‘Top’ 5½ Papers in General Internal Medicine Glen Drobot, MD, FRCPC, DTM&H Assistant professor, Section of General Internal Medicine [email protected]

‘Top’ 5½ Papers in General Internal

Medicine

Glen Drobot, MD, FRCPC, DTM&HAssistant professor, Section of General Internal Medicine

[email protected]

Conflict of Interest Disclosure

• Industry-funded trial:• Co-investigator, apixaban in VTE Bristol-

Myers Squibb & Pfizer

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Objectives

At the end of the presentation, the attendee will be able to:1) Develop strategies to stay abreast of recent literature2) List the highlights of five (and one-half) recent studies and their impact on general internal medicine practice3) Bombard the presenter with questions about the minutiae of the studies

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MethodsIn 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)

4) Subscribe to ACP Journal Wise

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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 medicationsgliclazide 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?

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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

VSall antihypertensives taken upon awakening

1° outcome: total CV morbidity and mortality2° 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)

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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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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 criterian=900 patients

IV and/or oral antibiotics VS

appendicectomy1° outcome: complications

secondary analysis: exclude 1 trial with crossover2° 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 appendicitisn=900 (470 antibiotics, 430 appendicectomy), ‘mean’ age 33

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

Antibiotics Surgery NNT RR (95% CI)

Complications 18% 25% 140.69 (0.54 to

0.89)

Complications (no crossover)

12% 19% 130.61% (0.40

to 0.92)


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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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Perioperative Statins and CV Events• 76-year-old male with hypertension, former 40-

pack-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-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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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?”

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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 embolism2° stroke, all-cause mortality, vascular mortality, MI1° 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 29)

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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

Placebo1° efficacy outcome: symptomatic, objectively verified recurrent of VTE1° safety outcome: major bleeding2° 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)

Mortality 2.9% 2.5% NS 4% (-231 to 68)

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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?– Risk stratify (clinically, D-dimer)– Continue warfarin at moderate or full intensity– Start EC-ASA 81mg daily

• But wait…

BREAKING NEWS

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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 VTE2° outcomes: major vascular events1° 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 VTE4.8% vs 6.5%/year, HR 0.74, p=0.09

• BUT significant decrease in major vascular eventsHR 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


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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 aspirin

OAC anticoagulation

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SummaryIn patients with HTN and CKD, moving at least 1 anti-hypertensive 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




Miller CS et al. Am J Cardiol 2012; 110:453-60.

Brighton TA et al. N Engl J Med 2012; 367(21):1979-87.

Becattini C et al. N Engl J Med 2012; 366(21):1959-67.


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Documents

‘Top’ 5½ Papers in General Internal Medicine Glen Drobot, MD, FRCPC, DTM&H Assistant professor, Section of General Internal Medicine [email protected]