with PMH of Polycystic Kidney Disease(PCKD) status post kidney transplant and atrial fibrillation presents to the ED with dyspnea and exercise induced left-sided CP for the past month. He currently denies chest pain, neck pain, back pain, or other anginal symptoms. He is not on anti-coagulation due to history of prior GI bleeding.

• EKG changes in the inferior and anteroseptal leads are shown below.

• Physical exam shows evidence of pulmonary edema, elevated JVP to 10, holosystolic flow murmur.

• Patient is started on aspirin. Initial troponin is 0.36. However, during the course of his stay, troponins begin to increase (0.86 at 3 hours, 1.44 at 6 hours).

• NSTEMI is diagnosed and the care team begins to debate if heparin administration is appropriate.

Clinical Question:

Is heparin administration warranted in this NSTEMI patient with a history of bleeding?

Summary of Evidence:

Does heparin have a mortality benefit in general for NSTEMI?

• The American College of Cardiology and the American Heart Association guidelines dictate heparin administration for patients presenting with NSTEMI.(1) However, the benefits of heparin must be balanced by the risk of hemorrhagic complications to determine in-hospital and discharge management.

• Literature does not demonstrate that heparin improves overall patient outcomes.

• In a systematic review published in the Cochrane Database investigating the usage of heparin vs. placebo in ACS, the authors investigated eightrandomized control trials of 3118 patients and found that heparin did not reduce mortality (risk ratio = 0.84, 95% confidence interval = 0.36 to 1.98) or non-fatal heart attacks in ACS patients.2-4, [1]

• Patients should be evaluated on a case-by-case basis to determine if heparin use is appropriate

Should heparin be used for patients with a prior serious bleeding episode?

• Research investigating characteristics of patients who experience major bleeding haveresulted in two major instruments used to stratify risk for major bleeding in patients presenting with NSTEMI: CRUSADE and ACTION.(5)

• The studies validating both instruments determined that bleeding is largely based on differences in baseline characteristics, comorbidities, and invasive treatment strategies rather than specific anticoagulant regimens and prior history of bleeding.

How do you risk stratify patients with a prior bleeding episode?

• A meta-analysis by Taha et al. comparing ACTION, CRUSADE, ACUITY, and GRACE showed that for NSTEMI patients, the CRUSADE score was the most accurate instrument to determine bleed risk.5-6

• The CRUSADE score uses heart rate, systolic BP, hematocrit, creatinine clearance, sex, signs of CHF at presentation, history of vascular disease, and history of diabetes mellitus to stratify patients into 4 groups:

• Very low risk (CRUSADE score ≤ 20) = 3.1% risk of major bleeding

• Low risk (CRUSADE score 21-30) = 5.5% risk of major bleeding

• Moderate risk (CRUSADE score 31-40) = 8.5% risk of major bleeding

• High risk (CRUSADE 31-40) = 11.9% risk of major bleeding

• Very high risk patients (CRUSADE score ≥ 41) = 19.5% risk of major bleeding7

Recommendations:

• Although heparin administration in theory is justified during NSTEMI to prevent clot formation in the coronary arteries, studies have shown that bleeding risk reduces potential benefits.

• A patient with a prior history of significant bleeding should be risk stratified using the CRUSADE score to determine if the benefits of heparin outweigh the risk of major bleeding in NSTEMI patients.

References:

1. Kadakia, M. B., Desai, N. R., Alexander, K. P., Chen, A. Y., Foody, J. M., Cannon, C. P., … National Cardiovascular Data Registry. (2010). Use of anticoagulant agents and risk of bleeding among patients admitted with myocardial infarction: a report from the NCDR ACTION Registry--GWTG (National Cardiovascular Data Registry Acute Coronary Treatment and Intervention Outcomes Network Registry--Get With the Guidelines). JACC. Cardiovascular Interventions, 3(11), 1166–1177. https://doi.org/10.1016/j.jcin.2010.08.015

2. Andrade-Castellanos CA, Colunga-Lozano LE, Delgado-Figueroa N, Magee K. Heparin versus placebo for non-ST elevation acute coronary syndromes. Cochrane Database of Systematic Reviews 2014, Issue 6. Art No.: CD003462.

3. Magee K et al. Heparin versus placebo for acute coronary syndromes. Cochrane Database Syst Rev. 2008 Apr 16;(2):CD003462.

4. Mukherjee et al. Heparin Given for Acute Coronary Syndromes (Unstable Angina, NSTEMI, STEMI). 2010 Jan 19. http://www.thennt.com/nnt/heparin-for-acute-coronary-syndromes/#"

5. Mathews R, Peterson ED, Chen AY, et al. In-hospital major bleeding during ST-elevation and non-ST-elevation myocardial infarction care: derivation and validation of a model from the ACTION Registry(R)- GWTG. Am J Cardiol 2011;107:1136-43.

6. Taha, S., D’Ascenzo, F., Moretti, C., Omedè, P., Montefusco, A., Bach, R. G., … Gaita, F. (2015). Accuracy of bleeding scores for patients presenting with myocardial infarction: a meta-analysis of 9 studies and 13 759 patients. Postępy w Kardiologii Interwencyjnej = Advances in Interventional Cardiology, 11(3), 182–190. https://doi.org/10.5114/pwki.2015.54011

7. Subherwal S et al. Baseline risk of major bleeding in non-ST segment elevation myocardial infarction: the CRUSADE (Can Rapid risk stratifcation of Unstable angina patients Suppress Adverse outcomes in he Early Implementation of the ACC/AHA Guidelines) Bleeding Score. Circulation. 2009; 119:1873-1882

[1]Limitations to the systematic review: The sample size was too small to detect small differences in mortality. There is significant heterogeneity in the length of heparin administration making it impossible to determine the best dosing. The evidence in the review is low GRADE and should be applied with caution. 4-6