ISAR-REACT 3A: Lower Heparin Dose Preferable in Elective PCI

August 30, 2010

August 30, 2010 (Updated August 31, 2010) (Stockholm, Sweden) — A new study has established that a 100-U/kg dose of unfractionated heparin appears to be preferable in elective PCI to higher doses previously recommended [1].

The ISAR REACT 3A study, reported here today at the European Society of Cardiology 2010 Congress and published simultaneously online in the European Heart Journal, found that the 100-U/kg dose shows a net clinical benefit over the previous dose of 140 U/kg, with the benefit driven by a reduction in bleeding. The trial also suggested that the 100-U/kg heparin was dose "noninferior" to bivalirudin in this setting of PCI in biomarker-negative patients.

Dr Stefanie Schulz

Presenting the trial, Dr Stefanie Schulz (Deutsches Herzzentrum, Munich, Germany) explained that although unfractionated heparin has been the standard antithrombotic agent in interventional cardiology for decades, there is still no solid evidence from large clinical trials to guide its dosing during PCI. The 140-U/kg dose used to be the accepted regimen, but doses have been drifting downward, and two regimens are currently recommended: an initial bolus dose of 70 to 100 U per kg body weight followed by additional boluses under activated clotting time (ACT) guidance; and a single bolus dose of 100 U/kg (more common in Europe).

"The results from ISAR-REACT 3A show that our intuitive lowering of the heparin dose, which has happened over the past few years, has been the right thing. We can now use this 100-U/kg dose with more confidence," Schulz told heartwire . "This reduced dose of heparin represents a simple and safe method of lowering the bleeding risk after PCI without increasing the risk of ischemic complications," she added.

Dose May Be Reduced Even Further

Dr Christian Hamm

Designated discussant of the trial, Dr Christian Hamm (Kerckhoff-Klinik, Bad Nauheim, Germany), said any data on heparin dosage were important, as so few trials of this issue had been conducted, but he pointed out that 100-U/kg was today actually thought of as a relatively high dose and that the question that now needs to be addressed was whether the dose can be reduced further than this. "My recommendation would be that we don't need to use more than 100 U/kg, but we can probably use even less," he concluded.

The ISAR-REACT 3A trial compared the 100-U/kg heparin dose with two historical controls--a 140-U/kg heparin dose and bivalirudin--from the previously conducted ISAR-REACT 3 main study.

Results of the comparison between the two heparin doses showed a reduction in bleeding with the lower dose, which became significant after adjustment for propensity scores. But this was not at the expense of an increased ischemic risk. In fact, the incidence of the triple ischemic end point was numerically lower in the reduced heparin-dose-group, Schulz noted. These effects led to a significant reduction in the primary quadruple end point (net clinical benefit).

ISAR-REACT 3A 30-Day Results: Comparison of Heparin 100 U/kg With Historical Control of Heparin 140 U/Kg

Outcome Heparin 100 U/kg (n=2505), % Heparin 140 U/kg (n=2281), % Adjusted HR (95% CI) p
Triple efficacy end point (death, MI, urgent TVR) 4.4 5.0 0.82 (0.62–1.08) 0.15
Major bleeding 3.6 4.6 0.71 (0.53–0.97) 0.03
Net clinical benefit (death, MI, urgent TVR, major bleeding) 7.3 8.7 0.75 (0.60–0.92) 0.007

TVR=target vessel revascularization

In the comparison of the lower heparin dose group with the historical bivalirudin group of ISAR-REACT 3, the 100-U/kg heparin dose met the criteria of noninferiority compared with bivalirudin.

ISAR-REACT 3A: Comparison of Heparin 100 U/kg With Historical Control of Bivalirudin

Outcome Heparin 100 U/kg (n=2505), % Bivalirudin (n=2289), %
Triple efficacy end point (death, MI, urgent TVR) 4.4 5.9
Major bleeding 3.6 3.1
Net clinical benefit (death, MI, urgent TVR, major bleeding) 7.3 8.3

TVR=target vessel revascularization