Heparin versus placebo for non-ST elevation acute coronary syndromes: Cochrane systematic review


Assessed as up to date: 2014/02/08


Non-ST elevation acute coronary syndromes (NSTEACS) represent a spectrum of disease including unstable angina and non-ST segment myocardial infarction (NSTEMI). Despite treatment with aspirin, beta-blockers and nitroglycerin, unstable angina/NSTEMI is still associated with significant morbidity and mortality. Although evidence suggests that low molecular weight heparin (LMWH) is more efficacious compared to unfractionated heparin (UFH), there is limited data to support the role of heparins as a drug class in the treatment of NSTEACS. This is an update of a review last published in 2008.


To determine the effect of heparins (UFH and LMWH) compared with placebo for the treatment of patients with non-ST elevation acute coronary syndromes (unstable angina or NSTEMI).

Search methods

For this update the Cochrane Heart Group Trials Search Co-ordinator searched the Cochrane Central Register of Controlled Trials on The Cochrane Library (2013, Issue 12), MEDLINE (OVID, 1946 to January week 1 2014), EMBASE (OVID, 1947 to 2014 week 02), CINAHL (1937 to 15 January 2014) and LILACS (1982 to 15 January 2014). We applied no language restrictions.

Selection criteria

Randomized controlled trials of parenteral UFH or LMWH versus placebo in people with non-ST elevation acute coronary syndromes (unstable angina or NSTEMI).

Data collection and analysis

Two review authors independently assessed quality of studies and independently extracted data.

Main results

There were no new included studies for this update. Eight studies (3118 participants) were included in this review. We found no evidence for difference in overall mortality between the groups treated with heparin and placebo (risk ratio (RR) = 0.84, 95% confidence interval (CI) 0.36 to 1.98). Heparins compared with placebo, reduced the occurrence of myocardial infarction in patients with unstable angina and NSTEMI (RR = 0.40, 95% CI 0.25 to 0.63, number needed to benefit (NNTB) = 33). There was a trend towards more major bleeds in the heparin studies compared to control studies (RR = 2.05, 95% CI 0.91 to 4.60). From a limited data set, there appeared to be no difference between patients treated with heparins compared to control in the occurrence of thrombocytopenia (RR = 0.20, 95% CI 0.01 to 4.24). Assessment of overall risk of bias in these studies was limited as most of the studies did not give sufficient detail to allow assessment of potential risk of bias.

Authors' conclusions

Compared with placebo, patients treated with heparins had a similar risk of mortality, revascularization, recurrent angina, and thrombocytopenia. However, those treated with heparins had a decreased risk of myocardial infarction and a higher incidence of minor bleeding. Overall, the evidence assessed in this review was classified as low quality according to the GRADE approach. The results presented in this review must therefore be interpreted with caution.


Andrade-Castellanos Carlos A, Colunga-Lozano Luis E, Delgado-Figueroa Netzahualpilli, Magee Kirk


Heparins reduce the number of heart attacks but caused more minor bleeding after non-ST elevation acute coronary syndromes compared with placebo

Blood clots in the arteries leading to the heart can cause acute coronary syndromes: unstable angina (a feeling of tightness in the chest) or a type of heart attack (non-ST segment myocardial infarction - NSTEMI). Drugs that prevent clots from forming (such as aspirin) or thin the blood (such as heparin) can relieve the problem. Unfractionated heparin (UFH) and low molecular weight heparin (LMWH) are two types of heparin. This review of trials found that UFH and LMWH when given to patients with high-risk unstable angina or NSTEMI in the acute phase of treatment, in addition to standard therapy with aspirin, prevent more heart attacks than placebo but do not reduce mortality, the need for revascularization procedures or recurrent angina. Although there was limited reporting of side-effects, heparins caused more cases of minor bleeding.

Reviewer's Conclusions

Implications for practice

This systematic review of randomized controlled trials supports the use of heparins in the early treatment of non-ST elevation acute coronary syndromes. Given in addition to aspirin to patients with a history of typical angina accompanied by either a past medical history of coronary artery disease or ECG/cardiac enzyme changes, heparins reduced the incidence of myocardial infarction, but not mortality. In this review, heparins were given within 24 to 72 hours of the onset of symptoms as a weight-adjusted dose for a five to eight day period, with most studies administering it for two to seven days. The small number of studies makes it impossible to recommend a particular dosing regimen. Indirect comparisons of the pooled results of trials of UFH versus placebo with the pooled results of trials of LMWH versus placebo may be interpreted as suggesting that LMWH is more effective than UFH as a subgroup. However, indirect comparisons are unreliable and potentially misleading because of differences in the kinds of patients randomized, outcome definitions, and treatment regimens.

Implications for research

Despite the strength of the findings of this review, there are several areas in which questions remain unanswered.

  • Currently, the optimal time of treatment initiation is unclear. The eight studies examined three different time periods: within 24, 48 and 72 hours. It would be interesting to determine whether the timing of heparin administration (in the emergency department versus on the ward) affects outcomes.
  • Given the interventional nature of the investigation and treatment of acute coronary syndromes, the optimal duration of heparin treatment remains controversial. Whether shorter duration treatments might be as effective remains an interesting, yet unresolved, question.
  • Patient-centered outcomes such as quality of life have not been studied and are particularly warranted. In addition, considering the cost of these drugs, prospective cost-effectiveness analyses will be desirable.

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