Current Management of Resistant Hypertension in Patients with Intracerebral Hemorrhage

Approximately 795,000 people experience new or recurrent strokes in the United States each year; between 10 to 20% of these are spontaneous intracerebral hemorrhages (ICH). Uncontrolled hypertension is not only the most common cause of ICH but also a major risk factor for hematoma expansion. Resistant hypertension, defined as persistently elevated blood pressure despite the use of three or more antihypertensives of different classes, is common in patients with ICH. A long-acting calcium channel blocker, angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB), and a thiazide diuretic are generally considered the mainstay for the treatment of resistant hypertension. However, due to the risk of hyponatremia and worsening cerebral edema, thiazide diuretics should be avoided during the first few weeks of ICH. Recent evidence supports the use of a mineralocorticoid receptor antagonist. While resistant hypertension may be idiopathic, a workup of secondary causes should be pursued. Adequate and timely control of elevated blood pressure remains one of the main cornerstones of treatment in patients with ICH. Previous studies have revealed that resistant hypertension in patients with ICH is associated with longer ICU stays, a higher risk of recurrent stroke, and can contribute to renal, cardiac, and neurologic complications. This emphasizes the need for early initiation of oral antihypertensives and adequate blood pressure control at hospital discharge. Landmark studies have shown that early lowering of SBP to 130-150 mm Hg with smooth, sustained BP control is safe and may improve functional outcomes in patients with mild to moderate ICH. After initiating oral antihypertensives with a calcium channel blocker, an ACEi or ARB beta-blocker, and a mineralocorticoid receptor antagonist to maximally tolerated doses, the next line of antihypertensive treatment should be tailored to the patient's co-morbidities, and may include a beta-blocker, central alpha agonist, hydralazine, and minoxidil. In this review, we discuss the epidemiology of resistant hypertension in ICH and its molecular basis, diagnostic workup, and acute and long-term treatment. We present novel mechanisms implicated in hypertensive ICH, including ferroptosis, neuroinflammation, the CNS-gut microbiome axis, and novel therapeutics. We also propose a simple algorithm for the optimal pharmacological management of resistant hypertension in ICH.