Antiplatelet, anticoagulant therapy may pose risk for patients with neovascular AMD

Study encourages collaboration between ophthalmologists and other medical specialists to prevent intraocular hemorrhage.

Daniel F. Kiernan

Antiplatelet/anticoagulant therapy may be associated with an increased risk of intraocular hemorrhage in patients with neovascular age-related macular degeneration, according to a study.

The study, published in Retina, reported that overall cumulative incidence, annual incidence and incidence density of intraocular hemorrhage were significantly higher in patients with neovascular AMD who were taking antiplatelet/anticoagulant (AP/AC) medications — in this case aspirin, clopidogrel and warfarin.

According to Daniel F. Kiernan, MD, lead author of the study, AP/AC medications are often necessary to treat life-threatening conditions, but in a few cases, they may be routinely prescribed when other effective therapies are available. For instance, high-dose aspirin is frequently used to treat hypertension or prescribed prophylactically in patients with a family history of heart attack or stroke.

“Our study reinforces the need for communication between eye care specialists and other medical experts,” he said. “It is my hope that the advent of electronic medical records will simplify cross-communication between ophthalmologists, cardiologists, internal medicine doctors, endocrinologists and other specialists involved in these complex treatments.”

In addition to assessing the relationship between AP/AC therapy and ocular hemorrhage in patients with neovascular AMD, the study took a broader look at the cumulative and annual incidence of subretinal and vitreous hemorrhage in neovascular AMD patients.

While it may seem obvious that these patients would be more prone to ocular hemorrhage, epidemiologic studies establishing this correlation did not previously exist in the ophthalmic literature. Moreover, the authors noted that this was the first study to report on the cumulative and annual incidence of vitreous hemorrhage in patients with neovascular AMD.

Study results

The retrospective, cross-sectional study reviewed data on 195 eyes of 195 patients with neovascular AMD and no history of intraocular hemorrhage. Data was collected over 73 months from 2002 to 2008.

Of the 96 study participants taking AP/ACs, 63.5% experienced intraocular hemorrhage. In the patients not taking AP/ACs, 29.2% experienced hemorrhage. Seventy-seven percent of those taking more than one AP/AC medication reported hemorrhage.

The annual incidence of intraocular hemorrhage for patients taking AP/ACs (0.1%) was significantly greater than that reported for patients not taking such medications (0.04%). Of those taking AP/ACs, incidence density of hemorrhage was 0.22 per patient-month; for those not taking AP/ACs, incidence density of hemorrhage was 0.013 per patient-month.

Although previous studies on patients receiving long-term AP/AC therapy have reported higher cumulative and annual incidences of major or minor systemic hemorrhage, Dr. Kiernan noted that these studies did not center on intraocular bleeding complications.

“Our study focused on a specific population of patients with neovascular AMD and only examined intraocular hemorrhage occurrence. The other studies we referenced analyzed all complications in patients taking long-term AP/AC agents,” Dr. Kiernan said.

Whereas the study established AP/AC use as an independent risk factor for intraocular hemorrhage, it showed no positive correlation between intraocular hemorrhage and gender, hypertension or diabetes. In patients not taking AP/AC medications, age was the only risk factor for hemorrhage, and in those taking AP/ACs, bilateral neovascular AMD was significantly associated with an increased risk.

Vitreous hemorrhaging, future research

Of seven patients who experienced a massive vitreoretinal hemorrhage, six were taking one or more AP/ACs. Even though such hemorrhaging was relatively uncommon, the study authors said that the severe visual risks associated with vitreous hemorrhage underscore the need for further research.

“We would require a much larger sample of patients with wet AMD in order to draw conclusions about predisposing conditions to vitreous hemorrhage,” Dr. Kiernan said. “If a meta-analysis could be carried out through the Blue Mountains Eye Study, the Age-Related Eye Disease Study and the Complications of Age-Related Macular Degeneration Prevention Trial, the data generated there would indicate what health conditions and medications may be associated with vitreous hemorrhage.”

Dr. Kiernan also stressed the need for further research on factors associated with intraocular hemorrhage complications, acknowledging that the risks associated with discontinuing AP/AC medications would preclude prospective studies from being carried out.

“Again, I think a collaborative effort to combine several larger retrospective studies into a meta-analysis of both neovascular and non-neovascular AMD patients would help to strengthen our knowledge of what predisposes these individuals to intraocular hemorrhage,” he noted.

In addition to these research efforts, the study authors mentioned investigating whether predisposing systemic reasons for using AP/AC medications may be associated with the onset of AMD as well as intraocular hemorrhage.

Dr. Kiernan and colleagues also suggested that neovascular AMD patients using AP/ACs should undergo more frequent dilated fundus examinations and that ophthalmologists should check with other medical specialists to ensure that these medications are absolutely necessary. – by Michelle Pagnani

Reference:

• Kiernan DF, Hariprasad SM, Rusu IM, Mehta SV, Mieler WF, Jager RD. Epidemiology of the association between anticoagulants and intraocular hemorrhage in patients with neovascular age-related macular degeneration. Retina. 2010;30(10):1573-1578.

• Daniel F. Kiernan, MD, can be reached at the Illinois Eye and Ear Infirmary, 1905 W. Taylor St., Chicago, IL 60618; 312-996-6660; e-mail: danielkiernan714@yahoo.com.
• Disclosure: Dr. Kiernan has no direct financial interest in the study discussed in this article.