Clot-dissolving therapy improves heart patients

ATLANTA, Georgia – Administering the clot-dissolving drug alteplase (Actilyse, Boehringer Ingelheim) early during massive pulmonary embolism prevents the disease from worsening, a new clinical trial showed.

Patients who benefited from the treatment had signs of right-heart strain at presentation. Their hearts were laboring to function despite the presence of clots obstructing the pulmonary arteries, but the patients appeared hemodynamically stable or they had normal blood pressure.

Previously, it was believed that thrombolytic therapy should be reserved for sicker patients – those whose right-heart strain had progressed to cardiogenic shock or other signs of hemodynamic instability.

These findings from the largest-ever trial of thrombolytic therapy in pulmonary embolism were presented here at the recent 51st annual Scientific Sessions of the American College of Cardiology.

"We know that alteplase therapy is appropriate in massive pulmonary embolism accompanied by hemodynamic instability, but only now do we have data indicating that patients should be treated earlier, before they reach this stage," said Prof. Stavros Konstantinides who presented the results at the sessions.

"Massive pulmonary embolism with hemodynamic instability kills more than 30 percent of affected patients. Wider application of thrombolytic therapy with alteplase may help reduce the high mortality associated with this condition," said Konstantinides, an associate professor of medicine at the Department of Cardiology, University of Goettingen, Germany.

The randomized, double-blind, multicenter trial of alteplase plus unfractionated heparin versus heparin alone, enrolled 256 patients with confirmed pulmonary embolism, normal blood pressure (hemodynamic stability) and right ventricular strain or dysfunction.

Right ventricular dysfunction due to pulmonary hypertension was diagnosed by established echocardiographic or ECG criteria, or by right-heart catheterization (mean pulmonary arterial pressure more than 20 mm Hg, and pulmonary capillary wedge pressure less than 19 mm Hg). Pulmonary embolism was confirmed by lung scan, spiral CT scan, or pulmonary angiography.

The trial’s primary endpoint was a composite of in-hospital mortality, worsening circulation, or need for additional therapy, such as surgical removal of the embolus or blood-pressure-elevating drugs to reverse cardiogenic shock two hours or longer after the test medication had been given.

The composite endpoint occurred in 11 percent of alteplase-treated patients, as opposed to 2.6 percent of unfractionated heparin-treated patients, a highly significant difference (p=0.0058), driven by a lesser need for additional therapy among patients treated with alteplase (10.2 percent vs 24.6 percent).

In-hospital mortality was low in both groups, 3.4 percent with alteplase and 2.2 percent with unfractionated heparin, p=ns. This may have been due, at least in part, to treatment crossover, that is, some patients scheduled to receive only heparin were also given alteplase because their condition worsened on heparin alone.

Another reason may have been the unexpectedly low mortality in the heparin-alone group. This was much lower than previously reported for such patients.