Ora.kku.ac.th

Comparison of the efficacy and safety of 10 mg amlodipine versus
12.5 mg captopril and combination 5 mg amlodipine with 6.25 mg captopril
in treating hypertensive urgency
Praew Kotruchin MD
Cardiovascular unit, Department of Internal Medicine
Faculty of Medicine, KhonKaen University
Corresponding author
Dr. Praew Kotruchin Department of Medicine, Faculty of Medicine, Khon Kaen University, THAILAND, 40002 Tel: 66-43-366869 Fax: 66-43-202401 Abstract
Objective: To compare the efficacy and safety of 10 mg amlodipine, 12.5 mg captopril and
combination of 5 mg amlodipine and 6.25 mg captopril in patients with hypertensive urgency at emergency room. Study design: This was a single-center, randomized, double-blinded clinical trial in
hypertensive urgency patients (systolic blood pressure (SBP) ≥180 mmHg and/or diastolic blood pressure (DBP) ≥110 mmHg). The patients were randomized to receive 10 mg amlodipine (group A), 12.5 mg captopril (group B) or combination of 5 mg amlodipine and 6.25 mg captopril (group C). Blood pressure was measured every 30 minutes during 4 hours after administration. The therapeutic response was defined as 15-25% reduction in mean arterial blood pressure (MAP). Safety threshold as a termination criteria included 1) decreased in MAP>15% within the first hour or >25% at anytime, 2) MAP was not achieved a goal after 4 hours of drugs administration, 3) increasing of MAP from baseline and 4) major adverse events were observed. Results: Eighty-two patients were recruited (23, 28 and 31 patients in group A, B, and C,
respectively). All three regimens achieved the blood pressure target around half of the patients (52.2, 53.5 and 51.6% in group A, B and C, respectively), but there was no statistical difference among three groups. In patients who did not achieve the targets (increased MAP or <15% decreased in MAP), the failure rate was highest in patients with 10 mg amlodipine group (10/23, 43.4%), while lower failure rates in 12.5 mg captopril (8/28, 28.6%) and 5 mg amlodipine plus 6.25 mg captopril group (7/31, 22.6%), respectively.There were only minor adverse events reported, i.e., headache, dizziness and fatigue, which were similar in all Conclusion: The efficacy of 10 mg amlodipine, 12.5 mg captopril and combination of 5 mg
amlodipine with 6.25 mg captopril in treating patients with hypertensive urgency to achieve target blood pressure was comparable. No major adverse events were observed and minor adverse events were minimal among three groups. This finding suggested that three regimens could be safely used in emergency room for treating hypertensive urgency. Key words: Hypertensive urgency; antihypertensive; amlodipine; captopril
Background
Hypertension, one of the most common health problems worldwide, is recognized as a major risk factor for fatal and non-fatal cardiovascular events [1-3]. Based on the data collected in the 2004 to 2008 National Health and Nutrition Examination Survey (NHANES), the estimated overall prevalence of hypertension in United State was 29-31% or 58-65 million people [4]. Likewise, the epidemiologic data in Thailand revealed that there were 1.4 million hypertensive patients or 5,000 per 100,000 of population in 2009, among this, there were 340,000 new cases [5]. The prevalence of hypertension varies by age, gender and racial composition of the population. Many studies show that hypertension tends to occur more frequently in men than in women and increases with advancing age, particularly in elderly(age more than 65 years old), while the effect of race on the prevalence of hypertension differed by gender and study countries[6,7]. Although risks posed by high blood pressure are well known and varieties of anti- hypertensive medications were developed; the condition remains underdiagnosed, untreated and poorly controlled around the world [8].From the seventh report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure (the JNC 7th report), only 50% of hypertensive patients achieve blood pressure control at the optimal level [9]. Uncontrolled hypertension can progress to hypertensive crisis which is a condition that happens when patients have exceptionally high blood pressure(systolic blood pressure(SBP) ≥180 mmHg and/or diastolic blood pressure(DBP) ≥ 110 mmHg)[10]. The prompt recognition of a hypertensive crisis with the appropriate diagnostic tests and triage will lead to the adequate reduction of blood pressure, ameliorating the incidence of mortality. The epidemiological data on hypertensive crisis are lacking both in the general population and emergency departments. Martin et al found that 1% of hypertensive patients had hypertensive crisis at least once in their lifetime [11] The 1993 report of the JNC proposed an operational classification of hypertensive crises as either "hypertensive emergency" or "hypertensive urgency" depending on end-organ involvement including cardiac, renal, and neurologic injury [12]. Distinguishing hypertensive emergency from urgency is critical in formulating a therapeutic plan.It has been accepted that patients with hypertensive emergency should have their blood pressure lowered within minutes to hours, but not to normal level, whereas patients with hypertensive urgency should have their blood pressure reduced within24 to 48 hours [13-15]. Hypertensive emergency is a critical condition and therefore rapid lowering of blood pressure is a cornerstone of treatment. Hypertensive emergency warrants admission to an intensive care unit for immediate reduction of blood pressure with a short-acting titratable intravenous antihypertensive medication. At present, standard practice guidelines are developed and available for healthcare providers [13]. For hypertensive urgency, the condition which patients with severe hypertension without target organ damage who have symptoms those bring them to hospital such as headache, dizziness or nausea, it may in general be treated with oral antihypertensive, and as outpatients. In contrast to hypertensive emergency, there is no standard practice guideline for this condition. A variety of oral antihypertensive drugs are available for use in patients with hypertensive urgency [15-17]. However, treatments are varied among hospitals and among doctors who work at the same institute. For instance, common drugs used for lowering blood pressure in hypertensive urgency are clonidine, nifedipine and captopril in Western countries [18-20], while a survey in our tertiary care setting (Srinagarind hospital) in 2013 found that hydralazine, amlodipine and angiotensin converting enzyme inhibitors (ACEIs) were commonly used for hypertensive urgency treatment in ER, the choice of which was based on physicians preference. It has been accepted that the effectiveness of blood pressure lowering in this condition means reducing mean arterial blood pressure (MAP) 15-20% from baseline within 4-24 hours[15,21,22]. Since in hypertensive urgency, the severe increasing in BP does not lead to target organ damage, an immediate reduction in blood pressure is not necessary and initiation of oral anti-hypertensive therapy is generally appropriate. Moreover, the reduction of blood pressure in a short time span (as short as minutes to an hour) may be harmful since it can lead to myocardial infarction or cerebrovascular diseases [23, 24]. With this in mind, anti- hypertensive drugs used in HT urgency are preferably administered in oral form such as calcium channel blockers (amlodipine, nifedipine), angiotensin converting enzyme inhibitors (captopril), hydralazine and beta-blocking agents (labetolol). However, there are no controlled studies which demonstrate long-term improved outcomes with acute treatment of hypertensive urgency and the drugs most effective in reducing blood pressure without causing side effects. Amlodipine is dihydropyridine calcium channel blocker. It lowers blood pressure by dilating vessels. An initial dose is 5 milligrams per day subsequently increased to 10 milligrams per day. This agent is commonly used because of its convenience; it requires only one dose per day, and can be prescribed in young adults, elderly, kidney disease patients and pregnant women. Its side effects are usually subtle, i.e., pedal edema (2-15%), skin rash and pruritus (1-2%), nausea or abdominal pain (1-3%), flushing or palpitation (1-4%), muscle cramp or weakness (1-3%), and all side effects are dose related[25, 26]. Captopril, an ACEI that inhibits renin-angiotensin-aldosterone system (RAAS) and reduces blood pressure. It is not administered as a prodrug and 70% of orally administered captopril is absorbed, therefore the onset of action is rapid in minutes to hour. It is widely recommended to use in hypertensive crisis. The recommended initial dose is 6.25-25 milligrams and can be repeated if the blood pressure is not achieved reduction target. Maximum dose is 100 milligrams per day. Side effects of captopril are skin rash (4-7%), hyperkalemia (1-11%), coughing (1-2%) and acute kidney injury particularly in dehydrated patients or patients with bilateral renal artery stenosis[25, 26]. It is well known that monotherapy does not provide therapeutic response in all hypertensive urgency patients. Some patients show an excellent response, while in others there is a limited response. Combination antihypertensive therapy is administered when blood pressure is inadequately controlled by monotherapy to achieve a balanced and additive antihypertensive effect with minimum adverse effects [27-29]. An understanding of differences in the mechanism of action of these agents allows a logical approach for the use of these agents as a combination therapy [25].Even though, previously reports demonstrate that the combination of these drugs is effective in hypertensive patients, there is no previous study to determine the efficacy of the combination compared with single agents and also a lack of data to evaluate the efficacy and adverse events when using half-dose of amlodipine- captopril in combination for hypertensive urgency patients. The present study's primary objective is to compare the efficacy of three regimens of antihypertensive agents (10 mg amlodipine, 12.5 mg captopril and combination of 5 mg amlodipine and 6.25 mg captopril) in reducing MAP of 15-25% from the baseline in hypertensive urgency patients. The secondary objective was to examine the adverse events of these three regimens during treatment at emergency room. Study design and setting
This study was a single-center, randomized, double-blinded clinical trial. We conducted the study in hypertensive urgency patients who presented at emergency outpatient department, Srinagarind hospital during August 2013 to December 2014.The study was formally approved by the Khon Kaen University Ethics Committee for Human Research. The written informed consent was obtained from each individual and the study protocol conformed with the ethical guidelines of the 1975 Declaration of Helsinki. Inclusion and exclusion criteria
The inclusion criteria were patients from both genders who age between 35 to 65 years old with a diagnosis of hypertensive urgency with thresholds determined by the Joint National Committee on Prevention, Detection, and Evaluation and Treatment of High Blood Pressure defined as a systolic blood pressure (SBP) ≥180 mmHg and/or a diastolic blood pressure (DBP) ≥110 mmHg after two measurements, ten minutes apart in the supine position. Patients were excluded if they exhibited any of the following criteria: a decrease in blood pressure after bed rest (15-20% from baseline), known chronic kidney disease or baseline serum creatinine >1.5 mg/dl within one month, known secondary hypertension (i.e., endocrine hypertension, arteritis, and drug induced hypertension), women who were pregnant or breast feeding, myocardial infarction with symptoms such as chest pain and abrupt variations in their electrocardiograms, pulmonary edema, cerebral symptoms of hypertensive encephalopathy and stroke, aortic dissection, ocular conditions, allergy to amlodipine or captopril and received an antihypertensive drug within the prior 60 minute. Baseline assessment
Baseline data on all patients were collected, including current and historical medical information about the emergency department visit and hypertensive status. Other data collected included age, gender, high blood pressure medications, individual and family past medical history of hypertension, prior emergency room visit, comorbidities, chief complaint, pain medication use, smoking status, history of herb, salt intake, and exercise. Following baseline assessment, patients were randomized into three groups: (a) 10 mg amlodipine, (b) 12.5 mg captopril, and (c) combination of 5 mg amlodipine and 6.25 mg captopril. Randomization was conducted using a permuted block design with random block sizes of 3, 6, and 9 using STATA (version 18.0). Randomization sequences were manually generated by the investigator who was not involved in treating the patients; placed in consecutively numbered, sealed, opaque envelopes; and opened only after obtaining each patient's consent to participate in the study. After patients were enrolled, they were taken to a restricted area of emergency room for 10-minutes of rest then blood pressure was measured in lying position with a automatic sphygmomanometer by a trained nurse and the higher blood pressure was used for analysis. Doctors examined subjects thoroughly to detect target organ damage (as in general standard of care). Blood samples were collected for complete blood count, the kidney function test and electrolytes measurement in all cases. Urine pregnancy test and urine toxic screening including cocaine and amphetamine were done in suspected cases. After measuring a blood pressure, the patients were randomized to receive treatment regimens including 10 mg amlodipine (group A), 12.5 mg captopril (groupB) or combination of 5 mg amlodipine and 6.25 mg captopril (groupC), (Figure 1). The drug names were blinded to all patients, heath care workers and study team. The patients' blood pressure measurement was taken 8 times every 30 minutes (at 30, 60, 90, 120, 150, 180, 210 and 240 minutes) after treatment administration. Both SBP and DBP were measured and any reported side effects and complications were recorded in a checklist until the primary endpoint was reached or the termination criteria were observed. Monitoring and outcome assessment
The primary outcome variable in this study was 15-25% lowering in MAP within four hours from the baseline. Since rapidly lowering in blood pressure in less than 1 hour is likely to be harmful, and previous reports suggested that patient's staying for treatment in the emergency room more than 4 hours had some disadvantages, i.e., emergency room overcrowded, increasing of malpractice, and loss of resources in economic point of view. Therefore, we defined the safety threshold as a termination criteria including 1) MAP decreased more than 15% from baseline within the first hour or more than 25% at anytime of study, 2) MAP was not achieved a goal after 4 hours of administration, 3) MAP increased from baseline and 4) major adverse events including death from any cause, cardiovascular death, myocardial infarction, cerebrovascular accident, or clinical presentation of severe headache, severe chest pain, blurred vision, and dyspnea were observed. Statistical analysis
Data were analyzed according to the randomly assigned groups of the participants, and all analyses were made on an intention-to-treat basis. Descriptive indices such as frequency, mean and standard deviation (SD) were used. Baseline characteristics of the enrolled subjects were presented to check balance among group A, B and C using the unpaired t-test or Fisher's exact test. The success of treatment (% of MAP controlled to the goal) between the three groups were compared using Chi-square test. The 95% confidence interval was reported and differences were statistically significant at level of5% (P < 0.05). All statistical analyses were performed using the STATA statistical package (version 18). Due to limitation of time to recruit the patients during training and the manuscript needed to submit before March, 2015; therefore the preliminary results has been reported with the final 82 hypertensive urgency patients. For the aims of this study, a total of 96 patients with hypertensive urgencies were initially identified for study inclusion (Figure 2). From those, 14 patients were excluded due to previous chronic kidney disease (n = 3), age more than 65 years (n = 1), incomplete data (n = 6), and decreasing of blood pressure after bed rest (n = 4). After exclusions, 82 patients (28 men and 54 women) were enrolled for analysis, and were randomized to three groups. There were 23, 28 and 31 patients randomized to receive 10 mg amlodipine (group A), 12.5 mg captopril (group B) and combination of 5 mg amlodipine and 6.25 mg captopril (group C), respectively. The average age was 49.5, 52 and 53.2 years old in group A, B and C, respectively and less than half of the patients had family history of HT in first degree relatives. There were no significant differences in age, duration of hypertension, clinical symptoms related with hypertension, prior hypertension treatment, discontinue antihypertensive drugs, family history of hypertension, herbal use among three groups; however, numbers of patients who had prior emergency room visiting due to hypertensive crisis trended to be higher in group C(41.9%) compared with 17.4 and 14.8% in group A and B, respectively. Interestingly, although there was no significant difference in salt intake and exercise among three groups, but most of patients (60%) who visited emergency room already restricted salt intake and only few patients had regular exercise. Moreover, there were no significant differences in serum creatinine, electrolytes, and left ventricular hypertrophy by electrocardiography and chest radiography among the groups, however, LVH detected by both techniques was higher in group B (45.5%) than group A (21.2%) and group C (33.3%) (Table1). In this present study, most patients visited emergency department due to accidentally finding of significantly high blood pressure from other clinics. Of 26 patients (31.7%) had clinical symptoms related with high blood pressure, i.e., dizziness, headache and fatigue, etc. Forty-eight patients (58.5%) were diagnosed hypertension and were already taken antihypertensive drugs (56.5%, 59.3% and 61.3% in group A, B and C, respectively). The primary endpoint in this study was to reduce MAP 15-25% from baseline. If MAP was higher than baseline, decrease less than 15% or decrease more than 25% from baseline or decrease too fast (more than 15% within 1st hour) would be considered out of goal. Based on preliminary results of 82 patients, the numbers of patients who achieve goal were comparable among three groups (52.2, 53.5 and 51.6% in group A, B and C, respectively); and 32.6 and 67.5% reached the target within 1 and 2 hours, respectively. We found that the percentage of achieving target within first hour was highest in group A (41.7%); while within two hours, the percentage was highest in group B (80%) compared with 58.4% and 62.5% in group A and C, respectively. Despite all patients received antihypertensive drugs, 12 of 82 patients (14.6%) still increased in blood pressure after treatment which found 21.7%, 14.3% and 9.7% in group A, B and C, respectively (Table 2). The changes in MAP, SBP and DBP among three groups were shown in Figure 1-3. We found that the MAP, SBP and DBP in group B (12.5 mg captopril) and group C (5 mg amlopine plus 6.25 mg captopril) decreased faster than group A, particularly within the first 120 minutes and then increasing after 120 and 150 minutes in group B and C, respectively. All MAP, SBP and DBP of patients in group A (10 mg amlodipine) decreased overtime up to 210 minutes and then trending toward higher level. In term of safety and adverse events, the proportion of overall patients who decreased inMAP above the safety criteria (reduction>25% of the baselineat any times or >15% in the first hour) was 17.1% (14 of 82); which was highest (25.8%, 8 of 31) in group C compared with 4.4% (1 of 23) in group A and 17.9% (5 of 28) in group C, however there were no statistical significantly differences among the group (group A vs. group B, p=0204; group A vs. group C, p=0.06; group B vs. group C, p=0.540). We found that 78.6% (11/14) and 100% (14/14) of patients decreased in blood pressure within first and two hour, respectively. There were two patients in group C, had a MAP decrease >30%. In this study, there were only minor adverse events reported, i.e., headache, dizziness and fatigue. Mild degree of headache was a most common adverse events in this present study, which found in 9 patients (2, 5 and 2 patients in group A, B and C. respectively). There was one patient in group A had experienced dizziness, another 2 patients in group A with fatigue and one patient in group C had backache after treatment but only mild symptom. Discussion
Hypertensive urgency is common clinical occurrence that may account one fourth of all emergencies presenting to the emergency department. Although most patients have only mild symptoms such as headache, dizziness, tiredness and chest tightness; without or delay lowering blood pressure may further to target organ damage. Notwithstanding, clinical practice management of this condition vary considerably [30]. The variability is because of the lack of evidence supporting the use of one therapeutic agent over another; and at present, there is no specific practice guideline for treatment patients with hypertensive urgency. This present study was designed to determine the efficacy in term of the agents' ability to reach a target blood pressure and to examine safety of commonly used medications including amlodipine, captopril. However, to prevent complication of both drugs, we also investigated the half-dose combination of amlodipine and captopril in our setting. From the preliminary analysis of 82 hypertensive patients, we found that all three regimens achieved the blood pressure target around half of patients (51.6-53.5%) within 4 hours, with the highest percentage in 12.5 mg captopril group, but there was no statistical significance among three groups. In patients who did not achieve the targets (increased MAP or less than15% decreased in MAP after administration), the failure rate was highest in patients in 10 mg amlodipine group (43.4%, 10/33), while lower failure rates in 12.5 mg captopril and 5 mg amlodipine plus 6.25 mg captopril group, which were 28.6% (8/28) and 22.6% (7/31), respectively. The findings from this study were difficult to compare with previous studies, since many studies defined hypertensive urgency differently, small sample size, differences in methodology, study designs, contamination, therapeutic response, lack of long-term blood pressure control (>24 hours after administration) and also cardiovascular When compared the efficacy of amlodipine in patients with hypertensive urgency, we found that the blood pressure response in our study (group A) was consistent with previous study by Grassi D et al [31]. The response rates in patients who received amlodipine in our study and Grassi's study [31] were similar (41.7 and 42.8%, respectively). However, the favorable response within 2 hours after drug administration was higher in Grassi study (70.7 vs 58.4%). Even the dosage of amlodipine for treatment in our study was higher than Grassi study (10 mg vs. 5 mg), the discrepancy in response could explain by the difference in the therapeutic threshold. In Grassi's study [31], which blood pressure satisfactory response was defined as SBP and DBP level <180 and <110 mm Hg after treatment, respectively; or with at least a 20-mm Hg reduction in basal SBP and/or a 10-mm Hg reduction in basal DBP, while the responder in our study was patients who decrease 15-25% in MAP and also exclude the patients who lowered blood pressure more than 25%. Both oral and sublingual captopril is a common used in emergency room. There are many studies demonstrated that sublingual captopril was effective for lowering blood pressure in patients with hypertensive urgency[32] and emergency[33-36]; however, some studies observed that rapid and fast blood pressure reduction by sublingual route was harmful [37,38].In term of efficacy, there were conflict results of the efficacy between oral and sublingual route of captopril. Many studies reported that the sublingual captopril lowered the blood pressure better than the oral captopril [39-41] while there was no difference in lowering blood pressure and plasma renin and angiotensin converting enzyme activity [42]. On the other hand, Karakilic et al [43] reported that in the first hour after administration, there was no significant difference between sublingual and oral captopril route to decrease blood pressure in patients with hypertensive crisis; and suggested that oral captopril use is more appropriate to control blood pressure and also prevent undesirable side effects (i.e., hypersensitivity, bitter taste, chemical burn on oral mucosa, etc) in patients with hypertensive urgency. In our study, 80% of patients who received oral captopril achieved the blood pressure goal within 2 hours while only 14% of patients were non-responder. These findings could explain that the dosage of oral captopril in this study was 12.5 mg, which was lower compared with most previous studies (25 mg) and the response threshold in previous studies was defined as a cut-offs instead of percentage reduction in blood pressure [44, 45] In this study, blood pressure lowering patterns including MAP, SBP and DBP were consistent with each drugs' pharmacokinetics. After single dose of amlodipine, blood pressure decreased gradually over 4 hours. This finding was consistent with previous studies by Pujadas R et al [46] that the time needed for blood pressure reduction ranged from 30 to 100 minutes in oral nifedipine which is also a dihydropyrine calcium channel blocker, while the studies of ACEIs, this time ranged was vary from 30 to 120 minutes [46, 47].However, in our study, captopril had onset of action within half an hour and blood pressure slowly raised after 120 minutes as the drug may be washed out. While in combination group, blood pressure start to decrease as early as in captopril alone group, however, the effect last longer till 150 minutes before blood pressure slowly increased again. Based on the pattern of blood pressure lowering from this study, it suggested that sequential treatment has a promising role as it may not only achieve target within appropriate time but also has long lasting effect for blood pressure control. However, our study was designed to limit for four hours, therefore further study with longer period is needed. Although in this study, target time for blood pressure lowering was within four hours and there was no statistically significant difference among groups; however, the highest target blood pressure achieving rate at two hours was obtained in 12.5 mg captopril group(80%), Moreover, we found that in both group B and C which patients received captopril (6.25 and 12.5 mg respectively), there were higher numbers of patients who lowered MAP more than 25% from baseline compared to 10 mg amlodipine group. These findings could be explained by drugs pharmacokinetics as described above. Interestingly, we found that the combination of half-dosed amlodipine and captopril compared to single amlodipine/captopril in achieving target blood pressure were similar, but the combination of drugs tended to over reach the safety threshold (25.8%). However, the patients who decreased in MAP more than safety threshold (> 25% from baseline) did not cause serious adverse event as well as minor adverse events. The results suggested that to reduce MAP more than 25% from baseline might be safe. Notwithstanding, to decrease more than 30% was controversial because there were only two patients in this study who reached this point and further study with more population is needed to investigate this cut-offs as a efficacy and safety issue before recommendation. The present study's findings should be interpreted within the context of strengths and potential weaknesses. The major strengths of this study are 1) an RCT which provide better control over possible bias through randomization and blinding, 2) the study's drugs are the common antihypertensive which have been used in daily clinical practice in most Thai hospital settings, and 3) this was the first study in Thailand to evaluate the treatment for patients with hypertensive urgency and also the first study to determine the efficacy for half-dose amlodipine and captopril combination. However, since the study was undertaken with limited time, the sample size was small and not enough to ensure the efficacy and safety of treatments. However, we planned to further recruit 255 patients and these results based on the preliminary results of 82 patients. Moreover, this study was designed to measure blood pressure in short time of period (only four hours after administration) and we did plan to collect the long-term blood pressure control i.e., after four or twenty-four hours and also other cardiovascular endpoints, thereforefurther research is needed to determine the best strategies to manage the patients with hypertensive urgency at emergency room and also the maintenance therapy to achieve a better long-term blood pressure control during follow up period to prevent the adverse events, cardiovascular morbidity and mortality, number of hospitalization, and complications in the In conclusion, this preliminary study demonstrated that the efficacy of 10 mg amlodipine, 12.5 mg captopril and combination of 5 mg amlodipine with 6.25 mg captopril for patients with hypertensive urgency to achieve target blood pressure control was similar. Even though, treatment with captopril alone or in combination with amlodipine decreased blood pressure more than those with amlodipine alone, but no statistical difference. Both major and minor adverse events among the treatments were minimal. This study suggested that three regimens can be can be safely used in emergency room for hypertensive urgency. This study was supported by the Khon Kaen university research fund. The authors thank Professor Chatlert Pongchaiyakul for helpful suggestions and assistance with the English-language presentation of the manuscript; Professor Pyatat Tasanawiwat and Associate Professor Songsak Kiatchoosakul for proving manuscript and also Mrs. Kaewjai Tepsuthammarut for statistical analysis. References
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Efficacy of captopril and nifedipine in black and white patients with hypertensive crisis. J Hum Hypertens Table 1: Baseline characteristics of the study subjects Amlodipine
Captopril
Amlodipine 5 mg
+ Captopril 6.25 mg
Number of patients Chief complaint associated Duration of HT (month) Prior HT treatment Prior ER visit due to HT Discontinuation of antihypertensive drug Salt restriction Regular exercise Family history of hypertension Left ventricular hypertrophy Table 2: Primary endpoints Mean blood pressure
Amlodipine
Captopril
Amlodipine 5 mg +
outcomes
Captopril 6.25 mg
Decrease <15% Decrease >15% at first hour or >25% at any times Figure Legends
Figure 1. Study design Figure 2. Flow diagram of patient recruitment and randomization Figure 3. Mean arterial pressure trend during study period Figure 4. Systolic blood pressure trend during study period Figure 5. Diastolic blood pressure trend during study period Figure 1. Study design Figure 2. Flow diagram of patient recruitment and randomization Figure 3. Mean arterial pressure trend during study period Figure 4. Systolic blood pressure trend during study period Figure 5. Diastolic blood pressure trend during study period

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