The Risk of Aspirin Withdrawal in ACS Patients

Pharmacology Watch

Stopping aspirin may be hazardous to your health, according to recent research. Patients with heart disease who developed acute coronary syndrome (ACS) were questioned to determine whether their aspirin therapy had recently been interrupted. Thirteen percent of patients with recurrent ACS had stopped aspirin within the previous month. The incidence of ST-segment elevation ACS was higher in those who stopped aspirin, compared to those who did not stop aspirin (39% vs 18%; P=0.001). The risk of stopping aspirin was particularly high for patients who had uncoated stents. The mean delay between aspirin withdrawal and acute coronary event was 10 days. Patients withdrew from aspirin for a number of reasons including minor surgery, endoscopy, dental treatment, bleeding, and noncompliance. The authors conclude that aspirin withdrawal in patients with coronary disease represents a risk for the occurrence of a new coronary event (J Am Coll Cardiol. 2005;45:456-459). The risk of ischemic stroke may be as much as 3 times higher with interruption of aspirin therapy, according to presentation at the International Stroke Conference. Researchers from Switzerland noted that the odds ratio for stroke or TIAs associated with aspirin discontinuation was 3.25 (95% CI). Seventy-seven percent of ischemic strokes related to aspirin discontinuation occurred in the first 8 days after aspirin was stopped, with remaining strokes occurring from day 9 to day 30. The reasons cited for discontinuing aspirin were primarily minor bleeding and minor surgical procedures—many of which can safely be performed (many dental procedures, cataract surgery among others) while patients are taking aspirin (http://strokeconference.americanheart.org/portal/strokeconference/sc/02.02.05c).

Neuropsychiatric Symptoms of Dementia

Treatment of neuropsychiatric symptoms in patients with dementia represents one of the biggest challenges in primary care. Dementia is diagnosed by the loss of cognitive function, but other symptoms are often more prominent including agitation, aggression, delusions, hallucinations, repetitive vocalizations, and wandering, among others. Many classes of psychiatric medications are used to treat neuropsychiatric symptoms in dementia including antidepressants, anxiolytics, anticonvulsants, cholinesterase inhibitors, typical antipsychotics, and atypical antipsychotics. Often these drugs are used in combination, and the cocktail can get confusing and even dangerous for patients and caregivers alike. A new review of the topic in the "Clinician's Corner" section of the February 2nd Journal of the American Medical Association helps clarify treatment options. The authors reviewed 29 articles that met their inclusion criteria. Among typical antipsychotics, which include haloperidol, thiothixene, chlorpromazine, trifluoperazine, and acetophenazine, there was no difference in the efficacy among these drugs in treating neuropsychiatric symptoms. Haloperidol may be somewhat more effective for treating aggression but not agitation. Side effects including extrapyramidal symptoms and somnolence are common with these agents. Antidepressants, including the SSRIs, were also relatively ineffective, except for treatment of depression associated with dementia. The best evidence for efficacy was found in the atypical antipsychotic group, especially risperidone (Risperdal) and olanzapine (Zyprexa). These drugs were found to have a modest effect on agitation/aggression, hallucinations, and delusions. A higher risk of stroke was found in the most recent trial (prompting a "Dear Doctor" letter from Janssen in April 2003). The cholinesterase inhibitors group including galantamine (Reminyl), donepezil (Aricept), and rivastigmine (Exelon) were somewhat disappointing with regard to neuropsychiatric symptoms, with minimal improvement of questionable clinical benefit. Memantine, the relatively new N-methly-D-asparte antagonist was seen to improve cognitive and functional parameters, but also did not improve neuropsychiatric symptoms. The authors stress that the management of neuropsychiatric symptoms in dementia "should always begin with an assessment of the medical (eg, pain and delirium) and environmental causes of the behavior." They also recommend starting with a cholinesterase inhibitor if the patient is not already receiving one, because they are relatively well tolerated and may benefit cognition and function (JAMA. 2005;293:596-608).

FDA Actions

Pfizer has received FDA approval to market pregabalin (Lyrica) for the treatment of painful diabetic neuropathy and post-herpetic neuralgia, the 2 most common types of neuropathic pain. Pregabalin was shown to be effective in a company-sponsored study of 338 patients with a 1-5 year history of painful, diabetic, peripheral neuropathy who were randomized to receive the drug at 1 of 3 doses or placebo for 5 weeks. Patients in the 300 and 600 mg/day doses showed improvements in mean pain score vs placebo (P = 0.0001 ), but no improvement was seen at the 75 mg/day dose. The higher doses also resulted in improvements in weekly pain score, sleep interferes score, patient global impression of change, clinical global impression of change, and lifestyle surveys. The most common side effects were dizziness and somnolence (Neurology. 2004;63:2104-2110). Pregabalin is a 3-substituted analogue of gamma-amino butyric acid (GABA), and is closely related to Pfizer's gabapentin (Neurontin), which recently lost its patent and is now available as a generic. Pregabalin is currently under review by the FDA for the treatment of partial seizures.

The FDA has also approved palifermin (Kepivance-Amgen) to decrease the incidence and duration of severe oral mucositis in patients with hematologic malignancies undergoing chemotherapy, with or without radiation, in preparation for bone marrow transplantation. The drug, which is the first agent to be approved for this indication, stimulates epithelial cell growth in mucous membranes. It is given prior to fractionated total body irradiation and high dose chemotherapy, and repeated after bone marrow transplantation. The drug's efficacy in non-hematologic malignancies has not been shown.

Citalopram (Celexa) is now available in generic tablets and liquid. The liquid formulation recently joined the tablet formulation for the popular SSRI antidepressant.

Extended release buproprion (Wellbutrin SR) is now available as a generic in the 200 mg strength.

Fosinopril/HCTZ (Monopril) has also joined the generic ranks in 10/12.5 mg and 20/12.5 mg strengths.

The FDA has also approved a generic fentanyl transdermal system (Duragesic) for the treatment of severe chronic pain. The new generic, which is produced by Mylan technologies, provides a constant dose of the drug for 72 hours.

Canada has suspended marketing of Adderall and Adderall XR because of reports of sudden unexplained death (SUD) in children taking the drugs. SUD has been associated with amphetamine abuse and has been reported in children with heart disease taking prescribed doses of amphetamines, including Adderall and Adderall XR. These latest reports of SUD have been in children without structural heart disease who were taking the drugs as prescribed. The FDA is looking at these reports, but "does not feel that any immediate changes are warranted in the FDA labeling or approved use of this drug." More information is available on the FDA web site at www.FDA.gov.


This supplement was written by William T. Elliott, MD, FACP, Chair, Formulary Committee, Kaiser Permanente, California Division; Assistant Clinical Professor of Medicine, University of California-San Francisco. In order to reveal any potential bias in this publication, we disclose that Dr. Elliott reports no consultant, stockholder, speaker’s bureau, research, or other financial relationships with companies having ties to this field of study. Questions and comments, call: (404) 262-5416. E-mail: leslie.hamlin@thomson.com