SAPPHIRE: The Gem Still Shines

“And I said of medicine, that this is an art which considers the constitution of the patient, and has principles of actions and reasons in each case.” – Plato: Georgias.

In his classic textbook of medicine, The Principles and Practice of Medicine, William Osler states the treatment of gastric ulcer includes:

A. Absolute bed rest;

B. A carefully and systematically regulated diet;

C. Medicinal measures are of very little value in gastric ulcer, and the remedies employed do not probably benefit the ulcer, but the gastric catarrh.¹

Therapies that were successful and thought to be appropriate in Osler’s days are no longer appropriate now. The author of the article “SAPPHIRE: Precious Gem or Fool’s Gold”, as well as physicians involved in treating patients with carotid disease, need to understand that treatment options change.

The paradigm has shifted for high-risk patients with carotid artery disease (CAD), not because the SAPPHIRE trial showed that carotid stenting with embolic protection device was superior, but because it was non-inferior!² As Plato has told us, we need to understand the constitution of the patient. Most patients, when given a choice of an invasive procedure under general anesthetic as opposed to a procedure under local anesthetic, will prefer the latter. A knowledgeable patient with CAD symptoms requiring intervention will likely prefer a less invasive approach, such as a percutaneous transluminal angioplasty to the more invasive, more intrusive bypass surgery. Likewise for a patient with symptoms of cholecystitis, a minimally-invasive cholecystectomy, as an outpatient is certainly preferred to an open operation with a “LBJ-like” scar.

Some of the arguments in this editorial are a bit outdated. The definition of “high risk” in Stenting and Angioplasty with Protection in Patients at High-Risk for Endarterectomy (SAPPHIRE) was in fact made by the surgeons involved with the trial. The investigators were definitely experienced surgeons, with a median annual volume of 30 endarterectomies (range 15–100) and as emphasized in the SAPPHIRE article, we studied patients for whom risks posed by surgery were high, because when our trial was designed, evidence-based medicine did not exist for the random assignment of patients at low risk to a percutaneous interventional treatment.² We studied patients who had been traditionally excluded from randomized trials of carotid endarterectomy. In a study of more than 100,000 Medicare patients undergoing endarterectomy, Wennberg et al found that the overall preoperative mortality rate at hospitals participating in the North American Symptomatic Carotid Endarterectomy Trial (NASCET) and Asymptomatic Carotid Atherosclerosis Study (ACAS) was 1.4% as opposed to .6% and 1% in the respective studies.^3–5 This mortality is significantly higher than randomized patients in NASCET and ACAS. Wennberg concluded that the patients in these trials were certainly not representative of patients routinely treated with endarterectomy.⁶ NASCET and ACAS both showed us that these patients are not appropriately treated non-surgically. It is not within guidelines of evidence-based medicine to consider medical management alone in these patients.

The population we enrolled was a much riskier population than normally involved with clinical trials. Patients undergoing carotid endarterectomy, and thought to be at high risk, carry the risk of adverse outcome of stroke and MI at 7.4%, as opposed to 2.9% among those at low risk.⁷ This formed the basis of considering the population in SAPPHIRE. Regardless, even though many of the patients in SAPPHIRE had previously undergone endarterectomy, radical neck surgery, or radiation therapy, the rate of cranial nerve palsy among patients in the surgical arm in our trial who underwent endarterectomy was lower than in NASCET. Complications in our study were 5.3% versus 7.6% for the NASCET sample.² In SAPPHIRE, the results support the technical excellence of the surgeons involved. There is no need to discuss outcomes of surgical patients in the SAPPHIRE trial; the results provide sufficient evidence. Even though many trials suffer from self-reporting of outcomes or self-reporting of neurologic exams, the SAPPHIRE trial involved neurologists who examined patients independently from the treating physician. It is possible that some in the profession are having the most difficulty dealing with this fact: ongoing practice changes. Treatments in the past that have been considered effective have evolved. Forward thinking vascular surgeons have now embraced carotid stenting and have undertaken additional training, even in our labs alongside their interventionalist colleagues. This should be encouraged.

Times have changed since Osler, and times have changed since Dr. DeBakey first performed carotid endarterectomy in 1953. The active and innovative practitioner looks for the evolution of technology and continues to improve the techniques to treat patients.⁸ CABERNET showed that carotid stenting with embolic protection can be done.⁹ Perhaps some surgeons should stop whining and think about partaking in the bouquet!!