Despite being given a level A recommendation by the AHA, it has never been clear that heparin helps ACS patients. (Amsterdam 2014) (This is one of the many guidelines that don’t seem to fit with the evidence that led to my rant about guidelines.) The most recent Cochrane review tells us that heparin doesn’t save lives, but might result in a small decrease in non-fatal MI, although that depends a lot on how you decide to analyse the data, and the benefit is balanced by a similar increase in major bleeding. (Andrade-Castellanos 2014) This is a look at some real world data on the issue:
Chen JY, He PC, Liu YH, 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 internal medicine. 2018; PMID: 30592483
This is a retrospective chart review.
Patients: Patients undergoing percutaneous intervention (PCI) for acute coronary syndrome, excluding STEMI patients.
- Exclusions: pregnant, in cardiogenic shock, required an intra-aortic balloon pump, or had other indications for anticoagulation.
Exposure: Parenteral anticoagulation.
Comparison: No parenteral anticoagulation.
Outcome: The primary outcome was all cause mortality. The primary safety outcome was in-hospital major bleeding.
They included 6804 patients (out of 8197 screened) from 5 hospitals in China over 5 years. 57% of patients had NSTEMI, while the remainder had a diagnosis of unstable angina. Low molecular weight heparin was used most often (79%), followed by fondaparinux.
There was no difference in in-hospital mortality (0.1% vs 0.3%, p=0.13). There was also no difference in mortality on long term follow-up (mean 3 years).
Major bleeding was increased with parenteral anticoagulation (2.5% vs 1%, p<0.001).
There was no change in the rate of MI (0.3% vs 0.3%, p=0.82).
I generally wouldn’t give a chart review its own blog post because, well, it’s a chart review. This chart review had reasonable methods, with multiple coders double checking key variables, but it is still a chart review. The fundamental question when looking at this data is: why did some patients get heparin while others didn’t? They performed adjusted analyses, but hidden confounders are always a huge problem in observational data.
However, when analyzing observational data, one of the key questions is: how does this data fit with existing literature? In the case of heparin for ACS, we have multiple RCTs looking at the same question, and despite heparin’s widespread use, the existing data is actually much the same. Heparin does not save lives. It isn’t clear that heparin provides any benefit. The only thing that is clear is that heparin results in more bleeding.
So I include this paper as a reminder that we should not be reflexively ordering heparing on non ST elevation ACS patients. If you want a full review of the literature, an updated summary will be uploaded at the same time as this post.
In a real world setting, patients who get heparin for non ST elevation ACS see no benefit, but are exposed to a higher rate of major bleeding. If you are using heparin routinely, you should probably question your practice.
Amsterdam EA, Wenger NK, Brindis RG, et al. 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014; 130(25):2354-94. [pubmed]
Andrade-Castellanos CA, Colunga-Lozano LE, Delgado-Figueroa N, Magee K. Heparin versus placebo for non-ST elevation acute coronary syndromes. Cochrane Database Syst Rev. 2014;6:CD003462. PMID: 24972265
Morgenstern, J. Heparin in ACS (Chen 2018), First10EM, January 7, 2019. Available at: