Feasibility of minocycline and doxycycline use as potential vasculostatic therapy for brain vascular malformations: pilot study of adverse events and tolerance.

BACKGROUND Tetracyclines may be useful in preventing pathological vascular remodeling, thus decreasing the risk of spontaneous hemorrhage from brain vascular malformations. METHODS Arteriovenous malformation (AVM) and intracranial aneurysm patients undergoing noninvasive management were treated with minocycline or doxycycline (200 mg/day) up to 2 years in a prospective open-label safety pilot trial. The primary outcome was to compare dose-limiting intolerance, defined as treatment-related dose reduction or withdrawal between the agents. RESULTS Twenty-six patients with AVMs (n = 12) or aneurysms (n = 14) were recruited. Adverse event rates were similar to other reported trials of these agents; 4 of 13 (31%) minocycline and 3 of 13 (23%) doxycycline patients had dose-limiting intolerance (hazard ratio = 3.1, 95% CI = 0.52-18.11, log rank p = 0.70). CONCLUSIONS It is feasible to propose a long-term trial to assess the potential benefit of tetracycline therapy to decrease hemorrhagic risk in brain vascular malformations.