Journal of The Association of Physicians of India ■ Vol.

66 ■ March 2018 59

Review Article

Amlodipine in the Era of New Generation Calcium Channel

Blockers
Mangesh Tiwaskar 1, Amit Langote 2, Resham Kashyap3, Archana Toppo4

generation CCBs, it still remains one

Abstract of the top global pharmaceutical
products. Its effectiveness in lowering
Amlodipine is a classical drug with varied properties extending from control of
blood pressure in addition to high
blood pressure to as an antianginal and anti atherosclerotic agent. Amlodipine
tolerability and minimal side effects has
is a longer acting dihydropyridine calcium channel blocker, effective for 24 hours
made it an agent of choice in both single
BP control and cause no BP variability. It is a powerful, well-tolerated, and safe
and combination drug treatment for
antihypertensive agents that is widely used either alone or as a key component reducing the burden of cardiovascular
of combination therapy for hypertension. Its effective BP reduction has shown disease across the globe. 9 The aim of
proven benefits in cardiovascular event reduction that is supported with strong the review is to assess the potential
evidences from large randomised controlled trials. Combination therapies of advantages of amlodipine above the
amlodipine with other agents eliciting renin-angiotensin-aldosterone system new DHPs with a focus of its benefits
blockade (angiotensin II receptor blockers or renin inhibitors) have shown in varied cardio vascular diseases.
effective blood pressure-lowering strategies in CV risk reduction and progression
of renal disease. Novel type of calcium channel blockers have been developed Pharmacodynamics and
which have additional properties of blocking T and N subtypes of calcium Pharmacokinetics
channels and apart from their class effects they exerts specific action on heart
rate and renin aldosterone system. They are considered to be more renoprotective C a l c i u m c h a n n e l s ( C a 2+) a r e
due to this additional properties. Amlodipine is most potent and longer acting classified into at least six subtypes;
namely, L-, N-, P-, Q-, R-, and T-type,
agent compared to the newer CCBs, its effectiveness in BP lowering still makes
based on electrophysiological and
it the agent of choice among all the CCBs.
pharmacological evidence. L-type
of voltage –gated calcium channel
blockers (CCBs) are potent vasodilators

H ypertension a universal public

health hazard, a leading cause
of mortality and ranked third as a
or as a key component of combination
therapy for hypertension. The initial
indication, besides hypertension, also
and often used as a first or second line
drug in management of hypertension.
Amlodipine, is a longer acting DHP,
cause for disability -adjusted life include angina and peripheral vascular no longer considered as L-type-specific
years. 1 It affects approximately 26% disease. 6,7 Amlodipine was introduced Ca2+ channel blockers (Figure 1). Studies
of the population worldwide, nearly in early 90’s’ has many unique qualities h a ve s h o w n , t h a t a m l o d i p i n e a n d
45% of deaths by heart disease and that set it apart from other agents cilnidipine blocked N-type Ca2+ channels
51% of deaths by stroke are due to in this class. It is a third generation as well. 10-12 Amlodipine along with
hypertension; accounting for 9.4 million Dihydropyridine (DHP) calcium benidipine, cilnidipine, nicardipine,
deaths worldwide every year. 2,3 In antagonist, with high selectivity for and barnidipine significantly blocked
India, its prevalence varies from 20-40% vascular smooth muscle, has minimal N-type and P/Q-type Ca 2+ channels .
in urban to 12-17% in rural areas. It impact upon heart rate, and no negative Amlodipine profoundly blocks the
is estimated that the prevalence of inotropic effects or electrophysiological N-type Ca(2+) channels with high
hypertension(HTN) might rise to 214 disturbances. 8 It is an extensively affinity[(3)H]amlodipine (K(d), 3.08nM
million by 2025. 4 For the management studied classical drug with varied and high potency (IC(50), 2.7 microM
of hypertension various classes of properties extending from control of at -60mV. 13
antihypertensive drugs are available blood pressure to as an antianginal Amlodipine inhibits the
such as diuretics, β-blockers (BB), α and anti atherosclerotic agent. The transmembrane influx of calcium
blockers, calcium channel blockers newer generation DHPs block L/N type i o n s i n t o va s c u l a r s m o o t h m u s c l e
(CCBs), angiotensin converting enzyme calcium channel of which cilnidipine cells and myocardial cells. It is a
(ACE) inhibitors and angiotensin is considered more renoprotective. peripheral arterial vasodilator that acts
receptor blockers (ARBs),that can Amlodipine, despite of the new directly on vascular smooth muscles
be used as monotherapy or in
combination.5 Dihydropyridine calcium
channel blockers are a class of powerful, Consultant Physician and Diabetologist, Asian Heart Institute, Mumbai, Maharashtra; 2Consultant Nephrologist and Transplant
1

Physician, Apollo Hospital, Nerul, Navi Mumbai, Maharashtra; 3Medical Advisor, 4Associate Director, Dr. Reddys Lab Ltd., Ameerpet,
well-tolerated, and safe drugs widely Hyderabad, Telangana
used is in the management of elevated Received: 27.03.2017; Accepted: 10.05.2017
blood pressure (BP) as a monotherapy
 60 Journal of The Association of Physicians of India ■ Vol. 66 ■ March 2018
Figure 1. Comparison of the potencies of various DHPs in blocking four subtypes of Ca2+ channels:

L-, N-, P/Q -, and R-types.

which was higher than all ARBs. 18
100
Across the CCBs, the 24h SI value
90 for amlodipine 5mg was higher than
L type those of manidipine, lercanidipine,
80
N type nifedipine felodipine and diltiazem. 17
70
P/q type Blood Pressure Variability
60
R type BP variability (BPV) is independent
50 risk factor for CVD events and target
Block %

organ damage. 17, 19 A 3 year follow up

40
study by Sander et al 20 has shown that
30 greater than 15-mm Hg s.d. of daytime
SBP increases the risk of development
20
of early atherosclerosis and CV events.
10 Early morning BP surges (EMBPS) a
transient increase in both Systolic BP
0
(SBP) and diastolic BP (DBP) during
-10
nifedipine nicardipine amlodipine benidipine cilnidipine the morning hours around the time
of rising, is one pattern of variability
Adapted from Furukawa T et al. J Pharmacol Exp Ther 291 (2), 464-473. 11 199913 linked with target organ damage and
Fig. 1: Comparison of the potencies of various DHPs in blocking four subtypes of Ca2+ c e r e b r o va s c u l a r e ve n t s . A 1 0 - m m
channels: L-, N-, P/Q-, and R-types Hg increase in the EMBPS has been
shown to increase stroke risk by 22%,
to reduce the peripheral resistance CCBs have been developed which independent of age and average 24
and reduction of blood pressure. The have additional properties of blocking h BP. 21 Also a long-term increase in
process of contraction is dependent T and N subtypes of calcium channels average BP values is risk factor for
on the movement of extracellular ca 2+ and apart from their class effects they endothelial dysfunction leading to
ions into these cells through specific exerts specific action on heart rate and atherosclerosis, and a relatively short
ion Channel. Amlodipine has a half-life renin aldosterone system. Cilnidipine term exaggerated BPV may trigger an
of 35-40 h, longest among all CCBs. through its dual L/N-type calcium atherothrombotic CVD event. 17
It is usually dosed on a once daily channel blocker property presumed According to Anglo Scandinavian
basis which is favourable for patient to effectively suppress neurohumoral Cardiac Outcomes Trial - Blood
compliance. 14 regulation of cardiovascular system P r e s s u r e L o we r i n g A r m ( A S C O T -
A starting dose of 5 mg is usually by inhibition of sympathetic over- BPLA) trial a good control of mean
recommended with a maximum daily activity and modulation of the renin- BP but greater residual SBPV had a 5
dose of 10 mg. In the elderly population angiotensin-aldosterone system. In times higher risk of stroke than those
and those with hepatic failure, a addition to blood pressure lowering with lower variability values hence
starting dose of 2.5 mg is recommended. effects these novel drugs are anticipated Visit-visit variability (VVV) is a key
Amlodipine has a gradual onset of to provide organ protection in predictor of the long-term risk of stroke
action and hence no significant reflex management of hypertension. 16 after transient ischemia. ASCOTBPLA
neuroendocrine activation. Activating compared Amlodipine-based regimens
24 Hours BP Control
reflex mechanisms, such as increased with Atenolol-based regimens in 19,257
peripheral vascular resistance and Both the magnitude of BP reductions patients with hypertension and other
elevated heart rate, can cause negative and the control of BP variability may vascular risk factors. It was found that
effects on lipid and carbohydrate be important in the prevention of within-visit, VVV and ABPM BPV were
metabolism. 14 These notable adverse Cardiovascular and cerebrovascular all reduced by amlodipine irrespective
effects are commonly seen with other events. Ambulatory blood pressure of its effect on mean BP, whereas BPV
agents including the first generation monitoring (ABPM) provides an increased with Atenolol-based regimen.
β-blockers (BBs; such as atenolol and opportunity to obtain measurements A significant reduction in CV event,
metoprolol) and earlier generation of BP throughout the 24 h period mortality and stroke was observed
of DHPs. Amlodipine has a high during an individual’s normal daily in amlodipine group compared to
bioavailability, ranging from 60% to routine. Amlodipine has the longest atenolol. 22 Similarly in the XCELLENT
80%; it undergoes hepatic metabolism elimination half-life and slow receptor trial Amlodipine significantly decreased
and shows some impaired elimination dissociation kinetic, it shows a gradual daytime, night-time and 24-hrs SBPV;
in the setting of liver cirrhosis but and prolonged reduction in BP. A whereas Indapamide SR significantly
no accumulation with renal failure. high trough to peak concentration decreased SBPV in the daytime and
Amlodipine also has a slow rate of (T:P =0.85) and high smoothness 24 hours. Amlodipine was efficacious
elimination over 40–60h. If amlodipine index (SI) indicates that amlodipine is a c r o s s a l l t i m e - f r a m e s e ve n a f t e r
is discontinued, BP generally returns consistent in BP reduction throughout adjustment for mean BP reduction. 23
to baseline over 1 week without any 24 hours. 17 In a meta-analysis of 5188 Antihypertensive and Lipid Lowering
dangerous rebound elevations in BP patients in 11RCTs, amlodipine 5mg Treatment to Prevent Heart Attack
(unlike clonidine). 15 Novel type of and telmisartan 80mg had similar SI Trial (ALLHAT) showed that even after
 Journal of The Association of Physicians of India ■ Vol. 66 ■ March 2018 61

adjusting for mean BP, Amlodipine Amlodipine in Diabetes with The UACR was seemingly decreased
and Chlorthalidone reduced VVV BPV Microalbuminuria after 3 or 6 months of treatment; In
to a greater extent than Lisinopril. 24 A cilnidipine group, UACR seems to be
pooled analysis of five studies (47,558 Endothelial dysfunction alters decreased largely to 85.05 mg/g (-23.72%
B P V - e va l u a b l e p a t i e n t s , d u r a t i o n the structural and functional effects reduction compared to baseline)
va r i e d f r o m 4 m o n t h s t o 6 ye a r s ) o n t h e t a r g e t ve s s e l . E n d o t h e l i a l in 3 months, 81.71 mg/g (-26.72%
showed that BPV with amlodipine was dysfunction within the glomerular reduction) in 6 months, whereas in
significantly (P < .0001) lower compared basement membrane may modify amlodipine group, UACR decreased
to atenolol, lisinopril, enalapril. glomerular barrier permeability, thus to 75.73 mg/g (-14.23% reduction)
Treatment difference (standard error ) leading to the excretion of albumin in 3 months, 78.53 mg/g (-11.05%
was −1.23 (0.46;  P  =  .008) mm Hg for into the urine. 29 In diabetic patients reduction) in 6 months. However,
amlodipine vs all active comparators. 25 presence of microalbuminuria helps UACR tended to return to the baseline
these findings suggest that amlodipine in early diagnosis of incipient diabetic value after 12 months of treatment with
is effective for minimizing BPV. nephropathy. Microalbuminuria is either drug. The change in the natural
considered as an independent risk factor logarithm of the UACR after 12 months
Side Effect Profile for renal impairment, cardiovascular of treatment was -0.21 ± 0.69 in the
disease and premature mortality. 30 cilnidipine group and -0.21 ± 0.86 in
The most commonly reported
A n e a r l y i n t e r ve n t i o n m a y r e t a r d the amlodipine group. The difference
adverse effect hindering compliance
the progression to end-stage renal between the groups was estimated to
with amlodipine is peripheral oedema.
disease (ESRD). CCBs are not always be 0.00 (95% confidence interval: -0.16
However, this adverse effect can be
able to protect against kidney injury, to 0.17, P = 0.96). Thus, cilnidipine
minimised if the agent is given at
as was shown in the Renoprotection and amlodipine had similar effects
bedtime, and lower doses (2.5 or 5 mg/
in Patients with Nondiabetic Chronic on UACR in hypertensive patients
day) are used. Other reported side effects
R e n a l D i s e a s e ( R E I N ) - 2 . 31 A n d , i n with diabetic microalbuminuria. CKD
include dizziness, fatigue, headache,
Gauging Albuminuria Reduction s t a g e wa s u n c h a n g e d i n 9 6 v s 8 9
palpitations and nausea, although these
with Lotrel in Diabetic Patients with patients, advanced in 20 vs 21 patients,
are generally not bothersome enough
Hypertension (GUARD) trials, the and regressed in 26 vs 34 patients
to cause discontinuation of the drug.
antialbuminuric effect of CCB was after treatment with cilnidipine and
Also, its vasodilatory effect can lead to
weaker than that of diuretics in RAS amlodipine respectively.
decreased cardiac output in the setting
of aortic stenosis. 14 inhibitor-treated hypertensive patients In diabetes, the main mechanisms of
with type 2 diabetic nephropathy. 32 glomerular hyperfiltration (which may
Angiotensin-converting enzyme The uncertain renoprotective effects underlie the initiation and progression
inhibitors (ACEIs) and angiotensin of L-type CCBs may be due to the of DN) are by increases in the levels of
receptor blockers (ARBs) cause post presence of L-type calcium channels hormones, such as insulin-like growth
capillary dilation and normalize at the afferent but not efferent factor 1, atrial natriuretic peptide,
hydrostatic pressure, and are thus arterioles. L-type CCBs cause afferent intracellular accumulation of sorbitol
ideally suited for prevention/reversal arteriole-specific vasodilation, which and protein glycosylation, and activated
of CCB-induced oedema. ARB/ increases the glomerular pressure. tubuloglomerular feedback, which are
CCB and ACEI/CCB combination This adverse action of L-type CCBs caused by increased tubular sodium
therapy is also more effective than in the glomerular microcirculation reabsorption through hyperinsulinemia
CCB monotherapy in controlling counteracts their ability to attenuate and hyperglycemia. Sympathetic
blood pressure. These combinations glomerular hypertension through the nerve activation is not thought to be
represent an important advance in the systemic decrease in BP. Thus, the use a major mechanism of glomerular
management of hypertension. Although of L-type CCBs is not always beneficial hyper filtration in DN. 51,52 The lack of a
the incidence of oedema recorded in in patients with renal dysfunction. clear difference in the antialbuminuric
the CCB monotherapy groups varies In contrast, L/ N -type CCBs are effects of cilnidipine and amlodipine
widely (range, 4.9–34.4%), the data able to inhibit renal sympathetic in the present study may be due to the
are consistent in showing lower rates n e r ve a c t i v i t y a n d c a u s e e f f e r e n t marginal contribution of sympathetic
of this side effect in the patients arteriolar vasodilation. Thus, protect nerve activation to the progression of
who receive ACEI/CCB or ARB/CCB the glomeruli through the attenuation DN. 35
combination therapy. 26 For example of glomerular hypertension. Since,
addition of olmesartan medoxomil 40 L-type calcium channels do not express Amlodipine and Atherosclerosis
mg to amlodipine 10 mg reduced the in glomerular efferent arterioles, the
placebo-subtracted rate of oedema renoprotective effects of an L-type CCB Amlodipine has a potential
by more than 50%. 27 In an additional are expected to be lower than those of benefit in atherosclerosis. It prevents
study, the incidence rate of peripheral an L-/N-type CCB. 33 the formation of free radicles thus
oedema was lower with valsartan and averting the oxidative damage to the
amlodipine in combination (5.4%) than H o w e v e r i n S A K U R A t r i a l , 34 lipid bilayer. 14 Zhang and Hintze in
with amlodipine monotherapy (8.7%). 28 L-/N-type CCB cilnidipine did not preclinical study found that amlodipine
result in a greater antialbuminuric effect increased NO production in canine
than L-type CCB amlodipine in RAS coronary microvasculature, which
inhibitor-treated hypertensive patients could be another plausible anti
with diabetes and microalbuminuria. atherosclerotic effect. 36 Additionally,
62 Journal of The Association of Physicians of India ■ Vol. 66 ■ March 2018

Table 1: Cardiovascular event and outcome with amlodipine in landmark trials

Trials Intervention No.of patients No. events odds ratio 95%(CI)
Stroke MI CHF MACE Total mortality CV mortality
AML vs ACEi AASK43 Ramipril 436 23 19 20 89 34 12
Amlodipine 217 9 5 8 28 23 7
OR 0.78 OR 0.52 OR 0.80 OR 0.58 OR 1.33 OR 1.18
(0.35-1.71) (0.19-1.41) (0.34-1.84) (0.36-0.92) (0.76-2.34) (0.46-3.04)
ALLHAT44 Lisinopril 9054 457 796 612 2514 1314 618
Amlodipine 9048 377 798 706 2432 1256 603
OR 0.82 OR 0.99 OR 1.17 OR 0.96 OR 0.95 OR 0.97
(0.71-0.94) (0.90-1.08) (1.04-1.31 (0.90-1.02) (0.87-1.03) (0.87-1.09)
AML vs ARBs VALUE45 Amlodipine 7596 281 313 400 1298 818 304
2004 Valsartan 7649 322 369 354 1349 840 304
OR 0.87 OR 0.85 OR 1.15 OR 0.96 OR 0.98 OR 1.01
(0.74-1.03) (0.73-0.99) (0.99-1.33) (0.89-1.05) (0.88-1.08) (0.86-1.18)
IDNT46 Amlodipine 567 15 27 93 161 83 37
2003 Irbesartan 579 28 44 60 172 87 52
OR 0.53 OR 0.61 OR 1.70 OR 0.94 OR 0.97(0.70- OR 0.71
(0.28-1.01) (0.37-1.00) (1.20-2.40) (0.73-1.21) 1.34) (0.46-1.10)
CASE J47 Amlodipine 2349 47 18 16 134 86 15
2008 Candesartan 2354 60 17 20 134 73 11
OR 0.78 OR 1.06 OR 0.80 OR 1.00 OR 1.19 OR 1.37
(0.53-1.15) (0.55-2.06) (0.41-1.55) (0.78-1.28) (0.86-1.63) (0.63-2.99)
AML vs ALLHAT44 Chlorthalidone 15255 675 1362 870 3941 2203 996
Diuretic 2002 Amlodipine 9048 377 798 706 2432 1256 603
OR 0.94 OR 1.00 OR 1.40 OR 1.06 OR 0.95 OR 1.02
(0.83-1.07) (0.91-1.11) (1.26-1.55) (0.99-1.12) (0.89-1.03) (0.92-1.14)
ACCOM- Amlodipine 5744 112 125 100 552 236 107
PLISH48 HCTZ 5762 133 159 96 679 262 134
2008 OR 0.84 OR 0.78 OR 1.05 OR 0.80 OR 0.90 OR 0.80
(0.65-1.09) (0.62-0.99) (0.79-1.39) (0.71-0.90) (0.75-1.08) (0.62-1.03)
AML vs BB ASCOT-BLPA41 Amlodipine 9639 327 429 134 1193 738 263
Atenolol 9618 422 474 159 1438 820 342
OR 0.77 OR 0.90 OR 0.84 OR 0.80(0.74- OR 0.89 OR 0.76
(0.66-0.89) (0.79-1.03) (0.67-1.06) 0.87) (0.80-0.99) (0.65-0.90
Adapted from Seung-Ah Lee et al. Korean J Intern Med 2014;29:315-32442; AASK The African American Study of Kidney Disease and Hypertension; ALLHAT
Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial; IDNT Irbesartan diabetic nephropathy trial; ASCOT Anglo-Scandinavian Cardiac
Outcomes Trial; VALUE Valsartan Antihypertensive Long-Term Use Evaluation; CASE J Candesartan Antihypertensive Survival Evaluation in Japan ; ACCOMPLISH
The Avoiding Cardiovascular Events in Combination Therapy in Patients Living with Systolic Hypertension trial; AML amlodipine, RAM Ramipril, MET Metoprolol,
CT chlorthalidone, LIS lisinopril, ATN atenolol, VAL valsartan; HCTZ hydrochlorthiazide

amlodipine has been shown to up in previous angiographic trials with and reduction in total peripheral
regulate the expression of interleukins, nifedipine or nicardipine in patients resistance, decreasing the occurrence
which may also have antiproliferative with stable coronary artery disease even of symptomatic angina, and silent MI. 14
effects, and to have favourable effects though with proved antianginal effects, In the PREVENT trial wherein 68 %
on extracellular matrix remodelling. 37 suggestive of fact that amlodipine may of participant had history of angina,
The PREVENT trail was a placebo have an additional effects. 38 a m l o d i p i n e s h o we d a s i g n i f i c a n t
controlled prospective randomized The Comparison of Amlodipine reduction in hospitalization for unstable
trial to study the effect of amlodipine vs Enalapril to Limit Occurrences angina compared to placebo (HR: 0.67,
upon atherosclerotic progression of Thrombosis (CAMELOT) study 95% CI: 0.48–0.93). 38 In ASCOTBPLA,
in patient with established CAD. compared amlodipine and enalapril, amlodipine vs atenolol significantly
Amlodipine reduced the progression of with placebo in normotensive patients reduced unstable angina (HR: 0.68,
atherosclerosis in the carotid arteries as with CAD. Amlodipine group vs 95% CI: 0.51–0.92; P <0.0115) but had
assessed with B-mode ultrasonography. placebo (P=.12), showed a trend towards no significant effect on chronic stable
Amlodipine had a significant effect less progression of atherosclerosis angina (HR: 0.98, 95% CI: 0.81–1.19). 41
in slowing the 36-month progression which was significant in patients with 89% patients enrolled In CAMELOT
of carotid artery atherosclerosis: the higher systolic blood pressure. 39 trial had history of Angina, the rate
placebo group experienced a 0.033-mm of hospitalization for angina showed
In the randomised trial Coronary
increase in Intima Media Thickness. a statistically significant difference
Angioplasty Amlodipine Restenosis
Amlodipine also reduced coronary between amlodipine and enalapril (HR,
S t u d y ( C A PA R E S ) , p a t i e n t s h a d
revascularizations (53 versus 86, HR 0.59; 95% CI, 0.42-0.84, P=.003) and
a reduced incidence of repeat
0.57 [0.41 to 0.81]) regardless of the amlodipine vs placebo (HR 0.58; 95%
percutaneous transluminal coronary
use of β-blocker, nitrates, or lipid- CI,0.41-0.82,P=.002 This study suggests
angioplasty when treated with
lowering therapy. Fewer events in the that normotensive patients treated with
amlodipine. 40
amlodipine group compared to placebo amlodipine show reduced rates of CV
(86 versus 116, HR 0.69 [0.52 to 0.92]), Amlodipine and Angina events and hospitalisations for angina
mostly attributable to a difference in compared with enalapril. 39
unstable angina and revascularization. Antianginal efficacy of amlodipine,
These beneficial effects were not seen is mediated by the amlodipine-
induced dilation of coronary arteries
 Journal of The Association of Physicians of India ■ Vol. 66 ■ March 2018 63

Table 2: Comparative analysis of amlodipine and cilnidipine

Amlodipine Cilnidipine Comments
24 h BP control long half-life of 35-50h, Shorter half-life 2.5h Amlodipine shows a good BP control for 24h
Blood pressure variability Reduces BPV Not known Amlodipine minimises BPV reducing the risk of cv
(BPV) and cerebrovascular events
Ca channel blockade Blocks L and N ca channels. Blocks L, N ca channels Both are Non selective DHP
Pedal edema Dose dependent and reversible. Relatively less Benefits outweighs pedal edema with the use of
amlodipine.
CV outcome trials Reduction in primary and secondary points Human data is unavailable Amlodipine offers proven CV mortality and CV
(composite of fatal non fatal MI, HF, angina, events reduction in large multicentric trials.
stroke, CV mortality, total mortality)
Stroke reduction Proven stroke reduction through long terms No proven benefits in stroke Amlodipine offers stroke reduction
outcome trials reduction
Renal outcomes (ESRD) Reduces the progression of CKD. No large trials available Amlodipine has proven reduction in progression to
ESRD in large multicentric trials.
Antiproteinuric effect Similar antiproteinuric observed in diabetic Similar antiproteinuric observed in Both have role in Renoprotection
patients with proteinuria(SAKURA TRIAL)34 diabetic patients with proteinuria
Affordability Less costly More costly Amlodipine is a cost effective therapy

Amlodipine and Cardiovascular the ventricular repolarization in the doubling of serum creatinine, ESRD,
Outcomes canine model of long QT syndrome. 50,51 and dialysis, treatment with an ACE-
Large multicentric trials in support of inhibitor (benazepril) plus amlodipine
Amlodipine has been most widely the above findings are still the need of wa s a s s o c i a t e d w i t h s i g n i f i c a n t l y
a n d e x t e n s i ve l y s t u d i e d C C B . I t s hour. Whereas amlodipine is backed reduced risk of kidney disease
effect on cardiovascular outcomes in with sufficient evidences to support the progression compared to treatment
hypertensive patient are evaluated in above findings. with ACE inhibitor plus a diuretic
many outcome trials.42 A data of around (hydrochlorothiazide) (HR: 0.52, 95%
87000 patients who were enrolled
Amlodipine and Renal CI: 0.41–0.65; P, 0.0001). In elderly
in different trials for a duration of Outcomes patients >65 years age amlodipine
3-6years has been shared in Table 1. group showed 70% RRR in progressing
Hypertension is a major cause of to dialysis compared to HCTZ group
A significant reduction in end stage renal disease (ESRD), and (p=0.053, for the difference). In the
cardiovascular events and total blood pressure levels have been shown intention-to-treat population, the
mortality was observed with amlodipine to be correlated with renal disease amlodipine group had a 48% RRR
compared to other antihypertensive progression. A strict BP control is for chronic kidney disease (CKD)
agents. Risk of MI was significantly the mainstay of treatment to prevent progression, defined as doubling of
decreased with amlodipine compared renal progression and to reduce serum creatinine, estimated glomerular
to other antihypertensives. Also cardiovascular risk in hypertensive filtration rate (eGFR) <15 mL/min,
amlodipine showed better results in patients with chronic kidney disease or dialysis compared with the HCTZ
s t r o k e p r e ve n t i o n . C H F i n c i d e n c e (CKD). 52 ALLHAT found no significant group. 48
seemed to be increased with amlodipine differences between amlodipine vs
compared with ACE inhibitors or ARBs, Conclusion
diuretic in the development of ESRD or
b u t wa s c o m p a r a b l e t o t h a t w i t h renal disease progression (by estimated Amlodipine is a superior option
ß-blockers and diuretics Amlodipine glomerular filtration rate [(GFR]) in the HTN armamentarium, not only
can be safely used in high-risk cardiac in high risk hypertensive patients. 44 for controlling BP but also for safely
patients and is associated with benefits CASE-J also noted no significant improving patient outcomes (Table 2).
for all major cardiovascular endpoints as difference in rates of renal events There has been a vast clinical experience
well as total mortality.41,42,48 Newer CCBs between candesartan- and amlodipine- with its use both as monotherapy or
like Cilnidipine have been introduced treated high-risk hypertensive patients combination in varied condition. It
shortly and clinical data on long term (HR: 0.70, 95% CI: 0.39–1.26; P <0.23). 47 has proven benefits in angina with
cardiovascular outcomes trials are Considerable clinical evidences lesser hospitalization and fewer
still lacking. Few animal studies are suggest that an inhibitor of the renin– revascularization rates. Its unique
available in support of cardio protective angiotensin system (RAS), such as an mechanism and property has shown
benefits of Cilnidipine. In a preclinical angiotensin-converting enzyme (ACE) benefits in reduction of progression
study for MI, Cilnidipine showed a inhibitor and an angiotensin II type 1 of atherosclerosis. Amlodipine unlike
decrease in the myocardial interstitial receptor blocker (ARB), has an apparent newer CCBs, has shown robust
norepinephrine levels during ischemia renoprotective effect. Adequate BP reduction in cardiovascular endpoints
and reperfusion periods, leading to levels are seldom achieved with only p a r t i c u l a r l y s t r o k e . E ve n i n r e n a l
reduction of the myocardial infarct one RAS inhibitor. A combination of impaired patients, amlodipine with
size and occurrence of ventricular two to three antihypertensive drugs effective BP control over 24hrs reduces
premature beats. 49 Likewise, in vivo is required to decrease BP to target the progression of ESRD. Hence,
experimental data have stated that levels, especially in patients with compared to all the CCBs, amlodipine
cilnidipine shows antianginal effects in kidney disease. 52 ACCOMPLISH found still stands the test of time.
the experimental model of vasopressin- that using the progression of chronic
induced angina and improvement of kidney disease endpoint comprised of
 64 Journal of The Association of Physicians of India ■ Vol. 66 ■ March 2018

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