Journal of Human Hypertension (2006) 20, 707–709 & 2006 Nature Publishing Group All rights reserved 0950-9240/06 $30.00 www.nature.com/jhh RESEARCH LETTER Comparison of intravenous urapidil and oral captopril in patients with hypertensive urgencies

Journal of Human Hypertension (2006) 20, 707–709. of the study was prospective, double-blinded and doi:10.1038/sj.jhh.1002063; published online 6 July 2006 both drugs (urapidil and captopril) were given in a double-dummy design, that is, the patient received simultaneously an i.v. agent (either urapidil or In a prospective, double-blinded, double-dummy, sodium chloride 0.9%) and an oral agent (captopril randomized study, 69 patients with a hypertensive or placebo) according to the randomization protocol. urgency (systolic blood pressure (SBP) 4220 mm Hg The primary inclusion criteria was a hypertensive and/or diastolic blood pressure (DBP) 4110 mm Hg) urgency defined as a systolic blood pressure (SBP) received either captopril or urapidil to reduce of 4220 mm Hg and/or a diastolic blood pressure SBP o180 mm Hg and DBP o90 mm Hg and blood (DBP) 4110 mm Hg without evidence of end-organ pressure was measured by an ambulatory blood damage on admission to the emergency department. pressure unit for at least 12 h. The area-under-the- After a resting period of 30 min, blood pressure was curve (AUC) of SBP and DBP was 163 (20)/85 recorded again. If blood pressure was still above (12) mm Hg for the urapidil group and 159 (17)/88 220 mm Hg systolic and/or 110 mm Hg diastolic, (9) mm Hg for the captopril group (P-values 0.38/ patients were finally included to the study. Before 0.40) and the AUC above 180/90 mm Hg was 4.6 the application of the study medication, the patient (4.9)/4.7 (5.7) mm Hg versus 2.7 (5.1)/5.3 (6.3) mm received an ambulatory blood pressure measure- Hg (P ¼ 0.12/P ¼ 0.42) demonstrating that intrave- ment device to record blood pressure every 15 min nous urapidil may be also an useful drug in the for next 12 h. Study medication was given in a treatment of hypertensive urgencies. double-dummy preparation. The patients were Hypertensive urgencies are commonly observed randomized either to urapidil (12.5 mg urapidil i.v. in emergency departments and walk-in-clinics.1 The and placebo oral) or to captopril (25 mg captopril Joint National Committee on Prevention, Detection, oral and 10 ml placebo ( ¼ 0.9% sodium chloride) Evaluation and Treatment of High Blood Pressure as i.v.). Aim of treatment was to reduce SBP below well as the International Society of Hypertension 180 mm Hg and DBP below 90 mm Hg within the (ISH) recommended the use of oral agents for the first hour after study medication was given. Patients treatment of hypertensive urgencies, as blood pres- with a sufficient blood pressure reduction were sure reduction should occur from 6 to 24 h.2,3 In the discharged and instructed to re-admit the emer- setting of an emergency department, a close follow- gency department at least 12 h later. If blood up of these patients is usually impossible. There- pressure was still above 180/90 mm Hg after 1 h, fore, many emergency departments have standard application of the study medication was repeated procedures that prohibit release of patients with (urapidil group: 12.5 mg urapidil i.v./placebo oral; blood pressure in excess of 180/110 mm Hg and treat captopril group: 12.5 mg captopril oral/placebo i.v.) patients with hypertensive urgencies using intrave- and patients were discharged 2 h after start of nous (i.v.) drugs like urapidil or labetalol.4,5 These treatment. The endpoints were the course of SBP drugs reduce blood pressure sufficiently within a and DBP expressed as area-under-the-curve (AUC) short time and with a low frequency of side effects.6 within the first 12 h after drug treatment, the AUC However, these procedures are controversially dis- for SBP and DBP above 180/90 mm Hg, and the cussed and data demonstrating safety and efficacy number of side-effects. of this treatment are lacking. We, therefore, aimed Finally, 56 patients (28 females; 56 (13) years) a study to evaluate the safety and efficacy of an i.v. were included to the study protocol (Table 1). The antihypertensive drug compared to the standard oral average observation period was 11.1 (1.9) h. treatment of patients with hypertensive urgencies. The AUC of SBP and DBP was 163 (20)/85 The study was conducted in the Emergency (12) mm Hg for the urapidil group and 159 (17)/88 Department of the General Hospital in Vienna (9) mm Hg for the captopril group, respectively between March 2004 and October 2004 and was (P-values 0.38/0.40). The course of SBP and DBP approved by the Ethical Committee of the University did not differ significantly between both groups of Vienna. All patients gave their written informed through the entire observation period (Figure 1). consent before inclusion of the study. The design Blood pressure decreased significantly within the Research Letter 708 Table 1 General characteristics of patients in both treatment trolled blood pressure reduction may be harmful in groups patients with hypertensive urgencies. However, the recommendations against the use of i.v. drugs are Urapidil Captopril P-value based on few reports, including a very small number N 27 29 of patients, which have demonstrated severe Age (years) 58 (53–63) 55 (50–61) 0.38 adverse events after the use of drugs like sodium Gender (f/m) 14/13 14/15 0.79 nitroprusside, diazoxide or clonidine.7–10 These Height (cm) 169 (166–173) 169 (166–173) 0.99 drugs are no longer first-line drugs in the treatment Weight (kg) 85 (77–94) 81 (74–88) 0.38 of hypertensive crisis and have been replaced by BMI (kg/m2) 29.4 (27.3–31.4) 28.2 (26.2–30.2) 0.94 Current smokers (n) 12 (44%) 10 (35%) 0.37 newer drugs like urapidil or labetalol. Safety data of these newer drugs used in the treatment of hyper- Hemodynamic data tensive urgencies have been evaluated in different Systolic BP (mm Hg) 216 (208–225) 211 (204–218) 0.23 settings.11 Diastolic BP (mm Hg) 110 (107–117) 110 (105–116) 0.53 Heart rate (beats/min) 97 (89–107) 99 (91–109) 0.94 However, no prospective comparative studies neither with a short-term nor long-term follow-up Abbreviations: BP, blood pressure; BMI, basal metabolic index. using a head-to-head design (i.v. drug versus oral drug) are available: the lack of scientific evidence concerning the benefit or harm of i.v. drugs in the 260 treatment of hypertensive urgencies was the primary 240 reason for the current study. 220 200 For the first time, our study demonstrated a 180 similar safety and efficacy of an i.v. drug in the 160 treatment of hypertensive urgencies compared to an 140 established oral treatment. Additionally, the use of 120

(mm Hg) 100 i.v. urapidil did not cause rapid and uncontrolled 80 blood pressure reduction. We are aware that addi- 60 tional comparative studies in patients with hyper- 40 20 tensive urgencies are required to assess the final 0 value of i.v. drugs in these patients. However, our 0123456789101112 (hours) data demonstrate that the frequently observed use of i.v. drugs in emergency departments is not harmful Figure 1 Course of blood pressure within the first 12 h after the application of urapidil (&) or captopril (K). for patients with hypertensive urgencies. Conflict of interest: None. first hour (urapidil: À46/26 mm Hg; captopril: À38/ 18 mm Hg) in both groups. An increase of blood pressure was observed from the 9th hour after the start of observation in both groups. The AUC above What is known on this topic the defined SBP and DBP of 180/90 mm Hg was 4.6 K Oral antihypertensive drugs are recommended to treat patients (4.9)/4.7 (5.7) mm Hg in the urapidil group and 2.7 with hypertensive urgencies. (5.1)/5.3 (6.3) mm Hg in the captopril group K Data evaluating the efficacy of oral antihypertensive drugs in these patients are rare. (P ¼ 0.12/P ¼ 0.42). Overall, nine adverse effects K No studies are available comparing the efficacy and safety of (urapidil: n ¼ 5; captopril: n ¼ 4) were observed oral and i.v. drugs in this clinical situation. during the study period. The follow-up of the patients after the hypertensive urgency revealed What this study adds K Our data demonstrate a similar efficacy of oral captopril and that 42 patients (urapidil: n ¼ 19; captopril: n ¼ 23) i.v. urapidil in patients with hypertensive urgencies. had elevated blood pressure values either evaluated K No severe side effects have been observed after the application by home blood pressure measurement or 24-h of i.v. urapidil. ambulatory blood pressure measurement. No evi- K Our data provide some evidence that i.v. drugs are not harmful dence of secondary hypertension was observed in in the treatment of hypertensive urgencies. the study group. Our data demonstrate that both drugs are safe and effective in the treatment of patients with hyperten- C Woisetschla¨ger1, A Bur1, M Vlcek1, sive urgencies. The hemodynamic data as well as U Derhaschnig1, AN Laggner1 and MM Hirschl2 the safety data clearly illustrate that the safety and 1Department of Emergency Medicine, University of efficacy of an i.v. drug like urapidil is comparable to Vienna, Vienna, Austria and oral treatment in these patients. We are aware that 2 the use of i.v. drugs in patients with hypertensive Department of Cardiology, Central Clinicum, III urgencies may be criticized, as current guidelines Medical Department, St Poelten, Austria recommend the use of oral agents in these patients. E-mail: [email protected] It has been hypothesized that rapid and uncon- Published online 6 July 2006

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