Transcript Overview and Management of Pulmonary Hypertension

‘Top’ 5½ Papers in
General Internal
Medicine
Glen Drobot, MD, FRCPC, DTM&H
Assistant professor, Section of General Internal Medicine
[email protected]
Conflict of Interest Disclosure
• Industry-funded trial:
• Co-investigator, apixaban in VTE
Bristol-Myers Squibb & Pfizer
Objectives
At the end of the presentation, the attendee will be
able to:
1) Develop strategies to stay abreast of recent
literature
2) List the highlights of five (and one-half) recent
studies and their impact on general internal
medicine practice
3) Bombard the presenter with questions about the
minutiae of the studies
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Methods
In my clinical life, I try to keep abreast of the medical
literature in the following ways:
1) Emailed Table of Contents of the major IM
journals (also cardiology, tropical medicine, HIV)
2) Emails from ‘news’ websites (theheart.org,
Physician’s First Watch, Medscape)
3) Participate in McMaster Online Rating of Evidence
(MORE)
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4) Subscribe to ACP Journal Wise
Methods
• I find TOCs to be too frequent to possibly keep up
with
• I do like to scan Physicians First Watch most days
areas outside of internal medicine
• MORE gives me really obscure articles to review!
• ACP Journal Wise is very helpful to peruse what’s
new
• Specific topic: UpToDate or Medline
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Antihypertensive Meds at Night
• 58-year-old female with DM 2, hypertension,
and creatinine 120 µmol/L (eGFR 36 ml/min) is
the following medications
gliclazide MR 60mg daily
EC-ASA 81mg daily
hydrochlorothiazide 25mg daily
lisinopril 20mg daily Amlodipine 10mg daily
• Home BP usually shows readings <130/75 but
sometimes morning BP is higher
• Is there anything else she should do?
6
Bedtime dosing of antihypertensive
medications reduces CV risk in CKD
• RCT, blinded (outcome assessors)
• Patients with HTN and CKD (eGFR <60 mL/ min
and/or microalbuminuria)
1 antihypertensive at bedtime
VS
all antihypertensives taken upon awakening
1° outcome: total CV morbidity and mortality
2° outcome: major CV events
Hermida RC et al. J Am Soc Nephrol 2011; 22:2313-2321.
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Bedtime dosing of antihypertensive
medications reduces CV risk in CKD
n=661, mean age 59, 60% men, follow-up 5.4 yrs
Bedtime
morning
NNT (CI)
RRR (95% CI)
Total CV morbidity
and mortality
11%
31%
5 (5 to 7)
65% (49 to
76)
Major CV events
2.7%
7.8%
18 (15 to 34)
71% (38 to
87)
Hermida RC et al. J Am Soc Nephrol 2011; 22:2313-2321.
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Antihypertensive Meds at Night
• 58-year-old female with DM 2, hypertension,
and CKD
• Is there anything else she should do?
 advised to move amlodipine to bedtime
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10
Antibiotics for Appendicitis
• Your 21-year-old son has a 12-hour history of
anorexia, and then RLQ pain. Physical exam:
afebrile, rebound tenderness. U/S confirms
appendicitis.
“Mom, I’m really scared of having an operation,
‘cos Granny didn’t wake up after her hip surgery”
(Dr. Battad hadn’t seen her pre-op…)
• You and the surgeon are insisting on surgery!
• Smart-aleck older sister in Med 2 performs a lit
search on her iPad and asks “why not just give
the cry-baby some antibiotics?”
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Safety and efficacy of antibiotics
compared with surgery for appendicitis
• Meta-analysis, 4 RCTs met inclusion criteria
n=900 patients
IV and/or oral antibiotics
VS
appendicectomy
1° outcome: complications
secondary analysis: exclude 1 trial with crossover
2° outcome: LOS, readmissions, clinical outcomes
Varadhan KK, Neal KR, Lobo DN. BMJ 2012; 344:2313-2321.
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Safety and efficacy of antibiotics
compared with surgery for appendicitis
n=900 (470 antibiotics, 430 appendicectomy),
‘mean’ age 33
Antibiotics
Surgery
NNT
RR (95% CI)
Complications
18%
25%
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0.69 (0.54 to
0.89)
Complications
(no crossover)
12%
19%
13
0.61% (0.40
to 0.92)
63% of patient in antibiotic arm  no surgery at 1 year
65 (20%) of patients had appendicectomy after readmission, 9
had perforated appendicitis, 4 had gangrenous appendicitis
Varadhan KK, Neal KR, Lobo DN. BMJ 2012; 344:2313-2321.
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Antibiotics for Appendicitis
• 21-year-old male with appendicitis
• Is there really an option for antibiotic therapy?
 Admitted for 3 days of ceftriaxone/
metronidazole and discharged on 7 days of
amoxicillin/clavulanate
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15
Perioperative Statins and CV Events
• 76-year-old male with hypertension, former 40pack-year smoking history, and claudication, is
going for cross-bifemoral bypass.
O/E BP 128/76, HR 64 (regular), and ↓↓ lower
extremity pulses. LDL cholesterol 2.1 mmol/L
Lisinopril/HCTZ 10/12.5mg daily
EC-ASA 81mg daily
• Is there anything else you would recommend?
Cardiac testing?
Beta blocker?
Statin?
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Effect of perioperative statins on
Death, MI, AFib and Length of stay
• Meta-analysis, patients undergoing cardiac,
vascular or other surgery
Statin
VS
Control (placebo or lower-dose statin)
Outcome assessed: death, perioperative MI &
atrial fibrillation, and length of stay
Chopra V et al. Arch Surg 2012; 147(2):181-9.
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Effect of perioperative statins on
Death, MI, AFib and Length of stay
n=2292 patients in 15 trials (1 high vs low dose)
Statin
control
NNT (CI)
RRR (95% CI)
Perioperative death
11%
31%
NS
38% (-14 to 66)
Perioperative MI
2.7%
7.8%
24 (19 to 44)
47% (26 to 62)
Perioperative AFib
20%
36%
7 (6 to 9)
44% (31 to 55)
Mean LOS, days
Chopra V et al. Arch Surg 2012; 147(2):181-9.
-0.32 (-0.53 to 0.11)
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Perioperative Statins and CV Events
• 76-year-old male with hypertension, former
smoker going for cross-bifemoral bypass
• Is there anything else you would recommend?
 started 2 days pre-op and continued for 30
days post-op
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20
Warfarin and new oral
anticoagulants in atrial fibrillation
• 77-year-old female with hypertension, former
smoker, who had cross-bifemoral bypass, in
atrial fibrillation for 6 months since operation
O/E BP 136/70, HR 90 (irregular), and normal CV
exam
Lisinopril/HCTZ 10/12.5mg daily
EC-ASA 81mg daily
simvastatin 10mg daily
“Oh dear. But I saw this ad for a blood thinner
while watching ‘Dancing with the Stars.’ I think it’s
made by Prada—can we get that in Canada?” 21
Efficacy and safety of new oral
anticoagulants versus warfarin in AFib
• Review of the 3 major trials comparing warfarin to
dabigatran, rivaroxaban or apixaban
new OAC VS
warfarin
‘you mean rat poison’
1° efficacy outcome: composite of stroke and
systemic embolism
2° stroke, all-cause mortality, vascular mortality, MI
1° safety outcome: major bleeding, 2° hem stroke
Miller CS et al. Am J Cardiol 2012; 110:453-60.
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Efficacy and safety of new oral
anticoagulants versus warfarin in AFib
n=44,474 patients in 3 trials
New OAC
warfarin
NNT (CI)
RRR (95% CI)
Stroke and systemic
embolism
2.7%
3.5%
133 (88 to 359)
22% (8 to 33)
Hemorrhagic stroke
0.4%
0.8%
234 (186 to 401)
55% (32 to 69)
All-cause mortality
5.6%
6.3%
132 (88 to 316)
12% (88 to 316)
MI
1.3%
1.4%
NS
4% (-26 to 27)
Intracranial bleeding
0.7%
1.3%
149 (119 to 223)
51% (34 to 64)
Major bleeding
5.0%
5.7%
NS
12% (-9 to 23
29)
Warfarin and new oral
anticoagulants in atrial fibrillation
• 77-year-old female with hypertension, recent
cross-bifemoral bypass, and permanent AFib
• What would recommend for anticoagulation?
Depends on patient preference, province, drug
plan, ability to have INRs, risk of bleeding…
‘Even though I’d love that Prada, I guess taking
another pill once a day isn’t that bad’
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ASA for preventing the recurrence of VTE
• 44-year-old female who has received 9 months
of warfarin for acute PE, comes to your office
asking about options at this point
– She’s worried about the risk of bleeding, more
worried about recurrence of a PE, but doesn’t like
the hassle of getting blood tests
• What are some of her options?
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Aspirin for the prevention of recurrent
of venous thromboembolism
• RCT, blinded
Aspirin 100mg daily
VS
Placebo
1° efficacy outcome: symptomatic, objectively
verified recurrent of VTE
1° safety outcome: major bleeding
2° outcomes: DVT,PE, non-major bleeding, mortality
Becattini C et al. N Engl J Med 2012; 366(21):1959-67. May 24
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ASA for preventing the recurrence of
venous thromboembolism
n=403 patients, over 2 years
aspirin
placebo
NNT (CI)
RRR (95% CI)
Recurrent VTE
14%
22%
11 (8 to 34)
44% (14 to 65)
Pulmonary
embolism
5.4%
7.1%
NS
29% (-51 to 67)
Deep venous
thrombosis
7.8%
14%
15 (10 to 127)
47% (6 to 71)
Bleeding
1.95%
2.03%
NS
2% (-284 to 76)
NNH (CI)
RRI (95% CI)
NS
4% (-231 to2868)
Mortality
2.9%
2.5%
ASA for preventing the recurrence of VTE
• 44-year-old female treated with warfarin for
unprovoked PE
BREAKING NEWS
• What are some of her options?
– Risk stratify (clinically, D-dimer)
– Continue warfarin at moderate or full intensity
– Start EC-ASA 81mg daily
• But wait…
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Low-dose aspirin for preventing
recurrent venous thromboembolism
• RCT, blinded, mostly Australia & New Zealand
• Published in print November 22 (6 months later)
Aspirin 100mg daily VS
Placebo
1° efficacy outcome: symptomatic, objectively
verified recurrent of VTE
2° outcomes: major vascular events
1° safety outcome: major or clinically relevant bleeding
Brighton TA et al. N Engl J Med 2012; 367(21):1979-87.
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Let’s talk cooperation!
Protocols prospectively harmonized
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Editorial in this issue of NEJM
• Non-significant decrease in recurrent VTE
4.8% vs 6.5%/year, HR 0.74, p=0.09
• BUT significant decrease in major vascular events
HR 0.66, p=0.01
• Pooling results for both trials (WARFASA, ASPIRE)
Recurrence of VTE
HR 0.68, p=0.007
Major vascular events
HR 0.66, p=0.002
Warkentin TE N Engl J Med 2012; 367(21):2039-41.
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Editorial in this issue of NEJM
Warkentin TE N Engl J Med 2012; 367(21):2039-41.
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ASA for preventing the recurrence of VTE
• 44-year-old female treated with warfarin for
unprovoked PE
• What are some of her options?
a continuum of treatment options
Full dose
moderate intensity
OAC
anticoagulation
aspirin
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Summary
In patients with HTN and CKD, moving at least 1 antihypertensive medication to bedtime reduces CV events.
Perioperative statin use is associated with significant
reductions in MI and atrial fibrillation.
Antibiotics are a reasonable, safe option in patients
with uncomplicated appendicitis, preventing surgery in
2/3 patients.
The newer oral anticoagulants are at least as efficacious
and slightly safer than warfarin.
Aspirin prevents about 1/3 of recurrences after first
episode of unprovoked venous thromboembolism.
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References
Hermida RC et al. J Am Soc Nephrol 2011; 22:2313-2321.
Varadhan KK, Neal KR, Lobo DN. BMJ 2012; 344:2313-2321.
Chopra V et al. Arch Surg 2012; 147(2):181-9.
Miller CS et al. Am J Cardiol 2012; 110:453-60.
Becattini C et al. N Engl J Med 2012; 366(21):1959-67.
Brighton TA et al. N Engl J Med 2012; 367(21):1979-87.
Warkentin TE N Engl J Med 2012; 367(21):2039-41.
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We have reached the end, er, summit
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