Introducing Anti-Vascular Endothelial Growth Factor Therapies for AMD Did Not Raise Risk of Myocardial Infarction, Stroke, and Death

Abstract

Purpose To assess the effect of availability of anti-VEGF therapy on mortality and hospitalizations for stroke and acute myocardial infarction (AMI) over a 5-year follow-up period in US Medicare beneficiaries newly diagnosed with exudative age-related macular degeneration (AMD) in 2006 compared to control groups consisting of beneficiaries newly diagnosed with exudative AMD at a time when anti-VEGF therapy was not possible and with a control group of beneficiaries newly diagnosed with non-exudative AMD. Design Retrospective cohort study Participants Medicare beneficiaries newly diagnosed with exudative and non-exudative AMD in 2000 and 2006 selected from a random longitudinal sample of Medicare 5% claims and enrollment files. Methods Beneficiaries with a first diagnosis of exudative AMD in 2006 were the treatment group; beneficiaries newly diagnosed with exudative AMD in 2000 or non-exudative AMD in 2000 or 2006 were control groups. To deal with potential selection bias, we designed an intent-to-treat study. Intent-to-treat analysis controls for non-adherence to prescribed regimens. In our study, the treatment group consisted of patients with clinically appropriate characteristics to receive anti-VEGF injections given that the therapy is available, by-passing the need to monitor whether treatment was actually received. Control groups consisted of patients with clinically appropriate characteristics but first diagnosed at a time when the therapy was unavailable (2000) and similar patients but for whom the therapy is not clinically indicated (2000, 2006). We used a Cox proportional hazard model. Main Outcome Measures All-cause mortality and hospitalization for stroke and AMI during follow-up. Results No statistically significant changes in probabilities of death and hospitalizations for AMI and stroke within a 5-year follow-up period were identified in exudative AMD beneficiaries newly diagnosed in 2006, the beginning of widespread anti-VEGF use, compared to 2000. As an alternative to our main analysis, which excluded beneficiaries from non-exudative AMD group who received anti-VEGF therapies during follow-up, we performed a sensitivity analysis with this group of individuals re-included (11% of beneficiaries newly diagnosed with non-exudative AMD in 2006). Results were similar. Conclusions Data from this study do not show that the introduction of anti-VEGF agents in 2006 for treating exudative AMD has posed a threat of increased risk of AMI, stroke, or all-cause mortality.

Risks of newly onset hemorrhagic stroke in patients with neovascular age‐related macular degeneration

“…In Taiwan, patients with nAMD might have received treatment with anti‐VEGF injections during their disease course since 2006. Although this treatment was reported to be safe in most studies, cerebral hemorrhage after the injection has been reported . This adverse effect might be one reason why patients with nAMD have a higher risk of developing hemorrhagic strokes.…”

Present bias and health

“…There is strong evidence from randomized controlled trials and studies based on observational data that patients who adhere to evidence-based treatment recommendations for diabetes care experience better health outcomes (e.g., Chen et al 2015). A high degree of adherence leads to better glycemic control, fewer complications (e.g., blindness, leg amputations), and lower risks for all-cause hospitalization and all-cause mortality (Ho et al 2006; Yashkin et al 2016). However, a substantial proportion of persons who are diagnosed with diabetes do not adhere to guidelines for diabetes care, despite the potentially large benefits.…”

SAVE-AMD: Safety of VEGF Inhibitors in Age-Related Macular Degeneration

“…Meta-analyses, combining the data from various randomized controlled trials, yielded an overall low thromboembolic event rate [16] . In addition, a recent retrospective cohort analysis of United States Medicare beneficiaries with AMD did not show an increased risk for acute myocardial infraction, stroke, or all-cause mortality comparing study cohorts prior and after the introduction of anti-VEGF agents as standard of care for neovascular AMD in 2006 [53] . 214 The SAVE-AMD study was stopped due to safety concerns, and, therefore, limited the power of the secondary ophthalmological outcomes.…”