Transcript Cardiovascular Update - Indiana Pharmacists Alliance

Cardiovascular
Update
Elise McCuiston, PharmD, BC-ADM
IU Health Southern Indiana Physicians
Disclosures
• I have no actual or potential conflicts of
interest to disclose in relation to this
presentation
Objectives
• Briefly review the Institute of Medicine
Report (2011) guideline standards
• Identify modifications in JNC8 and the impact
on hypertension management
• Review the ACC/AHA Blood Cholesterol
Guidelines and related hyperlipidemia
treatment
• Evaluate clinical controversies surrounding
the release of both JNC8 and ACC/AHA Blood
Cholesterol Guidelines
Institute of Medicine Report (2011)- Clinical
Practice Guidelines We Can Trust
• CPGs (clinical practice guidelines) may reduce
inappropriate practice variation, enhance translation
of research to practice, and improve healthcare quality
• Lack of transparency, inconsistent methodology, failure
to seek stakeholder input
• IOM recommended 8 best practice standards for
developing CPGs
http://iom.nationalacademies.org/Reports/2011/Clinical-Practice-Guidelines-We-CanTrust.aspx
Institute of Medicine Report (2011)- Clinical
Practice Guidelines We Can Trust
1.
2.
3.
4.
5.
Establishing transparency
Management of conflicts of interest
Guideline development group composition
Clinical practice guideline- systematic review intersection
Establishing evidence foundations for and rating
strength of recommendations
6. Articulation of recommendations
7. External review
8. Updating
http://iom.nationalacademies.org/Reports/2011/Clinical-Practice-Guidelines-We-CanTrust.aspx
2014 Evidence-Based Guidelines
for the Management of High Blood
Pressure in Adults: JNC 8
Paul A.James,MD1; SuzanneOparil,MD2; Barry L.Carter,PharmD1; William C.Cushman,MD3;
CherylDennison-Himmelfarb,RN, ANP, PhD4; JoelHandler,MD5; Daniel T.Lackland,DrPH6; Michael
L.LeFevre,MD, MSPH7; Thomas D.MacKenzie,MD, MSPH8; OlugbengaOgedegbe,MD, MPH, MS9;
Sidney C.Smith Jr,MD10; Laura P.Svetkey,MD, MHS11; Sandra J.Taler,MD12; Raymond
R.Townsend,MD13; Jackson T.WrightJr,MD, PhD14; Andrew S.Narva,MD15; Eduardo Ortiz,MD,
MPH16,17
JAMA. 2014;311(5):507-520. doi:10.1001/jama.2013.284427.
Question for Audience
Who here has read or are familiar with the new JNC 8
guidelines?
A.
B.
C.
D.
Yes, I use them daily
Yes, I use them occasionally
Somewhat, I am not involved in HTN management
No, JNC what??
Why do we care?
• About 70 million American adults (29%) have high blood
pressure—that’s 1 of every 3 adults.
• Only about half (52%) of people with high blood pressure
have their condition under control.
• Nearly 1 of 3 American adults has prehypertension—blood
pressure numbers that are higher than normal, but not yet
in the high blood pressure range.
• High blood pressure costs the nation $46 billion each year.
This total includes the cost of health care services,
medications to treat high blood pressure, and missed days
of work.
http://www.cdc.gov/bloodpressure/facts.htm
JNC 8
• Consists of 9 recommendations
• Evidence review limited to random controlled trials
(RCT)
• Following 3 questions guided the evidence review:
1. In adults with hypertension, does initiating
antihypertensive pharmacologic therapy at specific BP
thresholds improve health outcomes?
2. In adults with hypertension, does treatment with
antihypertensive pharmacologic therapy to a specified BP
goal lead to improvements in health outcomes?
3. In adults with hypertension, do various antihypertensive
drugs or drug classes differ in comparative benefits and
harms on specific health outcomes?
JNC 8
• Each recommendation is given a strength rating
Grade
Strength of Recommendation
A
Strong Recommendation
B
Moderate Recommendation
C
Weak Recommendation
D
Recommendation against
E
Expert Opinion
N
No recommendation
Old vs. New
Topic
JNC 7
JNC 8
Methodology
Nonsystemic literature
review with range of study
designs
Initial systemic review by
methodologists restricted
to RCT
Definitions
Defined hypertension and
prehypertension
Definitions of hypertension
and prehypertension not
addressed
Treatment Goals
Separate goals for
“uncomplicated”
hypertension and for
subsets with various
comorbid conditions
Similar treatment goals for
all hypertensive
populations except when
evidence review supports
different goals
Lifestyle Recommendations
Based on literature review
and expert opinion
Endorsement of evidencebased Recommendations of
the Lifestyle Work Group
Drug Therapy
5 classes considered for
initial, but thiazide-type
diuretics for most patients
4 classes and doses based
on RCT evidence
JNC 8: Recommendation 1
In the general population aged ≥ 60 years,
initiate pharmacologic treatment to lower
BP at SBP ≥ 150 mmHg or DBP ≥ 90 mmHg
and treat to a goal SBP < 150 mmHg and
goal DBP <90 mmHg.
Strong Recommendation: Grade A
JAMA. 2014;311(5):507-520.
JNC 8: Corollary Recommendation
In the general population aged ≥ 60 years, if
pharmacologic treatment for high BP results
in lower achieved SBP (eg, <140 mmHg) and
treatment is well tolerated and without
adverse effects on health or quality of life,
treatment does not need to be adjusted
Expert Opinion: Grade E
JNC 8: Recommendation 2
In the general population < 60 years, initiate
pharmacologic treatment to lower BP at
DBP ≥ 90 mmHg and treat to a goal DBP <
90 mmHg.
Ages 30-59 years, Strong Recommendation: Grade A
Ages 18-29 years, Expert Opinion: Grade E
JAMA. 2014;311(5):507-520.
JNC 8: Recommendation 3
In the general population <60 years, initiate
pharmacologic treatment to lower BP at SBP
≥ 140 mmHg and treat to a goal SBP <140
mmHg.
Expert Opinion: Grade E
JAMA. 2014;311(5):507-520.
JNC 8: Recommendation 4
In the population aged ≥ 18 years with CKD,
initiate pharmacologic treatment to lower
BP at SBP ≥ 140 mmHg or DBP ≥ 90 mmHg
and treat to goal SBP <140mm Hg and DBP
<90 mmHg.
Expert Opinion: Grade E
JAMA. 2014;311(5):507-520.
JNC 8: Recommendation 5
In the population aged ≥ 18 years with
diabetes, initiate pharmacologic treatment
to lower BP at SBP ≥ 140 mmHg or DBP ≥
90 mmHg and treat to goal SBP < 140 and
DBP < 90.
Expert Opinion: Grade E
JAMA. 2014;311(5):507-520.
JNC 8: Recommendation 6
In the general nonblack population, including
those with diabetes, initial antihypertensive
treatment should include a thiazide-type
diuretic, calcium channel blocker (CCB),
angiotensin-converting enzyme inhibitor
(ACEI), or angiotensin receptor blocker (ARB).
Moderate Recommendation: Grade B
*Note: No Beta Blockers
JAMA. 2014;311(5):507-520.
JNC 8: Recommendation 7
In the general black population, including
those with diabetes, initial antihypertensive
treatment should include a thiazide-type
diuretic or CCB.
General black population, Moderate Recommendation: Grade B
Black patients with diabetes, Weak Recommendation: Grade C
JAMA. 2014;311(5):507-520.
JNC 8: Recommendation 8
In the population aged ≥ 18 years with CKD,
initial (or add-on) antihypertensive
treatment should include an ACEI or ARB to
improve kidney outcomes. This applies to
all CKD patients with hypertension
regardless of race or diabetes status.
Moderate recommendation: Grade B
JAMA. 2014;311(5):507-520.
JNC 8: Recommendation 9
• The main objective of hypertension treatment is to attain and
maintain goal BP.
• If goal BP is not reached within a month of treatment,
increase the dose of the initial drug or add a second drug from
one of the classes in recommendation 6 (thiazide-type
diuretic, CCB, ACEI, or ARB).
• If goal BP cannot be reached with 2 drugs, add and titrate a
third drug from the list.
• May use antihypertensives from other classes if goal BP
cannot be reached using recommended drug classes because
of contraindication or need to use more than 3 drug classes to
reach goal BP
• Do NOT use ACEI and ARB together
JAMA. 2014;311(5):507-520.
JNC 8: Summary
For general population without DM or CKD:
Age ≥ 60 years:
BP goal < 150/90 mmHg
Age <60 years:
BP goal < 140/90 mmHg
JNC 8: Summary
For all ages with DM (no CKD):
BP goal < 140/90 mmHg
For all ages with CKD (with or without DM):
BP goal < 140/90 mmHg
JNC 8: Summary
For all ages and races with CKD
Initiate ACEI or ARB, alone or in combo with
other drug class
JNC 8: Summary
For Black Population
Initiate thiazide-type diuretic or CCB, alone
or in combo with other drug class
JNC 8: Summary
For Nonblack Population
Initiate thiazide-type diuretic or ACEI or ARB
or CCB, alone or in combo
JNC 8: Treatment Algorithm
JNC 8: Treatment Algorithm
The controversy
begins…
JNC 8 Controversy:
BP Recommendation of <150/90 for 60+
Pro
Con
• Less aggressive
treatment of high BP
• Less medication use in
elderly population (less
drug interactions,
adverse events, etc.)
• Possibility of increasing
goal in high risk
population will increase
CVD
• Evidence to increase goal
insufficient
• Could reverse reduction
in CVD rates over past
decades
JNC 8 Controversy:
BP Recommendation of <140/90 for DM
Pro
Con
• Less aggressive
treatment of high BP
• Less medication use in
population with other
comorbidities (less drug
interactions, adverse
events, etc.)
• Possibility of increasing
goal in high risk
population will increase
CVD
• Based on expert opinion,
not RCT evidence
Patient Case: 65 yr old white male
PMH:
DM
HTN
HLD
Pertinent Vitals:
BP 138/75
HR 74
Medications:
Enalapril 10mg daily
Simvastatin 40mg at
bedtime
Fish oil 1000mg twice
daily
Metformin 500mg
twice daily
Patient Case: 65 yr old male
What is the next step you would take to control patient’s
hypertension?
A.
B.
C.
D.
Recommend increasing enalapril to 20mg daily
Recommend adding chlorthalidone 25mg daily
No change, patient at goal
Both A and B
Patient Case: 52 yr old black female
PMH:
HTN
Pertinent Vitals:
BP 155/86
No medications
Patient Case: 52 yr old black female
What is the next step you would take to control patient’s
hypertension?
A. Recommend starting lisinopril 10mg daily
B. Recommend starting metoprolol tartrate 25mg twice
daily
C. Recommend starting hydrochlorothiazide 25mg daily
D. Start lisinopril 10mg daily and losartan 25mg daily
Patient Case: 70 yr old white female
PMH:
HTN
HF
CKD
Pertinent Vitals:
BP 146/90
Medications:
Amlodipine 10mg daily
Metoprolol succinate
100mg daily
Patient Case: 70 yr old white female
What is the next step you would take to control patient’s
hypertension?
A.
B.
C.
D.
No change, patient at goal
Recommend starting lisinopril 10mg daily
Recommend increasing metoprolol succinate dose
Recommend starting spironolactone 25mg daily
Patient Cases
Patients
JNC 7
JNC 8
65 yo white male with DM,
HTN, and HLD. Most
recent BP 138/75.
Currently on enalapril
10mg daily for HTN.
Goal BP < 130/80mmHg
Optimize enalapril dose or
add another drug (diuretic,
ARB, BB, CCB)
Patient at goal.
Continue current therapy.
52 yo black female recently
diagnosed with HTN, BP
155/86. What therapy
should be initiated?
Goal BP < 140/90mmHg
For Stage I HTN without
compelling indications:
start either thiazide-type
diuretic, ACEI, ARB, BB,
CCB, or combination.
Goal BP < 140/90mmHg
For black population, start
thiazide-type diuretic or
CCB.
70 yo white female with
HTN, HF, and CKD. BP
146/90. Currently takes
amlodipine 10mg daily and
metoprolol succinate
100mg daily.
Goal BP < 130/80mmHg
HF: Thiaz, BB, ACEI, ARB,
Aldo ant
CKD: ACEI, ARB
Goal BP < 140/90
For CKD, consider ACEI or
ARB.
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 Task Force on Practice Guidelines
Stone, Neil 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 Task Force on Practice Guidelines.”
Circulation, 85. Web 13 Nov. 2013.
Old vs New
Old Guidelines
• Treat to target LDL
• Use of multiple drug
classes to achieve LDL goal
• Monitor lipids to assess if
at goal
New Guidelines
• Assess cardiovascular risk
• Most benefit from statin
use
• Instead of treating to LDL
target, more important to
start statin dose to reduce
CV risk
• Monitoring only for
tolerability and adherence
to therapy
ATP III- Summary
Risk Category
LDL Goal
LDL Level at Which
to Initiate
Therapeutic
Lifestyle Changes
(TLC)
LDL Level at Which to
Consider Drug Therapy
CHD or CHD Risk
Equivalents* (10-year
risk >20%)
< 100 mg/dL
≥ 100 mg/dL
≥ 130 mg/dL (100-129
mg/dL: drug optional)
2+ Risk Factors** and
10-year risk 10-20%
< 130 mg/dL
≥ 130 mg/dL
≥ 130 mg/dL
2+ Risk Factors ** and
10-year risk < 10%
< 130 mg/dL
≥ 130 mg/dL
≥ 160 mg/dL
0-1 Risk Factor**
< 160 mg/dL
≥ 160 mg/dL
≥ 190 mg/dL (160-189
mg/dL: LDL-lowering
drug optional
*CHD Risk Equivalents: DM, PAD, AAA, CAD
**Risk Factors: Cigarette smoking, Hypertension (BP ≥ 140/90 or on antihypertensives), Low HDL (< 40 mg/dL),
Family History of CHD (male first degree relative <55 years; female first degree relative <65 years), Age (men ≥ 45
years; women ≥ 55 years)
2013 ACC/AHA Guidelines
• Goals:
• Prevent cardiovascular diseases
• Improve the management of people who have these diseases
through professional education and research
• Develop guidelines, standards, and policies that promote optimal
patient care and cardiovascular health
• Reviewed RCTs and systemic reviews and meta-analyses of
RCTs with ASCVD outcomes
• Atherosclerotic cardiovascular disease (ASCVD) defined as:
• Coronary heart disease (CHD)
• Stroke
• Peripheral arterial disease (PAD)
2013 ACC/AHA Guidelines
• Lifestyle as the Foundation for ASCVD RiskReduction Efforts
• Lifestyle modification remains crucial (diet, exercise,
avoiding tobacco, and healthy weight)
• Emphasize before and during treatment
2013 ACC/AHA Guidelines:
4 Major Statin Benefit Groups
Clinical
ASCVD*
LDL-C > 190
mg/dL
DM, 40-75
years, LDL 70190
LDL 70-189
and 10-year
ASCVD risk
> 7.5%
*Clinical ASCVD is defined as acute coronary syndrome, history of MI, stable/unstable angina,
coronary or other revascularization, stroke, TIA, or PAD.
Statin Therapy Intensity
High-Intensity
Statin
% LDL
~50%
reduction
Statin
and dose
ModerateIntensity Statin
Low-Intensity
Statin
~30-50%
<30%
Atorvastatin 40-80mg Atorvastatin 10Rosuvastatin 20-40mg 20mg
Rosuvastatin 5-10mg
Simvastatin 20-40mg
Pravastatin 40-80mg
Lovastatin 40mg
Fluvastatin XL 80mg
Fluvastatin 40mg BID
Pitavastatin 2-4mg
Simvastatin 10mg
Pravastatin 10-20mg
Lovastatin 20mg
Fluvastatin 20-40mg
Pitavastatin 1mg
* Statins and doses in italics indicate doses have been approved by FDA but were not tested in the
RCTs reviewed and boldface indicates evaluation in RCTs and demonstrated reduction in CV events.
ACC/AHA Recommendations
• Treatment Targets
• No recommendation on LDL or HDL targets
• Secondary Prevention
• High intensity statin for anyone age ≤ 75 years (A:
strong)
• Moderate intensity statin if contraindicated (A:
strong)
• For those >75 years, assess risk vs benefit of starting
high intensity or moderate intensity statin and of
continuing statin therapy (E: Expert Opinion)
ACC/AHA Recommendations
• Primary Prevention: age ≥ 21 years with
LDL ≥ 190 mg/dL
• Evaluate for secondary causes of hyperlipidemia for
LDL >190 or TG >500 (B: Moderate)
• High intensity statin regardless of 10-yr ASCVD risk,
or maximally tolerated statin (B: Moderate)
• Intensify statin therapy to achieve a 50% LDL
reduction (E: Expert Opinion)
• May consider adding non statin therapy for further
LDL reduction after maximum benefit from statin is
achieved (E: Expert Opinion)
ACC/AHA Recommendation
• Primary Prevention: DM and LDL 70-189
mg/dL
• Moderate intensity statin should be initiated or
continued for adults 40-75 years with DM (A: Strong)
• High intensity statin reasonable for 10-yr ASCVD risk
≥ 7.5% (E: Expert Opinion)
• Evaluate potential for ASCVD benefits for those with
DM < 40 years of age or >75 years (E: Expert
Opinion)
ACC/AHA Recommendation
• Primary Prevention: without DM and LDL 70189 mg/dL
• Estimate 10-yr ASCVD risk to guide initiation of statin
therapy (E: Expert Opinion)
• 10-yr ASCVD risk ≥ 7.5% treat with moderate-high
intensity statin (A: Strong)
• 10-yr ASCVD risk 5-7.5% reasonable to offer moderate
intensity statin (C: Weak)
• Before starting statin, engage in discussion with patient
regarding risk vs benefit (E: Expert Opinion)
• For those not identified in statin benefit group, or risk is
uncertain, additional factors may be considered (E:
Expert Opinion)
Additional factors to consider
• For individuals who do not fit into 1 of the 4 benefit
groups, the factors listed below may be considered to
make a treatment decision:
• LDL-C ≥160 mg/dL or evidence of genetic hyperlipidemia
• History of premature ASCVD with onset <55 yrs in first degree
male relative or <65 yrs in first degree female relative
• High-sensitivity C-reactive protein ≥2 mg/L
• Coronary artery calcium score ≥300 Agatson units or ≥75
percentile for age, sex, and ethnicity
• Ankle-brachial index <0.9
• Elevated lifetime risk of ASCVD
ACC/AHA Recommendation
• Heart Failure and Hemodialysis
• No recommendation regarding initiation or
discontinuation of statins in patients with NYHA
class II-IV ischemic systolic heart failure or
maintenance hemodialysis (N: No Recommendation)
ASCVD 10 year risk
• Clear net benefit of initiation of moderate-tohigh-intensity statin therapy with a risk of
>7.5%.
• When risk is between 5.0-7.5% there is still
net absolute benefit with moderate intensity
statin – need to discuss with patient the risk
and benefits of treatment.
ASCVD 10 year risk calculator
• http://clincalc.com/Cardiology/ASCVD/PooledCo
hort.aspx
• IPhone App – ASCVD Risk Estimator
•
•
•
•
•
•
•
•
•
Gender
Age
Race
Total cholesterol
HDL-cholesterol
Systolic Blood Pressure
Treatment for Hypertension (Y/N)
Diabetes (Y/N)
Smoker (Y/N)
Limitations of ASCVD Risk
Calculator
• Not used if history of ASCVD or LDL-C >190
mg/dl
• 10-year risk is only calculated for ages 40-79
years
• Lifetime risk is only calculated for ages 20-59
years
• Not accurate for races other than White or
African American
• Total cholesterol between 130 and 320 mg/dL
• HDL between 20 and 100 mg/dL
• SBP between 90 and 200 mmHg
ACC/AHA Statin Initiation
Recommendations
ACC/AHA Statin Initiation
Recommendations, cont.
ACC/AHA Recommendation:
Nonstatin Use
• Before adding nonstatin, reemphasize adherence to
lifestyle changes and statin therapy
• No data supporting routine use of nonstatin drugs +
statin to reduce ASCVD events
• No RCTs assess ASCVD outcomes in statin-intolerant
patients
• May consider in high risk individuals
• ASCVD
• LDL ≥ 190
• DM aged 40-75 years
Monitoring Therapeutic Response and Adherence
ACC/AHA Summary
• No longer treat to a target number
• Now target four focus groups:
•
•
•
•
With clinical ASCVD
LDL-C ≥190 mg/dL
Diabetes aged 40-75
Estimated 10-year ASCVD risk ≥ 7.5%
• Try to treat with maximum tolerated intensity of statin
that is recommended
• Goal of LDL-C reduction by ≥50% with high intensity
therapy or by 30-50% with moderate intensity therapy
• Monitoring is done to assess response and adherence
And the controversy
continues…
ACC/AHA 2013 Cholesterol
Guidelines
Pros
• Fairly clear steps of
identify risk group,
assess need for statin
and intensity
• May help reduce undertreatment
• Less monitoring
necessary
•
•
•
•
•
Cons
What about patients who
can’t tolerate any statins?
Some prefer treat to
target
ASCVD calculator may
overestimate CVD risk
May lead to
overtreatment
May hurt adherence
without routine
monitoring
Patient Case JR: 55 yr old female
PMH:
DM
HTN
Depression
BP 146/84
HR 82 bpm
Pertinent labs:
LDL 134 HDL 51
TG 253
TC 236
Medications:
Metformin 500mg bid
Lisinopril 20mg daily
Amlodipine 10mg daily
Patient Case JR: 55 yr old female
What would be a reasonable next step to help reduce JR’s
CVD risk?
A. Recommend high intensity statin
B. Recommend niacin 500mg twice daily
C. No change patient at goal
D. Recommend low intensity statin
Patient Case JR: 55 yr old female
ASCVD 10
YR RISK
8.4%
F-HAM
ATP III: STATIN
10 YR RISK INDICATED
5%
LDL lowering
therapy, may be
statin
ACC/AHA:
STATIN
INDICATED
Yes
High intensity
Patient Case JR: 76 yr old female
PMH:
DM
HTN
Depression
BP 146/84
HR 82 bpm
Pertinent labs:
LDL 134 HDL 51
TG 253
TC 236
Medications:
Metformin 500mg bid
Lisinopril 20mg daily
Amlodipine 10mg daily
Patient Case JR: 76 yr old female
What would be a reasonable next step to help reduce JR’s
CVD risk?
A. Recommend high intensity statin
B. Recommend niacin 500mg twice daily
C. No change patient at goal
D. Recommend low intensity statin
Patient Case JR: 76 yr old female
ASCVD 10
F-HAM
ATP III: STATIN
YR RISK 10 YR RISK INDICATED
49%
17%
ACC/AHA:
STATIN
INDICATED
LDL lowering
Maybe,
therapy, may be evidence for
statin
>75 yo unclear
Summarize
“… recommendations are not a substitute for clinical
judgment, and decisions about care must carefully
consider and incorporate the clinical characteristics and
circumstances of each individual patient.” from JNC 8
• National guidelines help guide care with evidencebased practice
• Must consider each individual patient and assess risk
vs benefit
Questions