Prescribing for Cardiovascular Conditions

Andy McLachlan,

NP Cardiology azmclachlan@middlemore.co.nz

Cardiology NP Counties Manukau Health

Self care support

Adherence

ABC - smoking cessation

Green prescription

Healthy eating support

Psychological support

Shared decision making “no decision about me, without me”

Non pharmacological interventions

Non adherence to medications is common and under recognised

Less than 75% of people prescribed antihypertensive medication are still using treatment after 6 months.

After acute myocardial infarction

hospitalization almost ¼ patients did not fill their cardiac medications by day 7 of discharge.

Jackevicius 2008 Circulation.

Non-adherence to cardioprotective medications increased risk of cardiovascular hospitalizations (10% to 40%) and mortality (50% to 80%)

Non-adherence causes ~30% to 50%

of treatment failures and 125,000 deaths annually

Non-adherence to statins

increased relative risk for mortality (~12% to 25%)

Ho 2009, Circulation; Edmondson 2013, Br J of Health Psychology; George & Shalansky 2006, Br J Clin Phar

Intentional non-adherence to medication

lack of information about the advantages and disadvantages of the treatment;

the benefits of treatment are not obviously apparent and;

the psychological adaptation required to see oneself as in need of treatment.

Elwyn G, Edwards A, Britten N, "Doing prescribing": how doctors can be more effective. British Medical Journal 2003; 327: 864-867.

…..not lacking in guidance…..

2014, The New Zealand Guidelines for Helping People to Stop Smoking 2014, ACC/AHA/AATS/PCNA/SCAI/STS focused update of the guideline for the diagnosis and management of patients with stable

ischemic heart disease 2014, AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease 2014, AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: 2013 AHA/ACC Guideline on Lifestyle Management to Reduce Cardiovascular Risk 2013, NZ CVD risk assessment update 2013, AHA/ACC/TOS Guideline for the Management of Overweight and Obesity in Adults 2013, ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction 2013, ACC/AHA Guideline on the Assessment of Cardiovascular Risk 2013, ACCF/AHA Guideline for the Management of Heart Failure 2012, ACCF/AHA Focused Update of the Guideline for the Management of Patients With Unstable Angina/Non–ST-Elevation

Myocardial Infarction 2012, Non ST-Elevation Acute Coronary Syndrome Guidelines Group and the New Zealand Branch of the Cardiac Society of Australia

and New Zealand 2012, ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012, Primary care Handbook 2011, Guidelines for the prevention, detection and management of chronic heart failure in Australia 2011 Addendum to the National Heart Foundation of Australia/Cardiac Society of Australia and New Zealand Guidelines for the

Management of Acute Coronary Syndromes (ACS) 2006 2009, NZ Guidelines on weight loss, adults 2002. NZGG. Cardiac rehabilitation guideline

Aspirin Statin *Blood pressure

Thiazide Calcium Channel Blocker ACE/ ARB Beta blocker

Managing CVD risk

* The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA 2002;

Aspirin

Aspirin- Primary prevention

Important trials Antithrombotic Trialists Collaboration. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet. 2009; 373(9678); 1849-60 Effect of aspirin on vascular and nonvascular outcomes: meta-analysis of randomized controlled trials.AUSeshasai SR, Wijesuriya S, Sivakumaran R, Nethercott S, Erqou S, Sattar N, Ray KK. Arch Intern Med. 2012;172(3):209

Up to date

Antiplatelet therapy for people with combined CVD risk >20% but without established cardiovascular disease

Aspirin can be considered taking into account harms and benefits

Aspirin not generally recommended for people with a risk < 20%

NZ CVD update 2013

New Zealand

“I don't even agree with my wife 100% of the time”

Statins for prevention

Dr Roger Blumenthal (Johns Hopkins Medical Institute, Baltimore, MD), who was not part of the writing committee, said he agreed with 90% of the information in the new guidelines

….on the basis of randomized, controlled clinical trials showing that the benefit of treatment outweighed the risk of adverse events. Individuals with clinical atherosclerotic cardiovascular disease.

LDL-cholesterol levels >(4.9), such as those with familial hypercholesterolemia. diabetes aged 40 to 75 years old with LDL-cholesterol levels between (1.8) and (4.9) and

without evidence of atherosclerotic cardiovascular disease. without evidence of cardiovascular disease or diabetes but who have LDL-cholesterol

levels between 1.8 and 4.9 and a 10-year risk of atherosclerotic cardiovascular disease >7.5%.

US Guidelines (2013)

Stone NJ, Robinson J, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: A report of the American College of Cardiology/American Heart Association. J Am Coll Cardiol 2013. Circulation 2013

Statin treatment

Offer atorvastatin 20 mg for the primary prevention of cardiovascular disease to people who have a 10% or greater 10-year risk of developing cardiovascular disease

For people 85 years or older consider atorvastatin 20 mg as statins may be of benefit in reducing the risk of non-fatal myocardial infarction.

Be aware of factors that may make treatment inappropriate

UK guidelines (2014)

NICE (2014) Lipid modification therapy for preventing cardiovascular disease

"We're talking about giving drugs to people who are very well, many of whom will not benefit and may be harmed by the

medication”

"surprisingly aggressive“

Prof Norm Sharpe NHF

5-year combined CVD risk between 10% and 20 % if the shared decision is to initiate a statin, start with a moderate LDL-lowering dose (atorvastatin 20mg)

NZ Updated Guidelines (2013)

……simply no evidence from randomized, controlled clinical trials to support treatment to a specific target.

…..new guidelines make no recommendations for specific LDL-cholesterol or non-HDL targets for the primary and secondary prevention of atherosclerotic cardiovascular disease

LDL targets

Clear statement on non statin lipid lowering therapies

(NICE 2014)

Do not routinely offer fibrates and do not offer nicotinic acid (niacin), a bile acid sequestrant (anion exchange resin) or omega-3 fatty acid compounds for the prevention of cardiovascular disease

…..no evidence that omega-3 fatty acid compounds help to prevent

cardiovascular disease. Do not offer the combination of a bile acid sequestrant (anion exchange

resin), fibrate, nicotinic acid or omega-3 fatty acid compound with a statin for the primary or secondary prevention of cardiovascular disease.

Do not offer coenzyme Q10 or vitamin D to increase adherence to statin treatment.

Ezetemibe

“none of the studies have shown that ezetimibe reduced heart attack, stroke or death. …ezetimibe should only be used as a last resort for patients who can't tolerate other drugs, and possibly not even then. …ezetimibe is overpromoted and overprescribed”…………..

Kastelein JJ, Akdim F, Stroes ES

et al.; ENHANCE Investigators: Simvastatin with or without ezetimibe in familial hypercholesterolemia. N. Engl. J. Med. 358, 1431–1443 (2008).

IMPROVE-IT: Examining

Outcomes in Subjects With Acute Coronary Syndrome: Vytorin (Ezetimibe/Simvastatin) vs Simvastatin

AIM High and HPS2-THRIVE

….results demonstrated that the addition of niacin to a statin-containing regimen did not improve cardiovascular outcomes.

…..the niacin arm experienced greater levels of hyperglycemia, diabetes and, concerningly, infectious complications.

The HPS2-THRIVE Collaborative Group "Effects of extended-release niacin with laropiprant in high-risk patients" N Engl J Med 2014;

371: 203-212.

Anderson TJ, et al "Safety profile of extended-release niacin in the AIM-HIGH trial" N Engl J Med 2014; 371: 288-290.

Niacin

Fibrates

Cardiac Rehab

Dual antiplatelet Asprin

Ticagrelor

High dose statin

ACE inhibitor

Beta Blockers

Managing risk after ACS

Aspirin – secondary prevention

Antiplatelet therapy, significantly reduced the relative risk of subsequent vascular events (nonfatal MI, nonfatal stroke, and vascular death) by approximately 22 %. • 36 vascular events per 1000 patients with a prior MI treated for 27 months; • 38 events per 1000 patients with an acute MI treated for one month, • 36 events per 1000 patients with a previous stroke or TIA treated for 29 months, • 9 events per 1000 patients with an acute stroke treated for 0.7 months, • and 22 events per 1000 patients with other high-risk features treated for 22 months. • 1 in 400 harmed by bleeding

Antithrombotic Trialists' Collaboration’s meta-analyses (2009)

Platelet Inhibition and Patient Outcomes (PLATO) trial Dual antiplatelet treatment with ticagrelor

and aspirin = lower risk of ischaemic events and death when compared to clopidogrel and aspirin

Special authority Twice daily continued for 12 months. No dose reduction is required for older

patients or patients with renal or mild hepatic impairment.

Ticagrelor

Statins – secondary prevention

CTT Collaborators. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90 056 participants in 14 randomised trials of statins. Lancet. 2005; 366: 1267-1278.

Early landmark studies

High-dose intensive statin therapy significantly reduces incident CV outcomes.

…..benefit was observed in both individuals with stable CAD as well as those with a recent acute coronary event - is likely to be independent of concomitant treatment and, in the post-ACS scenario, it may be attributable at least in part to the non lipid-lowering (pleiotropic) effects of statins, such as decreased inflammation

Cannon CP, Steinberg BA, Murphy SA, Mega JL, Braunwald E: Meta-analysis of

cardiovascular outcomes trials comparing intensive versus moderate statin therapy. J. Am. Coll. Cardiol. 48(3),438-445 (2006).

Statin dose after ACS-High better….

How often to check lipid levels (LDL)?

Monitoring liver function tests with statin use?

Monitoring creatine kinase (CK) is not required in those who are asymptomatic.

Check CK for unexplained muscle pain, tenderness or weakness.

What about statin side effects?

Heart failure

Ace inhibitors

SOLVD

Beta Blocker

COMET

+/- Spironolactone

EPHESUS

Heart failure

Rate Control Beta Blocker Calcium Channel Blocker Digoxin Amiodarone

Rhythm control Anticoagulation

CHADS2Vasc vs Bleeding risk Warfarin vs Dabigitran

Atrial Fibrillation

Dabigitran

RELY (2009) NEJM

As compared with warfarin, the 110-mg dose of dabigatran was associated with similar rates of stroke and systemic embolism and lower rates of major hemorrhage; the 150-mg dose of dabigatran was associated with lower rates of stroke and systemic embolism but with a similar rate of major haemorrhage.