Other therapies

• Intermittent urokinase: 500,000 IU i.v. three times a week, for 12 weeks. There is limited evidence, but some studies have suggested that it could reduce angina episodes by 70 percent and the need for nitrates by 84 percent. Authors advocate that the benefit is from improvement in the rheological properties of blood and improved blood flow.63 [IV]

• Laser revascularization: This consists of drilling channels into the myocardial wall with laser and has been performed transmyocardially (transmyocardial revascularization, TMR) via a minithoracotomy or percutaneously (percutaneous revascularization, PMR).

- Randomized, but not sham, trials in TMR have shown significant improvements by two angina classes at 12 months by Allen et al.39 (76 versus 32 percent; p< 0.001) and Frazier et al.40 ( 72 versus 13 percent; p<0.001). However, overall, no improvement in myocardial supply had been demonstrated and did not consistently improve exercise tolerance, dyspnea, or left ventricular function.20 The placebo effect cannot be excluded as a mechanism.

- In PMR, a laser fiberoptic lead is introduced through the peripheral artery into the left ventricle, and the channels are created with fluoroscopic and TOE guidance. A randomized unmasked trial looking at the effect of PMR, the PACIFIC trial, did reveal a reduction in angina class and an increase in exercise tolerance, but was associated with more morbidity in the PMR arm. However, sham randomized trials have not consistently reproduced this finding.42,434445 On this basis, PMR has not gained FDA approval.

• Gene therapy: This is still experimental, although several studies have shown encouraging results in terms of decrease in angina class. The Angiogenic

Gene Therapy (AGENT-2) trial and the vascular endothelial growth factor in ischemia for vascular angiogenesis (VIVA) trial have included placebo arms and revealed significant changes in ischemic defect and angina class, respectively, but further work is needed with clinical efficacy and immunological security.64,65

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