Category Archives: On Trial

The Carotid Revascularization Endarterectomy vs Stenting Trial (CREST)

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One discussion this week involved the Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST).

Reference: Brott TG, et al. Stenting versus endarterectomy for treatment of carotid-artery stenosis. New England Journal of Medicine. 2010 Jul 1;363(1):11-23. doi:10.1056/NEJMoa0912321.

Summary:  CREST is an RCT with blinded end-point adjudication whose aim was “to compare the outcomes of carotid-artery stenting with those of carotid endarterectomy among patients with symptomatic or asymptomatic extracranial carotid stenosis” (p.12).

Between December 2000 through July 2008, 2522 patients were enrolled in 108 centers in the US and 9 in Canada. Of those, 1271 patients were randomly assigned to undergo carotid-artery stenting.

Primary findings include (p.18):

  • Carotid revascularization performed by highly qualified surgeons and interventionists is effective and safe.
  • Stroke was more likely after carotid-artery stenting.
  • Myocardial infarction was more likely after carotid endarterectomy, but the effect on the quality of life was less than the effect of stroke.
  • Younger patients had slightly fewer events after carotid-artery stenting than after carotid endarterectomy.
  • Older patients had few events after carotid endarterectomy.
  • Low absolute risk of recurrent stroke suggests that both carotid-artery stenting and carotid endarterectomy are clinically durable and reflect advances in medical therapy.

The Asymptomatic Carotid Atherosclerosis Study (ACAS)

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One discussion this week included the Asymptomatic Carotid  Atherosclerosis Study (ACAS).

Reference: Endarterectomy for asymptomatic carotid artery stenosis. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. JAMA. 1995 May 10;273(18):1421-1428.

Summary: ACAS was a prospective, randomized trial conducted at 39 sites in the US and Canada between December 1987 and December 1993. Its purpose was to “determine whether the addition of carotid endarterectomy to aggressive medical management can reduce the incidence of cerebral infarction in patients with asymptomatic carotid artery stenosis” (p.1421).

The primary finding was that the risk of ipsilateral stroke and any periopoerative stroke or death over 5 years was 5.1% for surgical patients and 11.0% for medically treated patients (p.1425). Furthermore, those who are good candidates for elective surgery and have carotid artery stenosis of 60% or greater reduction in diameter will have a significantly reduced 5-year risk of ipsilateral stroke “if carotid endarterecomy performed with less than 3% perioperative morbidity and mortality is added to aggressive management of modifiable risk factors” (p.1421).

Additionally, ACAS concluded that CEA reduces the relative stroke risk 66% for men and 17% for women. This difference is perhaps due to higher rates of perioperative complications in women.When arteriographic and perioperative complications are excluded, the risk reduction was 79% for men and 56% for women (p.1427).

The North American Symptomatic Carotid Endarterectomy Trial (NASCET)

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One discussion this week involved the North American Symptomatic Carotid Endarterectomy Trial (NASCET).

Reference: Barnett HJM, et al. Benefit of carotid endarterectomy in patients with symptomatic moderate or severe stenosis. New England Journal of Medicine. 1998 Nov 12;339(20):1415-1425.

Summary: NASCET involved 2226 patients with stenosis of less than 70 percent. They were randomly assigned to treatment groups: 1118 to medical therapy, 1108 to surgical therapy (p.1417).

Four patient characteristics are associated with greater benefit from surgery: male sex, recent stroke, recent hemispheric symptoms, and taking 650 mg or more of aspirin per day (p.1419).

NASCET authors explain that the lack of significant benefit for women may be due to their low risk of stroke. Among participants with 50-69% stenosis, the risk of any ipsilateral stroke at 5 years in the medically treated group was 15% for women, and 25% for men. Endarterectomy reduced the risk to 14% for women and 17% for men (p. 1421).

The table below shows the rate of events at 5-year followup:

table5

To drain or not to drain…the GRECCAR 5 randomized trial

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One discussion this week focused on pelvic drains.

Reference: Denost Q, et al. To drain or not to drain infraperitoneal anastomosis after rectal excision for Cancer: The GRECCAR 5 randomized trial. Annals of Surgery. 2017 Mar;265(3):474-480. doi:10.1097/SLA.0000000000001991.

Summary: The GRECCAR 5 randomized trial sought to explore the benefit of a drain for postoperative pelvic sepsis, overall morbidity and mortality, rate of re-operation, length of stay, and rate of stoma closure at 6 months (p.474). It involved 469 patients (236 with drains, 233 without) between 2011 and 2014.

Ultimately, the trial did not find any benefit of the pelvic drain after low anterior resection for rectal cancer. Thus, the authors “recommend not using pelvic drain after rectal excision for cancer, except in case of operative bleeding or beyond TME surgery” (p.480).

The drain did not contribute to an efficient diagnosis of sepsis, for the time to diagnosis of pelvic sepsis was an average of 7.8 days, yet the drain was removed at 5.5 days postop (see figure below; p.1478).

pelvic sepsis

There was no significant difference between the two groups for any of the noted measurements. Pelvic sepsis occurred in 16.1% of those with the drain and 18.0% of those without drain. Re-operation for pelvic sepsis was done in 10.2% of those with drain and 12.0% of those without drain.

Additional reading: Placer C. To drain or not to drain infraperitoneal anastomosis after rectal excision for cancer: an unclosed debate [Letter to the Editor]. Annals of Surgery. 2018. doi:10.1097/SLA.0000000000003005. [Epub ahead of print]

The Prospective Peri-operative Enoxaparin Cohort Trial (PROSPECT)

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Reference: Dunn AS, Spyropoulos AC, Turpie AG. Bridging therapy in patients on long-term oral anticoagulants who require surgery: the Prospective Peri-operative Enoxaparin Cohort Trial (PROSPECT). Journal of Thrombosis and Haemostasis. 2007 Nov;5(11):2211-2218.

Summary: Due to limited data on the incidence of peri-operative thromboemobolic and bleeding during bridge therapy, there is no agreement on optimal peri-operative management of patients on oral anticoagulants (OACs). Dunn et al sought to “examine the incidence of major bleeding of a peri-operative strategy using once-daily therapeutic-dose enoxaparin administered primarily at home, and the effect, if any, of the extensiveness of the procedure on the risk of bleeding during bridge therapy” (p.2211-2212).

The study involved 24 sites in North America between January 2002 and August 2003. The figure below shows the study’s peri-operative management protocol (p.2212): periop mgmt2

 

Safety outcomes:

  • Incidence of major bleeding while on enoxaparin or in the 24 hours following cessation of enoxaparin treatment
    • Occurred in 3.5% (95% CI: 1.6-6.5)
    • Invasive procedures: 1.4%
    • Minor surgery: 0%
    • Major surgery:  27.5%
  • Rate of minor bleeding while on enoxaparin, or within 24 hours of discontinuation
    • Occurred in 108 patients (41.5%, 95% CI:35.7-47.6)
    • Invasive procedures: 44.6%
    • Minor surgery: 47.2%
    • Major surgery: 20.0%

Efficacy outcomes:

  • Incidence of arterial thromboembolic events for patients with afib
    • 4 events out of 176 patients (2.3%, 95% CI: 0.6-5.7)
    • 2 TIAs, 0 strokes, 2 patients had peripheral arterial thromboembolic events
  • Incidence of venous thromboembolic events for patients with a history of DVT.
    • 1 event out of 96 patients (1.0%, 95% CI: 0.03-5.7)
    • None fatal

Bleeding risk is high when bridging therapy is done peri-operatively in major surgery. In this study, there were 8 instances of major bleeding among 40 total patients in major surgery. Out of 220 invasive procedures or minor surgery, there was only 1 major bleeding event.