1. Kevin Overbeck, DO Assistant Professor, NJISA
Search for the Fountain of Youth: Cardiovascular Disease Management in the Geriatric Patient
Kevin Overbeck, DO
Assistant Professor, NJISA

2. Learning Objectives
Apply knowledge of Aging Physiology to JNC 8 + SPRINT to optimize strategy for HYPERTENSION management
Understand the benefits of STATINS in aging in the context of 2013 guidelines for HYPERLIPIDEMIA
Apply 2014 AHA/ACC/HRS guidelines for ATRIAL FIBRILLATION to decision-making for ANTICOAGULATION and RATE CONTROL in the elderly
Consider also the follow:
1. Review highlights and controversies of JNC 8 guidelines
2. Review AHA-ACC-CDC advisory recommendations

3. HYPERTENSION & THE elderly
Historical Perspective
Older adults frequently have elevated systolic blood pressures (BPs). For years, medical professionals have accepted both classic hypertension and isolated systolic hypertension (ISH) as a natural consequence of aging.
BEFORE SPRINT, there were two trials that demonstrated treatment of HTN in the ELDERLY – SHEP and HYVET ….

4. INCREASED VASCULAR STIFFNESS
Aging Physiology
Increased thickness of the intima and the media 
INCREASED VASCULAR STIFFNESS

5. Aging Physiology
Increased systolic and diastolic blood pressure; however, the increase in diastolic blood pressure is not as pronounced.
The average increase in diastolic pressure with aging is modest, appears to reach a plateau around mid-life, and is not as marked as the average increase in systolic pressure. Diastolic pressure in large part reflects the peripheral vascular resistance which increases minimally in men and moderately in women.
Reference (Graph reproduced from)
1. Pearson, J.D., Morrell, C.H., Brant, L.J., Landis, P.K., and Fleg, J.L. (1997). Age-associated changes in blood pressure in a longitudinal study of healthy men and women. Journal of Gerontology, 52, M177–83.
Pearson, J.D., Morrell, C.H., Brant, L.J., Landis, P.K., and Fleg, J.L. (1997). Age-associated changes in blood pressure in a longitudinal study of healthy men and women. Journal of Gerontology, 52, M177–83.

6. Aging Physiology Consequences of Baroreceptor Changes1
Increased BP variability
Impaired BP homeostasis
Hypertension
Postural (orthostatic) hypotension
Post-prandial hypotension
Post-Prandial Hypotension (“Meal Related Hypotension)
Mechanism is poorly understood – very limited evidence available – blood in the splanchic circulation pools following a meal combined with inadequate sympathetic outputs to maintain cardiac output / systemic vascular resistance2. Other mechanisms cited included “insulin-induced vasodilation and release of vasodilatory gastrointestinal peptides2.”
Treatment of post-prandial hypotension is similar to the treatment of orthostatic hypotension with an emphasis on limiting certain drugs known to exacerbate the condition including Furosemide (N=20 – removal of furosemide in these patients changed the maximum decline in SBP from -25mmHg to -11mmHg)3. Other recommendations include frequent small meals and AVOIDANCE of SALT RESTRICTION2.
Decreased Responsiveness of the Adrenergic Receptor
IV beta-blockers take “longer” to get reaction in older patients than younger patients
Normotensive Elderly vs HTN Elderly
HYPERTENSIVE elderly have MORE BP VARIABILITY
HYPERTENSIVE elderly have GREATER ALPHA-MEDIATED VASOCONSTRICTION
HYPERTENSIVE elderly have INCREASED SYMPATHETIC NERVOUS SYSTEM activity
References
Huang CC, et al. Effect of age on adrenergic and vagal baroreflex sensitivity in normal subjects. Muscle Nerve. 2007;36(5):
Jansen RW, et al. Postprandial hypotension: epidemiology, pathophysiology, and clinical management. Ann Intern Med. 1995;122(4):286
vvan Kraaij DJ, et al. Furosemide withdrawal improves postprandial hypotension in elderly patients with heart failure and preserved left ventricular systolic function. Arch Intern Med. 1999;159(14):1599.
Huang CC, et al. Effect of age on adrenergic and vagal baroreflex sensitivity in normal subjects. Muscle Nerve. 2007;36(5):
Jansen RW, et al. Postprandial hypotension: epidemiology, pathophysiology, and clinical management. Ann Intern Med. 1995;122(4):286

7. HTN & The Elderly Orthostatic BP Measurement
Sitting-Standing vs. Laying-Standing
After standing wait 1 minute vs. 3 minutes vs. 5 minutes
At least a 20 mmHg fall in systolic pressure
At least a 10 mmHg fall in diastolic pressure
Symptoms of cerebral hypoperfusion
Parkinson’s / Lewy Body Dementia
Decreased Baroreceptor Sensitivity1
Postprandial Hypotension
In addition, older patients are more likely than younger patients to exhibit an orthostatic fall in blood pressure and hypotension; thus, in older patients, it is ideal to measure their blood pressure in the standing as well as seated or supine positions prior to drug prescribing medications.
Orthostatic Hypotension is more common in the elderly2.
References
Huang CC, et al. Effect of age on adrenergic and vagal baroreflex sensitivity in normal subjects. Muscle Nerve. 2007;36(5):
Shibao C, et al. Orthostatic hypotension-related hospitalizations in the United States. Am J Med. 2007;120(11):

8. HYVET
Historical
At the time of this 2008 study, the evidence was considered inconclusive as to whether treatment of HTN in those individuals over 80 years old. It is also interesting to think whether a study like this could have ever been ethically performed in the United States in In fact the authors of this article cite a recent retrospective cohort analysis of patients 80 years of age or older with hypertension, of whom 84.5% were receiving antihypertensive medication, reported a shorter survival for those with systolic blood pressure levels below 140 mm Hg, even after adjustment for known predictors of death2.
Methods1
We randomly assigned 3845 patients from Europe, China, Australasia, and Tunisia who were 80 years of age or older and had a sustained systolic blood pressure of 160 mm Hg or more to receive either the thiazide diuretic indapamide (sustained release, 1.5 mg) or matching placebo. The angiotensin-converting–enzyme inhibitor perindopril (2 or 4 mg), or matching placebo, was added if necessary to achieve the target blood pressure of 150/80 mm Hg. The primary end point was fatal or nonfatal stroke.
Patients were instructed to stop all antihypertensive treatment and to take a single placebo tablet daily for at least 2 months and to undergo two blood-pressure measurements during each of two visits, 1 month apart, after having been seated for 5 minutes. On the third visit and thereafter, the standing blood pressure was taken twice, after the patient had been standing for 2 minutes. At the start of the trial, blood pressures were recorded with the use of either a mercury sphygmomanometer or a validated automated device, but by the end of the trial, a validated automated device was used in the majority of centers. If the mean of the four systolic blood-pressure
measurements taken at the second and third visits (two at each visit) was between 160 and 199mmHg, patients underwent randomization, provided that all inclusion and exclusion criteria were met. Randomization was stratified according to age.
Results1
The active-treatment group (1933 patients) and the placebo group (1912 patients) were well matched (mean age, 83.6 years; mean blood pressure while sitting, 173.0/90.8 mm Hg). At 2 years, the mean blood pressure while sitting was 15.0/6.1 mm Hg lower in the active-treatment group than in the placebo group. The active treatment was associated with
30% reduction in the rate of fatal or nonfatal stroke (95% confidence interval [CI], −1 to 51; P = 0.06),
39% reduction in the rate of death from stroke (95% CI, 1 to 62; P = 0.05)
21% reduction in the rate of death from any cause (95% CI, 4 to 35; P = 0.02)
23% reduction in the rate of death from cardiovascular causes (95% CI, −1 to 40; P = 0.06)
64% reduction in the rate of heart failure (95% CI, 42 to 78; P<0.001)
Fewer serious adverse events were reported in the active-treatment group (358, vs. 448 in the placebo group;P = 0.001).
References
Becket, NS, Peters, R, Fletcher, AE, et al. Treatment of hypertension in patients 80 years of age or older. N Engl J Med. 2008; 358(18):
Oates DJ, et al. Blood pressure and survival in the oldest old. J Am Geriatr Soc 2007;55:383-8.
Becket, NS, Peters, R, Fletcher, AE, et al. Treatment of hypertension in patients 80 years of age or older. N Engl J Med. 2008; 358(18):

9. HYVET
Historical
At the time of this 2008 study, the evidence was considered inconclusive as to whether treatment of HTN in those individuals over 80 years old. It is also interesting to think whether a study like this could have ever been ethically performed in the United States in In fact the authors of this article cite a recent retrospective cohort analysis of patients 80 years of age or older with hypertension, of whom 84.5% were receiving antihypertensive medication, reported a shorter survival for those with systolic blood pressure levels below 140 mm Hg, even after adjustment for known predictors of death2.
Methods1
We randomly assigned 3845 patients from Europe, China, Australasia, and Tunisia who were 80 years of age or older and had a sustained systolic blood pressure of 160 mm Hg or more to receive either the thiazide diuretic indapamide (sustained release, 1.5 mg) or matching placebo. The angiotensin-converting–enzyme inhibitor perindopril (2 or 4 mg), or matching placebo, was added if necessary to achieve the target blood pressure of 150/80 mm Hg. The primary end point was fatal or nonfatal stroke.
Patients were instructed to stop all antihypertensive treatment and to take a single placebo tablet daily for at least 2 months and to undergo two blood-pressure measurements during each of two visits, 1 month apart, after having been seated for 5 minutes. On the third visit and thereafter, the standing blood pressure was taken twice, after the patient had been standing for 2 minutes. At the start of the trial, blood pressures were recorded with the use of either a mercury sphygmomanometer or a validated automated device, but by the end of the trial, a validated automated device was used in the majority of centers. If the mean of the four systolic blood-pressure
measurements taken at the second and third visits (two at each visit) was between 160 and 199mmHg, patients underwent randomization, provided that all inclusion and exclusion criteria were met. Randomization was stratified according to age.
Results1
The active-treatment group (1933 patients) and the placebo group (1912 patients) were well matched (mean age, 83.6 years; mean blood pressure while sitting, 173.0/90.8 mm Hg). At 2 years, the mean blood pressure while sitting was 15.0/6.1 mm Hg lower in the active-treatment group than in the placebo group. The active treatment was associated with
30% reduction in the rate of fatal or nonfatal stroke (95% confidence interval [CI], −1 to 51; P = 0.06),
39% reduction in the rate of death from stroke (95% CI, 1 to 62; P = 0.05)
21% reduction in the rate of death from any cause (95% CI, 4 to 35; P = 0.02)
23% reduction in the rate of death from cardiovascular causes (95% CI, −1 to 40; P = 0.06)
64% reduction in the rate of heart failure (95% CI, 42 to 78; P<0.001)
Fewer serious adverse events were reported in the active-treatment group (358, vs. 448 in the placebo group;P = 0.001).
References
Becket, NS, Peters, R, Fletcher, AE, et al. Treatment of hypertension in patients 80 years of age or older. N Engl J Med. 2008; 358(18):
Oates DJ, et al. Blood pressure and survival in the oldest old. J Am Geriatr Soc 2007;55:383-8.
Becket, NS, Peters, R, Fletcher, AE, et al. Treatment of hypertension in patients 80 years of age or older. N Engl J Med. 2008; 358(18):

10. JNC 8: Clinical Practice Guidelines individuals >60 years old
Life style Modification (LSM)
Laboratory
Ambulatory BP Monitoring
Self Measuring BP
Assess Risk Factors
BP Classification
Systolic
(mmHg)
Diastolic
Initial Therapy
Pre-Hypertension
Deleted / Omitted DM
<140
<90
LSM + No Anti-Hypertensive Drug Indicated
CKD** (<70)
Previous less than 130/80
Goal
<150
LSM + ACE or ARB or DIURETIC or Calcium Channel Blocker
The panel members (n=18) appointed to JNC 8 were selected based on expertise and included geriatricians (n=2); not all JNC 8 recommendations had unanimous support [see below “controversy”]
JNC 8 guidelines are based on a systematic review of randomized controlled trials (RCTs)
PRE-HYPERTENSION
Deleted / Omitted --- not even mentioned in the article published in JAMA as if to pretend that JNC 7’s recommendation to treat patients to goals of less than SBP 130mmHg NEVER EXISTED!! In fact, it did exist as the “gold standard” recommendation for blood pressure for 10 years.
DIABETES
If a patient has DIABETES and is > 60, the treatment goal is SBP < 140/90; THIS IS AN INCREASE from JNC 7 [JNC-7 previously recommended to treat PRE-HYPERTENSION in DM and/or HTN patients; therefore, JNC 8 is a reduction in intensity of antihypertensive treatment].
CKD
If a patient has CKD and is > 70, the treatment goal is SBP < 140/90; THIS IS AN INCREASE from JNC 7 [JNC-7 previously recommended to treat PRE-HYPERTENSION in DM and/or HTN patients; therefore, JNC 8 is a reduction in intensity of antihypertensive treatment].
BP Management in Practice
According to JNC 8, treatment for high BP results in lower achieved SBP (e.g. <140mmHg) 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)2. In other words, if you treat at “proper threshold” and BP drops below 140 without adverse reaction – continue therapy; BUT consider the principle of GRADUAL DOSE REDUCTION (GDR).
If goal BP cannot be reached within a month of treatment, increase to dose of the initial drug OR add a second drug from one of the classes above [DO NOT use an ACE + ARB together].
Indapamide as well as chorthalidone is a more effective thiazide for reducing blood pressure than HCTZ
Did you know?
Guidelines should never be used to counter the treating physician's best clinical judgment
CONTROVERSY with the JNC-8 writing group:
1. Declined to partner with AHA/ACC
2. Published recommendations in JAMA Dec ‘13 without sponsorship or endorsements
4. AHA noted some “reservations” with the new guidelines. … expect “NEW” guidelines in 2015
MINORITY OPINION
Five members of 18 person writing group published a minority opinion in Annals of Internal Medicine APRIL The authors of this editorial note a less than unanimous decision to increase goal systolic blood pressures greater than 140mmHg for patients with DIABETES or CHRONIC KIDNEY DIEASE (CKD). In their article they DID agree about one thing in the treatment of the elderly noting, “however, we did believe that an SBP goal of less than 150mmHg for frail persons aged 80 years or older was a reasonable alternate approach to addressing the concern that elderly patients are at higher risk for treatment-related serious events.” In other words, treat octogenarians to a goal less aggressively to < 150/90. The authors also note that a “cut-score” of 80 would be in congruence with European, Canadian, and the UK (as well as ACC/AHA).
References
Wright JT, et al. Evidence Supporting a Systolic Blood Pressure Goal of Less Than 150mmHg in Patients Aged 60 Years or Older: The Minority View. Annals of Internal Medicine, 2014: 160 (7); pp
2. JNC 8, JAMA 2014; 311(5)
** “based on evidence the committee cannot make a recommendation for individuals 70 and older”
2014 Evidenced-Based Guideline for Management of High Blood Pressure in Adults: Reported from the Panel Members Appointed to the Eight Joint National Committee (JNC 8). JAMA FEB 2014.

11. SPRINT
REFERENCE
Williamson JD, et al. Intensive vs Standard Blood Pressure Control and Cardiovascular Disease Outcomes in Adults Aged >75 years: A Randomized Clinical Trial. JAMA 2016: 315(24):
Williamson JD, et al. Intensive vs Standard Blood Pressure Control and Cardiovascular Disease Outcomes in Adults Aged >75 years: A Randomized Clinical Trial. JAMA 2016: 315(24):

12. 27 61 41 90 SPRINT NNT Data: Older (aged>75) Overall Study Group
Primary Composite Outcome 27 61
All Cause Mortality 41 90
The SPRINT TRIAL was STOPPED EARLY (stopped at median 3.26 years rather than planned 5 years) because those in the INTENSE TREATMENT group had a survival benefit. Participants in the usual / standard treatment group were notified that their counterparts “had done better …”
PRIMARY COMPOSITE OUTCOME was Myocardial Infarction, other acute coronary syndromes, STROKE, HF, or Death from Cardiovascular Causes
POPULATION
ENROLLED COMMUNITY DWELLING with SBP mmHg
EXCLUSION CRITERIA
DM, history of stroke, symptomatic HF (within 6 months), systolic EF < 35%, diagnosis of DEMENTIA (or treatment for DEMENTIA or MOCA < 19), expected survival less than 3 years, UNINTENTIONAL weight loss >10% of body weight (during preceding 6 months), SBP < 110mmHg following 1 minute of standing, resides in LTC/NURSING HOME, resides in ASSISTED LIVING
OUTCOMES
MEAN SBP in the INTENSIVE GROUP was 123mmHg meaning that not all patients achieved the SBP goal of less than 120mmHg.
TIME to benefit 2-3 YEARS
Serious Adverse Effects (SAEs)
“In the intense treatment group, SAEs occurred in 637 participants (48.4%) compared with 637 participants (48.3%) in the standard treatment group (HR 0.99 [05% CI, ]; p = 0.90) …”
The absolute rate of SAEs was higher in the intense treatment group but was NOT statistically significant across several events including HYPOTENSION, SYNCOPE, ELECTROLYTE ABNORMALITY, ACUTE KIDNEY INJURY, ORTHOSTATIC HYPOTENSION with a report of DIZZINESS
The absolute rate of SAEs was higher in the standard treatment group but was NOT statistically significant with regard to INJURIOUS FALLS, ORTHOSTATIC HYPOTENSION
The increases observed appear to be more than offset by the benefits of treatment.
FRAILTY
“ … Exploratory analysis suggests that the benefit of intensive BP control was consistent among persons in this age range who were frail or had reduced gait speed …”
The overall SAE rate was comparable including among the most frail participants
The post hoc secondary analyses of frailty and functional ability on the primary outcome did not appear to show an influe of these factors on the benefits of intensive BP treatment.
LIMITATIONS
RANDOMIZATION in SPRINT was not stratified by categories of age. Also of note the baseline characteristics of HYVET trial was and for SPRINT it was 79.8(SD 3.9).
In addition the trial did NOT enroll older adults residing in nursing homes (or assisted living), persons with type 2 DM, or [stroke] …”
RECOMMENDATIONS Don’t EVEN think of an alternate TARGET unless you are MEASURING STANDING BP
Using the EXCLUSION CRITERIA, consider treatment to a target of 140mmHg – then consider 130mmHg
MEASURE LAYING + STANDING BP
If standing BP < 110mmHg at ANY TIME raise the target from 140mmHg back to 150mmHg MORE FREQUENT VISITS
WOULD NOT treat to a target of 120mmHg
Williamson JD, et al. Intensive vs Standard Blood Pressure Control and Cardiovascular Disease Outcomes in Adults Aged >75 years: A Randomized Clinical Trial. JAMA 2016: 315(24):
The SPRINT Research Group. A Randomized Controlled Trial of Intensive versus Standard Blood Pressure Control. NEJM 2015: 373(22):

13. SPRINT EXCLUSION CRITERIA
DIABETES
Previous history of STROKE
Dementia / Memory Loss or MOCA < 19
SBP < 110mmHg following 1 MINUTE of STANDING
Residents of a NURSING HOME / ASSISTED LIVING
Symptomatic HF within 6 months (or EF < 35%)
EXCLUSION CRITERIA
DM, history of stroke, symptomatic HF (within 6 months), systolic EF < 35%, diagnosis of DEMENTIA (or treatment for DEMENTIA or MOCA < 19), expected survival less than 3 years, UNINTENTIONAL weight loss >10% of body weight (during preceding 6 months), SBP < 110mmHg following 1 minute of standing, resides in LTC/NURSING HOME, resides in ASSISTED LIVING
Williamson JD, et al. Intensive vs Standard Blood Pressure Control and Cardiovascular Disease Outcomes in Adults Aged >75 years: A Randomized Clinical Trial. JAMA 2016: 315(24):

14. RECOMMENDATIONS ROUTINELY measure STANDING BLOOD PRESSURE
ADMINISTER COGNITIVE TEST – MOCA
If standing BP < 110mmHg at ANY TIME raise the target from 140mmHg back to 150mmHg MORE FREQUENT VISITS
TARGET SBP 140mmHg – once reached could consider 130mmHg
WOULD NOT treat to a target of 120mmHg

15. Applied Geriatrics
A 85 year old with community dwelling male with previous TIA (>5 years ago) and current CKD stage III (eGFR 55) presents to the office for routine evaluation of his chronic medical conditions
ACTIVE MED LIST:
Aspirin 81mg daily
Metoprolol XL 50mg daily
Amlodipine 2.5mg daily
HCTZ 12.5mg daily
KCL 10meq daily
Losartan 50mg daily
Atorvastatin 10mg daily
Tamsulosin 0.4mg daily
BP [sitting + standing]: 120/80mmHg
HR 68
MOCA: 26/30
What is the next best step in the management of this patient’s condition?
Stop Amlodipine (Norvasc®)
Stop Hydrochlorothiazide (HCTZ)
Reduce Metoprolol XL (Lopressor XL ®)
Reduce Losartan
Continue current medication regimen
Aggressive therapy is not appropriate if adverse side effects (e.g., postural hypotension) cannot be avoided.

16. Applied Geriatrics
A 85 year old with community dwelling male with previous TIA (>5 years ago) and current CKD stage III (eGFR 55) presents to the office for an evaluation of his increasing lower extremity edema
ACTIVE MED LIST:
Aspirin 81mg daily
Metoprolol XL 50mg daily
Amlodipine 2.5mg daily
HCTZ 12.5mg daily
KCL 10meq daily
Losartan 50mg daily
Atorvastatin 10mg daily
Tamsulosin 0.4mg daily
PHYSICAL EXAM BP [sitting + standing]: /80mmHg
HR: 68
CARDIO: (+) regular (+) 2+ bilateral pitting lower extremity edema (-) S3 (-) JVD
MOCA: 26/30
Aggressive therapy is not appropriate if adverse side effects (e.g., postural hypotension) cannot be avoided.
What is the next best step in the management of this patient’s condition?
Stop Amlodipine (Norvasc®)
Increase Hydrochlorothiazide (HCTZ)
Reduce Metoprolol XL (Lopressor XL ®)
Reduce Losartan
Continue current medication regimen

17. Applied Geriatrics
An 85 year old female presents to your outpatient ambulatory office following a hospital evaluation (09/04/2015 – 9/08/2015) for shortness of breath. She was diagnosed and treated for an acute exacerbation of COPD. She was upgraded from an inhaler to a nebulizer and prescribed PREDNISONE with a plan to taper She also reports that her blood pressure was high in the hospital with records indicating 172/92 on day 3 and they recommended that she start AMLODIPINE (NORVASC®) 5mg every AM and follow-up with you for blood pressure checks. Today her blood pressure is 144/88. Your records indicate that her blood pressure was controlled at the time of last visit during August 2015.
DISCHARGE MED LIST:
Aspirin 81mg daily
Amlodipine 5mg daily
Prednisone Taper
Albuterol Nebulizer QID PRN
Lisinopril 10mg daily
HCTZ 12.5mg daily
Omeprazole 20mg daily
KCL 10meq daily
Vitamin D 1000 IU daily
Alendronate 70mg qHS
Pravastatin 40mg qHS

18. Medications Known To Increase BP
Steroids
Sympathomimetic Drugs
Decongestants
NSAIDS
Erythropoietin
Mirabegron (Myrbetriq®)
Mirabegron (Myrbetriq®)
Adverse Reactions Significant >10%: Cardiovascular: Hypertension (9% to 11%)

19. Applied Geriatrics
An 80 year old male with PARKINSON’S DISEASE presents for an evaluation of deterioration in his GAIT evidence by FIVE FALLS in the home WITHOUT INJURY during the past SIX MONTHS despite strict adherence to utilization of TWO WHEELED ROLLING WALKER in the home CAD with previous MI (2008), Lower Extremity Edema, Barrett’s Esophagus MOCA: 21/30 BP (sitting): 154/70 BP (standing): 120/60 [asymptomatic] Lower Extremity 1++ bilateral edema BUN 20 / Creat 1.2 / eGFR > 60
CURRENT MED LIST:
Aspirin 81mg daily
Losartan 50mg daily
Carvedilol 6.25mg BID
HCTZ 12.5mg daily
Omeprazole 20mg daily
KCL 10meq daily
Vitamin D 1000 IU daily
Pravastatin 40mg qHS
What is the next BEST step in the management of this patient’s condition?

20. STATINS, DYSLIPIDEMIA & THE elderly

21. Dyslipidemia “Normal” Aging
LDL increases from puberty in men and women followed by a slight decrease in males after age 70 (some have argued that the decrease in LDL after age 70 is due to the CAD-death; other studies have not found this to be true – in one study the total cholesterol, LDL, and HDL decreased was predicted best by a weight change – gain or weight loss)1.
Women and men are about equal at age 55 to 65, at which time women LDL’s exceed their counterparts before plateauing or decreasing slightly.
HDL do not vary much with age.
The explanation for this LDL increase with normal aging is not well understood but thought to be due a decrease in LDL catabolism related to reduced activity of the hepatic LDL receptor2.
References
Ferrara A, et al. Total, LDL, and HDL cholesterol decrease with age in older men and women. The Rancho Bernardo Study Circulation. 1997;96(1):37.
Ericsson S, et al. Influence of age on the metabolism of plasma low density lipoproteins in healthy males. J Clin Invest. 1991;87(2):591.

22. Dyslipidemia Primary Prevention: CARDS Study
NNT Data:
Older
Younger
1st major cardiovascular even 22 32
Age yrs
Atorvastatin 10mg v. Placebo
4 years
CARDS Study (enrolled patients 45-75)
Patients with type 2 diabetes without known CHD, Atorvastatin 10 mg daily reduced first major cardiovascular events by 37 percent in patients younger than 65 and by 38 percent in patients 65 and older. The numbers needed to treat was 22 patients for 4 years to avoid one event (whereas, 33 patients for 4 years to avoid one event in younger patients)1.
All-cause mortality was reduced by 22% but not significantly1.
Treatment for Primary Prevention – typically recommend “low to moderate intensity”
Atorvastatin 10mg
Simvastatin 20mg
Pravastatin 40mg
Lovastatin 20-40mg
No LDL goal is recommended when primary prevention is the treatment goal.
References
Neil HA, et al. Analysis of efficacy and safety in patients aged years at randomization: Collaborative Atorvastatin Diabetes Study (CARDS). Diabetes Care. 2006;29(11):2378.
Neil HA, et al. Analysis of efficacy and safety in patients aged years at randomization: Collaborative Atorvastatin Diabetes Study (CARDS). Diabetes Care. 2006;29(11):2378.

23. Dyslipidemia Secondary Prevention: The LIPID Trial
NNT Data:
Older
Younger
All Cause Mortality 22 46
CAD Death 35 71
Fatal / Non-Fatal MI 30 36
Stroke 79
170
The LIPID trial (enrolled ages of and then analyzed individuals 65 and 75 years)
Patients enrolled who had a prior MI or unstable angina with a baseline total serum cholesterol of 155 to 271 mg/dL – showed risk reductions in all cardiovascular events AND all-cause mortality with pravastatin
This study illustrates the point from the previous slide - reductions are similar in older and younger patients but the benefit was magnified in the elderly because a greater incidence – this is reflected in the NNT data:
All-cause mortality 22 older patients versus 46 younger
CAD death 35 older versus 71 younger
Fatal or nonfatal MI 30 older versus 36 younger
Stroke older 79 versus 170 younger
References
Hunt D, et al. Benefits of pravastatin on cardiovascular events and mortality in older patients with coronary heart disease are equal to or exceed those seen in younger patients: Results from the LIPID trial. Ann Intern Med. 2001;134(10):931.
Age yr olds; Pravastatin v. Placebo
Hunt D, et al. Benefits of pravastatin on cardiovascular events and mortality in older patients with coronary heart disease are equal to or exceed those seen in younger patients: Results from the LIPID trial. Ann Intern Med. 2001;134(10):931.

24. ATRIAL Fibrillation & THE elderly
Q: How does Atrial Flutter AGE? A: >80% of patients who undergo radiofrequency catheter ablation of typical atrial flutter will have AF within the following 5 years (1,2)
REFERENCES
January CT, et al AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and Heart Rhythm Society. J Am Coll Cardiol 2014; 64:e1-76.
Ellis K, et al. Incidence of Atrial Fibrillation post-cavotricuspide isthmus ablation in patients with typical atrial flutter: left atrial size as an independent predictor of atrial fibrillation recurrence. J Cardiovasc Electrophysio 2007; 18:

25. Atrial Fibrillation Patient Centered Care / Goals of Care
Incidence increases with Age
Stroke Risk
Stroke Prophylaxis
Rate Control
Patient Centered Care
“The task of the 2014 writing committee was to establish revised guidelines for optimum management of AF … This guideline supersedes the ‘ACC/AHA/ESC 2006 guidelines for the management of patients with Atrial Fibrillation(1).”
“The guidelines attempt to define practices that meet the needs of most patients in most circumstances. The ultimate judgment about care of a particular patient must be made by the clinician and patient in light of all the circumstances prescribed by that patient(1).”
“Prescribed courses of treatment in accordance with these recommendations are effective only if followed. Because lack of patient understanding and adherence may adversely affect outcomes, clinicians should make every effort to engage the patient’s active participation in prescribed medical regimens and lifestyles(1).”
Increases with Age
More than a 1/3 of patients DIAGNOSED with Atrial Fibrillation are >80 years of age (2).
Stroke Risk
Stroke Risk increases with Age (3)
AF-Related stroke is likely to be more severe than non-AF related stroke (4)
AF associated with increased risk of HF (5-7)
AF associated with increased risk of DEMENTIA (8)
AF associated with increased risk of MORTALITY (9)
REFERENCES
January CT, et al AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and Heart Rhythm Society. J Am Coll Cardiol 2014; 64:e1-76.
Go AS, et al. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA 2001; 285:
Wolf PA, et al. Atrial Fibrillation a major contributor to stroke in the elderly. The Framinghman Study. Arch Intern Med 1987; 147:
Miller PS, et al. Are cost benefits of anticoagulation for stroke prevention in atrial fibrillation underestimated? Stroke 2005; 36:360-6.
Wang TJ, et al. Temporal Relations of Atrial Fibrillation and CHF and their joint influence on mortality: the Framingham Heart Study. Circulation 2003; 107:2920-5
Krahn AD, et al. The natural history of atrial fibrillation: incidence, risk factors, and prognosis in Manitoba Follow-up Study. Am J Med 1995; 98:
Stewart S, et al. A population-based study of the long-term risks associated with atrial fibrillation: 20-year follow-up of the Renfrew/Paisley Study. Am J Med 2002; 113:
Ott A, et al. Atrial Fibrillation and Dementia in a population-based study. The Rotterdam Study. Stroke 1997; 28:
Kannel WB, et al. Prevalence, incidence, prognosis, and pre-disposing conditions for atrial fibrillation: population-based estimates. Am J Cardiol 1998; 82:2N-9N.
January CT, et al AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and Heart Rhythm Society. J Am Coll Cardiol 2014; 64:e1-76.

26. Should WARFARIN be prescribed in this patient?
Anticoagulation
HPI: An 84 year old resident of an assisted living dementia unit presents to sub-acute rehabilitation following a hospital evaluation for a “change in mental status” ruled to DELIRIUM due to new onset ATRIAL FIBRILLATION with rapid ventricular response
Functional Hx: (+) ambulates with a rolling walker at baseline
PMHx: DM, HTN, Hx Recurrent Falls, Osteoporosis, Depression, Dementia, Chronic Constipation
MMSE (8/2012): Total Score 14/30 [noted deficits in the following areas – 1/5 with time orientation , 3/5 deficit with location orientation, 1/5 serial sevens, 0/3 recall, 2/3 three step command, 0/1 drawing pentagon, 0/1 writing sentence]
Medications
Insulin Glargine 12 units qHS
Lisinopril 20mg daily
Metoprolol XL 50mg daily
Alendronate 70mg qWeek
Calcium 500mg
Vitamin D 400IU BID
Docusate BID
Citalopram 20mg daily
Donepezil 10mg daily
Memantine10mg BID
Should WARFARIN be prescribed in this patient?
(A) YES
(B) NO

27. Should WARFARIN be prescribed in this patient?
Anticoagulation
HPI: An 84 year old resident of an assisted living dementia unit presents to sub-acute rehabilitation following a hospital evaluation for a fall with a hip fracture requiring ORIF. Functional Hx: (+) ambulates with a rolling walker at baseline PMHx: DM, HTN, Hx Recurrent Falls, Osteoporosis, Depression, Dementia, Chronic Constipation MMSE (8/2012): Total Score 14/30 [noted deficits in the following areas – 1/5 with time orientation , 3/5 deficit with location orientation, 1/5 serial sevens, 0/3 recall, 2/3 three step command, 0/1 drawing pentagon, 0/1 writing sentence]
Medications
Insulin Glargine 12 units qHS
Lisinopril 20mg daily
Metoprolol XL 50mg daily
Alendronate 70mg qWeek
Calcium 500mg
Vitamin D 400IU BID
Docusate BID
Citalopram 20mg daily
Donepezil 10mg daily
Memantine10mg BID
Let’s step back and look at the big picture -- in patients under the age of 65 with atrial fibrillation and other risk factors for a stroke, warfarin decreases the risk of stroke from 4.9% a year to 1.7% per year. In patients over the age of 75 with other risk factors for stroke, warfarin can reduce the risk of a major stroke from 12% per year to somewhere between 2-4% per year.
Those at the highest risk for stroke, those who are the oldest of the old, have had a prior stroke, have CHF and DM and HTN, are less likely to be given warfarin because of concerns for their comorbidities and risks, but is precisely this group that stands to gain the most “bang for the buck” with treatment
Should WARFARIN be prescribed in this patient?
(A) YES
(B) NO

28. Atrial Fibrillation Stroke Prophylaxis
We underutilize anticoagulation in the elderly with atrial fibrillation
Age has been well-established as a deterrent for prescription of anticoagulation. The risk of venous thromboembolism, for example, increases exponentially with advancing age, rising from an annual incidence of approximately3:
Age /100,000
Age /100,000
Age /100,000
References
Man-Son-Hing M, Nichol G, Lau A, et al. Choosing antithrombotic therapy for elderly patients with atrial fibrillation who are at risk for falls. Arch Intern Med 1999; 159:
Kappor J. Management of Atrial Fibrillation. The Lancet, Volume 370, Issue 9599, Page 1608, 10 November 2007
Anderson FA Jr, et al. A population-based perspective of the hospital incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism. he Worcester DVT Study. Arch Intern Med. 1991;151(5):933

29. Anticoagulation Clinician Concerns
Compliance
Monitoring
“Fall Risk1,2”
Cognitive Impairment
Drug-Drug Interactions
Bleeding Risk
Age has been well-established as a deterrent for prescription of anticoagulation. The risk of venous thromboembolism, for example, increases exponentially with advancing age, rising from an annual incidence of approximately3:
Age /100,000
Age /100,000
Age /100,000
References
Man-Son-Hing M, Nichol G, Lau A, et al. Choosing antithrombotic therapy for elderly patients with atrial fibrillation who are at risk for falls. Arch Intern Med 1999; 159:
Kappor J. Management of Atrial Fibrillation. The Lancet, Volume 370, Issue 9599, Page 1608, 10 November 2007
Anderson FA Jr, et al. A population-based perspective of the hospital incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism. he Worcester DVT Study. Arch Intern Med. 1991;151(5):933
Man-Son-Hing M, Nichol G, Lau A, et al. Choosing antithrombotic therapy for elderly patients with atrial fibrillation who are at risk for falls. Arch Intern Med 1999; 159:
Kappor J. Management of Atrial Fibrillation. The Lancet, Volume 370, Issue 9599, Page 1608, 10 November 2007

30. Anticoagulation Clinician Concerns
SUMMARY POINT: If one of your greatest fears was BLEEDING, evidence is mounting that even if your patient does bleed, there are benefits to RESTARTING / RESUMING anticoagulation.
Age has been well-established as a deterrent for prescription of anticoagulation. The risk of venous thromboembolism, for example, increases exponentially with advancing age.
These Danish researchers used a national database to follow the course of 4602 patients, average age 78 years [excluded VALVULAR HEART DISEASE and those <30 or >100, as well as DVT / PE within 6 months – if they truly wanted homogeneity they would have thrown out all of the NOAC patients and included only WARFARIN; NOAC total enrollees 13!!], discharged after hospitalization for GI bleeding associated with antithrombotic treatment for atrial fibrillation. Researchers used a “90 day blanking period – that is, follow-up did NOT start until inclusion day plus 90 days. All patients who died, experienced a thromboembolic event, major bleeding, or recurrent GI bleed within 90 days were excluded].
27% did NOT restart antithrombotic therapy AFTER their GI BLEED (in a comparable study 50% of patients with AFIB in America did NOT resume WARFARIN treatment after GI bleed2).
In this cohort study, restarting antithrombotic treatment following a gastrointestinal (GI) bleed in patients with atrial fibrillation was associated with decreased overall mortality over the next 2 years and a decrease in thromboembolisms, especially when using an oral anticoagulant. However, this treatment was also associated with an increase in major bleeding events. Recurrent GI bleeding was not higher among patients who restarted an antithrombotic treatment regimen than among those who did not resume treatment.
“A HAS-BLED score > 3 at the inclusion event showed an increased associated risk of recurrent GI bleeding in patients who restarted single treatment with oral anticoagulation …” The cumulative incidence of death was high 39% died within 2 years of having that first GI BLEED (the inclusion event) and includes ALL patients whether or not they restarted anti-thrombotic treatment. Preventing strokes among these high risk patients is a clinical challenge. For those of you who use the HAS-BLED bedside calculator to influence your decision-making it is included below:
SBP > 160mmHg 1 point
Creat > point
Cirrhosis / Bilirubin >2x normal; AST/ALT > 3x normal 1 point
Stroke History 1 point
Prior Major Bleeding / Predisposition to Bleeding 1 point
Labile INR point
AGE > point
Current Medictions (antiplatelets / NSAIDs) 1 point
Alcohol History (>8drinks / week) 1 point
This study was supported by a grant from Boehringer-Ingelheim – pharmaceutical company and manufacturer of DABIGATRAN (PRADAXA®) and IDARUCIZUMAB (PRAXBIND®), the reversal agent of the anticoagulant Dabigatran (Pradaxa®). ANTICOAGULATION was primarily WARFARIN in this study.
The STEP appearance of the graphs in this study (shown above) are due to the LOW NUMBERS of patients in this group and the fact that an event occurred.
TABLE 3 in this study show the HAZARD RATION for RESTARTING ANTITHROMBOITC TREATMENT AS COMPARED to the NON-RESUMPTIVE group
If it crosses 1 it is NOT statistically significant.
COHORT STUDY / OBSERVATIONAL DATA – what are the patient factors about those individuals that made the clinician at the bedside recommend to resume anti-thrombotic therapy with anticoagulation? The intangibles … likely MEMORY / FUNCTIONAL STATUS?? I demand a randomized controlled trial BUT there are many barriers to that type of study.
REFERENCES
Staerk L, et al. Stroke and recurrent haemorrhage associated with antithrombotic treatment after gastrointestinal bleeding in patients with atrial fibrillation nationwide cohort study. BMJ 2015; 351:h5876.
Qureshi W, et al. Restarting anticoagulation and outcomes after major gastrointestinal bleeding in Atrial Fibrillation. Am J Cardiol 2014; 113:
Staerk L, et al. Stroke and recurrent haemorrhage associated with antithrombotic treatment after gastrointestinal bleeding in patients with atrial fibrillation nationwide cohort study. BMJ 2015; 351:h5876.

31. Anticoagulation
Increased risk of ICH > 85 but not statistically significant
INRs less than 2.0 as compared to INRs 2-3 were not associated with lower risk of ICH
INRs > 3.5 associated with increased risk as should be avoided
Historical Information
At the time of this published study (~2004) “prominent recent guidelines [ACC/AHA] recommend using lower-intensity anticoagulation for the primary prevention of stroke in patients older than 75 years of age who have atrial fibrillation1 and suggest a target international normalized ratio (INR) range of 1.6 to 2.5, despite evidence that the risk for ischemic stroke increases sharply at INRs less than 2.0.” [excerpted from article Fang MC, 2004].
Age + Anticoagulation
170 Case controlled studies of individuals with ICH while being treated with warfarin for Atrial Fibrillation were matched with 1020 controls – ICH patients were older (75 vs 73 yrs old), had higher INRs (2.7 vs 2.3)
The authors of this 2004 study concluded that “the risk for intracranial hemorrhage increases at age 85 years. International normalized ratios less than 2.0 were not associated with lower risk for intracranial hemorrhage compared with INRs between 2.0 and 3.0. Therefore, anticoagulation management should focus on maintaining INRs in the 2.0 to 3.0 range, even in elderly patients with atrial fibrillation, rather than targeting INRs less than 2.0. Similarly, INRs of 3.5 or greater should be avoided.” Prior to this study, many have recommended a goal INR in elderly patients, but since the risk of bleeding is unchanged (compared to ) this seems futile.
References
Fuster V, Ryden LE, Asinger RW, Cannom DS, Crijns HJ, Frye RL, et al. ACC/AHA/ESC guidelines for the management of patients with atrial fibrillation: executive summary. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines and Policy Conferences (Committee to Develop Guidelines for the Management of Patients With Atrial Fibrillation): developed in Collaboration With the North American Society of Pacing and Electrophysiology. J Am Coll Cardiol. 2001;38:
2. Fang MC, et al. Advanced age, anticoagulation intensity, and risk for intracranial hemorrhage among patients taking warfarin for atrial fibrillation. Ann Intern Med. 2004;141(10):745
Fang MC, et al. Advanced age, anticoagulation intensity, and risk for intracranial hemorrhage among patients taking warfarin for atrial fibrillation. Ann Intern Med. 2004;141(10):745

32. CHA2DS2-VASc 1 1.3 2 2.2 SCORE Adjusted Stroke Rate (%/year) 3 3.2 41
1.3 2
2.2 3
3.2 4
4.0 5
6.7 6
9.8 7
9.6 8 9
15.2
With CHA2DS2- VASc = 0, it is reasonable to omit antithrombotic therapy
With CHA2DS2- VASc = 1, no antithrombotic therapy or treatment with oral anticoagulation or aspirin may be considered
With CHA2DS2- VASc > 2, oral anticoagulants are recommended
CHA2DS2-VASc is preferred according to AHA/ACC recommendations
C = CHF
H = HTN
A = AGE > 75 [2 points]
D = DM
S = previous STROKE / TIA [2 points]
VA = Vascular Disease (prior MI / PAD / Aortic Plaque)
Sc = Sex Category (i.e. female – get 1 point for being female)
Q: What’s the cut score for “when anticoagulation should be recommended?” A:
Q: Is reassessment necessary?
A: Yes, what happens to a 64 year old WOMAN with a CHADS-VASC score of a 1 who turns 65??? She goes from a score of 1 to a score of 2.
Q: What happened to CHADS2?

33. Warfarin vs Aspirin in the Elderly
973 patients > 75 years old (mean 81.5 years old)
Randomly assigned to Aspirin 75mg or Warfarin INR 2-3
The primary endpoint was fatal or disabling stroke (ischemic or hemorrhagic) or intracranial hemorrhage or significant emboli
Warfarin Group – 24 events
(21 strokes, 2 ICH, 1 embolism)
Aspirin Group – 48 events
(44 strokes, 1 ICH, 3 emboli)
“This issue was addressed in the Birmingham Atrial Fibrillation Treatment of the Aged (BAFTA) study, a randomized trial of warfarin (INR ) versus aspirin (75 mg/day) in elderly patients (age ≥75 years) with AF when tested in a primary care setting . In this trial, 973 patients (mean age 81) were followed for an average of 2.7 years, with a primary thrombotic event rate (ie, fatal or nonfatal disabling stroke or significant arterial embolism) of 1.8 percent/year in the warfarin arm, compared with 3.8 percent/year in the aspirin arm (hazard ratio 0.48; 95% CI ), while the risks of major hemorrhage (intracerebral as well as at all sites) were similar in the two treatment arms.” [copied from uptodate]
“Patients were excluded if they had any of the following: rheumatic heart disease; a major non-traumatic haemorrhage within the previous 5 years; intracranial haemorrhage; endoscopically proven peptic ulcer disease in the previous year; oesophageal varices; allergic hypersensitivity to either of the study drugs; a terminal illness, as judged by their primary care physician; surgery within the past 3 months; or blood pressure greater than 180/110 mm Hg. Patients were also excluded if their primary care physician judged, on the basis of risk factors for stroke and haemorrhage, that the patient either should or should not be on warfarin1.”
References
Mant J, et al. Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial. Lancet. 2007;370(9586):493.
Mant J, et al. Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial. Lancet. 2007;370(9586):493.

34. Warfarin vs Aspirin + Clopidogrel
CHADS2 Score of 2
Randomly assigned to receive Warfarin (target INR ) or the combination of Clopidogrel 75mg plus Aspirin 75mg-100mg
Trial Terminated Early due to WARFARIN superiority
ACTIVE-W results are noted above
ACTIVE-A compared CLOPIDOGREL combined with ASPIRIN versus ASPIRIN alone in patients with AF who were unsuitable candidates for oral anticoagulation and who had >1 additional stroke risk factor. The combination resulted in 28% RR in all strokes compared with aspirin alone.
REFERENCES
Connolly S, et al. Clopidogrel plus Aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE-W): a randomized controlled trial. Lancet 2006; 367:
Connolly S, et al. Effect of clopidogrel added to aspirin in patients with atrial fibrillation. N Engl J Med 2009; 360:
Connolly S, et al. Clopidogrel plus Aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE-W): a randomized controlled trial. Lancet 2006; 367:

35. Anticoagulation & The Elderly
Setting
% in Range
Self-Monitoring
72%
Randomized Trials
55-66%
Anti-Coagulation Clinics
66%
Community Physicians
57%
TTR = Time in Therapeutic Range (number reported for those taking WARFARIN)
References
van Walraven C, et al. Effect of study setting on anticoagulation control: a systematic review and metaregression. Chest. 2006;129(5):1155.
Connolly SJ, et al. Dabigatran versus Warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361:
Patel MR, et al. Rivaroxaban versus Wafarin in patients with non-valvular atrial fibrillation. N Engl J Med 2011; 365:
Granger CB, et al.
* Simple Finger Stick required
1. van Walraven C, et al. Effect of study setting on anticoagulation control: a systematic review and metaregression. Chest. 2006;129(5):1155.

36. WARFARIN superiority NNT 40 PRIMARY PREVENTON1
NNT 14 SECONDARY PREVENTION1
Q: What about new agents?
A: “… complex patients with multiple chronic conditions were excluded from all trials …”
WARFARIN vs NO THERAPY in FIB
NNT 40 PRIMARY PREVENTON1
NNT 14 SECONDARY PREVENTION1
WARFARIN vs ANTI-PLATELET
NNT 81 PRIMARY PREVENTON1
NNT 24 SECONDARY PREVENTION1
REFERENCE 1. Hart RG, et al. Meta-analysis antithrombotic therapy to prevent stroke in patients who have non-valvular atrial fibrillation. Ann Intern Med 2007; 146:
1. Hart RG, et al. Meta-analysis antithrombotic therapy to prevent stroke in patients who have non-valvular atrial fibrillation. Ann Intern Med 2007; 146:

37. NOVEL ANTICOAGULATION
Older patients take more medications, may metabolize medications more slowly, and are at an increased risk for bleeding complications
Primary outcome was MAJOR BLEEDING which was significantly less common with apixaban, edoxaban, and rivaroxaban, but was increased with dabigatran [THIS MED HAS ANTEDOTE] in the 150 mg dose
Of 19 studies, 11 reported data separately for patients 75 years and older in the original publication, in unpublished clinical trial reports, or provided these data on request. The studies were generally of good quality, although approximately half failed to mask the patients and healthcare providers.
An important limitation of the analysis is that most of the comparisons were based on or dominated by a single large manufacturer-sponsored study (eg, ReLy, ARISTOTLE, Engage-AF).
BOTTOM LINE: There were no major differences in the magnitude of benefits and harms between those 75 years and older and the total population studied. The bleeding risk is somewhat lower with apixaban and rivaroxaban, and is higher with dabigatran
REFERENCE
1. Shama, et al. Efficacy and harms of direct oral anticoagulants in the elderly for stroke prevention in atrial fibrillation and secondary prevention of venous thromboembolism systemic review and meta-analysis. Circulation 2015; 132(3):
Shama, et al. Efficacy and harms of direct oral anticoagulants in the elderly for stroke prevention in atrial fibrillation and secondary prevention of venous thromboembolism systemic review and meta-analysis. Circulation 2015; 132(3):

38. Atrial Fibrillation Rate Control
“Loss of atrial contraction may markedly decrease cardiac output, particularly when diastolic ventricular filling is impaired by MITRAL STENOSIS, hypertension, hypertrophic cardiomyopathy (HCM), or restrictive cardiomyopathy. After restoration of sinus rhythm, atrial mechanical function fails to recover in some patients, likely as a consequence of remodeling or underlying atrial disease and duration in AF (1,2).
REFERENCES
January CT, et al AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and Heart Rhythm Society. J Am Coll Cardiol 2014; 64:e1-76.
Wang YC, et al. Left atrial dysfunction in patients with atrial fibrillation after successful rhythm control for > 3 months. Chest 2005; 128:

39. Recommendations for Rate Control
Control ventricular rate with Beta-Blocker or Non-Dihydropyridine Calcium Channel Antagonist for AF
A heart rate control (resting heart rate < 80 bpm) strategy is reasonable for symptomatic management in AF
A lenient rate-control strategy (resting heart rate < 110bpm) maybe reasonable when patient asymptomatic & LV systolic function preserved
“In general, beta-blockers are the most common agents used for rate control followed by non-dihydropyridine calcium channel blockers, digoxin, and amiodarone(1)”
“In patients with HF, CARVEDILOL had efficacy for heart rate control and in combination with DIGOXIN resulted in improved LV function(1,2)”
REFERENCES
2014 AHA/ACC Guidelines
Khand AU, et al. Carvedilol alone or in combination with digoxin for the management of atrial fibrillation with patient with heart failure? J Am Coll Cardiol 2003; 42:
Non-Dihydropyridine Calcium Channel Antagonists should NOT be used in decompensated HF

40. An 88 year old male with systolic cardiomyopathy with an EF < 35% presents with complaints of fatigue and palpitations due to ATRIAL FIBRILLATION with HR bpm. He is euvolemic, BP 130/70, and presently taking CARVEDIOLOL 25mg BID. Which of the following strategies is the best next step in the management of his heart rate?
Prescribe Diltiazem
Prescribe Verapamil
Prescribe Digoxin
Prescribe Amiodarone
Consult Cardiology

41. Rate Control Medications
Beta-Blockers – Atenolol, Carvedilol, Metoprolol, Nadolol, Propanolol Nondihydropyridine Calcium Channel Blockers – Diltiazem + Verapamil Digoxin Amiodarone
Digoxin is not usually first-line therapy for ventricular rate control in patients with AF, despite its common use. It can be combined with Beta-Blockers or Calcium Channel Blockers to improve ventricular rate control … studies finding an association between digoxin therapy and mortality raise further concern about its use, particularly long term.
DIGOXIN is SAFER than alternative AMIODARONE

42. Craig T. January et al. Circulation. 2014;130:e199-e267
Approach to selecting drug therapy for ventricular rate control.* *Drugs are listed alphabetically. †Beta blockers should be instituted following stabilization of patients with decompensated HF. The choice of beta blocker (eg, cardioselective) depends on the patient’s clinical condition. ‡Digoxin is not usually first-line therapy. It may be combined with a beta blocker and/or a nondihydropyridine calcium channel blocker when ventricular rate control is insufficient and may be useful in patients with HF. §In part because of concern over its side-effect profile, use of amiodarone for chronic control of ventricular rate should be reserved for patients who do not respond to or are intolerant of beta blockers or nondihydropyridine calcium antagonists. COPD indicates chronic obstructive pulmonary disease; CV, cardiovascular; HF, heart failure; HFpEF, heart failure with preserved ejection fraction; and LV, left ventricular.
Craig T. January et al. Circulation. 2014;130:e199-e267