Transcript Journal Club - Physician assistant

New 2013 ACC/AHA Guidelines on
Treatment of Blood Cholesterol to Reduce
Atherosclerotic Cardiovascular Risk in
Adults
John Raymond MS, PA-C, MHP
February 7, 2015
There are no longer treatment targets for LDL or
non-HDL
• This is a huge change for patients and providers.
• No longer treat to target
• Doesn’t fit in well with “know your numbers.”
• Goal is no longer “lower is better.”
Four Major Statin Benefit Groups
1) Individuals with clinical ASCVD
2) Individuals with LDL >190
3) Individuals with dm, 40-75 yo with LDL 70-189 and without
clinical ASCVD
4) Individuals without clinical ASCVD or dm with LDL 70-189
and estimated 10-year ASCVD risk >7.5%
Don’t Forget Healthy Lifestyle
• Healthy diet
• Regular exercise
• No tobacco
• Maintain healthy weight
2013 ACC/AHA/NHLBI Guideline on Lifestyle for CVD
Prevention
• Eat a dietary pattern that is rich in fruit, vegetables, whole grains, fish, lowfat dairy, lean poultry, nuts, legumes, and nontropical vegetable oils
consistent with a Mediterranean or DASH-type diet.
• Restrict consumption of saturated fats, trans fats, sweets, sugarsweetened beverages, and sodium.
• Engage in aerobic physical activity of moderate to vigorous intensity
lasting 40 minutes per session three to four times per week
1. Patients with clinical ASCVD
• Defined by the inclusion criteria for the secondary prevention
statin RCT
• Coronary artery disease or peripheral artery disease
• Acute coronary syndromes
• Coronary or other arterial revascularization
• Stroke or TIA
• PVD presumed to be atherosclerotic
Identifying ASCVD
•
•
•
•
•
•
This could be identified in several ways
Heart catheterization
Q waves on ECG
TEE
Coronary CTA
Noninvasive testing including, carotid duplex, upper or lower
extremity arterial duplex
• Peripheral angiography
Dosing Statins
2. LDL greater than 190 mg/dl
• This is one of the few times level of cholesterol mentioned in
the guidelines
• These are patients with familial hyperlipidema
• They deserve special consideration
• Often start with untreated LDL of 325-400 mg/dl
3. Patients with diabetes, age 40-75 years
• All have indication for statin
• Level of intensity of statin treatment depends on calculated 10
year risk.
http://clincalc.com/Cardiology/ASCVD/PooledCohort.aspx
Diabetics aged 40-75 yoa
• Diabetics with > 7.5% 10 year risk get high intensity statin
therapy
• Diabetics with < 7.5% 10 year risk of CAD get moderate
intensity statin therapy
• Statin indicated in all patients with diabetes
4. Age 40-75 years that do not meet above criteria, but
have a 10 year risk of >7.5 %
• 10 year and lifetime risk as determined by CV Risk Calculator
• Specifically designed for this trial
• Downloadable on AHA or ACC site
• Not without controversy, as the calculator has never before
been published or validated
Non-statin therapies
• For hyperlipidemia, non statin therapies, alone or in combination with statins, do not
provide acceptable risk reduction benefits compared to adverse effects.
• These include:
– Zetia
– Fibrates
– Fish oil
– Niacin
• For the most part, these should be avoided with few exceptions
STATIN Safety recommendations
• conditions that could predispose pts to statin side effect:
o Impaired renal or hepatic function
o History of previous statin intolerance or muscle disorder
o Age >75
o Unexplained ALT elevation > 3x ULN
o History of hemorrhagic stroke
o Asian ancestry
STATIN Safety recommendations
• Select the appropriate dose
• Keep potential Side effects and drug-drug interaction In mind
(grade A)
• If high or moderate intensity statin not tolerated, use the
maximum tolerated dose instead
What is your patient cannot tolerate statin due to
muscle weakness?
• Readdress lifestyle issues
• Decrease the dose of statin
• Try another statin
• Check vitamin D levels and replace
• Evaluate for other conditions that may cause muscle weakness
Consider CoQ 10 at greater than 200 mg daily
Summary
• No longer use targets for cholesterol levels
• Identify patients at risk
• Know the 4 high risk groups
• Use medications proven to reduce risk, ie statins
• Encourage healthy lifestyle
• Understand that questions and concerns remain
Case 1
50 year old white female
• Total cholesterol 180
• HDL: 50
• SBP: 130
• taking anti-hTN meds
• +diabetic
• +smoker
• Calculated 10 yr ASCVD: 9.8%
Dosing Statins
Case 2
22 yo white male
• LDL: 195
• SBP: 120
• Not taking anti-hTN meds
• Non-diabetic
• Non-smoker
Dosing Statins
IMProved Reduction of Outcomes:
Vytorin Efficacy International 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
With Acute Coronary Syndrome
Study Design
Patients stabilized post ACS ≤ 10 days:
*3.2mM
**2.6mM
LDL-C 50–125*mg/dL (or 50–100**mg/dL if prior lipid-lowering Rx)
Standard Medical & Interventional Therapy
N=18,144
Simvastatin
40 mg
Uptitrated to
Simva 80 mg
if LDL-C > 79
(adapted per
FDA label 2011)
Ezetimibe / Simvastatin
10 / 40 mg
Follow-up Visit Day 30, every 4 months
90% power to detect
~9% difference
Duration: Minimum 2 ½-year follow-up (at least 5250 events)
Primary Endpoint: CV death, MI, hospital admission for UA,
coronary revascularization (≥ 30 days after randomization), or stroke
Cannon CP AHJ 2008;156:826-32; Califf RM NEJM 2009;361:712-7; Blazing MA AHJ 2014;168:205-12
LDL-C and Lipid Changes
1 Yr Mean
LDL-C
TC
TG
HDL
hsCRP
Simva
69.9
145.1
137.1
48.1
3.8
EZ/Simva
53.2
125.8
120.4
48.7
3.3
Δ in mg/dL
-16.7
-19.3
-16.7
+0.6
-0.5
Median Time avg
69.5 vs. 53.7 mg/dL
Primary Endpoint — ITT
Cardiovascular death, MI, documented unstable angina requiring rehospitalization, coronary
revascularization (≥30 days), or stroke
HR 0.936 CI (0.887, 0.988)
p=0.016
Simva — 34.7%
2742 events
NNT= 50
EZ/Simva — 32.7%
2572 events
7-year event rates
Major Pre-specified
Subgroups
Simva†
EZ/Simva†
Male
Female
34.9
34.0
33.3
31.0
Age < 65 years
Age ≥ 65 years
30.8
39.9
29.9
36.4
No diabetes
Diabetes
30.8
45.5
30.2
40.0
Prior LLT
No prior LLT
43.4
30.0
40.7
28.6
LDL-C > 95 mg/dl
LDL-C ≤ 95 mg/dl
31.2
38.4
29.6
36.0
*
0.7
1.0
Ezetimibe/Simva
Better
1.3
Simva
Better
†7-year
event rates
*p-interaction = 0.023, otherwise > 0.05
Conclusions
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
Hypertension
2014 Guidelines for Management of
High Blood Pressure in Adults (JNC 8)
 John Raymond MS, PA-C, MHP
 February 7, 2015
Hypertension
 Hypertension is the most common condition in
primary care.
 1 in 3 patients have hypertension according to NHLBI
 Risk factor for MI, CVA, ARF, death
What is the goal BP?
Joint National Committee (JNC)
 Panel appointed by the National Heart,
Lung, and Blood Institute (NHLBI)
 First guidelines (JNC-1) published in 1977
 Subsequent updates published in 3- to 6year intervals
 Last edition (JNC-7) published in 2003
Chobanian AV et al. JAMA 2003;289:2560-72.
Development of JNC-8
And then we wait…and wait…
JNC 8
 2014 Evidence-Based Guidelines for the
Management of High Blood Pressure in Adults
 JAMA. 2014;311(5):507-520
 December 18, 2013
JNC 8: Hypertension Management
Questions Guiding Review
 In adults with HTN:
Does initiating antihypertensive pharmacologic therapy at
specific BP thresholds improve health outcomes?
2. Does treatment with antihypertensive pharmacologic therapy to
a specified goal lead to improvements in health outcomes?
3. Do various antihypertensive drugs or drug classes differ in
comparative benefits and harms on specific health outcomes?
1.
BP goal in the elderly
Hypertension in the Elderly
 Fastest growing segment of the population
 Prevalence of hypertension is very high
 Several issues make managing HTN unique:
 Often present with isolated systolic HTN
 More likely to present with comorbidities
 Many clinical trials in HTN have excluded these patients (particularly
for those 80 years and older)
 Elderly are more susceptible to certain adverse effects (orthostatic
hypotension)
JNC-8 Recommendations
 In patients >60 years of age, start medications at blood
pressure of >150/90mm Hg and treat to goal of
<150/90mm Hg
 In patients >60 years of age, treatment does not need to be
adjusted if achieved blood pressure is lower than goal and
well-tolerated
James PA et al. JAMA 2014;311:507-20.
JNC-8 Recommendations
 In patients <60 years of age, start medications at blood
pressure of >140/90mm Hg and treat to goal of
<140/90mm Hg
 In all adult patients with diabetes or chronic kidney
disease, start medications at blood pressure of >140/90mm
Hg and treat to goal of <140/90mm Hg
James PA et al. JAMA 2014;311:507-20.
JNC-8 Recommendations
 For the non-black population (including diabetes), initial
antihypertensive treatment may include a thiazide, ACEI, ARB,
or CCB
 For the black population (including diabetes), initial
antihypertensive treatment should include a thiazide or CCB
 For all patients with CKD, initial (or add-on) therapy for
hypertension should include an ACEI or ARB
James PA et al. JAMA 2014;311:507-20.
JNC8: Treatment Strategies
 If goal BP not met after 1 month of treatment:
 Increase dose of initial drug, or
 Add a second drug (Thiazide, CCB, ACEi, or ARB)
 If goal BP not met with 2 medications:
 Add and titrate a third medication (Thiazide, CCB, ACEi, or ARB)
 Do not use ACE and ARB together
 Other classes may be used in the following scenarios:
 Goal BP not met with 3 medications
 Contraindication to thiazide, ACE/ARB, or CCB
Case 1
62 year old AA male
• Total cholesterol: 140
• Low HDL: 35
• SBP: 130 mmHg
• Not taking anti-hypertensive medications
• Non-diabetic
• Non-smoker
• Calculated 10 yr risk of ASCVD : 9.1%
Dosing Statins
Case 3
48 yo white female
• Total cholesterol 180
• HDL: 55
• SBP: 130
• Not taking anti-hTN meds
• +diabetic
• Non-smoker
• Calculated 10 yr risk ASCVD : 1.8%
Dosing Statins
Case 5
66 yo white female
• High Total cholesterol: 230
• HDL: 55
• SBP: 150
• taking anti-hTN meds
• Non-diabetic
• Non-smoker
• Calculated 10 yr risk of ASCVD : 2.0 %
Strategies to Dose Antihypertensive
Drugs
 Titrate to max dose, then add a second drug
 Add a second drug before achieving max dose of the
initial drug
 Start with 2 drugs at the same time
 If SBP ≥ 160mmHg and/or DBP ≥ 100 mmHg
 If SBP ≥ 20mmHg above goal and/or DBP ≥
10mmHg above goal.
CV Death, Non-fatal MI,
or Non-fatal Stroke
HR 0.90 CI (0.84, 0.97)
p=0.003
NNT= 56
Simva — 22.2%
1704 events
EZ/Simva — 20.4%
1544 events
7-year event rates
Safety — ITT
No statistically significant differences in cancer or muscle- or
gallbladder-related events
Simva
n=9077
%
EZ/Simva
n=9067
%
p
ALT and/or AST≥3x ULN
2.3
2.5
0.43
Cholecystectomy
1.5
1.5
0.96
Gallbladder-related AEs
3.5
3.1
0.10
Rhabdomyolysis*
0.2
0.1
0.37
Myopathy*
0.1
0.2
0.32
Rhabdo, myopathy, myalgia with CK elevation*
0.6
0.6
0.64
Cancer* (7-yr KM %)
10.2
10.2
0.57
* Adjudicated by Clinical Events Committee
% = n/N for the trial duration
Baseline Characteristics
Simvastatin
(N=9077)
%
EZ/Simva
(N=9067)
%
Age (years)
64
64
Female
24
25
Diabetes
27
27
MI prior to index ACS
21
21
STEMI / NSTEMI / UA
29 / 47 / 24
29 / 47 / 24
Days post ACS to rand (IQR)
5 (3, 8)
5 (3, 8)
Cath / PCI for ACS event
88 / 70
88 / 70
35
36
95 (79, 110)
95 (79,110)
Prior lipid Rx
LDL-C at ACS event (mg/dL, IQR)
Overview
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NHLBI
ACC/AHA
First new guidelines since ATP III guideline update in 2004
Review the most important statements or changes presented in these guidelines
– No longer have therapeutic targets
– New risk calculator
– Use medications proven to reduce risk, ie statins
– Avoid medications or supplements that may lower the cholesterol number, but have no data to
decrease CV risk
This guideline focuses on treatments to reduce ASCVD events
Not a comprehensive approach to lipid management
Finally, review questions and controversies that have arisen since publication.