# Abstract

 

## OBJECTIVES: To evaluate the importance of providing guidelines to patients via active telephone calls for blood pressure control and for preventing the discontinuation of treatment among hypertensive patients. 

## INTRODUCTION: Many reasons exist for non-adherence to medical regimens, and one of the strategies employed to improve treatment compliance is the use of active telephone calls. 

## METHODS: Hypertensive patients (n = 354) who could receive telephone calls to remind them of their medical appointments and receive instruction about hypertension were distributed into two groups: a) "uncomplicated" -- hypertensive patients with no other concurrent diseases and b) "complicated" - severe hypertensive patients (mean diastolic ≥110 mmHg with or without medication) or patients with comorbidities. All patients, except those excluded (n = 44), were open-block randomized to follow two treatment regimens ("traditional" or "current") and to receive or not receive telephone calls ("phone calls" and "no phone calls" groups, respectively). 

## RESULTS: Significantly fewer patients in the "phone calls" group discontinued treatment compared to those in the "no phone calls" group (4 vs. 30; p\<0.0094). There was no difference in the percentage of patients with controlled blood pressure in the "phone calls" group and "no phone calls" group or in the "traditional" and "current" groups. The percentage of patients with controlled blood pressure (\<140/90 mmHg) was increased at the end of the treatment (74%), reaching 80% in the "uncomplicated" group and 67% in the "complicated" group (p\<0.000001). 

## CONCLUSION: Guidance to patients via active telephone calls is an efficient strategy for preventing the discontinuation of antihypertensive treatment. # RESULTS The study included 398 patients. Of those, 44 were excluded for the following reasons: a) lack of enrollment in the Biosintética Assistance program (n = 17); b) body mass index >40 kg/m^2^ (n = 6); c) secondary hypertension (n = 4); d) white-coat hypertension (n = 3); e) white-coat normotension ("masked hypertension") (n = 3); f) alcohol use (n = 2); g) classification error (n = 4); h) refusal to do ABPM (n = 2); i) loss of blood pressure measurements from the first visit (n = 1); j) pregnancy (n = 1); k) death (n = 1). A total of 354 patients were evaluated. There were no statistically significant differences in age, gender, skin color, body mass index, blood pressure or heart rate between the groups classified as: "complicated" (n = 175) and "uncomplicated" (n = 179); "traditional" (n = 176) and "current" (n = 178); "phone calls" (n = 108) and "no phone calls" (n = 246) ([Table 1](#)). In addition, no differences were seen in marital status, education or occupation. 

## a) Control of Blood Pressure A marked reduction in blood pressure was seen in patients from both the "complicated" and "uncomplicated" groups ([Table 2](#)). The blood pressure was reduced by 19±10/20±14 mmHg in the "uncomplicated" group and by 18±14/22±17 mmHg (systolic/diastolic) in the "complicated" group (p>0.05; n = 354). The "phone calls" and "no phone calls" groups showed significantly lower blood pressures at the end of treatment (p< 0.00001). The "traditional" and "current" groups showed significantly lower blood pressures at the end of treatment ([Figure 1](#)). The percentage of patients with controlled blood pressure (\<140/90 mmHg) was also high at the end of treatment (74%). On the other hand, the percentage of patients with blood pressure reduced to \<120/80 mmHg was only 29%. There was no difference in the percentage of patients with controlled blood pressure between the "phone calls" and "no phone calls" groups or in the reduction of blood pressure and the percentage of patients with controlled blood pressure among the "traditional" and "current" treatments. However, patients in the "phone calls" group (80%) had better blood pressure control than those in the "no phone calls" group (71%), though the difference was not statistically significant. The "uncomplicated" and "complicated" groups had statistically significant differences in the percentage of patients with controlled blood pressure (\<140/90 mmHg) (80% vs. 67%, respectively; p\<0.000001). At the next to last study visit (visit 7), 90% and 66% of patients had blood pressure measurements \<140/90 mmHg in the "uncomplicated" and "complicated" groups, respectively. However, there was no difference in the percentage of patients with blood pressure \<120/80 mmHg (31% on the final visit in both groups, [Table 3](#)). Among patients with a blood pressure \<140/90 mmHg at the final visit, only 3% had received only one type of antihypertensive medication; most patients (56%) received 2 (34%) or 3 (22%) types of antihypertensive medication ([Table 4](#)). 

## b) Treatment Discontinuation A significantly lower number of patients in the "phone calls" group quit the treatment compared to the "no phone calls" group (4 vs. 30, respectively; [Figure 2](#)). There was no difference in the percentage discontinuation in the "complicated" and "uncomplicated" groups or in the "current" and "traditional" treatment regimens (p>0.05). 

## c) Tablet Count Patients in the groups: "complicated" and "uncomplicated"; "traditional" and "current"; "phone calls" and "no phone calls" did not show statistically significant differences in medication intake, as verified by counting the tablets returned at the visits. Compliance was over 85% at all visits. However, patients in the current + uncomplicated + phone call group had the highest rate of compliance (93%). The lowest rate of compliance occurred in the traditional + uncomplicated + no phone call group (85%) (p>0.05). 

## d) Body Weight Blood pressure reductions occurred in the presence of increased body weight (baseline visit: 73±14 kg; final visit: 74±14 kg, p = 0.0008, [Table 5](#)). 

## e) Adverse Events and Laboratory Tests Most of the adverse events that occurred during the study were of light or moderate intensity. Patients in the "traditional" group showed significantly more depression symptoms (5 vs. 0) and coughing (30 vs. 4) when compared with patients in the "current" treatment group. On the other hand, patients in the "current" group had a greater number of complaints of dizziness when compared to patients in the "traditional" treatment group (63 vs. 42, respectively). Compared to patients in the "uncomplicated" group, patients in the "complicated" group presented a larger number the following symptoms: abdominal pain (19 vs. 8), sleepiness (32 vs. 10), cough (23 vs. 11), weakness (23 vs. 11) and blurred vision (6 vs. 0). Conversely, compared to patients in the "complicated" group, patients in the "uncomplicated" group presented a larger number of complaints such as pain (74 vs. 53) and headache (80 vs. 59). Patients in the "phone calls" group reported a 34% rate of symptoms, while a 66% rate of symptoms was reported by patients in the "no phone calls" group. The most frequently (>10%) found adverse events were as follows: headache (62.1%), unspecific pain (58.2%), dizziness (45.8%), edema (40.1%), fatigue (15.3%), sleepiness (14.4%), cough (13.3%), precordial pain (13.3%), weakness (11.9%), tachycardia (11.3%), insomnia (10.5%) and paresthesia (10.5%). There were 26 (8%) severe adverse events: death (5), unstable angina (4), acute myocardial infarction (1), transient ischemic attack (1), hypertensive encephalopathy (1), breast cancer (3), bronchospastic crisis (1), cholecystopathy (1), diabetic decompensation (1), syncope (1), nephrectomy (2), trauma (2), peritoneal bypass (1), diarrhea (1) and gastrectomy (1). The results of the laboratory tests performed in the beginning and end of the study are shown in [Table 6](#). There was an increase in the 24-hour urinary sodium excretion from the beginning to the end of the study (120±46 vs. 129±45 mEq/L, respectively; p = 0.000036) ::::table-wrap

::: caption
Study groups demographics.
:::

```
                                       Uncomplicated n = 179   Complicated n = 175   Traditional n = 176   Current n = 178   No Phone Calls n = 246   Phone Calls n = 108
```

______________________________________________________________________

Age (years) 53±11 53±11 54±11 52±11 54±11 52±11
Gender (%)\
Male 27 41 33 34 33 34
Female 73 59 67 66 67 66
Skin color (%)\
Whites 62 52 60 54 56 60
Non-whites 38 48 40 46 44 40
BMI (kg/m^2^) 29±4 29±4 29±4 29±4 29±4 29±4
Blood Pressure at Randomization (mmHg)\
Systolic 155±12 163±24 159±19 158±19 159±19 158±19
Diastolic 91±10 102±20 96±17 97±16 97±16 97±17
Heart rate 80±13 83±13 81±13 82±13 82±13 82±13

Data are shown as mean±s.d.; BMI = Body Mass Index; p>0.05:
"complicated" vs. "uncomplicated", "traditional" vs. "current", "phone
calls" vs. "no phone calls" for age, gender, skin color and BMI.

Blood pressure at randomization: uncomplicated vs. complicated groups:
systolic -- t  =  3.78, p = 0.0002; diastolic -- t  =  6.44,
p\<0.000001; FC -- t  =  2.41, p = 0.016:::: ::::table-wrap
::: caption
Blood pressure (mmHg) at the beginning and end of the 12-month treatment
in the "uncomplicated" and "complicated" groups, according to the
"traditional" and "current" treatments and randomization into the "phone
calls" and "no phone calls" groups.
:::

Group Randomization Visit Final Visit

______________________________________________________________________

Uncomplicated (n = 179) 155±12/91±10 126±14\*/73±11\*
"Traditional" Treatment (n = 90) 155±12/91±9 126±14\*/71±11\*
"Current" Treatment (n = 89) 155±12/92±10 126±15\*/74±11\*
"No Phone Calls" (n = 119) 156±13/91±10 127±16\*/73±12\*
"Phone Calls" (n = 60) 154±11/92±9 125±11\*/73±10\*
Complicated (n = 175) 163±24/102±20 131±19\*/78±14\*
"Traditional" Treatment (n = 86) 164±24/102±21 132±21\*/77±16\*
"Current" Treatment (n = 89) 161±23/102±19 130±18\*/78±12\*
"No Phone Calls" (n = 127) 162±23/102±19 132±20\*/79±15\*
"Phone Calls" (n = 48) 163±25/103±22 127±18\*/75±11\*

Data are shown as mean±s.d.; \*p< 0.00001 -- Randomization Visit versus
Final Visit.:::: ::::table-wrap
::: caption
Percentage of patients with controlled blood pressure at the beginning
(randomization visit), at the next-to-last visit (visit 7) and at the
end (visit 8-final) of the 12-month treatment period.
:::

Group Randomization Visit Visit 7 Final Visit

______________________________________________________________________

"Uncomplicated" 0\*/0\*\* 90\*/31 80/30
"Complicated" 16/6 66/31 67/28
"Traditional" Treatment 8/3 75/32 73/31
"Current" Treatment 11/3 81/30 74/27
"Phone Calls" 8/3 84/32 80/33
"No Phone Calls" 8/3 75/30 71/27
Total 8/3 78/31 74/29

Controlled blood pressure: < 140/90 mmHg/120/80 mmHg.

p >0.05, except:

1. \*Uncomplicated versus complicated: Randomization visit - χ^2^~1~
   =  28.94; p\<0.000001 (SBP\<140/DBP\<90)

1. \*\*Uncomplicated versus complicated: Randomization visit - χ^2^~1~
   =  8.55; p = 0.0035 (SBP\<120/DBP\<80)

1. Uncomplicated versus complicated: Visit 7 - χ^2^~1~  =  28.84;
   p\<0.000001 (SBP\<140/DBP\<90):::: ::::table-wrap
   ::: caption
   Number of antihypertensive medications in use at the end of the study in
   patients who achieved control (\<140/90 mmHg) of their blood pressure at
   the end of the 12-month study.
   :::

Number of Antihypertensive Medications Blood Pressure \<140/90 mmHg Blood Pressure >140/90 mmHg Total

______________________________________________________________________

01 3.2% 1.0% 4.2%
02 34.4% 5.0% 39.4%
03 21.9% 6.8% 28.7%
04 12.2% 6.8% 19.0%
05 3.9% 2.9% 6.8%
06 1.6% 0.3% 1.9%
Total 77.2% 22.8% 100%:::: ::::table-wrap
::: caption
Weight (kg) at the beginning and end of the treatment.
:::

Group Randomization Visit Final Visit P Value

______________________________________________________________________

"Uncomplicated" 72±12 73±13 0.39
"Complicated" 74±15 76±15 0.007
"Traditional" Treatment 74±15 74±15 0.09
"Current" Treatment 73±13 74±13 0.005
"Phone Calls" 74±14 74±15 0.13
"No Phone Calls" 73±14 74±14 0.018
Total 73±14 74±14 0.0008

Data are shown as mean±s.d.:::: ::::table-wrap
::: caption
Results of laboratory tests measured at the beginning and end of the
study.
:::

```
                                         Initial      Final        Test value   P value
```

______________________________________________________________________

Fasting Glucose (mg/dL) 108±41 111±41 1.82 >0.05
Urea (mg/dL) 32±10 34±16 3.83  = 0.00015
Creatinine (mg/dl) 0.9±0.3 1.0±0.4 5.52 \<0.000001
Total Cholesterol (mg/dL) 199±44 190±38 5.07  = 0.000001
HDL Cholesterol (mg/dL) 49±13 48±14 1.19 >0.05
Triglycerides (mg/dL) 147±123 152±218 0.61 >0.05
Uric Acid (mg/dL) 5.1±1.5 5.3±1.8 3.90  = 0.00011
Sodium (mEq/L) 140±3.2 139±2.7 7.34 \<0.000001
Potassium (mEq/L) 4.2±0.5 4.2±0.4 1.21 >0.05
Hemoglobin (g/dL) 14.4±1.4 14.2±1.3 4.73  = 0.000003
Alkaline Phosphatase (U/L) 79.7±25.3 75.1±22.7 5.29 \<0.000001
ALT (U/L) 23.5±10.6 26.6±51.0 1.15 >0.05
AST (U/L) 24.4±15.9 30.2±92.5 1.18 >0.05
Sodium Urinary Excretion in 24 h (mEq/L) 119.6±45.6 128.8±45.3 12.81  = 0.000036

Data are shown as mean±s.d.::::


Extracted trial result:
Outcome: discontinued treatment (binary)
Intervention: "phone calls" group
Comparator: "no phone calls" group
Intervention events: 4
Intervention group size: 108
Comparator events: 30
Comparator group size: 246
Notes: Values from results section text.