ORLANDO – Coronary disease patients with a history of aspirin sensitivity who need to start a daily aspirin regimen can safely and quickly undergo desensitization, often as outpatients, that gets them on the drug, according to two case series reported at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.
The trickiest cases are patients with aspirin-exacerbated respiratory disease (AERD), but both of these programs have steered a handful of AERD patients through desensitization safely and effectively.
"Our cardiologists love that we do this for them," Dr. John A. Saryan said while presenting a poster at the meeting. "They started to ask us 6 years ago; they said they really needed aspirin for patients receiving drug-eluting coronary stents. We tried to talk the cardiologists out of it, but then decided to try it and we had no trouble. By now we’ve done 20, 25 patients," said Dr. Saryan, chairman of allergy and immunology at the Lahey Clinic in Burlington, Mass. He presented details from the first 14 patients he and his associates desensitized. "Ten years ago I would have said it’s nuts, I wouldn’t do it," but his recent experience changed his mind, he said in an interview.
Dr. H. James Wedner
"The patients do very well, with no problems; we have no worries about these patients, but the AERD patients are very different. We do them in a spirometry laboratory, and we get a FEV1 [forced expiratory volume in one second] before each desensitization dose," said Dr. H. James Wedner, professor of medicine and chief of the division of allergy and immunology at Washington University, St. Louis. He presented a poster on 23 coronary disease patients he treated for aspirin desensitization since 1996, but added that he has treated additional patients who required aspirin for treatment of arthritis.
Dr. Wedner’s usual protocol involves no prophylactic anti-allergy treatment. Patients identified as having true aspirin sensitivity by their history start on a supervised protocol of aspirin ingestion using a 10-mg/mL solution made by dissolving an Alka-Seltzer tablet in water. Patients start by drinking a 1-mg dose, waiting 15 minutes, and then taking a 10-mg dose, followed by doses of 20 mg, 40 mg, 80 mg, 160 mg, and 325 mg, each delivered 15 minutes apart. Patients who develop a rash as they progress through the doses receive an antihistamine, such as diphenhydramine (Benedryl) or cetirizine (Zyrtec). Three of the 23 patients in the series developed angioedema, two of them safely continued with the protocol. The third patient decided to withdraw from further desensitization, the only patient in the series who did not complete the process, Dr. Wedner reported.
Once patients do this, they can then safely take an aspirin a day. If they miss a dose for more than 48 hours they have to be desensitized again. In Dr. Wedner's series, 3 of the 23 patients needed a second desensitization course. Ten of the courses occurred on an inpatient basis, the other 16 on an outpatient basis.
Patients with a history of AERD go through the same desensitization steps, but with FEV1 monitoring. If their FEV1 drops by 20% or more at any point the protocol stops and the patient goes home but then comes back and continues the protocol the next day, and "they do better," Dr. Wedner said. Although AERD patients have reactions, they can safely proceed through full desensitization, he said. "Some patients drop their FEV1 twice, and it takes 3 days, but ultimately they all get through."
A key preliminary step is taking a careful history to identify patients with true aspirin sensitivity, he added. "There is no skin test or blood test for aspirin sensitivity. It’s all based on history." About 50% of patients Dr. Wedner sees with suspected aspirin sensitivity had been misidentified and don’t need desensitization.
The protocol Dr. Saryan and his associates at Lahey use involves systematic pretreatment with antihistamines, leukotriene-modifying drugs such as montelukast (Singulair) or zileuton (Zyflo), and in one case, prednisone. Many patients received prophylactic drugs from more than one class. The Lahey physicians gear the aggressiveness of the prophylaxis to each patient’s history: the severity of their past aspirin reactions, and their current medical state. "If a coronary patient is unstable, you don’t want them to have a reaction, as respiratory effects can lead to changes in heart rate" or have other cardiac consequences, noted Dr. David E. Riester, an allergist and immunologist at Lahey who also managed these cases.
They modeled their outpatient desensitization protocol on the method reported in 2000 by physicians at Massachusetts General Hospital in Boston (J. Allergy Clin. Immunol. 2000;105:997-1001). The Lahey group has its pharmacy prepare an aspirin solution that gets dosed to a patient starting with 0.1 mg, and then progressing through doses of 0.3 mg, 1 mg, 3 mg, 10 mg, 20 mg, 40 mg, 81 mg, 162 mg, and finishing with 243 or 325 mg. They separate each dose by 20-30 minutes.