CCS 2
Summary
TLDRThe presentation focuses on optimizing therapy for chronic coronary syndromes, highlighting the use of Ranolazine as a viable treatment option. The speaker discusses the prevalence and prognosis of angina, emphasizing Ranolazine's role as an add-on or first-line therapy for patients not well-controlled by beta blockers or calcium channel blockers. Clinical trials and guidelines support its efficacy in reducing angina frequency, improving exercise tolerance, and lowering healthcare costs, particularly in patients with diabetes. The talk underscores individualized treatment and the benefits of Ranolazine in enhancing patient outcomes without significant hemodynamic effects.
Takeaways
- π Chronic coronary syndrome (CCS) patients with angina have a poorer prognosis and greater risk of cardiovascular events.
- π Angina frequency is directly related to the risk of hospitalization after an acute coronary syndrome, impacting healthcare costs.
- π Renolazine is presented as a viable add-on therapy for CCS patients inadequately controlled with first-line agents like beta blockers and calcium channel blockers.
- π Guidelines suggest renolazine for CCS patients with persistent angina despite treatment with first-line therapies, emphasizing the need for individualized treatment plans.
- π‘ Renolazine's mechanism of action involves improving diastolic tone, coronary blood flow, and potentially having an anti-arrhythmic effect without affecting heart rate or blood pressure.
- π‘ The CARISA trial showed renolazine significantly reduced angina frequency and nitroglycerin consumption, with a more pronounced effect in non-diabetic patients.
- π€ Renolazine is considered for patients with comorbidities such as diabetes, heart failure, or those who cannot tolerate first-line agents, offering a tailored approach to treatment.
- π Renolazine has been associated with a reduction in HbA1c levels, suggesting a potential benefit for diabetic patients with CCS.
- πΌ The use of renolazine is supported by randomized control trials and meta-analyses, demonstrating its effectiveness and leading to guideline recommendations.
- π‘ The MERLIN-TIMI 36 trial and subsequent analyses highlight the drug's benefits in reducing angina and HbA1c levels, particularly in diabetic patients.
- π Optimal management of CCS should focus on improving prognosis and quality of life, with renolazine offering a non-inferior approach to revascularization in reducing cardiovascular death.
Q & A
What is the primary focus of the presentation?
-The presentation focuses on optimizing medical therapy for chronic coronary syndromes and discusses why renolazine is a viable option for treating patients with this condition.
Why is angina considered both a symptom and a prognostic marker?
-Angina is considered both a symptom and a prognostic marker because it indicates not only the presence of cardiovascular issues but also an increased risk for future cardiovascular events such as death, myocardial infarction, and hospitalization.
What are some key factors that increase the risk of cardiovascular death in patients with chronic coronary syndrome?
-Key factors that increase the risk include diabetes, history of heart failure, pulmonary disease, peripheral artery disease, and atrial fibrillation.
Why is renolazine considered a useful add-on therapy for angina?
-Renolazine is considered useful as an add-on therapy because it can help reduce the frequency of angina and improve exercise tolerance in patients whose symptoms are not adequately controlled by first-line agents like beta blockers and calcium channel blockers.
What are the recommended starting and maximum doses of renolazine in the Philippines?
-The recommended starting dose of renolazine is 375 mg twice a day, which can be titrated to 500 mg twice a day after 2 to 4 weeks, with a maximum dose of 750 mg twice a day.
How does renolazine help in managing angina without affecting hemodynamic parameters?
-Renolazine helps manage angina by improving diastolic tone and coronary blood flow without affecting heart rate or blood pressure. It acts by inhibiting late sodium channels, reducing sodium and calcium overload in the cells, and improving myocyte metabolic performance.
What evidence supports the use of renolazine as an effective treatment for angina?
-Evidence from various trials, including the CARISA and MERLIN-TIMI 36 trials, supports renolazine's effectiveness. These trials showed significant reductions in angina frequency and nitroglycerin consumption among patients taking renolazine compared to placebo.
How does renolazine benefit patients with diabetes and angina?
-Renolazine benefits diabetic patients by reducing both angina frequency and HbA1c levels, thus improving blood sugar control and angina symptoms simultaneously.
What is the role of individualized therapy in managing chronic coronary syndromes?
-Individualized therapy involves tailoring treatment to each patient's characteristics, comorbidities, and preferences to maximize symptom relief and prevent cardiac events. This approach ensures optimal management of chronic coronary syndromes.
Why is optimal medical therapy emphasized over revascularization for patients with chronic coronary syndrome?
-Optimal medical therapy is emphasized because it is non-inferior to revascularization in decreasing cardiovascular death and should be the primary approach to improve prognosis and quality of life for patients with stable chronic coronary syndrome.
Outlines
π Optimizing Medical Therapy for Chronic Coronary Syndromes
This paragraph provides an overview of the importance of choosing renolyzine as a treatment option for chronic coronary syndrome. It emphasizes the significance of angina as both a symptom and a prognostic marker, citing data from the Clarify registry and the Merlin trial. It explains that angina is linked to poorer prognosis and increased hospitalization costs. The paragraph concludes by introducing renolyzine as an effective add-on therapy to first-line agents like beta blockers and calcium channel blockers, highlighting its benefits and recommended dosages.
π Evidence and Guidelines for Treating Chronic Coronary Syndrome
This paragraph delves into the guidelines for treating patients with chronic coronary syndrome, emphasizing the need for optimal medical treatment before considering revascularization. It discusses the role of beta blockers and calcium channel blockers as first-line agents and the importance of individualizing patient therapy. The paragraph also highlights the benefits of renolyzine as an add-on therapy, particularly for patients with angina who are inadequately controlled with first-line treatments. It stresses the need to consider patient characteristics and comorbidities when selecting treatment options.
π§ͺ Clinical Trials Supporting Renolyzine
This paragraph reviews the clinical trials and evidence supporting the use of renolyzine in patients with angina and chronic coronary syndrome. It mentions the Carissa trial, which showed a significant reduction in angina frequency among patients receiving renolyzine compared to placebo. The paragraph also discusses the benefits of renolyzine in combination with other anti-anginal therapies, noting its positive effects on exercise capacity and angina symptoms. The importance of considering heart rate and blood pressure when prescribing anti-anginal agents is also highlighted.
π Renolyzine for Diabetic Patients with Angina
This paragraph focuses on the use of renolyzine in diabetic patients with angina, highlighting its potential benefits beyond angina relief. It discusses the Teresa trial, which showed a significant reduction in HbA1c levels among diabetic patients receiving renolyzine. The paragraph also explains the possible mechanisms behind renolyzine's glycemic effects, including its impact on pancreatic alpha cells and endothelial function. The importance of considering comorbidities, such as diabetes and peripheral artery disease, when selecting anti-anginal agents is emphasized.
πΌ Cost-Effectiveness and Clinical Outcomes of Renolyzine
This paragraph summarizes the cost-effectiveness and clinical outcomes associated with renolyzine use in patients with stable coronary artery disease. It notes the significant reduction in hospitalization rates and overall healthcare costs for patients taking renolyzine compared to those on beta blockers and calcium channel blockers alone. The paragraph concludes by emphasizing the role of optimal medical therapy in improving prognosis and quality of life for patients with chronic coronary syndrome, highlighting renolyzine's advantages in angina relief and HbA1c reduction.
Mindmap
Keywords
π‘Chronic Coronary Syndrome
π‘Renolazine
π‘Angina
π‘Prognostic Marker
π‘First-line Agents
π‘Beta Blockers
π‘Calcium Channel Blockers
π‘Diabetes
π‘Guideline Recommendations
π‘Hemodynamic Effects
Highlights
Renolyzine is presented as a viable option for treating chronic coronary syndromes.
Angina is identified as both a symptom and a prognostic marker for increased cardiovascular risk.
The Clarify registry data shows that patients with angina have poorer prognosis and greater events.
The MERLIN-TIMI trial links angina frequency to the risk of hospitalization after acute coronary syndrome.
Certain comorbidities like diabetes, heart failure, and pulmonary disease increase cardiovascular risk in chronic coronary syndrome patients.
Renolyzine can be an add-on therapy to first-line agents for better angina control.
Guidelines recommend Renolyzine as a second-line therapy for patients with uncontrolled angina.
The CARISA trial demonstrates Renolyzine's effectiveness in reducing angina frequency in diabetic and non-diabetic patients.
Meta-analysis supports Renolyzine's benefit in reducing weekly angina frequency and nitroglycerin consumption.
Renolyzine's mechanism involves improving diastolic tone, coronary blood flow, and potentially having an anti-arrhythmic effect.
The importance of individualizing therapy based on patient characteristics and preferences is emphasized.
Renolyzine is recommended for patients with contraindications or intolerance to first-line agents.
Diabetic patients may experience angina despite normal coronaries and may benefit from Renolyzine treatment.
Renolyzine has been shown to improve glycemic control, reducing HbA1c levels in diabetic patients.
The Severus meta-analysis supports Renolyzine's benefits in reducing angina and HbA1c levels in patients with diabetes.
Renolyzine is cost-effective, reducing revascularization rates and overall cardiovascular health care costs.
Optimal medical therapy with Renolyzine is non-inferior to revascularization in decreasing cardiovascular death.
Transcripts
optimizing medical
therapy for chronic coronary syndromes
so the following slides will at least
give you a background on the science
on why we should choose renolyzine as an option
or a viable option for the treatment of our patients
with chronic coronary syndrome
so this is just a disclaimer
and a declaration of my conflict interest
so this will be just a short outline of my thought
so I will be discussing to you first
the prevalence of Angelina
ask a symptom and ask a prognostic marker
so in this clarify registry
you can see here that patients were actually look into
know when they have Angena
or those patients with evidence of ischemia
based on non invasive tests
like your stress test and your to the echo
and they found out that those patients who
despite having
or not having ischemic evidence in non invasive tests
may actually present with angina
and those patients with angina have poorer prognosis
or have actually greater events
and those patients who have no symptoms of angina
basically angina is not just a symptom
but also a prognostic marker
that will actually tell us
of a patient with increased risk
for cardiovascular event
whether that's death or non fatal
and fatal myocardial infection
now this result from the Merlin
teeny trial showed that angiena frequency
is also directly related to the risk of pre
hospitalization after an acute coronary syndrome
so patients
who actually have been treated in the hospital
for acute coronary events
may later on experience angina
and those patients with recurrent angina
are also at risk current hospitalization
and that translates to increase cost in the hospital or
um people increase in their health care cost
so patients were actually in the solid bar
or solid line rather who are experiencing daily angina
have actually increased hospitalization rate
and that translates to increase hospitalization cost
now there are also certain capabilities
that may increase the risk of cardiovascular death
among patients with chronic coronary syndrome
and again
that is coming from the data of the clarified registry
so you look at this patients with diabetes
those patients with history of heart failure
or those with pulmonary disease
peripheral artery disease and HL
fibrillation are actually at increased
risk of cardiovascular outcomes
and those without those comradeities
now
why renollazine is an option in the tailored approach
in treating angiena
because renexa can be an add on therapy
in the first line agents that uh
the guidelines has been telling us
if that is actually your data blockers
and Calcium channel blockers
but there has been actually no evidence that um
beta blockers are actually greater in terms of outcome
or better in terms of outcome
compared with the second line options
so but still because these are first line agents
probably because these are uh
this has been available for a long time and uh
trials have been shown that in the past
now this drugs are actually uh
effective in treating angiena
so there they become the first line agent
besides they are also being used as drugs
not for treatment of hypertension and heart failure
so far it's like hitting two birds in one stone
that's why we may consider them as the first line agent
but when you consider an ex up for an add on therapy
in patients with angina
who are in adequately controlled or in polyureate
the first like anti anginal therapies
then we have to start the station on 370
375mg twice a day
and by trade them to 500 mg vid after 2 to 4 weeks
until you reach the maximum dose
in the Philippines of 750 mg
twice a day
now the guidelines as Doctor um
mighty Ramirez has emphasized earlier
has um
relegated rhinolazine or other agents as an add on
or a second line therapy
to reduce the frequency of angina
and improve exercise tolerance
among those stations
whose angina is not controlled with beta blockers
or Calcium channel blockers
or those stations is
can also be given as the first line therapy
if
among our patients who already had contraindications
or with symptoms
and cannot tolerate the first line agents
likewise the American College of cardiology
also recommends rettolazine
in patients who remain symptomatic
despite treatment with data blockers
Calcium channel blockers or long acting nitrates
so they are already guideline recommendations
now because these are recommended by guidelines
let's now take a look at the
evidence
as why guidelines have relegated them as class 1 or 2A
for the treatment of patients with Angelina
so how do we now treat the patients optimally
so the nice guidelines
still recommends that we have to
maximize medical treatment
for patients with chronic coronary syndrome
before revvascularization
and when we say optimal treatment
we consider the patients
symptoms has been satisfactorily controlled
and that there has been prevention of cardiac events
by giving your drugs that prevent secondary events
not like your anti platelets and your anti
or your status no
and we also consider the patients adherents
and minimal adverse events as possible
drug therapies according to uh
the guidelines also suggest that we need to adapt uh
we we should give them to adapt to each patients
characteristics and preferences
so we highlight
that we need to individualize patient therapy
not and occupise medical treatment
by making sure that patient symptoms are relieved
and that we prevent cardiac outcomes
so as I have mentioned earlier
first choice is not necessarily backed up by robbers
evidence as a matter of fact
beta blockers or culture channel blockers
been recommended as First Choice
has no randomized control trials today
when compared with other agents
asks better strategy to an alternative strategy
using your metabolic modulators
when you prescribe them in patients with angiena
so several second
add on antisemic drugs such as your nitrates
your metabolic modulators like a renolyzine
trimetazzidine and to a lesser extent
evaporative for your patients with tachycardia
or those who remains to have heart rate B
at 70 beats per minute may prove beneficial
in combination with a beta blocker
or galcium channel doctor ask your first line therapy
again we look at patients characteristics
so the manalis um diagram has given us
at least
to look at the heart rate and the blood pressure
as possible hemodynamic
paramic is that we need to consider
when we adjust or add on other agents
and we know that retholazine is hemodynamic
um uh
has no hypodynamic effect
nor in terms of heart rate and blood pressure
and its anti antigenal effect
uh acts through improvement in diastolic tone
coronary blood flow
and a potential anti arrhythmic effect
now rethonazine
acts by inhibiting your late sojum channels
by decreasing your sojum overload
and if it acts on that sodium Calcium channels
not it also prevents
or decrease Calcium overload in the cells
or inner vasculature
improving diastolic stiffness of the heart
and improving myocytes metabolic performance
so basically
it improves the diastolic stiffness of the heart
not
and that improves blood flow to your coronary arteries
again
there are certain measures that we need to consider
in patients with angina remember patients with C a
B may present with angina
and some of them may actually have hypertension
and because of procomitant
other diseases may have lower heart rate
or maybe not tolerate to other agents
okay so some of the side effects related to
hypodynamic agents may be
of course edema or headaches
now nitrates data blockers
and Calcium channel blockers
are all hemodynamic agents
affecting your heart rate
systemic blood pressure peripheral vascular assistance
but all of this
anti anginal drug definitely gives symptom relief
however not all have outcome benefits
but has certain recommendations by guidelines
as relegate at
which relegates them as Class 1A
when they are given as first line
or a second line treatment
now we emphasize here that agents such as uranotasim
and trinitazithe are he
would they not depending
neutral agents that gives symptom relief
no and has been recommended by guidelines
so again we emphasize individualizing therapy
and combining treatment for patient with Agina
to improve patients outcomes
and when we say individualized
we consider certain capabilities
for example
of course the presence of diabetes which can be common
a reason why patients may remain to be symptomatic
even despite re vascularization
now we also consider patients hemodynamics
and patient driven outcome
like functional capacity
side effect and cost of treatment
now we look at evidence when a redology has been given
that class 1
recommendation by the European Society of cardiology
and class 2 a by the American Heart Association
so there are a lot of
randomized control trials that back up
the benefit of rethology in patients
with Angelina and Carissa
trial which was done among diabetic
and non diabetic patients
compare the frequency of Argina at week 12
regardless of the diabetes status
among those patients who receive renolazine
and they found out that those patients
who were receiving 750 mg
twice a day of renolazine compared with placebo
actually have significant reduction by at least 42%
which is more pronounced in patients with no diabetes
than those patients with diabetes
and it is meta analysis
of patients with chronic coronary syndrome
involving 9,000 patients with symptoms of angina
who receive renalyzine
as an add on to conventional therapy
and conventional treatment would include beta blockers
Calcium channel blockers and nitrate
have significant reduction in the weekly
engine of frequency
and weekly nitroglycerin consumption
back to just taking those first line agents
without so much effect on their hymodynamic status
they also look at the systematic review
and meta analysis on the different parameters
which is laboratory parameters
not as seen in the exercise time duration
and the time to SD segment
depression in time to and gene
as you can see here
when retholazine was added to beta blockers
and Calcium channel blockers
there were actually better outcomes
compared to those patients who were receiving um uh
beta blockers and Calcium channel blockers
in addition to your long acting nitrates
and this diagnostic test
not also translates to clinical outcome
in such the patients who were on Rethologis
have actually fewer angile frequency and nitrate use
compared to just receiving alchem channel blockers
or beta blockers alone
now when you can see here
the individual effect of each agents
like your evaporine beta blockers
schaltium antagoniste and renolyzine
the addition of renolyzine at 750 mg
twice a day as the maximum dose of your renolyzine
when are dead on top of your baseline uh
therapy for angina
actually resulted in 23% relative risk production
in anti angina uh
in exercise capacity compared to those patients who is
who were receiving the uh
baseline drugs
such as your beta blockers or your Calcium antagonist
I'm sure you remember this light
which Doctor Ramirez has shown earlier
that there
are parameters that we need to take into account
when giving your anti andgenal agents
and that includes your heart rate
and your blood pressure why your heart rate
if the blood pressure remains to be tachycardic
beyond 60 feets per minute
then by no means you can add your evaporating
to lower your heart rate and improve the
the cardiac um outcomes
not of this station not the cardiac demand and supply
and for patients whose blood pressure uh
is beyond hundred twenty systemic millimeters mercury
you can opt to give them your hypodynamic agents
because you know that these drugs
can also affect your blood pressure
later on now
if the patient may remain to be symptomatic
or the patient cannot tolerate the drug
uh like your meta blockers and your nitrates
then you can already give your renolyzine
not if your patient's blood pressure is at
still elevated
or if your heart rate is still increased
then you can add on your evaporative
so
regardless whether your blood pressure is high or low
you can safely add your analyzine
or your trimetacidine ask your metabolic modulators
so
there are important issues when we talk about ischemia
especially among diabetic patients
so there are a lot of patients with diabetes
who are complaining of angina
even if their coronaries are normal
diabetic patients may present with a typical angina
shortness of breath instead of chest pain
they may also worsen with conventional data blockers
and data blockers may even block hypoglycemic symptoms
about patients taking diabetic medications
peripheral artery disease
which is fairly common in patients
be that with diabetes may not actually tolerate some
or the old beta blockers
and they even need non vasodilating beta block
vasodilating beta blockers
and the non vasodilating are types of data blockers
may even be contraindicated
hence in this group of patients
renollazine can still be an option
even as a first flight agent
also with an improved reduction in H d
A1C giving us a potential benefit
even in patients with microvascular dysfunction
and no negative endometabolic effects
so again highlighting this diagram by Doctor Vera
and showing to us
individualizing treatment by looking at patients
characteristics nor and ccommorbidities
and of course
looking into artificial logic mechanism of angina
hence leading us to select the better options of anti
anginal agents depending on the metabolic profile
hemodynamic profile at certain comrbidities
so again example for patients with diabetes
the possible option can be um
giving your retholazine burapamine
evaporating trimetasidine
or your long acting nitrates in some data blockers
making contraindicated in the substance of patients
that's why we consider
other safe agents in this population
so we need to have at least
make sure that we use drugs that have
not only benefit as an anti anginal agent
but may also have an additional benefit
in reducing blood sugar level
so we just show here
the effect of renolyzine
in diabetics with stable angina
as a result of the Teresa trial
wherein they look at subsets of patients with type 2
diabetes and underlying C a
d who were symptomatic
despite treatment with anti anginal agents
and you can see here
that patients who are receiving renolyzine
have actually reduction from baseline
in their mean number of anginal attack per week
and means of lingual nitroglycerine consumption
it also
resulted in a significant reduction in their HVA1C
by almost nearly 1% compared to placebo
so if you have a patient with diabetes
and you want to manage their angina
and you also want or looking for a drop
with significant production in their HVA 1 c
knowing that diabetes control
is also an important risk factor
and target
among patients with chronic coronary syndrome
then maybe adding
or considering renolazine is a wise option
because of the result of this trials
there is also a result uh that comes from the
from the study the Merlin PM thirty six
going to ask a significant reduction in H B
a 1 c compared to those patients with no diabetes
and this is clinically significant
or meaningful reduction in H B
a 1 c among those patients who were certified with
according to diabetes status
and who were receiving red dollars in
so in the Severus meta analysis published in 2,013
looking at the results
of patients who were included in Carissa Merlin
Demetrial
on substance of patients with diabetes
they found out that those patients were taking
retholazine
actually resulted in better anginal reduction
and HVA 1 c reduction as well
and the possible mechanisms of renologous
glycemic effect
is attributed by its effect on the pancreatic
alpha cells reduced
seeing the glucagon release
and also
a significant effect in their endothelial and smooth
muscle cells so
if you can see the effect of sgility to inhibitors
on the isogen channels
not reducing the blood sugar Red Level
the rebologies also significantly reduce isogen uh
channels no
it may affect this as a possible mechanism of its anti
or hip hypoglycemic effect okay
so in addition to that
it also have a good coronary microvascular um
function uh benefit so the clinically uh
the clinical outcomes
not related to the use of renolazine is
there is a significant reduction in recurrence chemia
although it did not achieve the primary
outcome of reduction in cardiovascular death
and MI when compared with placebo
the long term outcomes of renolazine
in patients with refractory angina
based on this trial resulted
significant improvement in their anginal attacks not
and also resulted in fewer hospitalization
due to anginal frequency
and revascularization rates was likewise reduced
which also translates in reduction in overall cost
among patients with stableschemic heart disease
as seen in this real world analysis of hundred
eight thousand patients
with stakeable coronary artery disease
therefore this is also a good um
option in patients who are taking renolyzine
for patients with stable coronary artery disease
and was proven to be cost effective
resulting in less revascularization
and reduction in all costs
in cardiovascular related health care utilization
compared to
those patients were just taking beta blockers
and Calcium channel blockers
or nitrates so
let me end by emphasizing that optimal management
consist of interventions to improve prognosis
and quality of life and for those patients with staple
chronic coronary syndrome
optimal medical therapy is non inferior
thirtyvascularization
in decreasing cardiovascular death
and should be emphasized in the treatment option
for patients with c a B
and this Reno
and renolazine has been proven to be advantageous
in its role in relieving angina
improving quality of life
without effect on hemodynamics
with an additional benefit of reducing HVA1C
and was seen to have a good side effect profile
and cost effective
so thank you very much for your kind attention
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