Practical Pearls for Primary Care Evaluation and Treatment of

When Thiazides Are Not A
Good Choice
Practical Pearls for
Primary Care
• History of Gout
• Creatinine > 1.6
• Lithium use
Diuretic Choice
and Treatment
of Hypertension
Evaluation
A 58 yo man is diagnosed with
hypertension. His BP'S are 160/96, 160/100,
and 158/96 on 3 outside readings. He has
been on a low sodium diet and he is not obese.
PMH- hyperlipidemia, GERD and gout. What
would be the most appropriate treatment?
A) Low salt diet and exercise
B) Hydrochlorathiazide
C) Doxazosin
D) AGE inhibitor
• strongly consider chlorthalidone
• Long acting, great data
• Major drawback has been hypokalemia
A 60 yo man presents for follow-up of
hypertension. He has been taking medication
(Lisinopril) for the past 3 months. His most recent
outside blood pressure readings are 156/94, 150/96,
158/92. PMH: Type 2 DM, GERD, depression. Meds:
Lisinopril 20mg qd, Rabeprazole 20mg qd, Sertraline
50 mg qd, Glyburide 10 mg qd.
What do you recommend?
A) No changes in therapy
B) Increase Lisinopril to 20 mg BID
C) Add Hydrochlorathiazide 12.5 mg qd
D) Add Amiodipine (Norvasc) 5mg qd
E) Add Clonidine .Img BID
Double the dose or add a second
agent?
Based on RCTs of HTN, at least 75%
of patients will require combination
therapy to achieve BP targets
Am J Hypertens 2010;4:42-50
Titrate single drug vs combo?
• Meta-analysis of 11,000 patients from
42 trials comparing single dose with up
titration vs switch to combo therapy
Combination Therapy
• Low doses of thiazide can be very effective in
combination with ACE inhibitors (12.5 mg of
thiazide)
• Thiazide ACE combination can be further
enhanced by moderate dietary salt restriction
• ACE/Amlodipine combination may have CV
benefi slightly better than ACE/diuretic in high
risk diabetic paients
Am J Med 2009;122:290-300
Adding a second agent is
about 5-fold more effective
A 58 yo woman is seen for treatment of hypertension. She
has not ever had good control of her hypertension since
treatment was started 2 years ago. She has been taking her
medications faithfully. Meds: Felodipine (Plendil), Atenolol ,
Clonidine, and Losartan (Cozaar). On exam her BP is 200/106
P-55.Labs- BUN 30, Cr 2.0, Na 137, K4.0. ECG- LVH
What would you recommend?
A) Increase felodipine from 10mg a day to 10mg BID
B) Increase losartan from 50mg BID to lOOmg BID
C) Add hydrochlorathiazide 12.5 mg qd
in
Am J Med 2009;122:290-300
D) Add hydrochlorathiazide 25 mg qd
E) Add furosemide 40 mg BID
Refractory Hypertension
• Occurs in 5% of hypertensive patients
• Always carefully evaluate for medication
adherence.
• Worse with increasing obesity
• Think of secondary causes
Beta-Blocl<ers
• Beta-blockers are no longer recommended as first
line therapy in most patients with HTN
• Atenolol has particularly poor outcomes in
comparison with other antihypertensives^
• Sleep apnea
• Ingestion of substances that interfere with
treatment (especially NSAIDS)
1. Lancet 2004;364:1684-89
Treatment of Refractory
Hypertension
• Most have too much volume. Furosemide
extremely useful, especially if renal
insufficiency present
• Strongly consider using spironolactone
c Simplify regimens if possible to improve
adherence
• Increasing drug dose usually not all that
effective- especially with ACEI and ARBS
Atenolol vs Placebo
All-cause mortality
1.01
0.89-1.15
CV mortality
0.99
0.83-1.18
Ml
0.99
0.83-1.19
Stroke
0.85
0.72-1.01
N = 6,825 followed for 4.6 years
Lancet 2004;364:1684-9
Atenolol vs other BP Agents
What happened to
Beta-Blockers?
All-cause mortality
1.13
1.02-1.25
CV mortality
1.16
1.00-1.34
Ml
1.04
0.89-1.20
Stroke
1.30
1.12-1.50
N = 17,671 followed over 4.6 years
Lancet 2004;364:1684-9
Beta-Blockers
• Beta-blockers are appropriate for patients
with compelling indications:
- heart failure
- migraines
-angina
- essential tremor
-atrial fibrillation
- hyperthyroidism
-Ml
--anxiety disorders
Pearls In the T r e a t m e n t of Hypertension
• Remember when not to use hydrochloathiazide:
renal insufficiency, gout
• Chlorthalidone has longer half life, better efficacy
than HCTZ
• Spironolactone avoids hypokalemia, avoid in
renal insufficiency, be careful if patient on an
ACEI or ARB. Remember gynecomastia
n Losartan can lower uric acid
T h e M u c h A w a i t e d J N C 8 is Here!!!!
• Major change is loosening of goals- goal of
BP <140/90 for diabetes and CKD, easy to
remember target not different based on
different populations
• Treatment initiation in patients > 60 at 150/90,
patients < 60 , 140/90
• Initial drug choice- Thiazide OR ACEI OR
ARB or Ca channel blocker
Prostate Cancer Screening
• JAMA. Published online December 18, 2013.
More From JNC 8
• Initial therapy for Black patientsThiazide OR Ca channel blocker
• Initial therapy for CKD patients- ACEI
or ARB as it has been shown to improve
outcomes
• A 66 yo man presents for follow up visit. He has
type 2 DM and hypertension. He wants has
questions on what screening tests are needed.
He had colonoscopy 4 years ago (no polyps).
His lipids were checked 6 months ago.
• He has not had a PSA checked
• Would you recommend a PSA?
W h o Recommends
Test Performance
Screening?
a ACS- YES (start age 50)
• AUA- YES (start age 54 for average risk men continue to
70)
• USPTF- NO
• CTF- NO
• United Kingdom National Screening - NO
• ACP- discuss, but inform on limited benefits and potential
tiarms, screen only ttiose with a clear preference
• But most importantly
• Sensitivity- PSA cut off of 4.0, 21 % (51 % for
high grade cancers)
• Specificity- 9 1 %
• Positive predictive value- 30% ( 2 5 % for PSA
4-10)
Negative predictive value 86%
•
Urology 1996:47(6)863
D JUrol. 1992;147(3Pt2):841.
Non C a n c e r C a u s e s of P S A Elevation
Prostate
Cancer
• Prostatitis
Awcireness
• Acute Urinary retention
• Ejaculation
• Biopsy
0 DRE
W h y Is It S o
Is t h e r e a Mortality Benefit T o
Controversial?
Screening With PSA?
• Perfornnance of the test
• Conflicting mortality data
• Severity of side effects of treatment
• European Randomized Study of Screening for
Prostate Cancer (ERSPC showed a 2 1 % reduction in
prostate cancer mortality over 11 years, no difference
in all cause mortality
z United States Prostate, Lung, Colorectal and Ovarian
Cancer (PLCO) Screening Trial showed no decrease
in prostate cancer mortality over 7 years followup
(also none at 10 and 13 year follow up)
European Randomized Study of Screening for
Prostate Cancer (ERSPC)
• 182,160 men between the ages of 50 and 74
were randomly assigned to PSA screening (an
average of once every four years) or not
offered screening
Harms of Prostate Cancer Screening
• Biopsy complications
• Overdiagnosis
• Treatment complications
• 2 1 % reduction in prostate cancer in the
screened group, no change in all cause
mortality, NNS 1055
0 N Engl J Med. 2009;360(13):1320.
United States Prostate, Lung, Colorectal and Ovarian
Cancer (PLCO) Screening Trial
• 76,693 men between the ages of 55 and 74 were
randomly assigned to annual screening with PSA and
DRE or to usual care
• Many of the men in the control group underwent PSA
testing (52 % by year 6 ) and > 40 percent of study
subjects had a PSA within 3 years of enrolling
• No prostate cancer mortality benefit (RR 1.13, 95%
CI 0.75-1.70 ) at 7 years. Also no benefit at 10 and
13 year follow up
n NEnglJMed. 2009;360(13):1310.
D J Natl Cancer Inst, 2012;104(2):125.
Looks Like W e Need a Meta-analysis
• Five RCTs with a total of 341,351 participants
were included in an updated Cochrane
systematic review.
• No difference in prostate cancer mortality
between screened and unscreened
populations , RR 0.95, 95% 01 0.85-1.07
• Prostate cancer diagnosis more common in
the screened group, RR 1.35, 95% C11,06-1.72
0 BJU Int. 2011 ;107(6):882.
Complications of Transrectal Biopsy
a The 30-day hospitalization rate was 6.9%
within 30 days of prostate biopsy, which was
substantially higher than the 2.7% in the
control population (1)
• discomfort during prostate biopsy was
reported by 64 (55%) of 116 men, 2% had
pain that persisted longer than 1 week (2)
• 1. J Urol. 2011;186(5):1830.
• 2. J Natl Cancer Inst. 1998;90(12):925.
Overdiagnosis
- Prostate cancer has been found in 35-40% of
men in their 50's and up to 80% of men in their
70's in autopsy series (1)
• The risk of being diagnosed with prostate
cancer has increased from 1 in 11, to 1 in 6
since PSA screening became available, yet the
risk of dying of prostate Ca is the same (1 in
34 men)
1) Eur Urol. 1996;30(2): 138-44.
Treatment Associated Complications
• ED- occurring in 58% of patients
undergoing prostatectonny and 43%
radiation therapy
c Urinary leal<age - 35% with
prostatectomy and 12% with radiation
• Ann Intern Med. 2008;148(6);435.
Genetic/Race and FH Risk
• Higher risl< of earlier/more aggressive prostate Ca in
blacl<s (Prostate Ca dx <50, 8.3% black men vs 3.3%
Caucasians)
• Black men have a higher lifetime risk of dying of
prostate cancer 5% vs 2.7% for Caucasians )*
-J BRCA2 and BRCA1 increase prostate Ca risk up to
5X (FH of early prostate ca which is usually more
aggressive may be explained by this)
• * Annals of Internal Medicine May 21, 2013 {volume 158,
pages 761-769)
Bottom Line
• NNT to prevent one death, using the positive
mortality study of the European randomized
study would be 48 (NNS 1055).
Using Common Drugs
• NNH is less than 2 for ED, 3-8 for urinary
leakage
• Using the most positive mortality data, would
harm 24 for every life saved
• A 50 yo black male comes to clinic to establish
care. He reports no active health problems.
• Would you recommend a PSA?
• A 60 yo man returns for annual follow up. He
has a history of hyperlipidemia and is being
treated with atorvastatin 40 mg daily. His other
medications include sertraline, omeprazole and
vitamin D. What would you recommend?
A) Check fasting lipids
B) Check fasting lipids , CPK
oCheck fasting lipids, CPK, ALT,AST
D)Check fasting lipids, AST,ALT
Is There Any Benefit to Checking Liver Enzymes
in Statin Treated Patients?
• 408 patients undergoing statin treatment with
at least one lab test (AST/ALT or CK) >10%
above normal
• 36 (8.8%) were symptomatic when tests were
drawn. Of 40 patients who had additional
evaluation, only 2 had treatment changes (both
symptomatic)
2 A 60 yo man
Type 2 DM presents for evaluation.
He has a strong family history of colon cancer. His
other problems include CRI and hypertension. Most
recent HBA1C v^as 7.4, He has been managing his
diabetes with diet. Most recent Cr 1.8 (CrCI 49). What
do you recommend for this patient?
• A) Metformin
• B) Glypizide
D C) Glyburide
• D) Glargine
• Expert Opinion Drug Saf 2011 (Nov 1)
W h a t is the Yield of Testing
Transaminases?
Reduced Risk of Colorectal Cancer With
Metformin in Patients With Type 2 DM
• Retrospective review of a primary care practice
• Meta-analysis of 4 studies, with 107,961
diabetic patients
; Metformin treatment was associated
with a significantly lower risk of
colorectal cancer (RR .63, CI .47-.84,
p=.002)
• 1014 of 1194 patients on a statin had a
monitoring test done in a 1 year period
• 10 of 1014 patients (1%) had a significant
transaminase elevation, and 5 (0.5%) had a
moderate transaminase elevation, but none
were due to the statin
• Diabetes Care 2011; 34: 2323-2328
• Arch Intern Med 2003;163():688-92
Side Effects of Statins
• Rhabdomyolysis (rare) 0.01%
• Hepatotoxicity (rare)
• Liver failure 0.0001%
• Myalgias 5-18 %
IVIetformin Package Insert
• Lactic acidosis risk of 0.03 cases/ 1000, with
a fatality rate of 0.015/1000
G Discontinuation if Cr >1.5 in men and >1.4 in
women, and advises against initiation in
people > 80 years of age unless they have a
normal creatinine clearance
z Other contraindications include congestive
heart failure requiring medical management,
acute or chronic metabolic acidosis, and
acute presentations of dehydration,
hypotension, and sepsis
Cochrane Review
Does IVIetformin Improve O u t c o m e s in
Patients With Type 2 D M and C H F ?
D 206 studies
• 47,800 person-year of exposure to metformin,
and 38,200 patient-years in ttie nonmetformin comparison group
• no cases of fatal or non-fatal lactic acidosis in
either group
D 96% of studies allowed for at least one high
risk group to be included
c 12,272 new users or oral diabetes agens between 1991-1996
reviewed. 1,833 had CHF
• Of these patients treated for DM with CHF, 208 received
metformin monotherapy, 773 were given sulfonylurea
monotherapy and 852 received combination therapy.
• Fewer deaths occurred in patients receiving metformin
monotherapy (52% receiving sulfonylurea's died, 33% receiving
metformin monotherapy died, 3 1 % receiving combination
therapy died)
0 Cochrane Database Syst. Rev.; 2005 Jul 20;(3)
Incidence of Lactic Acidosis in
Metformin Users (1)
• Patients with a metformin prescription from 1980-1995
in Saskatchewan Health administrative database.
• 11,797 patients with 22,296 person years of exposure.
Two patients had a hospital diagnosis for lactic
acidosis (rate 9 7100,000)
• Rate of lactic acidosis in diabetic patients not on
metformin 9.7/100,000 (2).
0 1. Diabetes Care 1999 Jun: 22(6) 925-7
• 2. Dialietes Care 1998; 21:1659-1663
eGFR
>60
Rational R e c o m m e n d a t i o n s for
Metformin Use
<60 and > 45
<45 and >30
<30
Action
No contraindications
Continue use, check Cr
every 3-6 months
Use lower dose (1/2 dose)
Check Cr every 3 months
Do not start new patients
Stop Metformin
Diabetes Care 2011:34:1431-1437
• Diabetes Care 2005; 28; 2345-2351.