endovascular therapy

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When The Guidelines Need Guidance

Saurav Chatterjee, MD

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.

 

Editorial Commentary

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.

 

References:

  1. 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.
  2. 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.

 
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How Far Can We Go in the Early Management of Acute Ischemic Stroke?

Reem Waziry, MD, MPH, PhD

(In anticipation of the International Stroke Conference 2019 – ISC19)

Not so long ago, the benefit of endovascular thrombectomy beyond six hours of ischemic stroke onset was uncertain, particularly among patients with ischemic brain tissue that has not yet undergone infarction. The volume of irreversibly injured ischemic tissue and the volume of brain tissue that is ischemic, but not yet infarcted, could be assessed by computed tomographic perfusion imaging or a combination of diffusion and perfusion magnetic resonance imaging.1,2

Early last year, the DAWN3 and DEFUSE 34 trials’ investigators presented findings at ISC18 that lead to immediate change in the guidelines5 with substantial implications for prevention of functional dependence among stroke survivors.

The DAWN trial was a multicentre, prospective, randomized, open labelled trial conducted at 26 centers in the United States, Canada, Europe and Australia, with at least 40 mechanical thrombectomy procedures performed annually. Patients were enrolled if they were last known to be well within 6 to 24 hours earlier and had occlusion of the intracranial internal carotid artery or proximal middle cerebral artery with a mismatch between the severity of clinical deficit and the infarct volume. The mismatch criteria were defined according to age, stroke severity, occlusion site, time to treatment and type of stroke onset. Primary end points included mean score for disability and functional independence at 90 days.

The mean score on the utility-weight modified Rankin scale and rate of functional independence at 90 days were 5.5 and 49% in the thrombectomy group, compared to 3.4 and 13% in the control group. The rate of symptomatic intracranial haemorrhage and death at 90 days did not differ between the two groups.

The DEFUSE 3 trial was a multicentre, randomized, open labelled trial that included 38 centers in the United States. Patients were enrolled if they were last known to be well within 6 to 16 hours and had remaining ischemic brain tissue that was not yet infarcted. Patients with proximal middle-cerebral artery or internal carotid artery occlusion, an initial infarct size of less than 70ml and ratio of ischemic tissue to infarct volume of 1.8 or more were randomly assigned to thrombectomy plus standard medical therapy or standard medical therapy alone. The primary outcome was the ordinal score on the modified Rankin scale at 90 days.

The 90-days mortality rate was 14% in the endovascular therapy group compared to 26% in the medical therapy group. The absolute difference in functional independence between groups was 28% points, indicating a better 90 day functional outcomes compared to patients who had standard medical therapy alone. This mainly applies to patients who had evidence of salvageable tissue determined on the basis of a formula that incorporates early infarct size and the volume of hypoperfused tissue on perfusion imaging.

The incidence of symptomatic cerebral haemorrhage was not statistically different, yet numerically higher in the endovascular compared to the medical therapy group. Mortality was numerically lower in the endovascular therapy group. In between group differences of 24-hour infarct volume and growth after thrombectomy were not significant. Further, patients treated within six hours after stroke onset had favourable outcomes compared to other trials. This difference could be attributed to the favourable collateral circulation and slower infarct growth in patients recruited in the DEFUSE 3 trial.

Enrollment in the DAWN trial was stopped at 31 months, because the results of an interim analysis met the prespecified criterion for trial discontinuation, which was a predictive probability of superiority of thrombectomy of at least 95% for the first primary end point. Similarly, the DEFUSE 3 trial was terminated early for efficacy after 182 patients had undergone randomization, given the interim analysis results exceeded the prespecified efficacy boundary (P<0.0025). Both the DAWN and DEFUSE 3 trials used the same automated perfusion software (RAPID) to measure the volume of early infarct and hypoperfused volume.

Further advancements are anticipated at ISC19, with key questions on benefits beyond those time points and among the broader population of ischemic stroke survivors.

 

REFERENCES

  1. Albers GW, Goyal M, Jahan R, et al. Ischemic core and hypoperfusion volumes predict infarct size in SWIFT PRIME. Ann Neurol 2016. 79: 76-89.
  2. Wheeler HM, Mlynash M, Inoue M, et al. Early diffusion-weighted imaging and perfusion-weighted imaging lesion volumes forecast final infarct size in DEFUSE2. Stroke 2013. 44: 681
  3. Nogueira, Raul G., et al. “Thrombectomy 6 to 24 hours after stroke with a mismatch between deficit and infarct.” New England Journal of Medicine 2018. 378:11-21.
  4. Albers, Gregory W., et al. “Thrombectomy for stroke at 6 to 16 hours with selection by perfusion imaging.” New England Journal of Medicine 378: 708-718.
  5. Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, Biller J, Brown M, Demaerschalk BM, Hoh B, Jauch EC. 2018 guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2018. 39:46-99.