Study reference

Study characteristics

Patient characteristics ²

Intervention (I)

Comparison / control (C) ³

Follow-up

Outcome measures and effect size ⁴

Comments

Park, 2017

Type of study: RCT

Setting: Emergency room

Country: South Korea

Source of funding: Not stated

Inclusion criteria:

• Age at least 20 years
• Hypertensive urgency (SBP > 179 mmHg and/or DBP at least 109 mmHg in two conservative BP measurements with 5-min interval

Exclusion criteria:

• Suspected target organ damage
• Pulmonary oedema
• Acute coronary syndrome
• Aortic dissection
• Acute trauma
• History of recent surgery
• Uncooperative and incommunicable condition

N total at baseline:

Intervention: 68

Control: 70

Important prognostic factors²:

Age ± SD:

I: 73 (SD 9)

C: 69 (SD 11)

Sex:

I: 84% M

C: 79% M

Groups comparable at baseline?

40 mg telmisartan

Rest, sitting for 2h

Length of follow-up:

24 h and 7 days (only among patients whose BP could be identified)

Loss-to-follow-up:

Not reported

Incomplete outcome data:

Not reported

1. Blood pressure

Defined as mean BP 2h after management, from 10% to 35%

10% ≤ MBP reduction, n (%)

I: 47 (69)

C: 48 (69)

20% ≤ MBP reduction, n (%)

I: 23 (34)

C: 25 (36)

30% ≤ MBP reduction, n (%)

I: 12 (18)

C: 12 (17)

35% ≤ MBP reduction, n (%)

I: 4 (6)

C: 3 (4)

Defined as level of BP

Initial ER admission

SBP, mmHg

I: 184.9 (SD 17.2)

C: 179.7 (SD 20.6)

DBP, mmHg

I: 100.7 (SD 16.1)

C: 104.4 (SD 17.2)

24h after ER admission

SBP, mmHg

I: 140.2 (SD 25.5)

C: 138.0 (SD 23.0)

DBP, mmHg

I: 77.0 (SD 13.0)

C: 75.2 (SD 16.0)

7 days after ER admission

SBP, mmHg

I: 134.7 (SD 19.0)

C: 133.0 (SD 16.7)

DBP, mmHg

I: 77.2 (SD 11.3)

C: 75.7 (SD 15.2)

2. Cardiovascular disease

Not reported

3. Mortality

Not reported

4. Acute hypertensive organ damage

Not reported

5. Adverse events

Not reported

Hypertensieve urgency was defined as a SBP at least 180 mmHg and/or a DBP at least 110 mmHg in two consecutive BP measurements with 5-min interval at visiting emergency room.

Yilmaz, 2011

Type of study: RCT

Setting: Emergency room

Country: Turkey

Source of funding: Not stated

Inclusion criteria:

• 18 years or older
• Initial SBP ≥ 160 mmHg or DBP ≥ 100 mmHg and repeat high BP after 10 min rest

Exclusion criteria:

• secondary hypertension
• malignant hypertension
• acute left cardiac failure
• chronic renal failure
• acute coronary syndrome
• aorta dissection
• cerebrovascular event
• conditions requiring analgesics use
• known allergy to

captopril or alprazolam

• pregnancy

N total at baseline:

Intervention: 26

Control: 27

Important prognostic factors²:

age ± SD:

I: 53 (11)

C: 57 (11)

Sex:

I: 54% M

C: 46% M

Alprazolam, 0.5 mg

Captopril, 25 mg

Length of follow-up:

2 hours

Loss-to-follow-up:

Not reported

Incomplete outcome data:

Not reported

1. Blood pressure

Defined as mean BP

Initial BP

SBP, mmHg

I: 200

C: 187

DBP, mmHg

I: 108

C: 107

1 h

SBP, mmHg

I: 177

C: 166

DBP, mmHg

I: 97

C: 92

2h

SBP, mmHg

I: 167

C: 159

DBP, mmHg

I: 93

C: 92

2. Cardiovascular disease

Not reported

3. Mortality

Not reported

4. Acute hypertensive organ damage

Not reported

5. Adverse events

Not reported

Grossman, 2005

Type of study: RCT

Setting: Emergency room

Country: Israel

Source of funding: Not stated

Inclusion criteria:

Exclusion criteria:

• Secondary hypertension
• Malignant hypertension
• Grade 2-4 retinopathy
• Acute congestive heart failure
• Renal failure
• Acute ischemic heart disease
• Suspected aortic dissection
• Acute cerebrovascular event

N total at baseline:

Intervention: 17

Control: 19

Important prognostic factors²:

age ± SE:

I: 62 (3)

C: 58 (4)

Sex:

I: 29% M

C: 16% M

Diazepam, 5 mg oral

Captopril, 25 mg sublingual

Length of follow-up: 3 hours

Loss-to-follow-up:

Not reported

Incomplete outcome data:

Not reported

1. Blood pressure

Defined as mean BP after 10 minutes

Baseline

SBP, mmHg

I: 213 (5)

C: 208 (5)

DBP, mmHg

I: 105 (3)

C: 107 (3)

After 3h

SBP, mmHg

I: 170 (8)

C: 181 (8)

DBP, mmHg

I: 88 (6)

C: 95 (3)

2. Cardiovascular disease

Not reported

3. Mortality

Not reported

4. Acute hypertensive organ damage

Not reported

5. Adverse events

Not reported

Sanchez, 1999

Type of study: RCT

Setting: ER admission

Country: Spain

Source of funding: Not stated

Inclusion criteria:

• Essential hypertension
• Aged 18-80
• Initial DBP and after 30 min rest ≥ 120 mmHg
• No evidence of end-organ damage
• Not taking antihypertensive drugs for the last 24h

N total at baseline:

Intervention: 15

Control: 14

Important prognostic factors²:

Age ± SD:

I: 55 (11)

C: 54 (12)

Sex:

I: 50% M

C: 40% M

Lacidipine, 4 mg, oral

Nifedipine, 20 mg, oral

Length of follow-up:

24 h

Loss-to-follow-up:

Not stated

Incomplete outcome data:

Not stated

1. Blood pressure*

Defined as mean BP

Baseline

SBP, mmHg

I: 222.5 (32.8)

C: 215.9 (20.6)

DBP, mmHg

I: 124.6 (8.4)

C: 128.0 (7.7)

8 h

SBP, mmHg

I: 169.6 (27.8)

C: 170.6 (25.3)

DBP, mmHg

I: 104.1 (16.0)

C: 102.9 (12.4)

24 h

SBP, mmHg

I: 165.0 (27.3)

C: 190.6 (18.2)

DBP, mmHg

I: 99.9 (12.3)

C: 117.2 (11.4)

2. Cardiovascular disease

Not reported

3. Mortality

Not reported

4. Acute hypertensive organ damage

One patient treated with nifedipine had a transient cerebrovascular ischemic attack 30 min after dose (BP decrease from 210/125 to 120/80 mm Hg).

5. Adverse events

Not reported

*Twenty-four-hour ABPM was performed by using an automated, noninvasive, oscillometric device. The appropriate cuff was placed on the nondominant arm, and BP and HR were registered automatically at 30-min intervals for the first 8 h and subsequently every 2 h until complete 24 h of follow-up. Mean values and standard deviation of SBP, DBP, and HR were obtained from each record in the 24-h period.

McDonald, 1993

Type of study: RCT

Setting: ER admission

Country: USA

Source of funding: Not stated

Inclusion criteria:

• 18 years or older
• Initial DBP ≥ 120 mmHg
• No taking any hypertensive medication for 24 hours, except diuretics.

Exclusion criteria:

• BP ≥ 250/150 mmHg
• Malignant hypertension
• Hypertensive encephalopathy
• Acute pulmonary edema
• Acute myocardial ischemia
• Myocardial infarction in past 6 months
• Sinus bradycardia <50 beats/min
• Second or third degree heart block
• Asthma
• COPD
• Creatinine > 2.0 mg/dl
• Pregnancy

N total at baseline:

Intervention: 10

Control: 10

Important prognostic factors²:

age ± SD:

I: 46 (11)

C: 48 (19)

Sex:

I: 40% M

C: 60% M

Black:

I: 100%

C: 100%

Labetalol, 200 mg oral

If the DBP was ≥120 mm Hg, 200 mg orally was repeated: if the DBP was > 110 mm Hg but <120 mm Hg, 100 mg was given.

Nifedipine, 10 mg oral

If DBP ≥ 110 mmHg one hour after dose, another 10mg were taken

Length of follow-up:

4 hour

Loss-to-follow-up:

Intervention:

N (%)

Reasons (describe)

Control:

N (%)

Reasons (describe)

Incomplete outcome data:

Intervention:

N (%)

Reasons (describe)

Control:

N (%)

Reasons (describe)

1. Blood pressure

Defined as mean BP after 10 minutes

Initial

SBP, mmHg

I: 195 (29.8)

C: 198 (24.9)

DBP, mmHg

I: 127 (10.1)

C: 128 (10.8)

4 h after treatment

SBP, mmHg

I: 154 (18.7)

C: 163 (14.9)

DBP, mmHg

I: 100 (14.8)

C: 100 (9.6)

2. Cardiovascular disease

Not reported

3. Mortality

Not reported

4. Acute hypertensive organ damage

Not reported

5. Adverse events

Not reported

Atkins, 1992

Type of study: RCT

Setting: ER admission

Country: USA

Source of funding: Commercial

Inclusion criteria:

• Aged between 18 and 65 years

Exclusion criteria:

• History or coexistence of accelerated or malignant hypertension
• Suspected aortic dissection
• Pheochromocytoma
• CVA within 6 months
• Active angina
• Coronary bypass surgery within 1 year
• Heartblock greater than first degree or significant arrhythmias
• Women of childbearing potential
• Significant medical illnesses
• Active seizure disorder
• Current alcohol or drug abuse
• Labetalol or clonidine up to 48 hours prior to entry into the study
• Known allergy to either drug

N total at baseline:

Intervention: 18

Control: 18

Important prognostic factors²:

Age (range):

I: 48 (23-63)

C: 46 (29-63)

Sex:

I: 61% M

C: 56% M

Phase I: acute drug administration

200 mg labetalol orally on an hourly basis to a maximum dose of 1200 mg at 6 hours

Phase I: acute drug administration

0.2 mg of clonidine orally followed by 0.1 mg of clonidine orally each hour to a maximum of 0.7 mg at 6 hours

Length of follow-up:

240 minutes

Loss-to-follow-up:

Not reported

Incomplete outcome data:

I: n=12 at 240 minutes

C: n=10 after 240 minutes

Reasons not reported

1. Blood pressure

Baseline

SBP (SE), mmHg

I: 200 (6.2)

C: 196 (4.8)

DBP, mmHg

I: 132 (2.0)

C: 131 (1.8)

1 h after treatment

SBP, mmHg

I: 175 (4.3)

C: 178 (4.5)

DBP, mmHg

I: 114 (3.3)

C: 121 (2.3)

4 h after treatment

SBP, mmHg

I: 166 (4.7)

C: 149 (7.2)

DBP, mmHg

I: 111 (4.7)

C: 107 (6.0)

2. Cardiovascular disease

Not reported

3. Mortality

Not reported

4. Acute hypertensive organ damage

Not reported

5. Adverse events

I:

Hypotension n=1

Mild dizziness/lightheadedness n=6/18 (33%)

Mild sleepiness n=5/18 (28%)

Headache n=2/18 (22%)

Scalp tingling n=1

C:

Sedation n=10/18 (56%)

Dizziness n=3/18 (17%)

Dry mouth n=2/18 (11%)

Results from phase II were not described, as only a selection of the included patients were included for phase II.

Blood pressure was determined by a blinded investigator with a standard mercury sphygmomanometer using phase V of Korotkoff’s sounds as the diastolic value.

Komsuoglu, 1991

Type of study: RCT

Setting: ER admission

Country: Turkey

Source of funding: Not stated

Inclusion criteria:

• Hypertensive urgencies with initial diastolic blood pressure 120 mmHg or greater.

Exclusion criteria:

• Evidence of malignant or accelerated hypertension
• Aortic dissection
• Chronic renal failure
• Valvular heart disease
• Recent cerebrovascular accident
• Recent myocardial infarction or symptomatic

angina pectoris

• Coronary bypass surgery
• Congestive heart failure
• Pregnancy

N total at baseline:

Intervention1: 23

Intervention2: 20

Important prognostic factors²:

Whole population

Sex: 51% M

Age range:

M: 41-68

F: 48-71

1. Nifedipine 20 mg

2. Captopril 25 mg

See intervention

Length of follow-up:

240 minutes

Loss-to-follow-up:

Not stated

Incomplete outcome data:

Not stated

1. Blood pressure

Before treatment

SBP (SE), mmHg

I1: 239.1 (38.1)

I2: 243.5 (26.0)

DBP, mmHg

I1: 131.5 (12.8)

I2: 132.5 (7.1)

1 h after treatment

SBP, mmHg

I1: 164.4 (23.8 )

I2: 164.1 (27.8)

DBP, mmHg

I1: 96.1 (13.3)

I2: 99.5 (10.3)

4 h after treatment

SBP, mmHg

I1: 175.8 (23.3)

I2: 165.1 (23.0)

DBP, mmHg

I1: 101.2 (11.3)

I2: 100.2 (10.7)

2. Cardiovascular disease

Not reported

3. Mortality

Not reported

4. Acute hypertensive organ damage

Not reported

5. Adverse events

Not reported

Sechi, 1989

Type of study: RCT

Setting: Unclear

Country: Italy

Source of funding: Not stated

Inclusion criteria:

Not stated

Exclusion criteria:

Not stated

N total at baseline:

Intervention: 13

Control: 12

Important prognostic factors²:

Age (range):

53 (17 to 68)

Sex: Not stated

Ketanserin 20 mg, sublingually

Nifedipine 20 mg, sublingually

Length of follow-up:

90 minutes

Loss-to-follow-up:

Not stated

Incomplete outcome data:

Not stated

1. Blood pressure*

Before treatment

SBP (SE), mmHg

I: 191 (5.0)

C: 183 (4.8)

DBP, mmHg

I: 118 (3.1)

C: 121 (2.6)

1 h after treatment

SBP, mmHg

I: 171 (5.0)

C: 147 (5.1)

DBP, mmHg

I: 106 (3.3)

C: 99 (3.1)

1.5 h after treatment

SBP, mmHg

I: 174 (4.3)

C: 149 (5.6)

DBP, mmHg

I: 109 (2.5)

C: 100 (3.0)

2. Cardiovascular disease

Not reported

3. Mortality

Not reported

4. Acute hypertensive organ damage

Not reported

5. Adverse events

I: no side effects reported

C:

Headache n=3

*Data was extracted from figure 1 with web plot digitizer.

Study reference

(first author, publication year)

Describe method of randomisation¹

Bias due to inadequate concealment of allocation?²

(unlikely/likely/unclear)

Bias due to inadequate blinding of participants to treatment allocation?³

(unlikely/likely/unclear)

Bias due to inadequate blinding of care providers to treatment allocation?³

(unlikely/likely/unclear)

Bias due to inadequate blinding of outcome assessors to treatment allocation?³

(unlikely/likely/unclear)

Bias due to selective outcome reporting on basis of the results?⁴

(unlikely/likely/unclear)

Bias due to loss to follow-up?⁵

(unlikely/likely/unclear)

Bias due to violation of

intention to treat analysis?⁶

(unlikely/likely/unclear)

Park, 2017

“(…), we randomly drew an envelope containing paper written with resting group or medication group from box (…).

Unlikely. “Absolutely, the envelope had no marking to identify the inner contents.”

Likely. No placebo was given.

Unclear. “All of patients in both groups were ordered to keep resting and not allowed to have any activity in emergency room.”

Unlikely for BP measured within 120 min, this was done by an automatic device.

Likely for BP measured 24h or 7 days after ER admission, as only patients with BP measurements were included.

Unlikely. Trial was registered and stated outcomes were reported.

Unlikely. BP measurements 24h or 7 days after ER admission were missing, but mostly likely not due to the intervention.

Unlikely. Not applicable.

Yilmaz, 2011

“The authors generated the allocation sequence using a random numbers table before the study.”

Unclear. “The patients were enrolled and assigned to a study group according to the previously established table by a senior resident.”

Unlikely. Both drugs were given orally.

Unclear. Not stated

Unclear. Not stated

Unlikely. Although the trial was not registered, the outcomes stated in the methods section were reported in the results section.

Unlikely. Although no information was given on follow-up, as the duration was only 2 hours, most likely none of the participants were lost to follow-up.

Unlikely. Although not specifically stated, most likely the data was analysed according to assigned groups.

Grossman, 2005

“Patients who were eligible were then randomized in an open manner to receive either oral diazepam, 5 mg (study group) or sublingual captopril, 25 mg (control group).”

Unclear. Not stated

Likely. Intervention was given in an open manner.

Likely. Intervention was given in an open manner.

Unlikely. “Blood pressure and heart rate were measured in the supine position, by a nurse who was unaware of the study”

Unlikely. Although the trial was not registered, the outcomes stated in the methods section were reported in the results section.

Unlikely. Although no information was given on follow-up, as the duration was only 3 hours, most likely none of the participants were lost to follow-up.

Unlikely. Although not specifically stated, most likely the data was analysed according to assigned groups.

Sanchez, 1999

“They were randomized in an open single-blind fashion to one of the two groups.”

Unclear. Not stated

Unlikely. Both drugs were given orally.

Unclear. Only stated that the study was single-blind, but not who was blinded.

Unclear. Only stated that the study was single-blind, but not who was blinded.

Unlikely. Although the trial was not registered, the outcomes stated in the methods section were reported in the results section.

Unlikely. Although no information was given on follow-up, as the duration was only 24 h, most likely none of the participants were lost to follow-up.

Unlikely. Although not specifically stated, most likely the data was analysed according to assigned groups.

McDonald, 1993

“Patients were assigned a random number list to two groups, one to receive labetalol and one to receive nifedipine.”

Unclear. Not stated

Likely. Although not stated, the medication was taken in a slightly different manner based on their pharmacokinetics.

Likely. Open-label trial

Unclear. Not stated

Unlikely. Although the trial was not registered, the outcomes stated in the methods section were reported in the results section.

Unlikely. Although no information was given on follow-up, as the duration was only 4 h, most likely none of the participants were lost to follow-up.

Unlikely. Although not specifically stated, most likely the data was analysed according to assigned groups.

Atkins, 1992

“(…) in a randomized double-blind prospective study.”

Unclear. Not stated

Unlikely. “Labetalol and clonidine were supplied in identical opaque capsules (…).”

Unlikely. “(…) and were administered by a blinded investigator.”

Unlikely. “Blood pressure was determined by a blinded investigator (…)”

Unlikely. Although the trial was not registered, the outcomes stated in the methods section were reported in the results section.

Likely. Blood pressure measurements were only available at 4 hours in 33% and 44% of the labetalol and clonidine group, respectively.

Unlikely. Although not specifically stated, most likely the data was analysed according to assigned groups.

Komsuoglu, 1991

“Each patient was randomized into one of three groups to receive nifedipine, nicardipine, or captopril.”

Unclear. Not stated

Unlikely. “A tablet whose content was known neither to physician nor patient was bitten by the patient and retained beneath the tongue until absorbed.”

Unlikely. “A tablet whose content was known neither to physician nor patient was bitten by the patient and retained beneath the tongue until absorbed.”

Unlikely. “Blood pressure and radical pulse rate were measured in the supine position by a blinded investigator (…).”

Unlikely. Although the trial was not registered, the outcomes stated in the methods section were reported in the results section.

Unlikely. Although no information was given on follow-up, as the duration was only 4 h, most likely none of the participants were lost to follow-up.

Unlikely. Although not specifically stated, most likely the data was analysed according to assigned groups.

Sechi, 1989

“(…) were randomly assigned to (…)

Unclear. Not stated.

Unclear. Stated that ketanserin was given in a powdered tablet and nifedipine in a pierced capsule. Unclear whether these were similar enough.

Unclear. Not stated

Unclear. Not stated

Unlikely. Although the trial was not registered, the outcomes stated in the methods section were reported in the results section.

Unclear. Not stated

Unlikely. Although not specifically stated, most likely the data was analysed according to assigned groups.