MANAGEMENT OFCHRONIC STABLE ANGINA

DR Suman Mitra

CHAIRPERSON- Dr DipankarGhosh Dastidar

Angina pectoris has been coined from the Greek word “ankhon” and the Latin word “pectus” meaning ‘strangling’ and ‘chest’ respectively.

Typical angina is defined as substernal chest discomfort with a characteristic quality and duration that is(1),provoked by exertion or emotional stress(2) and relieved by rest or nitroglycerin(3).

“Stability” usually implies that “there is no substantial change in symptoms over several weeks(60 days).”

Also includes the stable and often asymptomatic phases following an ACS.

SUPPLY

DEMAND

Reversible episodes of demand and supply mismatch.

Gradation of angina as per ccs scale:

Ischemia cascade:

TREATMENT BACKBONE

1. PATIENT EDUCATION

2. RATIONAL MEDICAL THERAPY

3.REVASCULARISATION

CONSIDERATION

PROPER FOLLOW UP

BASIC BACKBONE TO DIAGNOSIS:

BASIC TESTING:

• Biochemical tests- complete hemogram,lipidprofile(including LDL levels),thyroid profile,LFT,diabetic screening,creatinekinase(in patients on statins).

• Baseline ECG:

• For future comparisons.

• May help diagnosing vasospasm when taken at the time of pain.

• Detection of dyanamic ST segment changes.

• Other inherent abnormalities(lbbb,rbbb,lvh)

• Resting Echocardiography:

• To asses cardiac structure and function.

• May detect rwma even in presence of normal LV function which increases likelihood of CAD.

• May help ruling out AS,HCM as alternative causes of symptoms.

Essential decision making steps:

Pre test probability

Non invasive tests in

intermediate group

Initiation of OMT and

further risk stratification

Pre test probability determination(clinical)

Influenced maximally by age,gender,nature of symptoms

Achievement of management target

Essential non invasive modalities:

• Stress ECG:

• Simplest,elementary,most usefull.

• Performs best in a patient where the pre test probability is around 15-65%.

• Main diagnostic criteria-“horizontal/downsloping ST-segentdepression>0.1mV,persisting for at least 0.06-0.08 after qrs completion in one or more leads.”

• Mean sensitivity 68%,mean specificity 77%.(only valid when the baseline ecg was normal).

• Exercise tsting usually terminated after 85% of age-predicted maximum heart rate is reached.

• Stress Echocardiography(exercise>pharmacolgical stress)- asseseschanges in myocardial thickening compared to baseline.

• Overall sensitivity around 85%.

• Myocardial perfusion imaging:

• SPECT & PET.

• Tc99 is the most commonly used tracer.

• PET is qualitywise better while SPECT is more readily available.

Non invasive tests for coronary anatomy:

Computed tomography

Calcium scoring

CCTA

MRCA

INVASIVE PROCEDURE:

INVASIVE CORONARY ANGIOGRAPHY:

Usually rarely required for establishing the diagnosis in patients of chronic stable angina.

However,it may be indicated in:

o Patients who cannot undergo stress imaging techniques.

o Patients with typical angina and lvef<50%.

o In special professions like pilots for regulatory issues.

o For revascularization issues after risk stratification by non invasive means.

o In patients with very high PTP and clinical constellation suggesting high risk,it can be used as a first line of investigation.

SUSPECTED ISCHEMIC HEART DISEASE(or recent change in the clinical status in a patient

with known IHD)

Ruling out intermediate/high risk UA

Comprehensive clinical assesment of risk,comorbidities,health

status,cardiac medical associated conditions

Recent exercise/cardiac imaging study

Contraindications to stress testing

Previous history of coronary revascularization

resting ecg interpretation

MPI/ECHO without exercise.

PATIENT ABLE TO EXERCISE

Intermediate/high likelihood

PHARM STRESS MPI/ECHO

PHARM STRESS CMR/CC

TA

Interpretable baseline ECG

LOW LIKELIHOOD INTERME

DIATE

INTERMEDIATE TO

HIGH

STANDARD

EXERCISE ECG

STANDARD EXERCISE

ECG

MPI/ECHO with

E/ PHARM

CMR

IF SUGGESTIVE OF HIGH RISK LESION

MEDICAL THERAPY WITH REGULAR MONITORING

MEDICAL THERAPY INITIATION ALONG WITH

REVASCULARIZATION COUNCELLING TO IMPROVE

SURVIVAL

Known patient of stable IHD

Exercising ability? Interpretable

resting ecg?

MPI/Echo with

exerciseOr

Pharmstress CMR

Standard exercise test or MPI/Echo with

exercise

Not able to exercise

Pharm stress MPI/Echo

Pharmstress

CMR/CCTA

DO THE TESTS REVEAL EVIDENCE OF HIGH RISK CORONARY LESIONS?

Consider revascularization to

improve survival

Observe response to medical therapy

Consider revascularisation

monitoring

Known case of stable IHD

Irrespective of ability to exercise

LBBB on ECG

MPI/Echo with exercise

Known stenosis of unclear significance

Intermediate result from functional

testing

PharmMPI/Echo/CMR/CCTA

CCTA

DO THE RESULTS SUGGEST ANY HIGH RISK CORONARY LESION?

Patient Education:

Individualistaion of education plans to optimise care and well being.

Education plan

Medical adherence

Explanation of medical

management

Comprehensive review of therapeutic options

Physical activity encouragement

Self monitoring & adversity awareness

Medical therapy

Risk factor modification

Prevention of adverse

outcomes(MI/DEATH)

Relief of symptoms

OPTIMAL MEDICAL THERAPY

RISK FACTOR MODIFICATION

LIPID MANAGEMENTBLOOD PRESSUREDIABETES MELLITUSBODY WEIGHTPHYSICAL ACTIVITYSMOKINGPSYCHOLOGICAL FACTORS

PREVENTION OF ADVERSE OUTCOMES

ANTI PLATELATE THERAPY

BETA BLOCKERS

RAAS BLOCKADE

THERAPY

INFLUENZA VACCINATION

SYMPTOM CONTROL

ANTI ISCHEMIC MEDICATIONS

BETA BLOCKERS CALCIUM CHANNEL BLOCKERSNITROGLYCERINRANOLAZINEIVABRADINENICORANDILTRIMETAZIDINE

Risk factor modification:

Lipid management: With established CAD,reduction of LDL cholesterol irrespective of pretreatment levels, with statins.

Aggressive management recommended with target levels<70mg/dl.

In CKD stage 3/4/5- treat by reno protective statins.

Aggressive therapy also results in some amount of plaque regression as shown by IVUS.

Diabetes management: Target hbA1c levels < 7.(individualised approach). Target blood pressure is <140/85mm hg.

An ACEI or ARB should always be included in therapy considering the reno protective effects.

Risk factor modification:

Hypertension: Target B.P<140/90 mm hg.(elevated B.P is an independent risk factor for CAD as well as CVA,heart failure and renal failure).

Diet:

saturated fatty acids<10% of total energy intake.

Trans fatty acids<1%.

<5gms per day.

30-45gms of fibre per day.

200 gms of fruits and vegetable each.

Mediterranian diet closely resembles this.

Risk factor modification:

Physical exercise: isometric exercises are contrindicated.

Aerobic/isotonic exercise with the goal of achieving a sustained heart rate of about 70-85% of predicted heart rate atleast 3-4 times a week.(30 mins per session)

Definte mortality reduction value in all category of patients viz prior h/o MI,CABG,PCI or chronic stable angina.

ADVERSE EVENT PREVENTION

Aspirin (75mg) is the recommended therapy in chronic stable angina

(unless C/I). It reduces death,MI,stroke not only in high risk patients

but also in stable angina patients without previous h/o MI.

Clopidogrel is used as a second line drug in case of aspirin allergy or

C/I or adverse reactions.

Dual therapy with aspirin(75mg) and Clopidogrel(75mg) indicated

only in certain high risk patients.

DAPT- 1 month in BMS implant.

DAPT- At least 12 months in DES.

Long duration DAPT only in high risk groups (CHARISMA Trial).

ADVERSE EVENT PREVENTION…contd

Beta blockers- At least 3 yrs( if h/o MI or ACS,with

normal left ventricular function.

To be used in all patients with LV dysfunctin(EF<40%)

With heart failure or prior MI.

(carvedilol,metoprolol,bisoprolol reduce mortality)

RAAS BLOCKADE- ACEI indicated in all patients with

stable disease having comorbidities in the form of DM,

hypertension,LVEF<40% or CKD(unless contraindicated).

Symptom control and relief: anti-anginals

BETA BLOCKERS

CALCIUM CHANNEL BLOCKERS

NITROGLYCERIN

RANOLAZINE

IVABRADINE

NICORANDIL

TRIMETAZIDINE

Beta Blockers:

• Reduces rate,contractility,Atrioventricular

conduction,ectopic activity.

• May increase perfusion in ischemic areas by increasing

diastolic time and increasing vascular resistance in non-

ischemic areas.

• Prognostic benefit in patients post MI or heart failure.

• 30% risk reduction of death and adverse CV outcome in

post MI patients.

• Clearly effective in controlling exercise induced

angina,improving exercise capacity and limiting both

symptomatic/asymptomatic episodes.

Beta Blockers….contd

• Usually chosen based upon cardioselectivity,lipid

solubility,mode of excreation and dosing frequency.

• Atenolol,metoprolol,nebivolol,bisoprolol most widely

used.(doses?)

• Use metoprolol/carvedilol in renal compromise.

• Avoid combination with non dihydropyridine calcium

channel blockers.

Role of nitrates:

Nitrates act as arterial and veno dialators and decrease preload,which forms basis of symptomatic relief in patients.

Redistribute blood to the ischemic subendocardium.

Sublingual nitroglycerin (0.3-0.6mg) every 5 mins till subsidence of pain or maximum dose of 1.2 mg has been taken within 15 minutes.

Nitroglycerin spray actually acts even more rapidly.

Can be used prophylactically.

Isosorbide dinitrate(5mg sublingual) helps abort an attack for 1 hour(longer duration protection) but its onset > nitroglycerin.(owing to hepatic conversion).

Longer acting nitrates act as 2nd line to Beta Blockers in

symptom control.

Ineffective if used over longer periods(nitrate free interval

warranted).

Single dose>multiple dosing(Trial proven).

Single/dual dosing of mononitrates are adequate to provide

good antianginal coverage.

Tolerance is the main headache.

Never combine with PDE5 INHIBITORS!

CALCIUM CHANNEL BLOCKERS:

Act by vasodialation and decreasing peripheral vascular resistance.

Dihydropyridines(greater vascular selectivity) and Non

Dihydropyridines(heart rate lowering agents).

Metoprolol vs Verapamil similar anti anginal effects.

Atenolol vs Verapamil fewer new diabetes and anginal attacks

with verapamil.

Diltiazem has a better safety profile and can be used with equal

effectiveness as verapamil.

Non dihydropyridines should never be combined with the Beta

Blockers.

CALCIUM CHANNEL BLOCKERS….contd

Dihydropyridines

Long acting Nifedepine

•Powerfull vasodialtor

•Few side effects

•ACTION Trial proved it

to be safe in stable CAD

and it reduces the need

for angiography and CV

interventions.

Amlodepine

•Effective once-a-day anti-anginal and anti-hypertensive due to its long half life and tolerability.•Amlodepine>atenolol in reduction of exercise induced angina.•In a 24 month trial,in a patient of CAD with normal blood pressure,amlodepine reduces risk of CV events.

Symptom control and relief:…(CONTD)

Ranolazine- usually a 2nd line anti anginal agent that can be combined with Beta

blockers as and when required.(ADD ON THERAPY in patients of stable angina inadequately

controlled on the 1st line agents).

Acts by inhibiting late sodium entry selectively into cytosol and hence prevents sodium-

dependent calcium accumulation.

Has anti-ischemic and metabolic properties,reduces diastolic stiffness,improves diastolic

flow, reduces frequency of anginal attacks(proved in the MERLIN Trial),increases exercise

tolerance, time to ST changes on treadmill tests.

TERISA study proved the utility of adding this agent to other well established anti anginals

in patients with elevted HbA1c levels.

Usual dose of 500-2000mg/day(without changes in BP/H.R.

QT prolongation may be hazardous.

Newer agents:

IVABRADINE:

Heart rate lowering agent acting through selective inhibition of sinus node pacemaking currents without any effects on BP or inotropism.(it reduces myocardial o2 demands).

EMA approved for use in patients inadequately controlled or intolerant to Beta Blocker therapy.

Acts best at heart rates>60/min.

Ivabradine=atenolon=amlodepine(in patients with CAD).

Adding ivabradine at a dose of 7.5 mg twice daily to atenololtherapy gave better control of heart rate and angina control.

The BEAUTIFUL Trial on ivabradine proved its efficacy in reducing composite endpoint of death, MI and hospitalisation due to MI in patients with angina and heart rates>70/min.

Nicorandil:

Can be used both for long term treatment as well as prevention of angina.

May be added after Beta Blockers and CCBs.

Opens ATP-sensitive potassium channels in vascular smooth muscles and dialates the epicardial blood vessels.

In the IONA(impact of nicorandil on angina)study it significantly reduced adverse CV events.

Long term use may lead to plaque stabilisation in patients with chronic stable angina.

Trimetazidine- anti-ischemic metabolic modulator drug.

Has got non-mechanical anti-ischemic properties.

No change in heart rate or rate-pressure product at rest or at

peak exercise.

Usual dose of 35 mg twice daily.

Contraindicated in parkinsonism and motion disorders.

Has positive effect on HbA1c and glycemic control.

Has not been evaluated yet on large scale studies in patients

with SCAD.

Persistant symptoms despite OMT

Consideration of revascularisation to improve symptoms

Potential for revascularisation

After assesingcomorbidities

and patient preferences

Coronary angiography

“heart team”opinion

Lesions correlated with evidence of ischemia

CABG/PCI along with ongoing medications

medical therapy with carefull monitoring

Depending on definite factors

High risk lesions on non invasive testing

Assesment of comorbidities and

patient preferences

Potential revasularisationwarranted

Angiography performed

Positive “heart team” opinion about anatomy /clinical factors

Optimal revascularisation

procedure determination

AnatomyPatient preferencesClinical factorsLocal resources

Continue ongoing medical therapy

Continue ongoing medical therapy

Revascularization exploration:

HEART TEAM APPROACH

TO IMPROVE SURVIVAL

HYBRID CORONARY

REVASCULARIZATION

DAPT COMPLIANCE

TO IMPROVE SYMPTOMS

Revascularization exploration….CONTD

CLASS 1 Recommendations to improve prognosis/survival:

“Heart team” approach for unprotected left main disease,in diabetics, in multivesseldisease(2/3 vessel disease),comorbidities.

Left main coronary stenosis>50%

Proximal LAD stenosis>50%

2/3 vessel disease with impaired LV function/heart failure.

>50% stenosis in single remaining vessel

Proven large area of ishchemia(>10% of LV).

:

WHERE NOT TO DO?

PCI should not be done in stable patients with

significant(>50% stenosis) of unprotected left main coronary

artery who have unfavourable anatomy for PCI or are good

CABG candidates.

PCI/CABG not to be done with sole intent to improve survival

in patients with SIHD with:

1 or more coronary stenosis,not anatomically/functionally

significant(<70% in a non-left main coronary artery

stenosis,FFR>0.8,No/mild ischemia on non invasive testing)

Involve only left circumflex or right coronary artery or subtend

a small portion of viable myocardium.

Revascularization exploration….CONTD

CLASS 1 Recommendations for improving symptoms:

All class 1 Recommendations for survival improvement,PLUS,

Any significant stenosis with limiting symptoms or symptoms not controlled with OMT.

Multivessel disease(2/3) with features of CHF or compromised LV is not a CLASS 1 recommendation in symptom improvement.

Where not to do?

In patients who do not meet anatomic(>50% of

left main coronary artery stenosis or >70% of non

left main coronary artery stenosis) or

physiological(eg- FFR criteria) for revasculariztion.

PCI with stenting(BMS/DES) should not be done

in a patient who is not likely to comply to the

DAPT for the necessary duration depending on

the type of stent employed.

OMT

CABGPCI

DILEMMA PERSONIFIED?????????????

Who answers??

Trials?

OMT vs CABG:

CABG>OMT(survival advantage) at 3 years in left main/3 vessel CAD.(Veterans affairs cooperative study,CASS,European coronary surgery study).

CABG>OMT (in terms of less subsequent MI,need for revascularization,cardiacdeath)in a 10yr follow up.(MASS2 Trial).

BARI 2D Trial ( though excluded patients with left main LAD,Included very small fraction with prox left main LAD,or with LVEF<50%) could not show superiority of OMT+CABG>OMT alone.

OMT vs PCI:Survival advantage of PCI over OMT could

not be demonstrated.( BARI 2D and COURAGE Trial)- 2 MOST contemporary trials). (????)

RCTs failed to show that PCI reduces risk of death or MI in patients without recent ACS!

TO summarise,PCI compared to OMT,

• Reduces angina incidence

• Dose not improve survival

• May increase short term MI risk

• Doesn’t lower long term MI risk.

Potential causes of lack of benefit of PCI over OMT:

RELATIVELY BENIGN

PROGNOSIS OF SIHD

OMT IMPROVES ENDOTHELIAL

FUNCTION AND PLAQUE STABILITY

FUTURE CULPRIT LESIONS ARE MOSTLY NON OBSTRUCTIVE

PERIPROCEDURAL MI WITH PCI

EEFECT OF COLLATERALS

CABG vs PCI : SYNTAX(SYNergy between PCI with TAXus

and cardiac surgery) has been a landmark trial comparing efficacy of CABG with PCI.

Also led to fomulation of SYNTAX SCORE which acts as a surrogate marker for extent of CAD and its complexity.(based on location of lesion,its complexity and severity).

SYNTAX SCORE>32 depicts high risk critical lesion.

SYNTAX STUDY randomly assigned around 1800 patients to DES PCI vs CABG.

CABG vs PCI….contd..

At 3 years, the rate of MACE(death,MI,stroke,repeat revascularization) and repeat revascularization were significantly higher in the PCI group!

The rates of death and stroke were similar,but MI and repeat revascularization were significantly lower in CABG group.

In patients with intermediate(22-32) or high(>32) SYNTAX scores,the MACE was increased in patients undergoing PCI.

Outcomes comparable in relatively uncomplicated CAD whereas CABG>PCI(EFFICACY) in cases of complex and diffuse CAD.

Follow up of patients:

At least periodic follow up anually to asses clinical

function,symptoms,surveillance for heart failure and arrythmias.

Monitoring of cardiac risk factors and ensuring adherence to

recommended lifestyle changes and medical therapy.

Standard exercise ECG recommended in know patients of stable disease

who have new/worsening symptoms not consistent with UA,and have

modest physical activity,no comorbidity and interpretable ECG.(Go for

exercise nuclear MPI/ECHO if ECG cant be interpreted at baseline).

Patients with worsening symptoms but incapable of exercise are advised

pharmacological stress imaging with MPI/ECHO or CMR(2nd option).

Take Home Message:

Patient education,knowledge,awareness and rationality on the part

of the physician are essential for management of chronic stable

angina.

Risk stratification is essential with either non invasive stress testing

or imaging studies to formulate management plan.

OMT forms a cornerstone of therapy.

OMT refractory stable angina warrants evaluation by invasive

angiography and formulation of revascularization plans.

Revascularization procedures have their own set of pros and cons.

Pragmatic selection of procedure is the key to succsfull treatment

………thank you