Primary and Secondary Prevention

Anas Obeid, DO Bay Heart and Vascular

LH 50 y/o male with history of HTN presents with

worsening chest pressure 2 days prior he began experiencing flu like symptoms with

sore throat and ear pain No prior h/o CAD Presented to ED after developing chest pain radiating to

his left arm

PMHx: HTN

Social hx: Denies tob/etoh/illicit drugs

Work up Physical exam unremarkable

Initially vitals stable

EKG NSR with ST segment changes suggestive of acute posterior wall infarction

Decompensated in the ED developing unstable rhythm requiring defibrillation

Transferred emergently to cardiac cath lab

Initial EKG

Atheroma

Atheroma

Evolution of Atheroma Macrophage foam cells recruited to the arterial intima

and accumulate lipid particles

Foam cells serve as reservoir for pro-inflammatory mediators Cytokines, chemokines, platelet activating factors Oxidant species (superoxide anion) Promote inflammation and contribute to plaque

progression

Complications of Atheroma Disruption of atherosclerotic plaque leads to acute

thrombosis

Fracture/rupture of the plaque’s fibrous cap Pro-inflammatory cytokines inhibit smooth muscle cells

from producing new collagen to support the plaques fibrous cap

Inflammation threatens the stability of plaques thereby increasing their vulnerability for rupture and thrombosis (leading to ACS)

Risk Factors Modifiable

Smoking Dyslipidemia HTN DM Obesity ETOH Diet Sedentary lifestyle Elevated inflammatory biomarkers

Non-modifiable Age Gender Family History

Primary Prevention Seek to prevent the onset of specific diseases

Altering behaviors/exposures

Medical and surgical interventions

Help reduce the incidence of certain conditions

Primary Prevention Epidemic of atherosclerosis

Populations living longer with improved treatments of communicable diseases and addressing malnutrition

Urbanization has favored atherogenesis Poor diets (high saturated fats) Diminished physical activity

Primary Prevention Preventing coronary heart disease can mitigate

manifestations of atherosclerosis Stroke Peripheral vascular disease HTN DM Cognitive dysfunction Cancer Depression Chronic Conditions

The amount of risk determines the aggressiveness of the intervention.

Assessing Risk Category Estimate 10 year risk of developing atherosclerotic CV

disease

Framingham Score Gender, age, Total Cholesterol, HDL, Systolic BP, HTN

treatment, tob

ACC/AHA CV risk calculator Age, Gender, Race, Total Chol, HDL, Systolic BP, HTN

treatment, tob, DM

Blood Pressure Recommendations to Change Soon?

SPRINT Trial HTN is a leading risk factor for heart disease, stroke,

and kidney failure

Estimated 1 in 3 people in the US has HTN

Randomized over 9000 pts over the age of 50 with SBP > 130 and at least one CV risk factor Patients followed for about 6 years

Intensive BP management of < 120 mmHg systolic vs standard range of < 140 mmHg

SPRINT Outcomes Reduced rates of cardiovascular events and

complications with intensive BP management CHF, MI, CVA reduced by nearly 1/3 Risk of death reduced by ¼

Need to individualize medical regimen to address specific treatment objectives

Question A 62-year-old man with h/o HTN. He has no history of

CHD, but long standing HTN on amlodipine 5 mg and lisinopril 20 mg. He asks you if he should be on a statin

Past Medical History: HTN

10 pack year hx of tobacco

Quit 20 years ago

Question Cont. On ROS, he notes mild cramping in both calves on

steep inclines, but is asymptomatic on his daily 2 mile walk.

BP 122/62 mmHg, HR 72 bpm. He has a I/VI early peaking systolic murmur. Diminished popliteal, DP and PT pulses with no bruits.

Question Cont. EKG NSR with nonspecific abnormalities

Total Chol – 180 mg/dl

LDL – 124 mg/dl

HDL – 32 mg/dl

Triglycerides – 120 mg/dl

Fasting glucose – 105 mg/dl

Which recommendation is most appropriate?

Add chlorthalidone 25 mg PO

Add metformin 500 mg PO

Add niacin 1000 mg PO

Add simvastatin 40 mg PO

No change needed

High Risk! ACC/AHA CV Risk calculator 19.7% 10 year risk of atherosclerotic heart disease

(coronary death, nonfatal MI, fatal or nonfatal stroke)

Framingham Risk calculator 20% estimated 10 year risk of MI or CV death

Which recommendations is most appropriate?

Add chlorthalidone 25 mg PO

Add metformin 500 mg PO

Add niacin 1000 mg PO

Add simvastatin 40 mg PO No change needed

Five CAD Risk Equivalents Primary Prevention

PVD (claudication, ABI 20% 10 year risk

Aortic aneurysm

Symptomatic carotid artery disease (TIA or stroke)

Updated 2013 Guidelines Statin Initiation

Diabetic age >40

Clinical atherosclerotic CV disease

LDL > 190 Familial hypercholesterolemia

Primary prevention Non-diabetic pt with LDL < 190 Greater than 7.5% 10 year risk of of CV disease

PROVE – IT Trial Atorvastatin 80mg vs pravastatin 40mg

24 months study testing hypothesis that lower LDL levels in patients presenting with ACS is associated with reduction of CV events

Primary end points: All cause mortality, MI, USA requiring hospitalization, revascularization requiring PCI/CABG, or stroke

PROVE - IT Final LDL cholesterol levels Pravastatin 40mg – 95 mg/dl Atorvastatin 80mg – 62 mg/dl

Primary composite endpoints at 24 months Pravastatin 26.3% Atorvastatin 22.4% 16% relative risk reduction favoring atorvastatin

Benefit consistent across pre-specificed subgroups

Suggests early intensive lipid lowering therapy with high dose statins is beneficial

JUPITER Trial Cont Rosuvastatin lowered LDL by 50% and CRP by 37% Triglyceride reduction of 17% with statin Baseline LDL reduced from 108 to 55mg/dl Baseline CRP reduced from 4.2 to 1.8mg/L

44% reduction in primary end point associated with statin therapy Nonfatal MI, nonfatal stroke, hospitalization for USA,

revascularization, and cardiovascular death

Statin Safety Profile Slight increase in physician diagnosed DM 270 reports of DM in statin groups vs 216 HgA1c increase of 0.1

For pts with diabetes risk factors, 134 cardiovascular events of deaths were avoided for every 54 new cases of diabetes diagnosed

Secondary Causes of Dyslipidemia

Hypothyroidism

Liver disease

Uncontrolled DM (Increase Triglycerides, Decrease HDL)

Nephrotic Syndrome

Renal insufficiency

Drugs that Cause Dyslipidemia

Androgenic Steroids (Incr LDL, Lower HDL)

Progesterone/Estrogen (increase Trig)

Retinoic Acid (Accutane)

Corticosterioids (Incr LDL, Trig)

Protease Inhibitors

Thiazide diuretics (incr LDL, Trig)

Alternate therapies IMPROVE – IT Trial A Multicenter, Double-Blind, Randomized Study to

Establish the Clinical Benefit and Safety of Vytorin (Ezetimibe/Simvastatin Tablet) vs Simvastatin Monotherapy in High-Risk Subjects Presenting

Patients presenting with Acute Coronary Syndrome

Is There a Role for Zetia? IMPROVE-IT: First trial demonstrating incremental clinical benefit when adding a non-statin agent

(ezetimibe) to statin therapy:

YES: Non-statin lowering LDL-C with ezetimibe

reduces cardiovascular events

YES: Even Lower is Even Better

(achieved mean LDL-C 53 vs. 70 mg/dL at 1 year)

YES: Confirms ezetimibe safety profile

Reaffirms the LDL hypothesis, that reducing

LDL-C prevents cardiovascular events

Results could be considered for future guidelines

LDL Receptor Function and Life Cycle

PCSK9 Regulation of LDL Receptor

Impact of Anti-PCSK9 Antibody

PCSK9 Inhibitors Injectable antibody administered every 2 weeks 2 available formulations Praluent Repatha

Prevent PCSK9 from blocking LDL receptors Reducing circulating LDL cholesterol

PCSK9 Inhibitor for Significant Reduction of LDL in Patients With Clinical ASCVD and

FH Intensive, predictable LDL-C reduction

PCSK9 inhibitor + a statin lowered LDL-C up to 77% more than placebo + statin

PCSK9 inhibitor + a statin helped up to 90% of patients achieve LDL-C < 70 mg/dL

The efficacy and safety profile of PCSK9 inhibitor has been established over 52 weeks Common side effects: nasopharyngitis, back pain, URI

Significant LDL-C lowering in patients with HeFH or HoFH

Primary Prevention Screening

Screening Coronary calcium score

Calcium Scan Cont CT scan intended to detect calcium deposits found in

atherosclerotic plaques within the coronary arteries Evaluate risk of future CV events Limited use. Help further risk stratify patients with

potential risk factors Several limitations What about soft plaque Can lead to further testing What to do with a zero score?

Guidelines

Primary Prevention Screening

Which test is most reasonable for CV risk stratification in primary prevention patients? A resting ECG in asymptomatic adults with

hypertension or diabetes.

Computed tomography (CT) coronary angiography in asymptomatic adults with a family history of premature CHD.

Measures of arterial stiffness in asymptomatic adults with hypertension.

Transthoracic echocardiography in asymptomatic adults at intermediate risk.

Which test is most reasonable for CV risk stratification in primary prevention patients?

A resting ECG in asymptomatic adults with hypertension or diabetes.

Computed tomography (CT) coronary angiography in asymptomatic adults with a family history of premature CHD.

Measures of arterial stiffness in asymptomatic adults with hypertension.

Transthoracic echocardiography in asymptomatic adults at intermediate risk.

Stress Testing Multiple modalities Treadmill EKG Stress echo Dobutamine stress echo Nuclear myocardial perfusion imaging Treadmill Pharmacologic

COURAGE Trial 2287 pts with objective evidence of obstructive CAD

between 1999-2004 PCI + Medical therapy vs medical therapy alone

Stable CAD

No significant difference in composite death, MI, stroke Stable plaque have thick fibrous caps, small lipid cores,

more smooth muscle cells, fewer macrophages, and more collagen

Reduced angina with revascularization

Secondary Prevention Medical Therapies

Beta Blockers

ACE – Inhibitors/ARBs

Aldosterone inhibitors

Anti-platelet therapy

Statins

Antiplatelet Therapy Does aspirin play a role in primary prevention?

Who needs dual antiplatelet therapy Duration of dual therapy

Triple therapy??

Aspirin – secondary prevention

23% reduction in mortality in patients presenting with acute MI

25% reduction in CV events in patients who survived prior occlusive event

Dual Anti-platelet therapy Recommended after MI, ACS, PCI

Bare metal stents vs Drug eluting stents

Duration? Current AHA guidelines suggest 1 year Some studies suggest 3 months may be sufficient Is 30 months superior?

DAPT Trial DAPT trial 30 months of dual anti-platelet therapy perhaps superior to only

12 months of therapy Reduced rate of: MI (2.1% vs 4.1%) Stent Thrombosis (0.4% vs 1.4%) MACE (4.3% vs 5.9%)

Increased risk of moderate to severe bleeding with prolonged therapy (2.5% vs 1.6%)

Increased rate of death from all cause with prolonged therapy (2.0% vs 1.5%) – why?

Elevated risk of stent thrombosis and MI during the 3 months after discontinuation of thienopyridine treatment

Newer Antiplatelet Meds Vorapaxar (Zontivity) Secondary prevention Used in conjunction with aspirin and plavix PAR-1 antagonist Indicated for patients with prior MI or PAD Reduced combined primary endpoint CV death MI Stroke Urgent coronary revascularization