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Myocardial infarction more likely after anti-VEGF injections than PDT
Study suggests that increased myocardial infarction risk may be due to underlying AMD or VEGF inhibitor use itself.
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The risk of myocardial infarction was twice as high for patients in the 12-month period following intravitreal anti-VEGF injections than for those who received photodynamic therapy, according to a study.
The study, which appeared in Retina, found there was no difference in the rate of myocardial infarction (MI) for those who received either Avastin (bevacizumab, Genentech) or Lucentis (ranibizumab, Genentech). Furthermore, the risk for myocardial infarction did not increase with increased number of injections.
Relative risk
“Three previous trials have reported a small increase in the risk of thromboembolic events in patients treated with VEGF inhibitors, from 1.1% to 2.5%. So, there is only a small increase in the absolute risk, but relatively it is more than double,” lead author Anna R. Kemp, PhD, an assistant professor at the Centre for Health Services Research, School of Population Health, University of Western Australia, told Ocular Surgery News. “That evidence is not conclusive, though, because those trials had too few participants to statistically determine if the risk increase was significant.”
Anna R. Kemp
The three studies compared the risk of thromboembolic events in patients with wet age-related macular degeneration treated with anti-VEGF to those in patients who received some other form of treatment.
“Any differences in thromboembolic events between these groups would be due to the VEGF inhibitors themselves,” Kemp said. “But our group believes it is also important to compare rates of thromboembolic events in AMD patients, irrespective of treatment, to the general community, as this tests whether AMD itself increases risk.”
The current study included every registered AMD patient in Western Australia during a 7-year period. There were 1,267 VEGF-inhibitor patients, 1,763 community controls and 399 photodynamic therapy patients.
“The popularity of VEGF inhibitors in recent years meant that there were only a handful of patients receiving PDT therapy in the later years of the study,” Kemp said.
The risk of myocardial infarction occurring during the 12 months after the first treatment was 1.9% for anti-VEGF patients, 0.8% for PDT patients and 0.7% for community controls.
“When we adjusted for underlying differences between the groups for age, sex, history of MI and history of diabetes, we found that the risk of MI was 2.3 times higher for the VEGF-inhibitor group than the community. This difference was statistically significant,” Kemp said.
The risk of myocardial infarction was also 2.3 times higher for the VEGF-inhibitor compared with the PDT therapy group. However, this was not significant, possibly because of the small number of patients who received PDT, according to Kemp.
Understanding differences
The investigators believed there were two possible explanations as to why myocardial infarction rates were higher in the anti-VEGF group compared to those in the community.
“Either VEGF inhibitors themselves increase the risk of MI, or having AMD increases the risk of MI,” Kemp said. “However, to determine which one of these is more likely, we need to understand the difference between the PDT patients and the other two groups.”
The study found more cases of nonfatal than fatal myocardial infarction. Nonfatal myocardial infarction occurred within 12 months in 1.3% of anti-VEGF patients, 0.8% of PDT patients and 0.5% of community controls. Fatal myocardial infarction occurred in 0.6% of anti-VEGF patients, zero PDT patients and 0.2% of community controls.
The investigators were surprised by their finding that the number of intravitreal injections did not increase myocardial infarction risk, according to Kemp.
“A dose-response type effect is considered good evidence of a causal relationship, so if we had seen that it would have been more supportive of the theory that VEGF inhibitors themselves increase MI risk,” Kemp said. “These therapies might only increase risk for a short time after each treatment, so the risk doesn’t cumulate with monthly treatment. We also cannot rule out the possibility that AMD itself increases risk of MI because there are a number of common risk factors for both conditions.”
Previous studies have suggested that adverse events after anti-VEGF treatment are idiosyncratic rather than due to a dose-response effect, Kemp said, adding that further research is needed. The researchers did not recommend that clinicians change their protocol.
“At the moment, we do not have the evidence base to recommend clinicians do anything differently,” Kemp said. “It is clear that VEGF inhibitors improve vision and quality of life for these patients.” – by Bob Kronemyer