Heparin Anticoagulation in Acute Coronary Syndrome
STEMI:
· Anticoagulation for primary PCI addresses 2 pathophysiologic processes: initial thrombin generation caused by spontaneous coronary plaque rupture and secondary thrombin generation caused by iatrogenic introduction of foreign bodies (stents) and arterial dissection (balloon angioplasty)
· The thrombotic process does not cease on successful implantation of a coronary stent: platelet activation in the setting of endothelial disruption continues and peak ≈2 hours after coronary intervention
· AHA 2013 Latest Guidelines:
· European Society of Cardiology guidelines 2017:
· Both AHA/ ACC and European Society for Cardiology rate LOE as C for UFH but have Class I recommendation
· Stronger evidence for Bivalirudin and Enoxaparin with either the same Class recommendation or lower
· No RCTs have been performed since this has been standard of care in the PCI era
Undifferentiated NSTEMI and Unstable Angina:
This is more controversial in terms of choice of agent as well as the therapy but continues to be standard of care with guidelines supporting use of heparin
2014 AHA guidelines for the management of NSTEMI
- Recommend unfractionated heparin continued for 48 hours or until PCI is performed (LOE B)
- With even a higher level of evidence the same guidelines also recommend enoxaparin 1mg/kg subcutaneously every 12 hours with reduced dosing to 1mg/kg subcutaneously in patients with a creatinine clearance <30mL/min) (LOE A)
- The guidelines recognize that studies supporting this therapy were performed primarily on patients with a diagnosis of unstable angina and in the era before dual anti platelet therapy and early catheterization/revascularization.
· Recent retrospective Chinese review published in 2018 concluded that parenteral anticoagulation therapy did not decrease mortality in patients with NSTEMI undergoing PCI but did have more bleeding events compared to non-parenteral anticoagulation therapy
· Cochrane review à patients treated with heparins had a similar risk of mortality, revascularization and recurrent angina. However, those treated with heparins had a decreased risk of myocardial infarction (driven by the largest study (FRISC), and they used the 6 day outcome of that trial, rather than the 40 or 150 day outcomes that we know were negative) this was based on a higher incidence of minor bleeding.
· Shared decision making can be employed in this setting
· The risk versus benefit profile might be different for patient who have a history of GIB, known brain aneurysm, high fall risk patients etc
NSTEMI with noninvasive management
· Rebound effect- Heparin causes a transient reduction in MI rates, with a rebound in infarction after anticoagulation is withdrawn. There is no long-term sustained mortality benefit in literature
· Anticoagulation with heparin exposes the patient to a risk of hemorrhage without any known long-term benefit evidenced in literature.
· Furthermore, heparin delays the occurrence of ischemic events to a later time-point in their hospital course, when the patient may be less closely monitored.
· The potential benefit heparin “bridging” to definitive therapy is not realized when patients’ are managed medically and don’t receive an intervention (PCI or CABG)
· Decision to anticoagulated can be deferred to the consultants managing the patient as they would be more aware of the likely management of the patient with an intervention.
Special considerations:
Instent thrombosis- Benefit anticoagulation as secondary thrombin generation caused by iatrogenic introduction of foreign bodies
Effect of Hemodialysis on troponin levels in ESRD patients - “Troponinemia” could reflect chronic microinfarctions or correlate with left ventricular hypertrophy. HD process itself might cause undesirable myocardial injury and enhance post HD TnI levels. The effect of HD on TnI levels are unestablished, reporting either increasing, unchanged or decreasing of post-dialysis hsTnI levels
Rhabdomyolysis- The prevalence of false positive cTnI in the ED patients with rhabdomylolyiss was 17% in one study although there is significant paucity of evidence.
Reference:
Amsterdam, Ezra A., et al. "2014 AHA/ACC guideline for the management of patients with non–ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines." Journal of the American College of Cardiology 64.24 (2014): e139-e228.
Ibanez, Borja, et al. "2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC)." European heart journal 39.2 (2017): 119-177.
Dauerman, Harold L. "Anticoagulation Strategies for Primary Percutaneous Coronary Intervention." (2015).
Li, Siu Fai, Jennifer Zapata, and Elizabeth Tillem. "The prevalence of false-positive cardiac troponin I in ED patients with rhabdomyolysis." The American journal of emergency medicine 23.7 (2005): 860-863.
Tarapan, Tanawat, et al. "High sensitivity Troponin-I levels in asymptomatic hemodialysis patients." Renal failure 41.1 (2019): 393-400.
Chen, JY 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 2018. PMID: 30592483