Cardiac Drugs Adjustment in CKD :

Balancing the risk Have we done the right

thing?
Herlina Yulidia
Muhammad Aminuddin
Department of Cardiology and Vascular Medicine
DrSoetomo-General Hospital
Faculty of Medicine, Airlangga University
Surabaya
 Introduction

There was 17.3 million death based on CVD every year

and it might take 23.6 million death based on CVD on
2030.
CVD is the leading cause of death is often accompanied
by cardiac metabolic risk in chronic kidney disease (
CKD )
CVD and CKD are often closely linked , where fault on
one of them can , cause dysfunction of other organs
and cause damage to both the organ.
Introduction
(Epidemiology)
Introduction
(Epidemiology)
 Introduction

In the United States the prevalence of CVD in CKD

reaches 63 %
According to reports Renal Data System, 43 % of
patients with CKD have heart failure (HF) and 15
% had an acute myocardial infarction (AMI)
In patients with end-stage renal disease (ESRD)
the risk of mortality from CVD increased by 10 to
20 fold compared to non - CKD
 Introduction

The complexity of the correlation between the

cardiovascular system and renal system
ultimately affects the difficulty of determining
both therapeutic interventions or medical use in
CVD and CKD.
As has long been known that the administration
of CVD therapies based guidelines in general can
not be fully applied to patients with CKD .
Cardiac Drugs Adjustment in
Chronic Kidney Disease

1. LOW DOSE ASPIRIN VS HIGH DOSE ASPIRIN

Low Dose Aspirin vs High Dose Aspirin

Aspirin is an antithrombotic acetylates selective

cyclooxygenase- 1, which block the formation of
thromboxane A2 in platelets.
Prostaglandin which induces vasodilation plays an
important role in maintaining renal blood flow, by
inhibiting the synthesis of prostaglandins aspirin
makes CKD patients vulnerable to further
deterioration of renal function .
Low Dose Aspirin vs High Dose Aspirin
Jardine et al
(low-dose aspirin therapy on CKD and the risk of CVD)
eGFR Reduce risk of
CVD
> 60 ml/ min/ 1.73 m2 0.28 %
45 to 59 ml/ min/ 1.73 0.74 %
m2
< 45 ml/ min/ 1.73 m2 7%
Low Dose Aspirin vs High Dose Aspirin
Jardine et al (low-dose aspirin therapy on CKD)

Reduce mortality due to cardiovascular events and stroke in

subjects with eGFR < 45ml/min/1,73m2
Major and minor bleeding risk in the subgroup of CKD is 10
times higher than the general population
Low-dose aspirin was associated with 27 cases of bleeding per
1.000 people, with minor bleeding events of 12 per 1.000
people in low eGFR group
Low Dose Aspirin vs High Dose Aspirin

Meta-analysis study found 1 to 2 cases of bleeding per 1000

patients/ year with low-dose aspirin therapy or high doses
No significant difference in the incidence of bleeding due to
aspirin use in a variety of doses, ranging lowest dose 75mg to
500mg
2.ATORVASTATIN VS ROSUVASTATIN
 Atorvastatin vs Rosuvastatin

Statins (or HMG-CoA reductase inhibitors) are a class of

drugs used to lower cholesterol levels by inhibiting the
enzyme HMG-CoA reductase.
Studies show cholesterol has a role in the progression of
renal disease but also lower cholesterol levels have
renoprotective effects.
Several clinical studies about the effect of statins on renal
function are SHARP Study, JUPITER trial and PLANET
Study.
 Atorvastatin vs Rosuvastatin

PLANET study, observed the use of Atorvastatin and

Rosuvastatin and its effect on the incidence of Proteinuri and
the effect on the decline of renal filtration rate.

PLANET showed :
Decreased levels of proteinuria in the atorvastatin 80 mg
subject
Significant association of incidence of proteinuria and eGFR
reduced Rosuvastatin 40 mg subject
Atorvastatin vs Rosuvastatin
3.ACE INHIBITOR AND ARB
 ACE Inhibitor and ARB

ACE inhibitors may inhibit ACE

and reduce the stimulation of
both AT1 and AT2 receptor, ACE
inhibitors also cause
degradation of bradykinin to the
active group.
ARB works only inhibit the AT1
receptor
 ACE Inhibitor and ARB
(on CVD)

ACC/ AHA
ACE inhibitors In low-risk patients with STEMI Class
IIa/B.
ARB is recommended in patients who are intolerant of
ACE inhibitors and have heart failure or had a
myocardial infarction with LVEF 40 % (Class IA )
The use of combination therapy with an ACE inhibitor
and ARB is recommended in STEMI patients with
systolic heart failure ( Class IIb B )
ACE Inhibitor and ARB
(on CVD)
 ACE Inhibitor and ARB
(on renoprotective)

Decrease in proteinuria during

antihypertensive therapy correlates with
slowing the progression of kidney disease.
Controlled trials of CKD, ACE inhibitors and
ARBs reduce proteinuri of about 35%-40%,
which is larger than other antihypertensive
agents.
ACE Inhibitor and ARB
(on renoprotective)
 ACE Inhibitor and ARB
(on renoprotective)

RAAS suppression through either ACEis or ARBs in

monotherapy has shown favourable CV effects,
but it has several limitations
Dual blockade with aldosterone receptor
antagonists offers positive outcomes in
nephropathies and in CHF in a limited number of
patients.
4. BISOPROLOL VS CARVEDILOL
 Bisoprolol vs Carvedilol

Activation of beta-1 receptors results in an

increase AV nodal conduction, contractility, heart
rate and a decrease of the AV node refractory
Activation of beta-2 receptors produces mainly in
vasodilation and bronchodilation
Selective beta blockers are agents that specifically
block the beta-1 receptors, whereas nonselective
beta blocker blocking beta-1 and beta-2 receptors
 Bisoprolol selective block b 1 receptor
Carvedilol Block b 1 and 2 receptor
Bisoprolol vs Carvedilol
Bisoprolol vs Carvedilol
 Bisoprolol vs Carvedilol

COMET trial :

Carvedilol has been shown significantly

cardiovascular mortality decrease patients with
HF
Theres an incidence of renal function decrease
but not significant on CKD event induce by
Carvedilol
5 .WARFARIN VS NOAC (NOVEL ORAL ANTI
COAGULANT)
 Warfarin vs NOAC

Kidney is not a major elimination organs for

warfarin and acenocoumarol (antagonist Vit K).
Nonetheless dose adjustment is recommended
especially in CKD stage 3 due to the risk of
bleeding
NOAC (eg: dabigatran) is a thrombin inhibitor.
Elimination majority (85%) in kidneys, with 80%
of the dose excreted in urine.
Warfarin vs NOAC
Warfarin vs NOAC
 Summary

Cardiovascular disease (CVD) knowing as world number

one cause of death. Where CVD and CKD are often
closely linked.
The complexity of the correlation between the
cardiovascular system and renal system ultimately
affects the difficulty of determining both therapeutic
interventions or medical use in CVD and CKD.
Bleeding risk, proteinuria, decrease on eGFR are things
that we have to look up to in adjusting CVD drugs on
CKD.
THANK YOU