Istanbul, Turkey - Administration of low-dose intracoronary streptokinase immediately after primary PCI improved myocardial reperfusion but not long-term left ventricular size or function in a new pilot study [1]. The authors say these findings require clarification in a larger trial.

The study, published in the May 3, 2007, issue of the New England Journal of Medicine, was conducted by a team led by Dr Murat Sezer (Istanbul University, Turkey). They note that myocardial damage is not immediately stopped after primary PCI, and it is thought that reperfusion injury and embolization of residual thrombus debris may jeopardize tissue-level perfusion. They suggest that in addition to thromboemboli of proximal origin, a thrombus may also form in the microvasculature itself, which may explain why recent trials have failed to show a beneficial effect of distal-protection devices on microvascular perfusion during primary PCI, despite effective retrieval of thrombus and plaque content from epicardial coronary arteries.

They thus conducted a pilot study to investigate whether intracoronary infusion of low-dose streptokinase immediately after primary PCI might further improve tissue-level perfusion by dissolving thrombi at the microvascular level.

The study included 41 primary PCI patients who were randomized to receive intracoronary streptokinase (250 kU) or no additional therapy. Two days later, cardiac catheterization was repeated, and coronary hemodynamic end points were measured with a guidewire tipped with pressure and temperature sensors. In patients with anterior MI, the deceleration time of coronary diastolic flow was measured with transthoracic echocardiography. At six months, angiography, echocardiography, and technetium-99m single-photon-emission computed tomography (SPECT) were performed to assess left ventricular function.

Results showed that all measures of microvascular perfusion were significantly better in the streptokinase group than in the control group, including coronary flow reserve, the index of microvascular resistance, the collateral-flow index, mean coronary wedge pressure, systolic coronary wedge pressure, and diastolic deceleration time. The streptokinase group also had a lower TIMI frame count. But at six months, there was no significant difference between the two study groups in left ventricular size or function, although there were some trends favoring the streptokinase group, which the authors suggest may raise the possibility that the study was underpowered for these analyses.

In an accompanying editorial, Dr Jan Piek (Academic Medical Center, Amsterdam, the Netherlands) comments that the evaluation of the effect of coronary interventions on the hemodynamics of the microvasculature is still "terra incognita," considering the limited number of studies performed in dedicated centers.

He notes that to account for the large range of microvascular resistance among patients, such studies should really allow the patients to serve as their own controls, and as this was not done, the main conclusion of this study, that intracoronary streptokinase reduces microvascular resistance, has to be interpreted with caution. He adds that an appropriate interpretation of the complexity of the coronary microvasculature ideally requires simultaneous intracoronary pressure and flow-velocity measurements, which were not performed in this study. "Nevertheless, the uniform results of the various invasive and noninvasive techniques applied by Sezer et al for evaluation of the coronary microvasculature provide support for their conclusions," he writes.

On the observation of no improvement in LV function, Piek suggests that as left ventricular remodeling is a multifactorial process, it probably requires a broader therapeutic approach than just the dissolution of microemboli. But he adds that the limited number of patients in this study may preclude an accurate interpretation of the effect on LV function. For this purpose, he suggests that magnetic resonance imaging with contrast enhancement may be more sensitive than echocardiography and SPECT. He also points out that about 20% to 30% of the patients in this study had a nonanterior MI, which could have obscured the effect of streptokinase on regional left ventricular hemodynamics.

Piek notes that intracoronary administration of streptokinase has the advantage over systemic therapy of inducing adequate fibrinolysis at the site of injury while placing the patient at lower risk for bleeding complications. "The use of intracoronary fibrinolysis for myocardial reperfusion can be considered a pendulum swing, given the pioneering studies performed decades ago and the fact that intracoronary streptokinase had almost disappeared from the therapeutic armamentarium," he comments.

He concludes: "In view of their clinical relevance, the findings of Sezer et al warrant further analysis in larger-scale clinical studies aimed at a multifactorial therapeutic approach to minimizing reperfusion injury. Sensitive noninvasive and invasive diagnostic techniques should be used to evaluate the potential of this new approach as an adjunct to our current therapeutic strategy in patients with an acute myocardial infarction."