Katrina Brogden CCU pharmacist FSH

Katrina Brogden

CCU pharmacist

FSH

Mr PW 64yr old admitted with NSTEMI

PMH – diabetes, hypertension, ex-smoker, PCI (2006), hypercholesterolemia

Previous medications:

Metoprolol 25mg morning

Atorvastatin 40mg morning

Empagliflozin/Linagliptin 25/5mg

morning

Metformin 1000mg morning

Mr PW Had angiogram and received a DES to the proximal

LAD

Medications on discharge 2/7 later:

Aspirin 100mg morning

Ticagrelor 90mg twice a day

Metoprolol 25mg twice a day

Ramipril 2.5mg morning


Diabetes medications unchanged

Mr PW So what are the recommended doses we should use?

What do the guidelines say?

Should we titrate the doses? And how/when can this occur?

What factors will affect our ability to titrate (either up or down)?

What observations are we aiming for?

Antiplatelet - Aspirin Inhibits cyclo-oxygenase pathway which inhibits

platelet activation

300mg load, then 100mg daily

Reduces coronary disease by 25%

Lifelong in most patients, particularly with stents

Consider enteric coated options in patients with GI concerns

Clopidogrel

PY12 inhibitor which provides platelet inhibition leading to a reduction in ischaemic events

300-600mg load, then 75mg daily

Prodrug – converted to active metabolite via the liver

Available in a combination tablet with Aspirin

Clopidogrel For at least 12 months in DES patients, but may be

longer in high risk patients

May cause a widespread red, itchy rash

Patient resistance is possible due to genetic variability in liver enzymes

Ticagrelor Same action as clopidogrel, PY12 inhibitor

180mg load then 90mg twice a day

For at least 12 months in DES patients

Common ADRs:

dyspnoea (10-15%)

bradycardia (5%)

switch to clopidogrel and re-load if these occur

Triple therapy Mr PW had an admission 2 weeks after d/c for new onset

AF. Started on Apixaban 5mg twice a day.

What do we do with his antiplatelets?

Most evidence says triple therapy should only be used for the shortest period of time possible.

Usually 1-3 months (although sometimes 6 months), then stop either the aspirin or clopidogrel (if the anti-coag can’t be stopped)

Usually change to clopidogrel

Use PPI cover (ie pantoprazole) for length of triple therapy

ACE inhibitors Ramipril/Perindopril etc

Block the Angiotensin Converting Enzyme (ACE) involved in the renin-angiotensin-aldosterone system

Used in ACS to reduce myocardial injury, to stabilize blood pressure and reduce risk of MI (30% risk reduction)

Starting doses are very varied, although usually start low and go slow. Ramipril starting doses 1.25-2.5mg daily in ACEi naïve

patients

Perindopril 2.5-5mg daily

ACE inhibitors Guideline doses are up to 10mg daily of Ramipril or

Perindopril with the ‘as tolerated’ caveat

When can we up-titrate?

High or unstable blood pressure (aiming for resting SBP<110)

LV impairment/reduced ejection fraction

Diabetic patients

Unstable heart failure symptoms

ACE Inhibitors

When do we need to down titrate

Dizzy/lightheaded on getting up

Recurrent falls

Low BP and patient is symptomatic

Increased creatinine or potassium

May need to stop if dry cough occurs (15%)

Try splitting dose to help increase tolerance

ARBs Irbesartan/Candesartan/Olmesartan/Valsartan etc

Angiotensin receptor blocker

Used in ACS only when a patient can’t tolerate ACEi

No trials in ACS patients

Same concerns for up/down titration, but shouldn’t cause a cough

ACEi/ARBs and COVID-19 No evidence of any correlation

No increased risk of death associated with the use of ARB/ACEi in trial of 8910 patients

Beta Blockers Metoprolol/Bisoprolol/Atenolol etc

Block Beta 1 receptors in heart and peripheral arteries

Used in ACS to reduce heart rate, decrease myocardial oxygen consumption and reduce risk of MI. They have also shown a 23% reduction in all cause mortality.

Starting doses are varied, although usually start fairly low unless patients are already on beta blockers or other heart rate medications

Beta blockers Metoprolol

Should be twice a day dosing

25-50mg BD up to max of 100mg BD

Bisoprolol

Once a day, but dose may be BD to increase tolerance

1.25mg daily, up to 10mg daily (guideline recommendations)

Atenolol

25-50mg daily (max 100mg daily)

Good if patients have disturbed dreams/hallucinations as it doesn’t cross the blood-brain-barrier

Beta blockers When can we up-titrate?

Increased HR (aiming for resting rate around 60)

Irregular heart rhythms

Reduced ejection fraction

Ongoing angina

Residual ischaemia

Beta blockers When do we need to down titrate?

Increased SOB

Bradycardia (if no PPM) and patient is symptomatic

Lethargy/weakness

Acute HF/cardiogenic shock – they need to be withheld

May need to split doses to increase tolerance

If no LV impairment or ongoing angina, the beta blocker may be stopped at 12 months.

Statins Rosuvastatin/Atorvastatin

HMG CoA reductase inhibitors which lower the plasma cholesterol concentration

Used to reduce plaque build-up in arteries and stabilise plaque against artery walls

Guidelines recommend to aim for:

Total cholesterol <4.0

LDL <1.8

Triglycerides <2.0

Statins Increase to maximum dose in acute setting

Can cause up to 50% reduction in LDL (diet alone can only provide 10% reduction)

Recommended doses:

Atorvastatin 40mg or 80mg daily

Rosuvastatin 20mg or 40mg daily

Statins Up titrate when

LDL remains >1.8

New event on statin

Plaque rupture causing MI

Significant CAD

Down titrate Increased LFTs

Patient tolerance (muscle aches)

Some is better than none – maybe use alternate day dosing

Other cholesterol agents Ezetimibe

Good to lower LDL after maximum statin trialled

Many combinations with statins available

Fenofibrate Good for high triglycerides

Evolocumab Fortnightly injection

Used if maximum doses of statins and ezetimibe trialled and LDL remains elevated

Recommended in familial hypercholesterolemia

What are the recommended guideline doses?

Aspirin 100mg daily

Ticagrelor 90mg twice daily

Clopidogrel 75mg daily

Perindopril/Ramipril 5-10mg daily

Metoprolol 25-50mg twice daily

Statin 40-80mg daily

Mr PW Admission meds Discharge meds

Metoprolol 25mg morning


Empagliflozin/Linagliptin 25/5mg morning

Metformin 1000mg morning







Mr PW Can you identify the changes made?

Can you think about why we might have made these changes?

Do Mr PW’s meds follow guideline recommendations?

Mr PW – changes made and reasons for change Increased metoprolol to BD as not effective once daily

(short half life)

Increased statin as LDL 2.2 and patient has had a new ACS event

Added DAPT for DES (incl. restarting Aspirin – which should be lifelong for him)

Added ACEi at a low dose as BP 130/78

Diabetic meds remained the same, HbA1c was 7.2%

Do the changes follow guidelines? Mr PW Guidelines







Aspirin 100mg daily

Ticagrelor 90mg twice daily

Clopidogrel 75mg daily

Perindopril/Ramipril 5-10mg daily

Metoprolol 25-50mg twice daily

Statin 40-80mg daily

Mr PW 8 weeks after d/c You see him in clinic 8 weeks after his hospital stay.

His BP is 145/91, HR at rest 67.

He states he has been taking his medications since discharge.






Mr PW 8 weeks after d/c Would you titrate any of his medications?

Would you like to know a few things before changing his medications?

What other questions would you ask the patient?

Mr PW post d/c questions Has he had any BP readings done since d/c?

How is he actually taking his medications (does he have his medication list to show you?)

Did he get new scripts from the GP/pharmacy?

How has he been feeling since d/c?

Any symptoms of dizziness/lightheadedness/lethargy? (or other side effects relating to the medications)

Risks of non-adherence Inappropriate dose escalation (with potential for

harm)

Increased cardiac events +/- CV mortality

Repeat presentations to hospital (some registry data suggests 64% of readmissions is related to medication non-adherence)

Increased decompensations in heart failure

Increased symptoms of ACS

Risks of non-adherence

Poor adherence to medications in patients with stable coronary artery disease is associated with

10-40% increased risk of cardiovascular admissions

10-30% increased risk of coronary interventions

50-80% increased risk of cardiovascular mortality

Thakkar JB, Chow CK. Adherence to secondary prevention therapies in acute coronary syndrome. MJA 2014;201 (10):S106-S109

Non-adherence readmissions: Patient stopped DAPT 10 days ago for a surgical procedure,

wasn’t sure when/if to restart. Presented with USA and required new stent

Patient who had stent 10 months ago stopped second antiplatelet as couldn’t afford it until next pay. 3 days later presented with a STEMI and was restented.

Patient travelling for work from Sydney and forgot his meds, presented after 3 days with USA.

Patient living 30km out of Collie and his car broke down, so couldn’t get his script filled. Stopped all medications and presented to hospital one week later (mate drove him) with stenosis of his stent.

How prevalent is non-adherence? Most studies of ACS medications report around 60-

70% compliance

Some registries in Canada report that only 78% of patients filled an ACS script within 120 days of an MI and at 2 years only 36% were still

getting scripts dispensed

Reasons for non-adherence Lack of understanding of CAD

Not believing/understanding evidence for medication

Beliefs of friends/family or culture

Expectation of ADRs

Dr Google

Financial issues

Forgetting doses

Fasting for procedure

Don’t want to take medications

Reasons for non-adherence Travelling

Depression or other mental health diseases

Busy

Moved house/suburb

Lost the scripts

Too many tablets

Felt well

‘names change all the time’ – use of generics by pharmacies

Overcoming non-adherence Knowledge about CAD, what the medications are for

and the risks of not taking them

Ensuring counselling and information is provided in a format the patient can read/understand

Provision of the 1st month supply from the hospital on d/c

Cardiac rehabilitation groups/classes

Team approach to patient care

Higher doses split to last longer

Dosing once a day to increase compliance

Overcoming non-adherence Setting alarms/family reminders for dosing times

Updating patient lists when changes are made

Following days of the week on the pill packet

Mark off doses in a calendar

Poly pills/combinations

Use of Dose aids

Use of phone apps/text messages

Overcoming non-adherence A good medication reconciliation during hospital

admission

Communication with other prescribers/healthcare providers

Regular review of medications and removal of any that are no longer required

Enrolment of patients in the CTG program

Use 0f patient focussed medication information leaflets

Webster® pack Packed by local pharmacy in 1 or 2 week supply (or

sachet of 1 month in a long roll)

One pack instead of multiple packs of medications

Labelled with days of the week and times of the day

Warning of scripts running out

Consistent list of medications

$3-8/week for service

Dosette Box Readily available

Lots of different sizes

Pack once a week

Easy for travel

Phone apps MHML – heart foundation

Pharmacy app

My Heart My Life App

Manage and search for medicines

List the dose and frequency of medicines and set reminders to take them

Record and monitor health information such as weight, blood pressure and cholesterol

Learn about heart attack warning signs and what to do.

Search recipes to find healthier meals.

Missing doses Try not to miss doses

Better to miss than double up

If ever unsure/can’t remember – miss and take the next scheduled dose

Doubling up of doses can cause increased risk of ADRs or admissions to hospital

Mrs LC 46yr old female

Admitted with ACS May 2020

Brought her meds to hospital:

Aspirin/Clopidogrel 100/75mg morning

Ramipril 5mg morning

Atorvastatin 80mg night

Metformin/Sitagliptin 1000/50mg BD

Amlodipine 5mg morning

Gliclazide 120mg morning

Mrs LC Patient had all her usual medications charted and was

prepared for an angiogram.

A couple of hours after morning medications, Mrs LC suddenly dropped her BP, felt dizzy and nauseous.

What could be the cause??

Pharmacist did a medication reconciliation the day after her admission and discovered the patient’s boxes/bottles were all dispensed in January 2020!

Mrs LC On further questioning by the pharmacist:

Patient admitted to only taking the medications occasionally

She had issues with the costs of the medications

There were too many for her to remember

She felt well

She isn’t too sure of what they are for

Mrs LC Had an angiogram and received a new DES.

Agreed to take tablets as she didn’t ‘want to come back to this place or have that pain again’

Her medications were simplified to a once daily regimen and combined where possible.

She was given a new medication list and had the pharmacist write what each was for and explain the rationale for use after her stent.

Mrs LC Admission meds D/C meds

Clopidogrel 75mg morning


Atorvastatin 80mg night

Metformin/Sitagliptin 1000/50mg BD

Amlodipine 5mg morning

Gliclazide 120mg morning

Aspirin/Clopidogrel 100/75mg morning

Metformin XR 1000mg morning

Empagliflozin 25mg morning

Rosuvastatin 40mg morning


Atenolol 25mg morning

Mr PW post d/c Has he had an BP readings

done since d/c? How is he actually taking his

medications (does he have his medication list to show you?)

Did he get new scripts from the GP/pharmacy?

How has he been feeling since d/c?

Any symptoms of dizziness/lightheadedness/lethargy? (or other side effects relating to the medications)

No

Yes he has the list in his phone

Yes, although he missed a few days of some of them as he couldn’t get to the pharmacy

Dizzy when he gets up sometimes

Some muscle aches at night

Questions What should we recommend to Mr PW?

Check BP regularly, pharmacy can provide this for free

Reminders about taking the medications regularly, setting an alarm on his phone etc

Move Ramipril to night to see if dizziness settles and consider up titration of the dose next visit depending on his BP readings

Magnesium for muscle aches as first line (before altering statin dose)

Mr LH 64yr old known heart failure patient who is admitted

in cardiogenic shock

Admission meds

Sacubitril/valsartan (Entresto®) 24/26mg morning

Bisoprolol 2.5mg morning

Apixaban 5mg twice daily

Spironolactone 25mg morning

Furosemide 40mg morning


Entresto® Sacubitril/Valsartan (neprilysin inhibitor and ARB)

Used to decrease HF mortality, admissions and progression

Trial doses recommend 97/103mg twice daily

DO NOT use with ACEi (should have 36-48 hour wash out when swapping), but must have trialled ACEi or ARB first

Start with lowest dose and increase slowly

Common for causing dizziness and a fall in BP

Can cause hyperkalaemia and renal dysfunction

Entresto® Up titrate:

High BP

Regular HF admissions/decompensations

Down titrate:

Low BP

Dizziness or syncope

Hyperkalaemia

Worsening renal function

Spironolactone/Eplerenone Aldosterone Antagonists to help cardiac remodelling

Reduce HF mortality

Usually 12.5-50mg daily

Eplerenone is used only if patients have had recent MI

Spironolactone may cause galactorrhea or breast development in males

Watch for hyperkalaemia, increased creatinine

Spironolactone/Eplerenone up titrate when patients have more frequent HF

admissions or decompensations if:

BP can tolerate AND

Renal function remains stable

Down titrate if:

BP low and patient symptomatic

Renal function deterioration

Hyperkalaemia

Intolerance to side effects

Nitrates Used for symptomatic relief only (no mortality

benefit)

Short acting option is Nitrolingual® Spray

No dose titration, should be 1-2 doses over 10 mins then call an ambulance

Can drop BP and cause dizziness

Long acting option isosorbide mononitrate tablets (30-120mg daily) or glyceryl trinitrate patches (5-15mg daily)

Needs a nitrate free period (minimum 8 hours a day)

Nitrates Up titrate

Increasing angina symptoms

Increased BP

Increased nocturnal dyspnoea

Down titrate Low BP

Headache

Dizziness

No change to angina symptoms

Caution with other meds effecting BP – sildenafil etc

Diuretics Symptomatic relief, no mortality benefits To decrease fluid overload/SOB/ankle oedema Up-titrate

Increasing weight Increased SOB/inability to lay flat etc.

Down titrate: Dehydration Low BP Increased creatinine Rapid weight reduction

Patient’s often self titrate based on their fluid intake/daily weight

Mr LH Admission meds

Discharge meds

Bisoprolol 2.5mg morning

Sacubitril/valsartan (Entresto®) 24/26mg morning

Apixaban 5mg twice daily

Spironolactone 25mg morning

Furosemide 40mg morning


Bisoprolol 1.25mg twice daily

Entresto® 24/26mg twice daily

Spironolactone 12.5mg morning

Glyceryl trinitrate 5mg patch (on at night, off in the morning)

Apixaban 2.5mg twice a day


How do we involve the patient? Reporting symptoms – what do we want to know?

Does something cause them dizziness/light headedness?

Do they have to stop ADLs for any reason?

What are their weights? Is this changing?

When did they have a BP check?

Do they feel palpitations?

Do they have angina?

Are they having issues taking/remembering their medications?

What are “normal” obs? There are NO normal obs

What is normal for this patient?

What can a patient actually tolerate without symptoms?

In general we try to aim for:

SBP <110

Resting HR in 60s

Titration tips Try not to look at the numbers – look at the clinical

picture

Check adherence to medications before changing anything

Is the patient symptomatic?

Are they able to perform ADLs?

Treat the CV disease and not the number

References National Heart Foundation ACS guidelines

Non adherence to cardiovascular medications, EurHeartJ 2014

Cardiovasc Disease, Drug Therapy and Mortality in Covid -19, NEJM 1st May 2020

Heart Foundation website

FSH cardiac rehab talk and pharmacy department

Documents

Katrina Brogden CCU pharmacist FSH