Author + information
- Gregg W Stone, MD, FACCa ()
- Paul S Teirstein, MD, FACC
We agree with Perin et al. that a pressing clinical need exists for an effective therapeutic approach for the large number of patients with advanced coronary artery disease and no revascularization options (1). However, given the potential risks and resource utilization of laser myocardial revascularization, it is mandatory that its clinical utility be definitively demonstrated in appropriately designed randomized trials, especially as most studies have not shown a reduction in inducible ischemia with this technique. In this regard, few would question that blinding and placebo effect issues have clouded the promising new field of laser myocardial revascularization and have delayed the regulatory approval of this potentially useful modality.
We attempted to address these issues with a multicenter, randomized prospective trial of percutaneous myocardial revascularization (PMR) incorporating blinding. Our trial revealed significant periprocedural complications associated with the laser technique (including pericardial tamponade or effusions in 7.0% of patients, and ventricular arrhythmias necessitating cardioversion in 5.6%), without enduring improvement in symptoms or exercise tolerance (2). Perin and Colleagues bemoan the lack of 12-month follow-up in our study. Unfortunately, such data was requested and not supplied by the sponsor. Moreover, the weak trend in our study toward less angina in PMR-treated patients at 3 months was diminishing at 6 months, making it doubtful that 12-month follow-up would have revealed significant symptomatic improvement. Their second comment reiterates our acknowledged limitation that the rate of paired exercise testing was lower than anticipated. However, as statistically discussed in the report (2), given the observed mean difference in exercise tolerance of only 17 s between groups, it is highly unlikely that a greater number of patients would have altered our conclusions.
Third, Perin et al. question the fact that our study was adequately blinded, which may have contributed to the negative findings. This is counterintuitive; lack of blinding would have favored the active treatment group, making the trial more positive. Moreover, it is unclear how blinded the BELIEF study was; the laser in the sham group was connected to a “lead box,” which likely precluded the characteristic visual and acoustic signals when the laser was fired. This small (only 82 randomized patients) though well-designed study also showed no difference in exercise tolerance between PMR and placebo groups, and incremental improvement in angina by ≥1 class at 12 months in only 24% of treated patients (n = 10), which may have been due to chance given the small sample size (3). We therefore cannot agree with their statement that BELIEF has “effectively addressed” the placebo question, given the results of the much larger, blinded DIRECT trial (4).
Finally, although we agree with Perin and Co-workers that the three holmium yttrium-aluminium-garnet (YAG) laser systems subjected to clinical trials are different, and stated so in the last paragraph of our report (2), we strongly disagree with their statement that “Based on the negative outcome for the DIRECT trial utilizing the DMR system, it is clear that fiberoptic penetration into the myocardium and significant channel formation, as with PMR, are essential to achieving clinical benefit.” Evaluating whether the different modes of energy delivery or myocardial penetration has anything to do with clinical efficacy would require a comparative study between the two systems, or absent this, at least a positive adequately sized multicenter blinded study of PMR using the CardioGenesis system.
We suggest that rather than arguing the merits of the currently completed trials, all of which are flawed to some degree, Perin et al. focus on lobbying for an adequately powered, appropriately blinded clinical trial to once and for all either prove the safety and efficacy of PMR, or, alternatively, demonstrate its futility. Otherwise, it is doubtful that this once promising approach will ever become widely accepted by the clinical community.
- American College of Cardiology Foundation
- Stone G.W.,
- Teirstein P.S.,
- Rubenstein R.,
- et al.
- Salem M.,
- Rotevatn S.,
- Stavnes S.,
- et al.
- ↵Leon MB. DIRECT (DMR in Regeneration of Endomyocardial Channels Trial). Late Breaking Trials Presentation, Transcatheter Cardiovascular Therapeutics, October 19, 2000, Washington, DC