Professional Documents
Culture Documents
Objectives
Identify specific blood pressure thresholds and
goals for antihypertensive pharmacologic therapy!
Construct an individualized blood pressure
lowering regimen based on patient characteristics!
Identify groups of patients who will benefit
frompharmacological lipid-lowering therapy!
Devise an appropriate intensity lipidloweringtreatment and monitoring regimen
This is Bob
Bob is a 50-year old male who has not seen a
health care professional for many years. His
father (age 70) recently had a myocardial
infarction. That has led Bob to think he should
start taking care of himself better.!
Family History:
!
Dad (70) - alive, HTN, MI at age 70
!
Mom (69) - alive, diabetes
!
2 brothers - alive and healthy
Smokes cigarettes (20 pack/yr history) and drinks alcohol socially
Weight: 220 lbs, Height: 68 inches
BMI: 34 kg/m2, Waist circumference 44 inches
His blood pressure today is 150/106 mm Hg (left arm), 151/107 (right arm)
Fasting lipid panel: total cholesterol 215; LDL 136; HDL 35; triglycerides 220.
PMH: He has no past medical history or surgeries.
Medications: Famotidine 20 mg as needed.
Age 60
Age 18-59
Age 18!
Age 18!
Diabetes!
CKD!
No CKD
Diabetes
SBP 150 !
DBP 90
SBP 140 !
DBP 90
SBP 140 !
DBP 90
SBP 140 !
DBP 90
Age 60
Age 18-59
Age 18!
Age 18!
Diabetes!
CKD!
No CKD
Diabetes
SBP 150 !
DBP 90
SBP 140 !
DBP 90
SBP 140 !
DBP 90
SBP 140 !
DBP 90
Total Mortality!
(21% reduction)
170
160
150
140
P=0.019
130
120
Placebo
Indapamide SR +/- perindopril
Placebo
Indapamide SR +/- perindopril
110
100
90
80
70
Follow-up (years)
N Engl J Med 2008;358/ACC 2008
200
190
180
170 rj
160
RR 0.63 (0.49-0.82)
it:
150-1
140
130
120
110
100
90
80
70.
! feg--g-g-
60
0<
12
I I I I I I I I I
60
24
Follow-up,
I I I I 1 I I I I
mo
lin
24
36
Follow-up,
48
60
mo
The
5-year average SBP was 143 mmHg Figin2.Cumulative
treatment
group and 155 mmHg in
fatal plus nonfatal stroke rate per 100 participants in the
Fig 1. Average systolic and diastolic blood pressure during the Systolic Hyper
tension in the Elderly Program follow-up plotted at 1, 3, 6, and 12 months and
active treatment (solid line) and placebo (broken line) groups during the Systolic
placebo
group
therafter.
with
indicates
blood
Solid line
open squares
average systolic
Hypertension in the Elderly Program.
yearly
-
pressure for the active treatment group; broken line with closed circles, average
systolic blood pressure for the placebo group; solid line with triangles, average
JAMA.
1991;265:3255-3264
diastolic
blood pressure for the active treatment group; and broken line with open
22 (1.4)
1.6 (0.63.4)
0 (0.00)
0.0 (0.00.8)
16 (1.0)
1.1 (0.32.7)
1 (0.05)
0.3 (0.01.5)
24
Mild-treatment group
180
Strict-treatment
Blood pressure during treatment. *Intergroup differences were significant from this point (p<
0.001). Systolicgroup
and dias- 2212
group
s were lower by 9.7 mmHg and 3.3 mmHg, respectively, in the strict-treatment group than inMild-treatment
the mild-treatment
group at 2206
Population:
HTN
patients
age 70
of treatment mmHg
(both p< 0.001).
Events
140
1883
1885
1815
1797
1755
1742
1482
1500
160
Incidences
of Nonfatal and Fatal Components of
mary Endpoint
- 85
1964
1959
24
0.10
0
10
Moderate control group (12.0/1000patients-year)
Fig. 3. The Kaplan-Meier time-to-event analyses for the primary
endpoint.
cumulative rates of morbidity from the p
Strict control
groupThe
(10.6/1000patients-year)
Strict
control
group
endpoint were similar in the two groups. To estimate cumulative incidence rates of morbidity, data up to 2 years after ad
vival maytration
vary around
75used.
years of
age (24),
anmore
age of than
75 years
were
Data
from
2 0.08
years after treatment were excluded.
Moderate control group
180
2055
2042
20
endpoint 120
86 (9)
86 (8)
vascular disease
52 (3)
49 (3)
significant during the follow-up period.
Organization
in sex, age, body mass index, smoking status, baseline BP, the
ing efonidipine alone or in combination with other ant
al infarction
36 (2)
30 (0)
100
prevalence
of study
an enlarged
or LVH, a past history (6
tensive drugs. One thousand thirteen subjects (45.8%)
al hemorrhage
7 (0)
8 (1)
The details
of the JATOS
group andheart
the investigators
p<0.001
<0 001
(ANOVA)
0 02
0.02
achnoid hemorrhage
1 (1)
4 (2)
or more before enrollment) of cerebrovascular
disstrict-treatment group and 1,246 (56.5%) in the mild
are shownmonths
in the Appendix.
ent ischemic80
attack
8 (0)
7 (0)
ease or cardiac and vascular disease, prevalence of renal disment group were receiving monotherapy with efonidi
and vascular disease
26 (6)
28 (4)
ease, diabetesResults
mellitus or hyperlipidemia, or
the proportion of
another antihypertensive drug (p < 0.001). As shown in
0.00
a pectoris
9 (0)
10 (0)
2, at the end of treatment, a combination of antihyper
patients who had received prior antihypertensive treatment
60
ardial infarction
6 (1)
6 (0)
0
3
6
9 12 15 18 21Study
24 Profile
27 301). 33
39rates
42 of various antihypertensive
0
0 strict-treatmen
6
12
18 more frequently
24
36
42
drugs was
used in3the
(Table
The 36
usage
drugs
stive heart failure
8 (4)
7 (1)
than in the mild-treatment
(40.7% vs. 30.9% for
did not differmonths
significantly betweenexcluded
the twoofgroups.
months ofgroup
follow-up
ctive arterial disease
2 (0)
1 (0)
patients followed
Although 4,508 subjects were registered, 50 wereNumber
N
tensin-converting enzyme [ACE] inhibitors or angiote
minalJATOS
aortic rupture
0
(0)
1
(1)
because
they
did
not
return
for
follow-up
appointments,
and
Study Group. Hypertens Downloaded
Res. 2008;31(12):21152127.
1545
1482
1408
1336
1306
1295
336
from http://hyper.ahajournals.org/ by guestStrict
on July 18, 2014
S
aneurysm enlargement
0 (0)
2 (1)
14.3%924
vs. 11.6%
for adre
receptor
blockers,
p < 0.001;
40 were excluded because of violations of the study protocol
Moderate
1534
1461
1375
1304
1279
1265
902
335
Age 60
Age 18-59
Age 18!
Age 18!
Diabetes!
CKD!
No CKD
Diabetes
SBP 150 !
DBP 90
SBP 140 !
DBP 90
SBP 140 !
DBP 90
SBP 140 !
DBP 90
Age 60
Age 18-59
Age 18!
Age 18!
Diabetes!
CKD!
No CKD
Diabetes
SBP 150 !
DBP 90
SBP 140 !
DBP 90
SBP 140 !
DBP 90
SBP 140 !
DBP 90
Age 60
Age 18-59
Age 18!
Age 18!
Diabetes!
CKD!
No CKD
Diabetes
SBP 150 !
DBP 90
SBP 140 !
DBP 90
SBP 140 !
DBP 90
SBP 140 !
DBP 90
Age 60
Age 18-59
Age 18!
Age 18!
Diabetes!
CKD!
No CKD
Diabetes
SBP 150 !
DBP 90
SBP 140 !
DBP 90
SBP 140 !
DBP 90
SBP 140 !
DBP 90
Age 18!
Age 18!
Diabetes!
CKD!
No CKD
Diabetes
Age 18-59
Age 60
At what level should
you treat BP?
SBP 150 !
DBP 90
SBP 140 !
DBP 90
SBP 140 !
DBP 90
SBP 140 !
DBP 90
CENTRAL AGENTS
! Clonidine
! Reserpine
! Moxonidine
CATECHOLAMINE
INHIBITORS
DIURETICS
SVR
Na+ loss
RENIN
? Vasodilation
ANGIOTENSIN II
ACE INHIBITORS
VASODILATORS
! DHPs: nifedipine,
amlodipine, others
! Verapamil, diltiazem
! Prazosin, doxazosin
! Hydralazine (direct)
Opie 2012
AT-1 BLOCKERS
(ARBs)
Age 60
Age 18-59
Age 18!
Age 18!
Diabetes!
CKD!
No CKD
Diabetes
SBP 150 !
DBP 90
SBP 140 !
DBP 90
SBP 140 !
DBP 90
SBP 140 !
DBP 90
Age 60
Age 18-59
Age 18!
Age 18!
Diabetes!
CKD!
No CKD
Diabetes
SBP 150 !
DBP 90
SBP 140 !
DBP 90
SBP 140 !
DBP 90
SBP 140 !
DBP 90
Age 60
Age 18-59
Age 18!
Age 18!
Diabetes!
CKD!
No CKD
Diabetes
SBP 150 !
DBP 90
SBP 140 !
DBP 90
SBP 140 !
DBP 90
SBP 140 !
DBP 90
Age 60
Age 18-59
Age 18!
Age 18!
Diabetes!
CKD!
No CKD
Diabetes
SBP 150 !
DBP 90
SBP 140 !
DBP 90
SBP 140 !
DBP 90
SBP 140 !
DBP 90
Nonblack
How do you do it?
Black
Initiate thiazide or
CCB, alone or in
combination.
All Races
Initiate ACEI or ARB,
alone or in combination
with other drug class.
Details
Start one drug and Start with one drug then add a second drug before achieving the maximum recommended
then add a second
dose of the initial drug, then titrate both drugs up to the maximum recommended doses of
before achieving
both to achieve goal BP !
maximum dose of If goal BP is not achieved with 2 drugs, select a third drug from the list (thiazide, CCB, ACEI,
the initial drug!
or ARB), avoiding the combined use of ACEI and ARB. Titrate the third drug up to the
maximum recommended dose to achieve goal BP
Begin with 2 drugs Initiate therapy with 2 drugs simultaneously, either as 2 separate drugs or as a single pill
at the same time,
combination. !
either as 2
Start therapy with 2 drugs when SBP is >160 mm Hg and/or DBP is >100 mm Hg, or if SBP
separate pills or
is >20 mm Hg above goal and/or DBP is >10 mm Hg above goal. !
single pill
If goal BP is not achieved with 2 drugs, select a third drug from the list (thiazide, CCB, ACEI,
combination!
or ARB), avoiding the combined use of ACEI and ARB. Titrate the third drug up to the
maximum recommended dose.
MANN Report
Special Report
Trials
Chlorthalidone
HCTZ
is a paltry antihypertensive
MANN Report !
Special Report
1 Month follow-up
At goal BP?
No
Yes
1 Month follow-up
At goal BP?
No
Yes
1 Month follow-up
At goal BP?
No
Yes
No
At goal BP?
Yes
Continue! current
treatment and
monitoring
SBP 140 !
DBP 90
SBP 140 !
DBP 90
Strategy C!
Start therapy with 2 drugs when SBP is >160 mm
Hg and/or DBP is >100 mm Hg, or if SBP is >20 mm
Hg above goal and/or DBP is >10 mm Hg above
goal.
SBP 140 !
DBP 90
Strategy C!
Start therapy with 2 drugs when SBP is >160 mm
Hg and/or DBP is >100 mm Hg, or if SBP is >20 mm
Hg above goal and/or DBP is >10 mm Hg above
goal.
Example regimen:!
Benazepril 20 mg Daily!
Amlodipine 5 mg Daily
CHOLESTEROL CONCEPT #1
3.7
2.9
2.2
1.7
1.3
1.0
40
70
100
130
LDL-C (mg/dL)
160
190
CHOLESTEROL CONCEPT #2
Absolute benefit from statin
therapy is proportional to baseline
ASCVD risk!
Patients with lower baseline
ASCVD risk have lower absolute
benefit from statin therapy that
may approach the risk for
adverse effects
Diabetes !
Age 40-75!
LDL cholesterol 70-189*
No diabetes or ASCVD !
Age 40-75!
LDL 70-189*!
Estimated 10-yr ASCVD
risk >7.5%
Yes
High-intensity statin
There migh
Evidence
Intensity
of
Statin
Therapy
High-Intensity Statin
Moderate-Intensity Statin
Low-Intensity Statin
Although
Daily dose lowers LDL on
Daily dose lowers LDL on
Daily dose lowers LDL on
recomm
average by 50%
average by 30% to <50%
average bynot
<30%
Atorvastatin 10 (20) mg
Rosuvastatin (5) 10 mg
Simvastatin 20-40 mg
Pravastatin 40 (80) mg
Lovastatin 40 mg!
Fluvastatin XL 80 mg
Pitavastatin 2-4 mg
Simvastatin 10 mg
Pravastatin 10-20 mg!
Lovastatin 20 mg!
Pitavastatin 1 mg
Clinical ASCVD:
Age 75 y!
without contraindications,
conditions or drug-drug interactions
influencing statin safety, or a
history of statin intolerance
panel is required.
It is reasonable to evaluate
the potential for ASCVD
benefits and for adverse
effects, and to consider patient
Age >75 y!
preferences, in initiating or
OR!
with conditions or drug-drugcontinuing a moderate- or highintensity statin, in individuals
interactions influencing statin safety,
with ASCVD >75 years of age.
or a history of statin intolerance
PRIMARY PREVENTION
Diabetes
Age 40-75
LDL cholesterol 70-189*
No diabetes or ASCVD
Age 40-75
LDL 70-189*
Estimated 10-yr ASCVD
risk >7.5%
therapy, across the range of LDLC levels in primary-prevention individuals aged >40 years and
38)(21,82,107-110).
Similar RRR in ASCVD and major CVD events between primary- and secondary-prevention populations!
Yes
Elevated LDL
Diet
Drugs
Diuretics, cyclosporine,
glucocorticoids, amiodarone
Diseases
Yes
Yes
No
Diabetes?
Moderate-intensity statin!
if 10-yr ASCVD risk < 7.5%
Yes
High-intensity statin!
if 10-yr ASCVD risk > 7.5%
10 mg
Mobile Version
http://my.americanheart.org/professional/StatementsGuidelines/PreventionGuidelines/
Prevention-Guidelines_UCM_457698_SubHomePage.jsp
INDIVIDUALS NOT
IN A
Yes
No
Diabetes?
Yes
Moderate-intensity statin!
Yes
Moderate-to-high
intensity statin
(High-intensity if 10-yr
ASCVD risk > 7.5%)
No
Calculate 10-yr
ASCVD risk using
Pooled Cohort
Equations
AFCAPS
JUPITER
Lovastatin 2040 mg
Rosuvastatin 20 mg
27%
115 vs. 156 (41 mg/dL)
50%
55 vs. 110 (55 mg/dL)
NNT to prevent
1 ASCVD event
26%
56
44%
30
Yes
No
Diabetes?
Yes
Moderate-intensity statin!
Yes
Moderate-to-high
intensity statin
(High-intensity if 10-yr
ASCVD risk > 7.5%)
No
Calculate 10-yr
ASCVD risk using
Pooled Cohort
Equations
No
ASCVD prevention benefit less clear, but may be considered
MODERATE!INTENSITY!STATIN!TREATMENT!
Assumes a 35% relative risk reduction in ASCVD from moderate intensity statin treatment
NNT to prevent 1 ASCVD event varies by baseline estimated 10-year ASCVD risk.
NNH based on 1 excess case of incident diabetes per 100 individuals* treated with statins for 10 years.
Assumes a 45% relative risk reduction in ASCVD from high intensity statin treatment
NNT to prevent 1 ASCVD event varies by baseline estimated 10-year ASCVD risk
NNH based on 3 excess cases of incident diabetes* per 100 individuals treated with statins for 10 years.!
120!
NNT(to(prevent(1(ASCVD(event(over(10(years(
110%
100%
2.5%%
NNH=100%
90%
80%
70%
60%
5.0%(
50%
40%
30%
7.5%(
10.0%%
20%
15.0%%
10%
0%
0.0%%
5.0%%
10.0%%
15.0%%
20.0%%
20.0%%
25.0%%
25.0%%
10Ryear(ASCVD(risk(
*A conservative estimate of adverse events includes excess cases of incident diabetes, myopathy, and hemorrhagic
stroke. The NNH is dominated by excess cases of diabetes, with minimal contribution by myopathy (approximately
0.01 excess case per 100) and hemorrhagic stroke (approximately 0.01 excess case per 100 for hemorrhagic stroke)
(90,114,116)
NNT!to!prevent!1!ASCVD!event!over!10!years!
120%
110!
100!
90!
80!
2.5%!
70!
60!
50!
5.0%!
40!
NNH=33!
30!
20!
7.5%!
10.0%!
10!
0!
0.0%!
15.0%!
5.0%!
10.0%!
15.0%!
20.0%!
20.0%!
25.0%!
25.0%!
10?yearASCVD!risk!!
*A conservative estimate of adverse events includes excess cases of incident diabetes, myopathy, and
Clinician-Patient discussion
regarding
:! by excess cases of diabetes, with minimal contribution by
hemorrhagic stroke.
The NNH is dominated
myopathy (approximately 0.01 excess case per 100) and hemorrhagic stroke (approximately 0.01
ASCVD indicates atherosclerotic cardiovascular disease
ASCVD risk reduction
benefits !
excess case per 100 for hemorrhagic stroke) (90,114,116).
Adverse
Figure 6. Visual aid to illustrate relationship between NNT and NNH for high-intensity
statin: Teneffects!
-year
ASCVD indicates atherosclerotic cardiovascular disease
ASCVD risk and number- NNT to prevent 1 ASCVD event over 10 years compared with the NNH from
Drug-drug interactions!
adverse events* over 10 years for high-intensity statins
Patient preferences
INDIVIDUALS NOT
IN A
High-intensity statin !
! ! ! ! ! ! moderate-intensity statin when
predisposing characteristics present
http://www.fda.gov/cder/drug/infopage/rosuvastatin/crestor_cp.pdf
EVALUATE
AND
Mild to moderate
muscle symptoms
Discontinue the statin until the
symptoms can be evaluated.
Evaluate the patient for other
conditions that might increase the
risk for muscle symptoms
Hypothyroidism!
Renal or hepatic dysfunction!
Rheumatologic disorders
such as polymyalgia
rheumatica!
Steroid myopathy!
Vitamin D deficiency!
Primary muscle diseases!
Drug-drug interactions
Unexplained, severe
muscle symptoms
Discontinue the statin and
evaluate for rhabdomyolysis
(CK, creatinine, urine
myoglobin)
EVALUATE
AND
Mild to moderate
muscle symptoms
Unexplained, severe
muscle symptoms
EVALUATE
AND
Mild to moderate
muscle symptoms
Unexplained, severe
muscle symptoms
EVALUATE
AND
Mild to moderate
muscle symptoms
Unexplained, severe
muscle symptoms
Risk of developing diabetes is limited to patients who are already at high risk
of developing diabetes
Statin intensity
5.4
189
1,002
High-intensity vs.
moderateintensity statin
6.5
155
498
High-intensity
(rosuvastatin) vs.
placebo
5.9
169
332
Expected
Response?
No
No
Statin
Intolerance?
Reinforce medication
adherence
No
Yes
Manage Intolerance
Expected
Response?
Yes
Reinforce continued
adherence!
Follow-up in 3-12 months
Lifestyle Recommendations!
AHA/ACC guidelines stress the importance of lifestyle modifications to lower cardiovascular
disease risk. This includes eating a heart-healthy diet, regular aerobic exercises, maintenance
of desirable body weight and avoidance of tobacco products.
Lifestyle Recommendations!
AHA/ACC guidelines stress the importance of lifestyle modifications to lower cardiovascular
disease risk. This includes eating a heart-healthy diet, regular aerobic exercises, maintenance
of desirable body weight and avoidance of tobacco products.
Example regimen:!
Benazepril 20 mg Daily!
Atorvastatin 20 mg/Amlodipine 5 mg Daily
Implications
Practitioner
Questions?
Contact me:!
Nicholas B. Norgard, Pharm.D. BCPS!
University at Buffalo School of Pharmacy &
Pharmaceutical Sciences!
Office: 716-645-4779!
nnorgard@buffalo.edu