Cardio-, Cerebrovascular Safety of Ranibizumab in DME Evaluated
Findings from a pooled analysis published in JAMA Ophthalmology suggest that intravitreous ranibizumab does not increase the risk of systemic vascular events for patients with diabetic macular edema (DME).
DME patients have a higher risk of vascular complications such as stroke and myocardial infarction (MI). The relationship between vascular endothelial growth factor inhibitors in DME and increased cardiovascular/cerebrovascular adverse events have been questioned.
Lead study author, Marco A. Zarbin, MD, PhD, from New Jersey Medical School, Newark, NJ and colleagues sought to assess the cardiovascular and cerebrovascular safety of ranibizumab 0.3mg and 0.5mg vs. sham with and without laser in DME. They analyzed patient-level data from 6 randomized, double-masked, sham- and laser-controlled clinical studies sponsored by Genentech or Novartis.
The main outcome were relevant safety endpoints, which included arterial thromboembolic events, MI, stroke or transient ischemic attack, vascular deaths, and major vascular events as defined by the Antiplatelet Trialists' Collaboration (APTC). The study population included 936 patients treated with ranibizumab 0.5mg, 250 patients treated with ranibizumab 0.3mg, and 581 patients who received sham/laser.
For all key cardiovascular and cerebrovascular safety endpoints, the hazard ratios for ranibizumab 0.5mg vs. sham/laser and ranibizumab 0.3mg vs. sham were:
- Arterial thromboembolic events, 1.05 (95% CI, 0.66–1.68) and 0.78 (95% CI, 0.43–1.40);
- MI 0.84 (95% CI, 0.41–1.72) and 0.94 (95% CI, 0.43–2.06);
- Stroke or transient ischemic attack, 0.94 (95% CI, 0.44–1.99) and 0.53 (95% CI, 0.19–1.42);
- Stroke (excluding transient ischemic attack), 1.63 (95% CI, 0.65–4.07) and 0.59 (95% CI, 0.14–2.46);
- Vascular death, 2.17 (95% CI, 0.57–8.29) and 2.51 (95% CI, 0.49–12.94); and
- APTC-defined events, 1.09 (95% CI, 0.63–1.88) and 1.00 (95% CI, 0.51–1.96)
Dr. Zarbin added," Although still underpowered to detect small differences for infrequent events, such as stroke, the findings suggest that intravitreous ranibizumab does not increase the risk of systemic vascular events." Data is not definitive for patients with DME who are at high risk for vascular disease as they were not included in these trials.
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