Cardiovascular Update Elise McCuiston, PharmD, BC-ADM IU Health Southern Indiana Physicians
Jan 02, 2016
Cardiovascular UpdateElise McCuiston, PharmD, BC-ADMIU 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-Can-Trust.aspx
Institute of Medicine Report (2011)- Clinical Practice Guidelines We Can Trust
1. Establishing transparency2. Management of conflicts of interest3. Guideline development group composition4. Clinical practice guideline- systematic review intersection5. Establishing evidence foundations for and rating
strength of recommendations6. Articulation of recommendations7. External review8. Updating
http://iom.nationalacademies.org/Reports/2011/Clinical-Practice-Guidelines-We-Can-Trust.aspx
2014 Evidence-Based Guidelines for the Management of High Blood Pressure in Adults: JNC 8
Paul A. James, MD1; Suzanne Oparil, MD2; Barry L. Carter, PharmD1; William C. Cushman, MD3; Cheryl Dennison-Himmelfarb, RN, ANP, PhD4; Joel Handler, MD5; Daniel T. Lackland, DrPH6; Michael L. LeFevre, MD, MSPH7; Thomas D. MacKenzie, MD, MSPH8; Olugbenga Ogedegbe, MD, MPH, MS9; Sidney C. Smith Jr, MD10; Laura P. Svetkey, MD, MHS11; Sandra J. Taler, MD12; Raymond R. Townsend, MD13; Jackson T. Wright Jr, 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. Yes, I use them dailyB. Yes, I use them occasionallyC. Somewhat, I am not involved in HTN managementD. 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
Topic JNC 7 JNC 8Methodology 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 evidence-based 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
Old vs. New
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 AAges 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 BBlack 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 togetherJAMA. 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• Less aggressive
treatment of high BP• Less medication use in
elderly population (less drug interactions, adverse events, etc.)
Con• 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• Less aggressive
treatment of high BP• Less medication use in
population with other comorbidities (less drug interactions, adverse events, etc.)
Con• 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:DMHTNHLD
Pertinent Vitals:BP 138/75HR 74
Medications:Enalapril 10mg dailySimvastatin 40mg at bedtimeFish oil 1000mg twice dailyMetformin 500mg twice daily
Patient Case: 65 yr old male
What is the next step you would take to control patient’s hypertension?
A. Recommend increasing enalapril to 20mg dailyB. Recommend adding chlorthalidone 25mg dailyC. No change, patient at goalD. 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 dailyB. Recommend starting metoprolol tartrate 25mg twice
dailyC. Recommend starting hydrochlorothiazide 25mg dailyD. Start lisinopril 10mg daily and losartan 25mg daily
Patient Case: 70 yr old white female
PMH:HTNHFCKD
Pertinent Vitals:BP 146/90
Medications:Amlodipine 10mg dailyMetoprolol succinate 100mg daily
Patient Case: 70 yr old white female
What is the next step you would take to control patient’s hypertension?
A. No change, patient at goalB. Recommend starting lisinopril 10mg dailyC. Recommend increasing metoprolol succinate doseD. Recommend starting spironolactone 25mg daily
Patient CasesPatients 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 < 130/80mmHgOptimize 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 < 140/90mmHgFor Stage I HTN without compelling indications: start either thiazide-type diuretic, ACEI, ARB, BB, CCB, or combination.
Goal BP < 140/90mmHgFor 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 < 130/80mmHgHF: Thiaz, BB, ACEI, ARB, Aldo antCKD: ACEI, ARB
Goal BP < 140/90For CKD, consider ACEI or ARB.
2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in AdultsA 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- SummaryRisk 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)
http://www.nhlbi.nih.gov/guidelines/cholesterol/atglance.pdf
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 Risk-Reduction 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 70-
190
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 IntensityHigh-Intensity Statin
Moderate-Intensity Statin
Low-Intensity Statin
% LDL reduction
~50% ~30-50% <30%
Statin and dose
Atorvastatin 40-80mgRosuvastatin 20-40mg
Atorvastatin 10-20mgRosuvastatin 5-10mgSimvastatin 20-40mgPravastatin 40-80mgLovastatin 40mgFluvastatin XL 80mgFluvastatin 40mg BIDPitavastatin 2-4mg
Simvastatin 10mgPravastatin 10-20mgLovastatin 20mgFluvastatin 20-40mgPitavastatin 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 70-189 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-to-
high-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.
• http://clincalc.com/Cardiology/ASCVD/PooledCohort.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)
ASCVD 10 year risk calculator
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 under-
treatment• 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 HTNDepression
BP 146/84HR 82 bpm
Pertinent labs:LDL 134 HDL 51TG 253 TC 236
Medications:Metformin 500mg bidLisinopril 20mg dailyAmlodipine 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 statinB. Recommend niacin 500mg twice dailyC. No change patient at goalD. Recommend low intensity statin
Patient Case JR: 55 yr old female
ASCVD 10 YR RISK
F-HAM10 YR RISK
ATP III: STATIN INDICATED
ACC/AHA: STATIN INDICATED
8.4% 5% LDL lowering therapy, may be statin
Yes
High intensity
Patient Case JR: 76 yr old female
PMH:DM HTNDepression
BP 146/84HR 82 bpm
Pertinent labs:LDL 134 HDL 51TG 253 TC 236
Medications:Metformin 500mg bidLisinopril 20mg dailyAmlodipine 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 statinB. Recommend niacin 500mg twice dailyC. No change patient at goalD. Recommend low intensity statin
Patient Case JR: 76 yr old female
ASCVD 10 YR RISK
F-HAM10 YR RISK
ATP III: STATIN INDICATED
ACC/AHA: STATIN INDICATED
49% 17% LDL lowering therapy, may be statin
Maybe, evidence for >75 yo unclear
Summarize
“… recommendations are not a substitute for clinicaljudgment, and decisions about care must carefullyconsider and incorporate the clinical characteristics andcircumstances of each individual patient.” from JNC 8
• National guidelines help guide care with evidence-based practice• Must consider each individual patient and assess risk
vs benefit
Questions