When The Guidelines Need Guidance
I recently had the opportunity to be part of a team looking at the ‘evidence base and quality’ of recommendations enumerated in the current American Heart Association/American College of Cardiology guidelines for peripheral vascular interventions. The study led by my friend and colleague, Dr Partha Sardar, and Dr Herbert Aronow of the Warren Alpert Medical School at Brown University, found that the strength of evidence for the different recommendations vary significantly, underscoring the need for higher-quality evidence in this area as published in Circulation: Cardiovascular Interventions.
Our team identified 134 recommendations from five current full guidelines for endovascular and surgical procedures for peripheral vascular disease. For all peripheral vascular interventions, only 13% of recommendations were supported by level A evidence, whereas 48% were supported by level B evidence and 39% were supported by level C evidence.
The majority of recommendations were supported by level C evidence for pulmonary embolism or deep vein thrombosis interventions (76%) and inferior vena cava filter placement (69%), and level B evidence for renal artery stenosis interventions (67%).
However, levels of evidence were higher for endovascular therapy for stroke (level A, 24%; level B, 52%; level C, 24%), carotid revascularization (level A, 23%; level B, 52%; level C, 24%) and endovascular or surgical treatment for abdominal aortic aneurysm and lower-extremity aneurysm (level A, 26%; level B, 67%; level C, 7%). Quality of evidence for surgical revascularization for lower-extremity peripheral artery disease (level A, 18%; level B, 37%; level C, 45%) was also lower than for endovascular therapy (level A, 18%; level B, 55%; level C, 27%), which likely leads to greater emphasis on endovascular therapy in the current Appropriate Use Criteria (AUC for PAD) published by the national societies. (Bailey SR, Beckman JA, Dao TD, et al. ACC/AHA/SCAI/SIR/SVM 2018 appropriate use criteria for peripheral artery intervention: a report of the American College of Cardiology Appropriate Use Criteria Task Force, American Heart Association, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, and Society for Vascular Medicine. J Am Coll Cardiol. 2018;Epub ahead of print.)
Of significant surprise was the degree of variation in level of evidence supporting different procedural guideline recommendations. There was no level A evidence to support pulmonary embolism/deep vein thrombosis, inferior vena cava filter or renal artery stenosis intervention. In contrast, nearly 1 in 4 endovascular stroke therapy recommendations were supported by level A evidence.
Strength of recommendations
The researchers also noted that, overall, most recommendations were class II (54%), followed by class I (35%) and class III (11%).
For lower-extremity PAD endovascular revascularization, IVC placement, carotid revascularization and endovascular therapy for stroke, most recommendations were class II rather than class I or class III. For renal artery stenosis revascularization, recommendations were split evenly between class I and class II, with none falling into class III. For surgical or endovascular treatment of PE, there were no class I recommendations and 80% were class II. The classes of recommendation also varied for other peripheral vascular interventions, including DVT interventions, endovascular or surgical treatment for mesenteric artery disease, interventions for subclavian and brachiocephalic arteries, and endovascular or surgical treatment for AAA or lower-extremity aneurysms.
Results also showed significant variation in the strongest recommendation (class I, level of evidence A) between procedures:
- 24% for endovascular therapy for stroke;
- 18% for endovascular or surgical revascularization for lower-extremity PAD;
- 20% for endovascular or surgical treatment for aneurysms of the abdominal aorta and the lower extremities; and
- 0% for all other peripheral vascular interventions.
The most common recommendation for all peripheral vascular interventions was class II-C (C-‘expert’ opinion) (27%), followed by class II-B(B-Single RCT /multiple observational data) (26%).
Changes over time
From the 2005 to 2011 guidelines, the researchers observed some changes in the total number of recommendations.
For lower-extremity PAD, the number of recommendations decreased from 20 to 11 for endovascular therapy and from 29 to 11 for surgery. There were no increases in recommendations supported by level A evidence for either treatment, but the number of class I indications decreased from 10 to three for endovascular therapy (P = .27) and from 19 to five for surgical revascularization (P = .29).
For endovascular stroke therapy, there were no major changes in the number of recommendations or in level A evidence over time. However, level B evidence increased and level C evidence decreased.
The variation in the guidelines indicates that many recommendations in this area are based on lower quality of evidence or expert opinion.
In an accompanying editorial, David W. Lee, MD, and Matthew A. Cavender, MD, MPH, both from the University of North Carolina at Chapel Hill, echoed the need for better evidence.
Research networks that facilitate comparative effectiveness studies in patients with peripheral vascular disease could help advance the field. Furthermore, the clinical trial infrastructure put in place for ongoing studies such as BEST-CLI and CREST-2 could provide a framework for additional studies in PAD, and multidisciplinary initiatives such as the Pulmonary Embolism Response Team Consortium can help secure funding for high-quality research. The use of existing registries, formulation of pragmatic trials nested in such registries, as well as improving data collection within these registries, could supply important information. The overarching goal of research in this field is to determine which treatments are most effective best on higher quality evidence.
- Lee DW, Cavender MA. Guidelines for Peripheral Vascular Disease: Where Is the Evidence? Circulation: Cardiovascular Interventions. 2019;12(1). doi:10.1161/circinterventions.118.007561. Lee DW, et al. Circ Cardiovasc Interv. 2019;doi:10.1161/CIRCINTERVENTIONS.118.007561.
- Sardar P, Giri J, Jaff MR, et al. Strength of Evidence Underlying the American Heart Association/American College of Cardiology Guidelines on Endovascular and Surgical Treatment of Peripheral Vascular Disease: Circulation: Cardiovascular Interventions. 2019;12(1). doi:10.1161/circinterventions.118.007244. Sardar P, et al. Circ Cardiovasc Interv. 2019;doi:10.1161/CIRCINTERVENTIONS.118.007244.