Editor's Note: Commentary based on Briones E, Lacalle JR, Marin-Leon I, Rueda JR. Transmyocardial laser revascularization versus medical therapy for refractory angina. Cochrane Database of Systematic Reviews 2015, Issue 2; CD003712. DOI: 10.1002/14651858.CD003712.pub3.

Background

Acute and fatal presentations of ischemic heart disease have attracted much attention but chronic angina and advanced manifestations are becoming more relevant due to increasing patient survival and improvements in medical and surgical treatments. Patients with refractory angina have limited exercise tolerance, poor quality of life and may not be candidates for antianginal medications, percutaneous coronary angioplasty (PTCA) +/- stenting, or coronary artery bypass surgery (CABG). Transmyocardial laser revascularization (TMLR) was used in association with CABG as a complementary technique for patients with refractory angina not amenable to conventional therapies. Proposed mechanisms include creating channels that provide direct myocardial perfusion, denervation or neoangionesis. Despite a few positive preliminary unrandomized studies, rapid adoption led to safety concerns, necessitating randomized control trials (RCTs) that showed contradictory results and methodologic problems.

Methods

Searches up to June 2014 were conducted of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the metaRegister of Controlled Trials database, ClinicalTrials.gov, and the WHO International Clinical Trials Registry. Selected studies fulfilled the following criteria: randomized controlled trials (RCTs), in patients with Canadian Cardiovascular Society or New York Heart Association angina grade III-IV who were excluded from other revascularization procedures. Three authors independently extracted data for each trial about the population and interventions compared and assessed the risk of bias of the studies, evaluating randomization sequence generation, allocation concealment, blinding (of participants, personnel and outcome assessors), incomplete outcome data, selective outcome reporting, and other potential sources of bias.

Results

From a total of 502 references, 47 papers were selected for more detailed evaluation. Finally, 20 papers from seven studies which included 1137 participants, of which 559 were randomized to TMLR though participants and professionals were unblinded. Overall, 43.8% of participants in the treatment group decreased two angina classes, as compared with 14.8% in the control group: odds ratio (OR) 4.63, 95% confidence interval (CI) 3.43 to 6.25). Mortality by intention-to-treat analysis was similar in both groups at 30 days (4.0% in the TMLR group and 3.5% in the control group), and one year (12.2% TMLR group and 11.9% control group). However, the 30-day mortality as-treated was 6.8% in the TMLR group and 0.8% in the control group (pooled OR was 3.76, 95% CI 1.63 to 8.66), mainly due to a higher mortality in participants crossing from standard treatment to TMLR.

Conclusion

The review shows that the benefit of TMLR is limited and risks including early procedural post-operative mortality and other safety outcomes may be unacceptable. Outcomes are subject to high risk of bias and no differences in survival were found.

Commentary/Perspective

The current ACC/AHA guidelines do not advocate TMLR with or without CABG in the management of refractory angina.¹

Although there have been no new trials for TMLR in the past 10 years, significant advances have been made in the medical and interventional therapies for chronic angina. Drug eluting stents (DES) which contain antiproliferative agents that elute locally were introduced to minimize restenosis and requirement for reintervention in 2001 and presently account for 90% of stents placed in the US and Europe. Based on the MARIZA, CARISA, and ERICA trials, ranolazine was approved for the management of chronic angina in January 2006. In 2004, the Adult Treatment Panel III gave clear guidelines for the widespread use of high potency statins use. The ACC/AHA SIHD guidelines also upgraded recommendations for the use of thienopyridine antiplatelet agents and implementation of regional system wide levels of care ensured better streamlining of transfer of patients for thrombolytic and percutaneous coronary intervention (PCI) therapies all reducing the morbidity and mortality from acute and chronic forms of angina.

Most of the practice-altering RCTs in cardiology have used predefined outcomes like myocardial infarction, arrhythmia or congestive heart failure. However, RCTs for TMLR did not and this is a major weakness.

The role of TMR remains limited. With the advancements in medical and interventional therapies over the past 10 years, a strong case cannot be made for TMLR in the management of chronic angina, given the uncertain benefit and strong safety concerns with early procedural mortality. In the rare instance that a patient cannot be optimally medically managed or for clinical trial purposes, it can be considered an alternative procedure for alleviating angina, but with careful consideration of the potential risks.

This review reinforces the idea that lack of blinding is one of the main pitfalls in studies assessing subjective outcomes and highlights the importance of comparing a procedure without any recent trials against the backdrop of significant advances in the medical management of chronic angina. Although no further TMLR studies are currently planned, rapid advances in therapy for ischemic heart disease may have consigned TMLR to a purely historical role in procedural therapies for IHD.

References

1. Fihn SD, Gardin JM, Abrams J, et al. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol. 2012;60:e44-e164.
2. Briones E, Lacalle JR, Marin-Leon I, Rueda JR. Transmyocardial laser revascularization versus medical therapy for refractory angina. Cochrane Database of Systematic Reviews 2015, Issue 2; CD003712. DOI: 10.1002/14651858.CD003712.pub3.

Keywords: Acetanilides, Angina Pectoris, Angioplasty, Balloon, Coronary, Arrhythmias, Cardiac, Confidence Intervals, Control Groups, Coronary Artery Bypass, Coronary Artery Disease, Denervation, Drug-Eluting Stents, Exercise Tolerance, Heart Failure, Intention to Treat Analysis, MEDLINE, Myocardial Infarction, Odds Ratio, Piperazines, Platelet Aggregation Inhibitors, Quality of Life, Random Allocation, Randomized Controlled Trials as Topic, Registries, Thienopyridines, Transmyocardial Laser Revascularization

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