1. John Raymond MS, PA-C, MHP February 7, 2015
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
Let me talk to you about the recent guidelines on treatment of blood cholesterol which just came out in November of 2013

2. 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.”

3. Four Major Statin Benefit Groups
Individuals with clinical ASCVD
Individuals with LDL >190
Individuals with dm, yo with LDL and without clinical ASCVD
Individuals without clinical ASCVD or dm with LDL and estimated 10-year ASCVD risk >7.5%
-Based on extensive review of the evidence, the expert panel identified 4 groups that would benefit from statin therapy:
Individuals with clinical ASCVD
Individuals with LDL >190
Individuals with dm, yo with LDL and without clinical ASCVD
Individuals without clinical ASCVD or dm with LDL and estimated 10-year ASCVD risk >7.5%
Note that Clinical ASCVD is defined by the inclusion criteria for the secondary prevention statin RCTs (acute coronary syndromes, or a history of MI, stable or unstable angina, coronary or other arterial revascularization, stroke, TIA, or peripheral arterial disease presumed to be of atherosclerotic origin).

4. Don’t Forget Healthy Lifestyle
Healthy diet
Regular exercise
No tobacco
Maintain healthy weight

6. 2013 ACC/AHA/NHLBI Guideline on Lifestyle for CVD Prevention
Eat a dietary pattern that is rich in fruit, vegetables, whole grains, fish, low-fat 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, sugar-sweetened beverages, and sodium.
Engage in aerobic physical activity of moderate to vigorous intensity lasting 40 minutes per session three to four times per week

7. 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

8. 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

9. This algorithim summarizes the major guidelines in one page
You see the 4 statin benefit groups in the middle: on top, you see the patient’s group with clinical ASCVD, below that you see the group with LDL >190, below that you see the patient’s with history of DM years old, and in the bottom, you see patients who don’t have the characteristics of the first 3 groups but their 10 year ASCD risk is greater than 7.5%
For the first group: based on the guidline, if you have clinical ASCD, are younger than 75 and don’t have any history of intolerance to statin, you should be started on high intensity statin. On the other hand, if you are older than 75, or not a candidate for high intensity statin due to lets say intolerance to statins, you are a candidate for moderate-intensity statin
For the second group, if your LDL is greater than 190, you need to be started on high-intensity statin, unless you have contra-indication to high dose start on moderate dose
For the third group, individuals with diabetes with above mentioned group age, you need to calculate the 10 year ASCVD risk using a new equation/calculater called “pooled Cohort Equations” if the 10 year risk is greater than 7.5%, start them on high-intensity, otherwise, you can start them on moderate-intensity statin
For the last group, you need to calculate patient’s risk factor and start them on moderate-to-high intensity statin if their estimated 10-y ASCVD risk is greater than 7.5%
Keep that in mind that what we mean by “high intensity” statin, is the daily dose of statin that lowers the LDL by appox greater than 50%, and what we mean by moderate intensity statin, is the daily dose of statin that lowers the LDL by appox 30-50%.

10. Dosing Statins

11. 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 mg/dl

12. This algorithim summarizes the major guidelines in one page
You see the 4 statin benefit groups in the middle: on top, you see the patient’s group with clinical ASCVD, below that you see the group with LDL >190, below that you see the patient’s with history of DM years old, and in the bottom, you see patients who don’t have the characteristics of the first 3 groups but their 10 year ASCD risk is greater than 7.5%
For the first group: based on the guidline, if you have clinical ASCD, are younger than 75 and don’t have any history of intolerance to statin, you should be started on high intensity statin. On the other hand, if you are older than 75, or not a candidate for high intensity statin due to lets say intolerance to statins, you are a candidate for moderate-intensity statin
For the second group, if your LDL is greater than 190, you need to be started on high-intensity statin, unless you have contra-indication to high dose start on moderate dose
For the third group, individuals with diabetes with above mentioned group age, you need to calculate the 10 year ASCVD risk using a new equation/calculater called “pooled Cohort Equations” if the 10 year risk is greater than 7.5%, start them on high-intensity, otherwise, you can start them on moderate-intensity statin
For the last group, you need to calculate patient’s risk factor and start them on moderate-to-high intensity statin if their estimated 10-y ASCVD risk is greater than 7.5%
Keep that in mind that what we mean by “high intensity” statin, is the daily dose of statin that lowers the LDL by appox greater than 50%, and what we mean by moderate intensity statin, is the daily dose of statin that lowers the LDL by appox 30-50%.

13. 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.

14. This is the new equation, the pooled cohort risk assessment equation
As you can see, there are different parameters that you need to plug in to the equation to calculate the risk: gender, age, race, total cholesterol, HDL, systolic BP, whether or not you are on any anti-HTN meds, any history of DM or being a smoker

15. Diabetics aged 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

16. This algorithim summarizes the major guidelines in one page
You see the 4 statin benefit groups in the middle: on top, you see the patient’s group with clinical ASCVD, below that you see the group with LDL >190, below that you see the patient’s with history of DM years old, and in the bottom, you see patients who don’t have the characteristics of the first 3 groups but their 10 year ASCD risk is greater than 7.5%
For the first group: based on the guidline, if you have clinical ASCD, are younger than 75 and don’t have any history of intolerance to statin, you should be started on high intensity statin. On the other hand, if you are older than 75, or not a candidate for high intensity statin due to lets say intolerance to statins, you are a candidate for moderate-intensity statin
For the second group, if your LDL is greater than 190, you need to be started on high-intensity statin, unless you have contra-indication to high dose start on moderate dose
For the third group, individuals with diabetes with above mentioned group age, you need to calculate the 10 year ASCVD risk using a new equation/calculater called “pooled Cohort Equations” if the 10 year risk is greater than 7.5%, start them on high-intensity, otherwise, you can start them on moderate-intensity statin
For the last group, you need to calculate patient’s risk factor and start them on moderate-to-high intensity statin if their estimated 10-y ASCVD risk is greater than 7.5%
Keep that in mind that what we mean by “high intensity” statin, is the daily dose of statin that lowers the LDL by appox greater than 50%, and what we mean by moderate intensity statin, is the daily dose of statin that lowers the LDL by appox 30-50%.

17. 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

18. This algorithim summarizes the major guidelines in one page
You see the 4 statin benefit groups in the middle: on top, you see the patient’s group with clinical ASCVD, below that you see the group with LDL >190, below that you see the patient’s with history of DM years old, and in the bottom, you see patients who don’t have the characteristics of the first 3 groups but their 10 year ASCD risk is greater than 7.5%
For the first group: based on the guidline, if you have clinical ASCD, are younger than 75 and don’t have any history of intolerance to statin, you should be started on high intensity statin. On the other hand, if you are older than 75, or not a candidate for high intensity statin due to lets say intolerance to statins, you are a candidate for moderate-intensity statin
For the second group, if your LDL is greater than 190, you need to be started on high-intensity statin, unless you have contra-indication to high dose start on moderate dose
For the third group, individuals with diabetes with above mentioned group age, you need to calculate the 10 year ASCVD risk using a new equation/calculater called “pooled Cohort Equations” if the 10 year risk is greater than 7.5%, start them on high-intensity, otherwise, you can start them on moderate-intensity statin
For the last group, you need to calculate patient’s risk factor and start them on moderate-to-high intensity statin if their estimated 10-y ASCVD risk is greater than 7.5%
Keep that in mind that what we mean by “high intensity” statin, is the daily dose of statin that lowers the LDL by appox greater than 50%, and what we mean by moderate intensity statin, is the daily dose of statin that lowers the LDL by appox 30-50%.

19. 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

20. STATIN Safety recommendations
conditions that could predispose pts to statin side effect:
Impaired renal or hepatic function
History of previous statin intolerance or muscle disorder
Age >75
Unexplained ALT elevation > 3x ULN
History of hemorrhagic stroke
Asian ancestry

21. 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
The next few slides tells you the new guidelines on the safety recommendations for statins

22. 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

23. 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

24. 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%

25. Mention that patient is a diabetic with 10 yr risk is greater than 7
Mention that patient is a diabetic with 10 yr risk is greater than 7.5% so he or she is candidate for high intensity statin

26. Dosing Statins

27. Case 2 22 yo white male LDL: 195 SBP: 120 Not taking anti-hTN meds
Non-diabetic
Non-smoker
Ask the learner whether or not you need to calculate the 10 yr risk for developing the ASCVD in a patient with LDL>195. The answer is NO. This patient belongs to the second statin benefit group and is a candidate for high intesntity Statin regardless of 10 year risk

29. Dosing Statins

30. 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

31. Patients stabilized post ACS ≤ 10 days:
Study Design
Patients stabilized post ACS ≤ 10 days:
LDL-C 50–125*mg/dL (or 50–100**mg/dL if prior lipid-lowering Rx)
*3.2mM
**2.6mM
Standard Medical & Interventional Therapy
N=18,144
Uptitrated to Simva 80 mg if LDL-C > 79
(adapted per FDA label 2011)
Ezetimibe / Simvastatin 10 / 40 mg
Simvastatin 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

32. 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
+0.6
-0.5
Median Time avg
69.5 vs mg/dL

33. Primary Endpoint — ITT
Cardiovascular death, MI, documented unstable angina requiring rehospitalization, coronary revascularization (≥30 days), or stroke
HR 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

34. Major Pre-specified Subgroups
Simva†
EZ/Simva†
Male
34.9
33.3
Female
34.0
31.0
Age < 65 years
30.8
29.9
Age ≥ 65 years
39.9
36.4
No diabetes
30.2
Diabetes
45.5
40.0
Prior LLT
43.4
40.7
No prior LLT
30.0
28.6
LDL-C > 95 mg/dl
31.2
29.6
LDL-C ≤ 95 mg/dl
38.4
36.0 *
†7-year event rates
0.7
1.0
1.3
Ezetimibe/Simva Better
Simva Better
*p-interaction = 0.023, otherwise > 0.05

35. 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

36. Hypertension

37. John Raymond MS, PA-C, MHP February 7, 2015
2014 Guidelines for Management of High Blood Pressure in Adults (JNC 8)
John Raymond MS, PA-C, MHP
February 7, 2015

38. 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

39. What is the goal BP?

40. 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 6-year intervals
Last edition (JNC-7) published in 2003
Chobanian AV et al. JAMA 2003;289:

41. And then we wait…and wait…
Development of JNC-8
And then we wait…and wait…

42. JNC 8
2014 Evidence-Based Guidelines for the Management of High Blood Pressure in Adults
JAMA. 2014;311(5):
December 18, 2013

43. JNC 8: Hypertension Management Questions Guiding Review
In adults with HTN:
Does initiating antihypertensive pharmacologic therapy at specific BP thresholds improve health outcomes?
Does treatment with antihypertensive pharmacologic therapy to a specified goal lead to improvements in health outcomes?
Do various antihypertensive drugs or drug classes differ in comparative benefits and harms on specific health outcomes?

44. BP goal in the elderly

45. 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)

46. 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:

47. 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:

48. 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:

49. 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
JNC8 does make a recommendation for follow-up (based on expert opinion-GRADE E)
Recheck BP after 1 month of treatment
***Main objective of HTN treatment is to attain and maintain goal BP
Referral to a HTN specialist may be indicated for patients in whom goal BP cannot be attained using the above strategy

50. QUESTIONS???

51. 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%

52. Mention that patient belongs to the fourth group meeting the criteria for moderate to high intensity statin given the 10 year risk of ASCVD is greater than 7.5%

53. Dosing Statins

54. 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%

55. Mention that patient is a diabetic but since his or her ASCVD is less than 7.5%, he or she is a candidate for moderate intensity statin

56. Dosing Statins

57. 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 %

58. Mention that despite the fact that the total cholesterol is high, since the LDL is less than 195, and patient doesn’t meet any other statin benefit group, there is no indication for statin therapy

59. 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.
JNC8 does not make a recommendation for dosing strategy----providers should use their own judgement
Some JNC8 committee members starting with 2 medications when SBP ≥ 160mmHg and/or DBP ≥ 100 mmHg or if SBP ≥ 20mmHg above goal and/or DBP ≥ 10mmHg above goal
There are studies comparing each of these strategies, but they were based on intermediate outcomes (more rapid attainment of BP goal or improved adherence) and were not included in the evidence review for JNC8

60. 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

61. 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
0.96
Gallbladder-related AEs
3.5
3.1
0.10
Rhabdomyolysis*
0.2
0.1
0.37
Myopathy*
0.32
Rhabdo, myopathy, myalgia with CK elevation*
0.6
0.64
Cancer* (7-yr KM %)
10.2
0.57
* Adjudicated by Clinical Events Committee
% = n/N for the trial duration

62. Baseline Characteristics
Simvastatin
(N=9077) %
EZ/Simva
(N=9067)
Age (years) 64
Female 24 25
Diabetes 27
MI prior to index ACS 21
STEMI / NSTEMI / UA
29 / 47 / 24
Days post ACS to rand (IQR)
5 (3, 8)
Cath / PCI for ACS event
88 / 70
Prior lipid Rx 35 36
LDL-C at ACS event (mg/dL, IQR)
95 (79, 110)
95 (79,110)

64. Overview 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.