An anticoagulant, bivalirudin, may not be safer than the alternative, heparin, when unblocking arteries in the heart

Bivalirudin is currently recommended as an alternative option to heparin to prevent clotting during percutaneous coronary intervention. This is a common procedure to unblock the heart’s arteries. It is more costly but may have advantages relative to heparin, such as a more rapid action and less risk of lowering the platelet count.

This review found that bivalirudin reduced risk of major bleeding compared with heparin. However, this was only when heparin was combined with a higher dose of another anti-clotting drug, a glycoprotein platelet IIb/IIIa inhibitor. When there was equivalent use of these inhibitors, there was no difference in bleeding. Bivalirudin was also associated with very small increased risks of heart attack and re-blockage of the blood vessel being treated.

For now, bivalirudin remains an alternative option to heparin, but individual patient characteristics should guide the best drug to use.

Why was this study needed?

Percutaneous coronary intervention is a common procedure to unblock heart arteries. In 2013, over 92,000 procedures were carried out in the UK. It involves inserting a small tube called a stent into the heart’s arteries, to hold them open. Anticoagulant treatment is needed at the same time to reduce the risk of clotting during and after the procedure. Heparin is the long established anticoagulant, but newer bivalirudin may now be used as an alternative.

To date, different trials have produced contradictory evidence comparing the safety and effectiveness of the two anticoagulants when given to patients undergoing percutaneous coronary interventions. This trial drew together the evidence and pooled the findings in a meta-analysis.

What did this study do?

This review included 17 randomised controlled trials in 40,655 patients undergoing percutaneous coronary intervention who received either bivalirudin or heparin. The researchers considered three groups of patients.

  • Those that had a “classic” heart attack (ST-elevation myocardial infarction).
  • Those with signs and symptoms of heart attack but without the classic findings on ECG (non-ST-elevation acute coronary syndrome).
  • Patients having planned interventions for heart disease, but not following an acute heart event.

They also looked at the effect of whether patients were given other types of anti-clotting drugs.

The main outcome was mortality rates at 30 days or one year after percutaneous coronary intervention. Other outcomes included the rate of major cardiovascular events and re-blockage of the artery being treated. The main safety outcome was major bleeding within 30 days.

The overall quality of the evidence was high for the main outcomes, with a low risk of bias, except for the outcome of mortality and major cardiovascular events. For these outcomes the results were imprecise due to a lower than ideal sample size. Other minor limitations to the trials, including differences in the dose and type of heparin used (some older trials using unfractionated heparin rather than low molecular weight heparin), and the possibility that patient characteristics may have influenced which patients received which treatment.

What did it find?

  • There was no significant difference in mortality between patients who received bivalirudin compared with heparin.
  • There was no significant difference between groups in the frequency of overall major cardiovascular events, but there were slightly more heart attacks within 30 days in the bivalirudin group compared with the heparin group (5.7% vs. 5.1%; risk ratio [RR] 1.10, 95% confidence interval [CI] 1.02 to 1.19).
  • Bivalirudin was also associated with increased risks of clots in the stent (1.3% vs. 1.0%; RR 1.32, 95% CI 1.08 to 1.60) and need for repeat procedure within 30 days (2.0% vs. 1.6%; RR 1.20, 95% CI 1.04 to 1.38).
  • There was significantly lower risk of major bleeding for patients who received bivalirudin compared with those who received heparin (3.3% vs. 4.8%; RR 0.65, 95% CI 0.52 to 0.80). However, subgroup analysis demonstrated that this was only in trials where more glycoprotein platelet IIb/IIIa inhibitor was used with heparin than with bivalirudin. There was no difference in bleeding risk where equivalent amounts of glycoprotein platelet IIb/IIIa inhibitor were used.

What does current guidance say on this issue?

A NICE technology appraisal from 2011 recommends bivalirudin as an option for adults receiving percutaneous coronary intervention for the initial treatment of STEMI. NICE advise that bivalirudin is given with aspirin and clopidogrel. The trials included in this review do not specifically state whether or not these drugs were also given, so it is not clear how well they reflect recommended practice in the UK.

What are the implications?

The review suggests that bivalirudin may not be a safer alternative to heparin. The reduced risk of major bleeding seemed to be explained by higher use of glycoprotein platelet IIb/IIIa inhibitors with heparin. Despite no difference in mortality or overall cardiovascular events, bivalirudin seems to be associated with increased risk of stent clotting and need for repeat procedure, but the absolute risk of these events is still very small.

One point is the uncertain applicability to UK practice and the possible influence of patient characteristics upon treatment allocation. For example, most trials used the femoral approach to percutaneous coronary intervention (via the leg). Radial access (via the arm) is less likely to cause bleeding and may limit the benefit of bivalirudin in this regard.

Further research is needed before changing practice or guidance. In the meantime, clinicians may wish to continue selecting the best anticoagulant based on individual patient factors.


Citation and Funding

Zhang S, Gao W, Li H, Zou M, et al. Efficacy and safety of bivalirudin versus heparin in patients undergoing percutaneous coronary intervention: A meta-analysis of randomized controlled trials. Int J Cardiol. 2016;209:87-95.

No funding information was provided for this study.



NICE. Bivalirudin for the treatment of ST-segment-elevation myocardial infarction. TA230. London: National Institute for Health and Care Excellence; 2011.

NICE. Myocardial infarction with ST-segment elevation: acute management. CG167. London: National Institute for Health and Care Excellence; 2013.

NICE. Unstable angina and NSTEMI: early management. CG94. London: National Institute for Health and Care Excellence; 2010.

NICOR. National audit of percutaneous coronary interventions annual public report. London: National Institute for Cardiovascular Outcomes Research; 2014.

NHS Choices. Coronary angioplasty and stent insertion. London: Department of Health; updated 2015.

Produced by the University of Southampton and Bazian on behalf of NIHR through the NIHR Dissemination Centre

Percutaneous coronary intervention is a procedure to unblock the arteries that supply the heart’s muscle, when they have become narrowed by fatty, hardened deposits. This can be done soon after someone has a heart attack or another acute heart event. It can also be done if they have established heart disease with chest pain on exertion (angina). To carry out the procedure, a thin, flexible tube is inserted into an artery in the arm, wrist or groin. The tube is guided to the blocked heart artery, where a small balloon is inflated to compress the blockage against the artery walls. A small tube, or stent, can then be left in place to hold the artery open.

Percutaneous coronary interventions do carry risks of major bleeding that may need a blood transfusion, or lead to a heart attack, stroke or death. The risk of this is less than one in a hundred cases.


Expert commentary

Bivalirudin is recommended as an option by NICE for patients presenting with heart attacks, and who are undergoing procedures to clear the blockage in the blood supply to the heart muscle. In this setting, bivalirudin has been thought to be both effective and safe, with a lower risk of causing harm from blood loss. However, this meta-analysis of 17 trials suggests that bivalirudin may not actually be effective in preventing recurrence of the blockage, or further heart attacks. Moreover, bivalirudin did not have demonstrable benefit in reducing number of deaths, and thus its role in treatment currently remains debatable.

Yoon K Loke, Professor of Medicine and Pharmacology, Norwich Medical School