Can Medication For Severe Retinopathy Lead to Stroke?
Avastin risks low but still too great for some
By A.Paul Chous, MA, OD, FAAO
I recently came across the story of a young woman who suffered a stroke shortly after receiving a medication injected into her eye for treatment of severe diabetic retinopathy. The medication in question, bevacizumab, goes by the trade name Avastin and was FDA approved for the treatment of metastatic colorectal cancer. Avastin belongs to a group of drugs known as vascular endothelial growth factor inhibitors (VEGF inhibitors, for short) and is being increasingly used by eye specialists to treat a number of eye diseases wherein new, abnormal blood vessels grow within the eye (a process known as ocular neovascularization), then leak, break, bleed, and ruin vision. Examples of eye diseases characterized by neovascularization and blood vessel leakage include neovascular age-related macular degeneration (AKA "wet" macular degeneration), retinal vein occlusion, neovascular glaucoma, proliferative diabetic retinopathy and diabetic macular edema. Several other VEGF inhibitor drugs have been approved specifically for use in the eyes, including Macugen R and Lucentis R, but these medications are significantly (twenty times) more expensive than Avastin and often are not covered by medical insurance which, along with its effectiveness, is a major reason many eye specialists favor Avastin – at least up until this point in time.
In clinical trials for cancer, Avastin was found to cause acute elevations in blood pressure in some patients. Avastin also increased the risk of thromboembolism – blood clots – that have the potential to block important blood vessels within the heart, brain and lungs and lead to heart attackor stroke. Because VEGF inhibitors are injected in small quantities into the eye, rather than large quantities directly into the circulation (as happens in treatment of colorectal cancer), it had been assumed that the risk of such serious side effects was minimal. In fact, one large study of patients receiving anti-VEGF drugs for various eye diseases, including those caused by diabetes, found the risk of serious side effects to be about 1.5% , with a 0.5% risk of stroke and a 0.4% risk of heart attack. This represents a "mere" 1 in 75 risk which, of course, doesn't seem that small if you're a patient and especially if you're one of the unfortunate 1.5 percent. Nonetheless, it's important to put this risk into some context.
In both clinical trials and the real world, VEGF inhibitors like Avastin have had a huge positive impact on preserving patients' eyesight from the devastating effects of neovascularization, particularly in the case of "wet" macular degeneration. Prior to anti-VEGF treatments, most patients with this disease experienced significant and permanent vision loss, whereas with anti-VEGF drugs most patients' vision remains stable and many patients' vision actually improves. Diabetic macular edema (swelling of the central, most sensitive portion of the retina) is another difficult condition to treat and for which VEGF inhibitors, including Avastin, have proven very helpful. It is also important to realize that many patients with severe eye disease also are at increased risk for cardiovascular diseases, including those of us with diabetic retinopathy (see my last dLife column), so it may be that at least some adverse events like stroke occur as a coincidence rather than as a consequence of Avastin. Patients with pre-existing cardiovascular or kidney disease, especially those on renal dialysis (as was the young woman mentioned at the start of this article) are at even greater risk for stroke and heart attack.
Still, at least some retinal specialists have stopped using Avastin in their patients with diabetes, opting for the much more expensive but possibly safer drugs like Macugen or Lucentis, or deferring use of VEGF inhibitors altogether. The best decision for any given patient depends, in my view, on a careful discussion of the risks and benefits of treatment, alternative treatments, and no treatment. The VEGF inhibitors, especially Avastin, have saved thousands of patients from severe vision loss or blindness. Further research will undoubtedly clarify which combination of drugs and other treatments are best for which patients.
For more information on diabetic eye disease, consult Dr. Chous' book Diabetic Eye Disease: Lessons From a Diabetic Eye Doctor, Fairwood Press, Seattle, 2003.
Read more about Dr. Chous here.
Visit Dr. Chous' website here.
NOTE: The information is not intended to be a replacement or substitute for consultation with a qualified medical professional or for professional medical advice related to diabetes or another medical condition. Please contact your physician or medical professional with any questions and concerns about your medical condition.
1 - Twelve-month safety of intravitreal injections of bevacizumab (Avastin): results of the Pan-American Collaborative Retina Study Group (PACORES). Pan American Collaborative Retina Group (PACORES). Graefes Arch Clin Exp Ophthalmol. 2008 Jan;246(1):81-7.
2 - Long-term effect of intravitreal bevacizumab (avastin) in patients with chronic diffuse diabetic macular edema. Retina. 2008 Oct;28(8):1053-60.
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