Hypertension
is a common cardiac disorder, the prevalence of which is increasing
in our country. Although many drugs are available for its treatment,
it is often undertreated. Calcium channel blockers are widely used
in this condition. However, comparative studies of such drugs are
rare in Indian population. Hence, a single blind study was conducted
to compare the efficacy and safety of amlodipine and felodipine. Patients
of grade I and II essential hypertension were selected. They were
treated with either amlodipine or felodipine-ER for four weeks. Clinical
assessment was done at weekly intervals. Blood pressure was measured
by mercury sphygmomanometer. Compliance was assessed by return pill
count. Adverse effects, if any, were recorded. Results were analysed
by analysis of covariance. Fifty two patients completed the study.
Both drugs, amlodipine (n=27) and felodipine- ER (n=25) were found
to be equally effective in lowering the blood pressure. However, the
incidence of adverse effects was slightly more in the amlodipine group.
Large scale studies are needed to confirm these findings.
Introduction
Hypertension is a common cardiac disorder. Its incidence and prevalence
is increasing in our country.1 It is an important risk factor, for
coronary artery disease, which can be controlled. Many drugs are available
for the management of hypertension. However, it remains poorly controlled,
both in industrialized societies2 and even more so, in less developed
countries.3 Calcium channel blockers are widely used in hypertension,
because of their efficacy and safety.4 Many members of this class
are available. However, comparative studies of efficacy and safety
amongst this class are few, especially in Indian population. Hence,
this study was designed to compare the efficacy and safety of amlodipine
and felodipine in patients of essential hypertension.
Patients and Methods
Eligible patients were identified from outpatient clinic of our hospital.
All patients had mild to moderate essential hypertension (Clinic DBP:
90-110 mm Hg on ³ 3 occasions, SBP: 140-180 mmHg) or uncontrolled
hypertension (BP ³ 140/90 mmHg) despite monotherapy with antihypertensive
drugs other than calcium channel blockers. Essential hypertension
was diagnosed when complete clinical, biochemical and radiologic assessment
suggested no other cause for BP elevation.
Exclusions were renal impairment (serum creatinine >1.5 mg/dl),
papilloedema, evidence of cardiac failure, aortic stenosis or severe
LV dysfunction. Patients with any severe concomitant disease were
also excluded, as were women who were lactating or pregnant or of
childbearing potential.
No other antihypertensive drugs or any other drugs with effects on
cardiovascular system were allowed during the study period.
All patients gave
their informed written consent. This was a single blind randomised
study. In an initial two week period, patients underwent washout of
previous antihypertensive treatment, if any. Blood pressure was measured
at weekly intervals; routine biochemistry was done initially and at
end of 6 weeks. Eligible patients were randomised to receive either
amlodipine or felodipine-ER. Starting doses were 5 mg/d for each drug.
If clinic DBP was 
90 mmHg at or after two weeks, the dose was increased to 10 mg/d.
Patients were followed at weekly intervals for 4 weeks after beginning
the treatment. They were instructed to take their medication between
8 and 9 am daily and were assessed during 10:00 to 12:00 during their
visit to the clinic. Compliance was defined as having taken between
85% and 115% of the assigned medication and was assessed by return
pill count at each clinic visit.5
A 12 lead ECG was recorded at 0-2 and 6 weeks of treatment. At the
clinic, BP was measured by mercury sphygmomanometer with the patient
in sitting position. Three successive readings were obtained at 3
min. Intervals. The mean of three values was recorded. DBP was recorded
at disappearance of Korotkoff sounds (phase V). Adverse effects were
recorded with the help of a questionnaire at clinic visit. Patients
whose clinic BP was less than 140/90 mmHg at 6 week of treatment were
considered to have achieved BP control. Patients achieving a DBP reduction
of more than or equal to 10 mmHg after two weeks of treatment were
considered as responders.6
Data obtained was analysed by Pearson chi- square test and analysis
of co-variance. All values were expressed as mean ± SD. P value
less than 0.05 was considered as statistically significant.
Results
Eighty patients were screened. Sixty one were enrolled and randomised.
Of these, 52 completed the study. Nine patients discontinued the treatment
and were lost in the follow-up. Study period was from December 2001
to September 2002. Ten patients (6 on amlodipine, 4 on felodipine)
required dose titration to 10 mg/d. The base-line characteristics
of the two groups are shown in Table 1. There was no significant difference
between the groups with respect to age, sex, BMI, biochemical parameters
or clinic BP readings. Table 2 lists the BP values at 2 and 6th week
of treatment. Both treatments significantly (p < 0.05) reduced
the blood pressure from baseline values, from two weeks onwards. However,
there was no significant difference in the degree of reduction in
blood pressure achieved by the two treatments (Fig. 1).
Strict BP control was obtained in 10 patients on amlodipine and 12
patients on felodipine at the end of treatment. The response rates
were also similar with the two drugs (23 with amlodipine and 20 with
felodipine). Compliance with treatment was similar in the two groups
(98% with amlodipine and 100% with felodipine). There was no significant
difference in the overall incidence of adverse effects between the
two groups. However, ankle oedema was slightly more common with amlodipine
treatment.
Discussion
In this study, monotherapy with amlodipine was compared with that
of felodipine ER in patients of essential hypertension (Grade I and
II). Both drugs were equally effective in reducing the blood pressure.
Clinic DBP was reduced by > 10 mm Hg in > 80% patients treated
for four weeks with either amlodipine or felodipine ER. However, BP
was normalized (clinic BP < 140/90 mmHg) in only about 40% of patients.
Addition of another antihypertensive drug might have increased the
efficacy.7
Although the incidence of overall adverse effects was similar in both
the treatment groups, pedal oedema was slightly more common with amlodipine.
There is no satisfactory explanation for this difference. Minor difference
in structure of these two drugs may have contributed to this finding.
Large scale studies are necessary to confirm these results. Experimental
pharmacologic studies using vascular smooth muscle might explain the
difference in risk of pedal oedema.
|
| Fig.
1 : Effect of amlodipine and felodipine-ER on blood pressure |
Conclusions
Amlodipine and felodipine were equally effective in patients of mild
to moderate essential hypertension. Both drugs were well tolerated.
However, ankle oedema was more common with amlodipine.
Acknowledgements
The author is thankful to M/s. Pfizer Ltd. and Astra-zeneca Ltd. for
free supply of amlodipine and felodipine ER, respectively.
References
1. Reddy KS. Cardiovascular diseases in India. Wld H stat Quart
1993; 46 : 101-7.
2. Wilhelmesen L, Starasser T - on behalf of the Study Collaborators.
WHO- WHL hypertension management audit project. J Human Hypertens
1993; 7 : 257-63.
3. Nan L, et al. Prevalence and medical care of hypertension in four
ethnic groups in the newly industrialized nation of Mauritius. J Hypertens
1991; 9 : 859-66.
4. Buhler FR. The case for calcium antagonists as first-line treatment
of hypertension. J Hypertens 1992; 10 : S17-S20.
5. Pullar T. Compliance with drug therapy. Br J Clin Pharamacol 1991;
32 : 535-9.
6. Coca A, Calvo C, Garcia-Puig J, et al. A multicenter, randomized,
double blind comparison of the efficacy and safety of Irbesartan and
Enalapril in adults with mild to moderate essential hypertension,
as assessed by ambulatory blood pressure monitoring: the MAPAVEL study.
Clinical Therapeutics 2002; 24 : 126-38.
7. The sixth report of the JNC on prevention, detection, evaluation
and treatment of high blood pressure. Arch Intern Med 1997; 157 :
2413-6.
*Research Associate; **Consulting Physician; Dhanashree Hospital,
Navi Sangavi, Pune - 27.
