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M. El Wardani, F. Ziemssen, S. Peters, Tuebingen Bevacizumab Study Group; Intensified Monitoring of Circadian Heart Rate and Blood Pressure Before and After Intravitreal Bevacizumab Injection . Invest. Ophthalmol. Vis. Sci. 2006;47(13):5227.
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Marked elevation of systemic blood pressure (BP) is a serious side effect after intravenous application of Bevacizumab (AvastinTM) and therefore limiting the therapeutic range in patients with pre–existing hypertension. Intraocular installation of 400fold less drug could be a promising anti–angiogenic approach in neovascular age–related macular degeneration (AMD). Casual BP measurements being used in most of the previous anti–VEGF studies might underestimate the cardiovascular effects in a group at risk for acute hypertensive crisis.
A subgroup of patients (11 of 140) receiving antihypertensive therapy were recruited to circadian monitoring before intravitreous injection of 1mg of Bevacizumab for the treatment of macular oedema or neovascular maculopathy. Automatic 24h–recording instruments (Boso GmbH, Jungingen, Germany) were used assessing BP and heart rate (HR) in accordance to the recommendations of the German Hypertension Society. Preoperative measurements were performed at least 12 hours before injection. Postoperative measurements took place between the 1st and 3rd postoperative day when highest plasma levels are presumed.
Before injection, median of mean systolic BP was measured with 149 mmHg (median of mean standard deviation 24.6 mmHg) and median of mean diastolic BP was 84 mmHg (median of mean standard deviation 15.1 mmHg). Therefore, we found a high percentage of systolic values exceeding 135mmHg (median, 77.1%) and diastolic values over 85 mmHg (median 47.2). Postoperatively, there was a tendency to non–significant lower BP (mean systolic BP, 135 mmHg; mean diastolic BP, 75 mmHg), but still a median of 51.6% (systolic BP), respective 16.7 % surpassed the aimed limits. Only 2 of 11 patients showed an increase in mean systolic BP (0.6%, 5.0%). There was no significant change for each evaluated parameter (Wilcoxon Signed Rank test, p> 0.01). Mean HR decreased from 68.2 to 59.2 /min, median decline of HR during night was 7.7% before and 6.6% after the injection.
The percentage of patients with insufficiently treated BP has to be assumed relatively high in pre–existing, treated hypertension. Preoperative stress of patients expecting the injection has to be discussed as well as deficient implementation of guideline recommendations. Nevertheless, intravitreal Bevacizumab does not generally cause an additional rise in BP when released systemically. Perioperative monitoring of BP seems to be justified even before minimal invasive outpatient procedures not to overlook cardiovascular events in AMD patients.
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