A randomized controlled trial (RCT) comparing the efficacy and safety of cilnidipine and amlodipine in hypertensive adults has been reported in various scientific journals. These studies assess the antihypertensive effects and potential renoprotective actions of these calcium channel blockers. Efficacy of Cilnidipine: A study concludes that cilnidipine has similar antihypertensive effects compared to other first-line antihypertensive drugs commonly used in practice [2]. Renoprotective Action of Cilnidipine: Research suggests that cilnidipine is a better anti-hypertensive and renoprotective drug than amlodipine, particularly in subjects with proteinuria [1]. Another study indicates that cilnidipine is superior to amlodipine in preventing the progression of proteinuria in hypertensive patients when coupled with a renin-angiotensin system inhibitor [4]. Comparative Study: A randomized open-label parallel-group study concludes that cilnidipine therapy is comparable to amlodipine therapy in reducing 24-hour systolic and diastolic blood pressure in mild to moderate hypertensive adults [5]. These studies contribute valuable insights into the selection and effectiveness of antihypertensive medications in the management of hypertension in adult populations.

1. Journal
Reporting
Presented by:-
Dr. Sneha Pawar,
Junior Resident-3
Department of Pharmacology,
GMCH, Nagpur

3. Introduction
● In modern era of changing lifestyles & globalization, non-
communicable diseases → leading cause of morbidity &
mortality
● Common non-communicable diseases : cardiovascular disease,
diabetes, cancer & chronic lung disease
● In 1o care setting, commonest CV disease : Hypertension
● Implications of effective treatment are tremendous
● Mainstay of pharmacotherapy of HTN : ACE-I, ARBs , CCBs,
thiazide type diuretics, β-blockers & aldosterone antagonists

4. Introduction
● Most commonly used CCB as monotherapy → Amlodipine
● Newer drugs - with better efficacy & safety profiles
Eg.: Cilnidipine , Lacidipine , Felodipine, Lercanidipine,
Isradipine, Nisoldipine , Nicardipine , Benidipine

5. ❖ Cilnidipine :
● Cilnidipine blocks both N-type + L-type calcium channels
● Blockade of : N-type channels → (-) release of norepinephrine
from sympathetic nerve endings
● L-type channel blockade → vasodilation
● Thus, this two-pronged approach in anti-hypertensive effect of cilnidipine is unique
● This sympathetic blockade may also help in treating comorbidities of hypertension

6. ● Amlodipine - most commonly used CCB , hence this drug was chosen
to compare the efficacy and safety of new drug Cilnidipine
● Amlodipine - pure L-type CCB
● Hence, unique properties of Cilnidipine (N-type CCB) - demonstrated
by comparing its effect
● Properties brought out can be used to reduce sympathetic
overactivity that is inherent / induced as a reflex by CCBs

7. Objectives
❏ Primary Objective:
1. To compare the efficacy of Cilnidipine with Amlodipine in lowering the Diastolic & Systolic
blood pressure in patients with mild to moderate essential hypertension.
❏ Secondary Objective:
1. To compare the effect of Cilnidipine with Amlodipine on the resting heart rate of the
patients
1. To assess the safety of Cilnidipine with Amlodipine in terms of adverse effects reported as
well as physical finding

8. Material & Methods
Study Design
A randomized controlled parallel-arm two-group open-label
study with an active comparator
Study Location
Department of General Medicine, Sri Ramachandra Medical
College Hospital, Chennai
Study Duration September 2014 to May 2015
Ethics Approval Institutional Ethics Committee approval was taken
Informed Consent Obtained from all study participants

9. Material & Methods
Inclusion Criteria Exclusion Criteria
● Both Genders ● Patients with mean sitting diastolic BP of ≥110 mmHg
or mean sitting systolic BP of ≥180 mmHg
● 18 to 60 years ● CV complications (angina pectoris, MI, arrhythmia in
previous 6 months, cerebrovascular disease)
● Newly diagnosed patients with
mean sitting diastolic BP of ≥90
and ≤109 mmHg measured at 2 or
more office visits
● CKD
● Type 1 & 2 DM
● 2o HTN
● Pregnant, lactating women
● Mean sitting Systolic BP of ≥140
and ≤179 mmHg measured at 2 or
more office visits
● Any comorbid conditions & clinical emergencies during
the trial

10. Patients randomized into 2 parallel groups
in 1:1 ratio
Study Procedure
Group 1
Dose:- 2.5 mg
Amlodipine was
given orally in
the morning O.D
for 12 weeks
Group 2
Dose:- 5 mg
Cilnidipine was
given orally in
the morning O.D.
for 12 weeks
Cilnidipine is twice as potent as amlodipine, i.e.
2.5 mg of amlodipine = 5 mg of Cilnidipine

11. ● Duration of treatment was 12 weeks
● The baseline mean sitting diastolic BP (MSDBP), mean sitting systolic BP (MSSBP) &
heart rate (HR) were measured
● Baseline investigations were done before prescribing either drug
● Repeated during any study visit / at end of study if necessary
Study Procedure

12. Procedure at Each Visit
Follow-up every 2 weeks
At every visit, the patient’s Mean sitting Systolic & Diastolic BP & pulse rate were
recorded & systemic examination done
BP was recorded using a mercury
sphygmomanometer in Rt. UL in sitting
position after 15 mins
Pulse rate - palpation of radial artery in
sitting position after 15 mins
Report S/E - dizziness, flushing, headache, peripheral edema, palpitations & GI
disturbances
Also examined for ankle edema at each visit
Ankle edema was assessed by sustained
pressure over medial malleolus for 30
seconds using ball of thumb
At each scheduled visit, a 2 week pill pack along
with compliance card are given to study subjects &
assessed periodically
There were 7 scheduled visits during the study

13. Study Endpoints
Efficacy endpoints :
● Mean change in mean sitting diastolic
BP≥ 10 mmHg after 12 weeks of
therapy
● Mean change in mean sitting systolic
BP ≥ 20 mmHg after 12 weeks of
therapy
● Mean change in resting HR in patients on
Cilnidipine after 12 weeks of therapy
Safety endpoint :
● Mean change in resting HR in
patients after 12 weeks of therapy
● Incidence of adverse effects within
12 weeks of therapy

14. ● The statistical analysis was done using Statistical Package for Social Sciences for
Windows (SPSS) version 17
● Mean & S.D. were calculated for continuous variables
● Frequencies & percentage for categorical variables
● The mean diastolic & systolic BP and HR in each group before & after treatment
were compared using paired ‘t’ test
● The mean diastolic and systolic BP and HR from baseline to 12 weeks between
both groups were compared using unpaired ‘t’ test
Statistical Analysis

15. ● The adverse events in each group were compared using Chi Square test
● P value < 0.05 was taken to be statistically significant
● All the analyses were based on Intention to treat (ITT) principle
● All the study participants who had come for at least 1 follow-up visit were
included in the Intention-to-treat analysis
Statistical Analysis

16. The baseline patient
characteristics in
the amlodipine &
cilnidipine groups
were found to be
similar

17. Efficacy profile :
-Reduction in systolic BP and
diastolic BP after 12 weeks
was highly significant when
compared to baseline in
both the groups
In the amlodipine group,
systolic BP decreased by 11.57% (p<0.001) &
diastolic BP decreased by 11.97% (p<0.001).
In the cilnidipine group,
the systolic BP was proven to reduce by 11.97% &
diastolic BP reduced by 11.47% (p<0.001).

18. ● There was no
statistically significant
difference in the
reduction of systolic
and diastolic BP
between the groups
treated with amlodipine
& cilnidipine after 12
weeks of therapy
(p>0.05)

19. ● The heart rate in the amlodipine group showed a change from a baseline value of 88.04±6.31
bpm to 89.11 ± 4.21 bpm at the end of 12 weeks
● In the cilnidipine group showed a change from baseline 90.09±6.10 bpm to 88.93±3.31 bpm at
the end of 12 weeks
● This is shown in (Figure 3) [BUT Figure 3 is not mentioned in the article]*
● The HR , showed an increase by 1.07 bpm in mean value after treatment with amlodipine
● And decreased by 1.16 bpm on an average after treatment with cilnidipine.

20. Tolerability profile :
● The study drugs were well-tolerated in both the
groups
● It was significant to note that S/E common to CCB
as a group, like pedal edema & palpitations, were not
seen with cilnidipine group
● No discontinuation of treatment due to adverse
effects was seen
● No serious / life threatening adverse events were
seen in either group during the 12 weeks study
period.

21. DISCUSSION

22. ● CCB act to reduce the BP by causing arteriolar smooth muscle relaxation & thus a
reduction in peripheral vascular resistance
● CCB are effective both as monotherapy & in combination therapy in treatment of HTN
● Short acting CCB by virtue of their baroreceptor-mediated reflex sympathetic
stimulation , may not entirely reduce risk of cardiovascular disease
● Increase in peripheral vascular resistance & vascular smooth muscle contraction seen in
HTN is dependent on free intracellular calcium concentration
● According to JNC-7 guidelines, long-acting CCB with lesser sympathetic stimulation are
now recommended in the treatment of HTN
DISCUSSION

23. ● In the present study there is reduction in the systolic & diastolic BP after 12 weeks of
therapy of amlodipine & cilnidipine
● The reduction is due to long half-life of amlodipine which causes gradual relaxation of
smooth vascular muscle through L-type channels & decreased peripheral resistance &
less baroreceptor mediated sympathetic discharge
● Cilnidipine causes smooth vascular muscle relaxation through L-type calcium channels
& it has the added advantage of causing lesser sympathetic discharge through N-type
channel blockade
DISCUSSION

24. ● The decrease in HR is an added benefit because a higher resting HR is proven as an
independent risk factor causing cardiovascular mortality
● Cilnidipine caused a significant reduction in BP without increasing the HR, but not
Amlodipine
● The JNC-7 guidelines → calcium channels that have a lesser sympathetic stimulatory
effect are preferred treatment of HTN
● Thus, cilnidipine can be used safely used in patients with cardiovascular disease
like coronary heart diseases
DISCUSSION

25. ● Ankle edema is an adverse effect that is commonly seen with amlodipine, an L-type
CCB, with incidence rates approaching 15%.
● Amlodipine induced edema is mostly self-limited & minor, but can become severe & reach
proportions like anasarca in some patients
● But even mild edema can result in poor drug compliance & discontinuing therapy by causing
cosmetically undesirable effect
● An otherwise highly effective anti-HTN drug is hindered by this seemingly minor adverse
effect
DISCUSSION

26. Limitations :
● Small sample size
● Larger population would increase the power of the study
● Relatively short duration of 12 weeks
● If followed up for a longer period, the anti-hypertensive effect could be studied whether
it is sustained & long-term safety profile could be better characterized
● Open labelling : a potential cause for bias, with respect to reporting of adverse events
● Double-blinding → resolve this bias
DISCUSSION

27. ● Cilnidipine is comparable to amlodipine in reducing 24 hour systolic & diastolic BP
in mild - moderate essential HTN
● Despite similar BP reduction, cilnidipine therapy causes no increase in the HR
& there is a lower incidence of pedal edema
● Cilnidipine group : Better patient compliance & less treatment discontinuation
rates
● Can be used as a 1st line anti-HTN drug since its efficacy is comparable to that of
amlodipine with a better safety profile than amlodipine
● To conclude, cilnidipine therapy is an effective & safe alternative in treatment
of essential HTN
Conclusion

28. CONSORT Checklist
● Title is appropriate – Study type , blinding mentioned
● Abstract : well structured
● Introduction :
○ Scientific background : mentioned
○ Rationale : mentioned
○ Aim : mentioned
○ Objectives & hypothesis specified
○ Institutional Ethics Committee approval taken

29. ● Material & Methodology :
○ Trial design : described
○ Eligibility criteria : mentioned
○ Intervention : for each group described
○ Outcome : primary & secondary outcome assessment was defined
● Sample size : Calculation not mentioned
● Randomization :
-Sequence & generation: method used to generate- mentioned
-Allocation & concealment mechanism : mentioned
-Implementation: who generated randomization & allocation mentioned
CONSORT Checklist

30. ● Blinding : mentioned but procedure not mentioned
● Statistical methods : methods to compare primary &
secondary outcomes mentioned
● Results :
- Participants flow chart given
- Recruitment : dates defining periods of trial & follow up mentioned
- Baseline data : mentioned
- * Figure 3 was not provided but was written in the text
- Tables do not have *P values mentioned anywhere
CONSORT Checklist

31. - Numbers analyzed : mentioned
- Study outcomes : primary & secondary outcomes mentioned
- Adverse event profile mentioned
● Discussion :
○ Limitations : declared
● Other information :
○ -Registration : CTRI Registration not mentioned
○ -Protocol : not available
○ -Conflict of interest : not mentioned
○ -Sources of funding : not mentioned
CONSORT Checklist

32. Thank You
Next PG Activity:
Dr. Shivaji Dhande
Topic- PT of Gout
Junior Resident
Department of Pharmacology,
GMCH, Nagpur