Acute blood pressure reduction exceeding safety and autoregulatory limits following rapid-acting antihypertensives for hypertensive urgency

INTRODUCTION: Severe hypertension without associated hypertensive target organ injury is termed hypertensive urgency. Treatment guidelines for the initial 4-6 hours uniformly warn against extreme (e.g. >80 mmHg) reduction in SBP and reduction more than 25% below baseline mean arterial pressure (MAP), the approximate lower limit of cerebral autoregulation. We hypothesized that rapid-acting antihypertensive regimens commonly employed for hypertensive urgency can reduce SBP and MAP in excess of these limits, potentially compromising cerebral blood flow. METHODS: Retrospective cohort study in 1553 patients with hypertensive urgency to assess 5-hour SBP and MAP responses to the most commonly administered single-drug regimens (n = 453), combined single-drug and multiple-drug regimens (n = 1051), and no drug (n = 199). Co-primary endpoints: number (%) SBP reduction greater than 80 mmHg and number (%) MAP reduction more than 25%. RESULTS SINGLEDOSE: rapid-acting oral clonidine (n = 214), intravenous hydralazine (n = 93), and intravenous labetalol (n = 40), produced 5-hour SBP reduction of more than 80 mmHg in 38/214 (18%), 17/93 (18%), and 8/40 (20%) patients, respectively, and MAP reduction of more than 25% in 98/214 (46%), 41/93 (44%), and 15/40 (38%) patients, respectively. Conversely, oral extended-release nifedipine (n = 84) and oral lisinopril (n = 22) produced SBP reduction of more than 80 mmHg in 1/84 (1%) and 1/22 (5%) patients. MAP reductions of more than 25% were also fewer: 18/84 (21%) and 2/22 (9%) patients.Combined single-drug/multidrug combinations (n = 1051) and no drug (n = 199) demonstrated similar excessive SBP and MAP reductions. DISCUSSION: Our results demonstrate frequent extreme SBP and MAP reductions exceeding safety and autoregulatory limits with rapid-acting antihypertensives and the crucial need to develop and test novel clinical algorithms for the well tolerated and effective management of hypertensive urgency.