Update in Hospital Medicine - Internal Medicine | ACP · For treatment of her DVT, she refuses to inject herself with low molecular weight heparin shots. ... Research Question: What

Update in Hospital Medicine Efrén Manjarrez, M.D., SFHM

Associate Professor of Clinical Medicine

Division of Hospital MedicineUniversity of Miami Miller School of

[email protected]

Nothing to disclose

Agenda• Preoperative Risk Assessment• VTE and Active Cancer• Risk Prediction for C Difficile Infections• Complex Orthopedic Infections• Treatment of Endocarditis • Treatment of Bacteremia• Treatment of Stroke• Heart Failure and Valves• Perioperative DOAC management

Case

You are asked to preop a 71‐year old woman for surgical management of a colovesical fistula as a complication of diverticulitis. PMH: CAD (NSTEMI with CABG 10 years ago), HTN, DMMeds: insulin, ACEI, statin, aspirin 81 mg dailyNo CP/SOB but sedentaryPE: normal except obese and goiterLabs: Cr 2.1, Gluc 150, EKG ‐ NSR, Non‐specific T wave ∆’s

What is your next step?

A. Per your subjective assessment, she can “probably do 4 METS”, so send her straight for surgery!

B. Have her fill out the Duke Activity Status IndexC. Get an N‐Terminal B‐type Natriuretic Peptide D. Just stress her like the guidelines say and be done with it

METS StudyAssessment of functional capacity before

major non‐cardiac surgery: an international prospective study

Duminda Wijeysundera et alLancet 2018; 391:2631‐40

METS StudyBackground: Per ACC, functional capacity is an important component of preoperative risk, but MD subjective assessments have little agreement with validated measures of functional capacity and poorly predict post op outcomes.Research Question: Compare MD subjective assessment of METS with 3 other measures: Cardiopulmonary Exercise TestingDASI = Duke Activity Status Index NT‐ProBNP = N‐Terminal B‐type Natriuretic Peptide Design: Prospective Cohort Study 25 hospitals Canada, UK, NZ, Aus1401 patients age ≥ 40 ≥ 1 RF for CAD‐ major, elective NCS (>1 overnight hospital stay)Outcomes: 1°= Death or MI ≤ POD 30

2°= Death ≤ 1 year postopOther outcomes: Death or myocardial injury (MINS) ≤ POD 30; Mod‐severe complications during hospitalization

Wijeysundera, D Lancet 2018; 391:2631‐40

Duke Activity Specific Index Can you Points

Take care of yourself, that is, eat dress, bathe or use the toilet? 2.75

Walk indoors, such as around your house? 1.75

Walk 200 yards on level ground? 2.75

Climb a flight of stairs or walk up a hill? 5.50

Run a short distance? 8.00

Do light work around the house like dusting or washing dishes? 2.70

Do moderate work around the house like vacuuming, sweeping floors, or carrying groceries? 3.50

Do heavy work around the house like scrubbing floors or lifting or moving heavy furniture? 8.00

Do yard work like raking leaves, weeding or pushing a power mower? 4.50

Have sexual relations? 5.25

Participate in moderate recreational activities like golf, bowling, dancing, doubles tennis, or throwing a ball?

6.00

Participate in strenuous sports like swimming, singles tennis, football, basketball, or skiing? 7.50

Total Wijeysundera, D Lancet 2018; 391:2631‐40

Limitations: Cohort not very sick….Nor were surgeries very high risk

Baseline Results

Subjective Assessment of Functional Capacity

Percent

Poor < 4 METS 7.9Moderate (4‐10 METS) 56.9Good (> 10 METS 35.2

Functional AssessmentsVO2 Peak (mL/kg/min) 19.2Duke Activity Status Index Score Mean = 41; Median = 42.7NT pro‐BNP (normal = 0‐300 ng/L) 84


Subjectively, 92 % assessed as doing “at least 4 METS”

Subjectively, we are not identifying high risk patients!

Subjective Assessment of Functional Capacity

VO2 peak < 14 ml/kg/min VO2 peak ≥ 14 ml/kg/min

Poor < 4 METS 19% 5%

Moderate (4‐10 METS)

60% 55%

Good (> 10 METS 21% 39%

We are correctly picking up patients who do well,but we are doing a poor job detecting patients at risk!!


In reality, only 81% could perform 4 METSWe are overestimating functional capacity

Correlation between measures of preop functional capacity

Peak O2 consumption(+) correlates with Duke Index i.e. higher scoreis protective

Peak O2 consumptioninversely correlates with NT pro BNP i.e. high pro BNP is bad


Predictive performance of different measures of preop functional capacity


Results

Subjective Assessment of functional capacity had NO association with the main study outcomes: 30 day death or MI, 1 year death Yet, moderate or severe complications (mainly noncardiac) were common and identified by poor performance on cardiopulmonary exercise testing:• Respiratory failure 9%• Pneumonia 11%• Surgical site infection 18%• Unexpected ICU admission 20%• Re‐operation 16.5%


Conclusions

• Subjective assessment of functional capacity should not be used for preoperative risk assessment• Does not accurately identify patients with poor fitness or those at risk for postop complications

• ↓ Duke Index score predicted risk of 30 day MI or death • ↑ProBNP predicted 30‐day MINS or death and mortality at 1 year• Consider more objective measures: Duke Index, NT‐proBNP, +/‐ CPET, to predict complications as subjective assessment only correctly identified < 20% of poor oxygen consumption


I always take life with a grain of salt….Plus a slice of lemon…..And a little tequila!!

You admitted a lovely lady with lymphoma admitted with neutropenic fever and sepsis from pneumonia. She was frail, and she was subsequently discharged home but developed a hospital acquired DVT in the right lower extremity before discharge….She has already received 5 days of LMW heparin during your care in the hospital….

For treatment of her DVT, she refuses to inject herself with low molecular weight heparin shots. What do you prescribe that is non‐inferior to LMW Heparin?

A. EdoxabanB. RivaroxabanC. Dose adjusted WarfarinD. ApixabanE. Fondaparinux

Treatment of Cancer‐Associated Venous Thromboembolism:

Design: RCT: N=1,050 pts. w/ cancer & symptomatic VTE

LMWH (Dalteparin) SC x 5 days, then

A. Edoxaban: Edoxaban 60 mg po QD x 6‐12 mos.

B. Dalteparin: Dalteparin 200 IU/kg QD x 1 mo. then by 150 IU/kg QD

Design: RCT: N=406 patients w/ cancer & symptomatic VTERivaroxaban: Rivaroxaban 15 md po BID x 3 weeks, then 20 mg QD to complete 6 mos.Dalteparin Cohort: Dalteparin 200 IU/kg daily for 1 month then by 150 IU/kg daily

Raskob GE et al. N Engl J Med 2018;378:615‐624 Young. J Clin Oncol 2018: 36:2017‐2023.

Background: Low‐molecular‐weight heparin is the standard treatment for cancer‐associated venous thromboembolism. The role of treatment with direct oral anticoagulant agents is unclear. Research Question: Are the direct oral anticoagulants, Edoxaban and Rivaroxaban, non‐inferior to LMW heparin, Dalteparin, for the treatment of cancer‐associated symptomatic VTE events?Outcomes: Primary= Recurrent VTE : Secondary= Major bleed

Recurrent VTE Reduced: HOKUSAI and SELECT‐D

Raskob GE et al. N Engl J Med 2018;378:615‐624

Edoxaban had lower thrombosis rates

Rivaroxaban had lower VTE rates: 11% vs. 4%HR= 0.43 (0.19‐0.99)

Young. J Clin Oncol 2018: 36:2017‐2023.

Major Bleed Increased: HOKUSAI and SELECT‐D

Raskob GE et al. N Engl J Med 2018;378:615‐624

Edoxaban had higher bleeding rates than LMW Heparin OR 1.77 Young. J Clin Oncol 2018:

36:2017‐2023.

Rivaroxaban had higher bleed rates: Major 4% vs. 6% Non‐major:4% vs. 13% HR 3.76 (1.63‐8.69)

Cancer Associated VTE TreatmentTake Home Points

• Remember, patients must receive 5 days of LMW Heparin prior to switch to Edoxaban monotherapy, not Rivaroxaban.

• Edoxaban and Rivaroxaban are now options in addition to LMWH for treating cancer associated VTE events

• Major bleeding was higher with Edoxaban and Rivaroxaban, and risk higher in GI tract malignancies.

You are discharging a man you just made the diagnosis of pancreatic cancer. He presented with painless jaundice. He is also a type 2 diabetic, morbidly obese. Notable labs include a hemoglobin of 9.5 g/dL .Prior to sending him to the oncologist, you did your duty and had a port inserted for chemotherapy….

The oncologist would like to discharge the patient with something to prevent VTE.Are any of these a good idea to consider?

A. Dose adjusted WarfarinB. FondaparinuxC. ApixabanD. Rivaroxaban E. Peter Pan

Rivaroxaban & Apixaban for Thromboprophylaxis High‐Risk Ambulatory Patients with Cancer

CASSINI and Avert TrialsBackground: Ambulatory patients receiving systemic cancer therapy are at varying risk for VTE events. Research Question: What is the efficacy and safety of Rivaroxaban and Apixaban for 6 months in primary prevention of VTE events in high risk patients with cancer x 6 in patients with Khorana score of ≥2 out of 6 for VTE; solid tumor or lymphoma and new chemo regimen Outcomes: Primary Efficacy = Symptomatic or asymptomatic VTE event OR death

Primary Safety = Major BleedCassini: RCT N=841 pts. Rivaroxaban 10 mg po QD vs. placebo Avert: RCT 574 pts. Apixaban 2.5 mg po BID vs. placebo

Khorana AA et al. N Engl J Med 2019;380:720‐728

Khorana Score Predictor PointsCancer Type 2=Stomach or Pancreas

1=Lung, Lymphoma, Gynecologic,Bladder, or TesticularOther=0

Pre‐chemotherapy platelet count ≥350x10⁹/L

Yes= 1No=0

Hemoglobin level <10 g/dL or using RBC growth factors

Yes=1No=0

Pre‐chemotherapy WBC count >11x10⁹/L Yes=1No=0

BMI ≥35 kg/m² Yes=1No=0

Khorana AA et al. N Engl J Med 2019;380:720‐728

Rivaroxaban for Thromboprophylaxis inHigh‐Risk Ambulatory Patients with Cancer

CASSINI Trial

ITT: 8.8 vs. 6% On Treatment: 6.4 vs. 2.6%

Major Bleed 1% vs. 2% Rivaroxaban

Carrier M et al. N Engl J Med 2019;380:711‐719

Apixaban had lower thrombosis rates 4.2% vs. 10.2% HR 0.4 (0.26‐0.65)

AVERT Trial: Apixaban for Thromboprophylaxis inHigh‐Risk Ambulatory Patients with Cancer

G Agnelli. NEngl J Med 2019;380:781‐783.

Combined Analysis AVERT and CASSINI Trials

Combined direct oral anticoagulantsNNT 24 via ITT; NNT was 21 on treatment

Combined direct oral anticoagulantsNNH 77 via ITT;

CASSINI and AVERT Take Home Points

• Hospitalists not likely to start these agents• Expect to see these meds started over time• Oncologists cautious over bleed risk‐ caution with GI tract cancers• Some Oncologists may want to target a better risk/benefit ratio

Short Take: Prediction Model for Mortality and Adverse Outcomes

With Peripheral Eosinopenia on Admissionfor Clostridium Difficile Infection

Background: Animal models suggest loss of eosinophils in Clostridium difficile infection (CDI)= severe disease. Identifying high‐risk patients on admission could improve outcomes. Life threatening CDI make toxins A &B PLUS BINARY TOXIN ‐associated with ↑severity and ↑ mortality.Research Questions: Is peripheral eosinopenia on admission for CDI associated with ↑ odds of mortality and other outcomes?Design: Cohort study: development cohort at Penn State (N=1,064) and validation cohort at UVA (N=1,001) Exposure: Eosinophil count: 0 vs. > 0

Kulaylat JAMA Surg. 2018;153(12):1127‐1133.

• EOS=0=39%• EOS >0=61%• Eosinopenia=

↑ mechanical ventilation ↑hypotension, ↑tachycardia ↑leukocytosis!

Which of the following patients would you discharge home with oral antibiotics?

A. 75 yo man admitted with pan sensitive E. Coli UTI with bacteremia after a recent urologic “procedure” now on day 3 afebrile VSS and tolerating po FU BCX (‐)? B. 75 yo man admitted 7 days earlier with MSSA aortic valve endocarditis. VSS FU BC (‐) CT Surgery believes he does not need a valve replacement this admission given no valve abscess.C. A 34 yo soccer star with ankle osteomyelitis‐ a complication of a an open puncture during a gameD. None of themE. All of them

Oral vs. IV Therapy for Enterobacteriaceae Bacteremia

• Background: Conversion to oral therapy for Enterobacteriaceae may have many quality of life benefits

• Research Question: Is their a difference in 30 day mortality between IV therapy and early oral step‐down therapy for this bacteremia?

• Design: Retrospective cohort over 6 yearsN=4,967 patients at 3 sites admitted with monomicrobial Enterobacteriaceae bacteremia with response/ source control by day 5Intervention was oral therapy by day 5 versus continue IV therapy to complete 7‐15 days

• Primary Composite Outcome: 30 day all cause mortality

Tamma JAMA Intern Med. 2019;179(3): 316‐23



Enterobacteriaceae isolates

Percent range

Citrobacter 1.6‐2.4Enterobacter 11.1‐12.4Escherichia coli 39.9‐48.0Klebsiella pneumoniae

30.4‐36.2

Klebsiella oxytoca 1.3‐1.9Proteus mirabilis 3.3‐5.4Serratia marcescens 2.6‐4.1

Source of Infection Percent rangePulmonary 3.3‐9.1Skin and soft tissue 2.5‐3.9Urinary Tract 29.8‐46.2Biliary 11.5‐14.5Gastrointestinal Tract

18.3‐22.6

Catheter Associated 15.6‐22.0



No mortality differences between the groups in 30 day survival 13% mortality each group

Take Home Points: Oral vs. IV Therapy for Enterobacteriaceae Bacteremia • Oral step‐down therapy is effective for patients who have achieved appropriate source control and demonstrated favorable clinical response to initial IV therapy

• May not be appropriate for patients requiring ICU level of care at the outset or patients on tube feeds

• These patients also had a 2 day lower hospital length of stay• Rare bacteremic relapse (<1%)

Partial Oral vs. IV Antibiotic Treatment of Endocarditis: POET StudyBackground: Left sided endocarditis is typically treated with 6 weeks of IV antibiotics per ESC and AHA guidelinesResearch Question: Is the efficacy and safety of oral antibiotics any different from IV antibiotics once the patient is stable after initial high risk period?Design: Randomized Clinical Trial for non‐inferiorityN=400 stable Danish adults with left sided endocarditis caused by:

Enterococcus Faecalis, Staph Aureus, or Coagulase (‐) StaphylococcusAll patients get 10 days of IV antibiotics, then oral vs. IV to complete 6 weeksPrimary Composite Outcome (4) till 6 months post antibiotic treatment: All cause mortality + Unplanned cardiac surgery+ Embolic events+ Relapse bacteremia with primary pathogen

Iversen N Engl J Med 2019; 380:415‐24

Key Demographics: POET for EndocarditisCharacteristic IV Treatment N=199 Oral Treatment N=201Streptococcus 104 (52.3%) 92 (45.8%)Enterococcus Faecalis 46 (23.1%) 51 (25.4%)Staph Aureus 40 (20.1%) 47 (23.4%)CRP mg/l 124 141Prosthetic valve 53 (26.6%) 54 (26.9%)Pacemaker 15 (7.5%) 20 (10%)Other known valve disease 82 (41.2%) 90 (44.8%)Mitral Valve Endocarditis 65 (32.7%) 72 (35.8 %)Aortic Valve Endocarditis 109 (54.8%) 109 (54.2%)Mitral & Aortic Valve Endocarditis 23 (11.6%) 20 (10%)Moderate/ severe valve regurgitation 19 (9.5 %) 23 ( 11.4%)Valve surgery during current disease 75 (37.7%) 77 (38.3%)


Key: Very few IV drug abusers in the cohort ; good representation of DM and renal disease

Partial Oral Treatment of Endocarditis shows no difference in composite outcome


No differences between the groups

Partial Oral Treatment of Endocarditis


Subgroup analysis failed to identify high risk groups for oral stepdown failure!

Examples of Daily Oral RegimensPenicillin and methicillin sensitive Staphylococcus aureus and coagulase‐negative staphylococci: 1) Amoxicillin 1 g x 4 and fusidic acid 0.75 g x 2 2) Amoxicillin 1 g x 4 and rifampicin 0.6 g x 2 3) Linezolid 0.6 g x 2 and fusidic acid 0.75 g x 2 4) Linezolid 0.6 g x 2 and rifampicin 0.6 g x 2Methicillin resistant coagulase‐negative staphylococci 1) Linezolid 0.6 g x 2 and fusidic acid 2) Linezolid 0.6 g x 2 and rifampicin 0.6 g x2 Enterococcus faecalis: 1) Amoxicillin 1 g x 4 and rifampicin 0.6 g x 2 2) Amoxicillin 1 g x 4 and moxifloxacin 0.4 g x 1 3) Linezolid 0.6 g x 2 and rifampicin 0.6 g x 2 4) Linezolid 0.6 g x 2 and moxifloxacin 0.4 g x 1

Parting thoughts: POET

• Only left sided endocarditis with above pathogens, so may not be able to generalize other pathogens (25‐30% other pathogens)

• Only 5 IVDA patients, so may not apply to my population in Miami• On average, oral patients switched to po on day 17, so about half way through course

• Need to be able to ensure follow up multiple times a week initially• Otherwise, it seems safe‐ no subgroups at risk for treatment failure!


Oral versus IV Antibiotics for Bone and Joint Infections: OVIVA Study

Background: Complex orthopedic infections usually require prolonged IV antibiotic therapy and surgeryResearch Question: Is oral antibiotic treatment for these infections non‐inferior to IV? Design: Randomized Clinical Trial for non‐inferiorityN=1,054 patients in the UK from 26 centersWithin 7 day of surgery OR if nonsurgical, within 7 days of starting

treatment, patients switch to oral for 6 weeks total or continue IVPrimary Outcome: Treatment failure at 1 yearSecondary Outcomes: Multiple

Li N Engl J Med 2019; 380:425‐36

Inclusion Diagnoses and Treatment Failure Criteria

Acute or chronic bone or joint infectionNative osteomyelitis (extraaxial skeleton) Native joint infection requiring excision arthroplastyProsthetic joint infectionOrthopedic fixation‐device infectionVertebral osteomyelitis +/‐ diskitis or soft tissue infection

• Draining sinus tract from bone• Draining sinus tract from prosthesis• Frank pus near bone• Frank pus near prosthesis• Microbiologic criteria• Histologic criteria of inflammation

Li N Engl J Med 2019; 380:425‐36

29% no implant24% implant retained but debrided40% prosthesis removed

Oral versus IV Antibiotics for Bone and Joint Infections: OVIVA Study

Li N Engl J Med 2019; 380:425‐36

Oviva Take Home Points

• No difference in treatment failure 14.6% (IV) vs. 13.2% (oral)• No difference in serious adverse events 27.2% (IV) vs. 26.2% (oral)• Catheter complications (9.4%) and LOS (3 days) higher in IV cohort • Oral antibiotics non‐inferior to IV for first 6 weeks of treatment for complex orthopedic infections

• Work with pharmacy and ID consultants if take this route to ensure excellent oral bioavailability and routine monitoring for safety

* Boucher N Engl J Med 2019; 380:5: 487‐9

Case Presentation

Your patient 77 year old diabetic, hypertensive man is admitted to you for stroke versus TIA evaluation. MRI Brain (‐) for acute CVA. MRA brain/neck revealed up to 30% stenosis, but no severe vascular occlusions. The overnight nocturnist initiated a statin….

What antiplatelet regimen was initiated to decrease the risk of an ischemic stroke in the short term of 90 days?

1. ASA 81 mg daily2. ASA 325 mg daily3. Clopidogrel 75 mg daily after loading with 300 mg4. ASA 162 mg and Clopidogrel 75 mg daily after loading with 600 mg5. Mickey Mouse vitamins with cherry flavored baby aspirin

Clopidogrel and Aspirin in Acute Ischemic Stroke and High‐Risk TIA:

POINT TrialBackground: The risk of progression to major ischemic CVA ranges from 3‐15% in 90 days after TIA or minor ischemic CVA. ASA has reduced this risk by 20%.Research Question: In patients with TIA (ABCD2 score ≥ 4) or minor ischemic CVA (NIHSS ≤ 3), does ASA + Clopidogrel reduce the risk of ischemic CVA at 90 days?Design: Randomized Clinical N=4,881 at 269 international sites Dual Group: ASA (50‐325 mg daily) + Clopidogrel load 600 mg day 1, then 75 mg QD ASA only group: ASA (50‐325 mg daily) Primary Efficacy Outcome: Composite Ischemic CVA+ MI+ Vascular deathPrimary Safety Outcome: Major Hemorrhage

Johnston N Engl J Med 2018; 379: 215‐25.

Point Trial:Primary outcome reduced with dual therapy


NNT=67 for composite outcomeNNT=59 for ischemic CVANNH= 200

Point Trial:Caution: bleed risk higher in dual therapy


Point Trial Take Home

• Clopidogrel + ASA reduced risk of recurrent ischemic events.• Benefit best seen in stroke• For patients with high‐risk TIA (ABCD2 score ≥ 4) or minor stroke (NIHSS ≤ 3) without tPA or endovascular therapy, adding clopidogrel to aspirin improves outcomes

Case continues…

You handed the patient off to your colleague on Friday afternoon, but he stopped Clopidogrel. He was discharged Saturday on Mickey Mouse vitamins with cherry flavored baby aspirin, a statin and continued home BP and DM regimen.A month later, his daughter found him in bed in the morning around 9am. He was unable to speak nor move the right side of his body. EMS called…He was last well last night watching family videos till 11.Exam revealed right sided hemiplegia. CT brain was negative for bleed but there was a new small infarct, acute per the radiologist.

What is the best reperfusion strategy?

A. tPA is now approved after 8 hours per 2019 guidelinesB. Aspirin 325 mgC. Aspirin 325 mg plus clopidogrel 600 mg loading, then 150 mg dailyD. Endovascular thrombectomyE. Cat’s out of the bag. Send him to acute rehab with a PEG because he is gonna fail his swallow eval…

Thrombectomy > 6 Hours after StrokeThe Dawn and DEFUSE 3 Trials • Background: Prior trials of ischemic CVA showed little benefit when endovascular thrombectomy done > 6 hours after onset of symptoms

• Design: Thrombectomy Group: Thrombectomy + usual care• Usual care: Anti platelet and lipid lowering• Primary Outcomes: Disability + Functional independence at 90 days • Secondary Outcomes: Intracerebral bleed + 90 day mortality• DAWN Trial: RCT N=206 patients with ICA or proximal MCA ischemic CVA with clinical deficit >> infarct volume last well 6‐24 hours ago

• DEFUSE 3 Trial: RCT N=182 patients with ICA or proximal MCA ischemic CVA with initial infarct size < 70 ml & ratio of volume of ischemic tissue to ischemic volume ≥ 1.8 and last well 6‐16 hours ago

Nogueira N Engl J Med 2018:378;11‐21. Albers N Engl J Med 2018;378:708‐18.

Nogueira N Engl J Med 2018:378;11‐21.

Dawn Trial shows Thrombectomy 6 to 24 Hours after Ischemic Stroke was superior

Thrombectomy 6‐24 hours after ischemic CVA was superior to medical management!~ 50% independent↑ Early responders↑ Recanaliza on↓ Infarct volume

Albers N Engl J Med 2018;378:708‐18.

Example of Perfusion Image with Disproportionately Large Region of Hypoperfusion vs. Size of Early

Infarction.

The Penumbra in green is salvageable tissue


Thrombectomy for Stroke > 6 HoursDEFUSE 3 and DAWN

Nogueira N Engl J Med 2018:378;11‐21.

Modified Rankin Scale:↑ (dark) is bad, seen on usual care group

Side by Side Comparison DAWN and DEFUSE 3DAWNOutcomes

Thrombectomy Usual Care Risk Difference

P Value NNT

Functional Independence*at 90 days

49% 13% 36% <0.01 3

Neurologic deterioration at 24 hrs.

14% 26% 12% <0.01 9

SymptomaticICH 5.6% 3% 2.4% >0.05 NS

*Functional Independence: modified Rankin scale of 0 or 1 DAWN. N Engl J Med. 2018;378:11‐21. DEFUSE 3. N Engl J Med. 2018;378:708‐18.

DEFUSE 3 Outcomes

Thrombectomy Usual Care Risk Difference

P Value NNT

Functional Independence*at 90 days

45% 17% 28% <0.01 4

Mortality at 90 days 14% 26% 12% 0.05 (9)Large ICH 9% 3% 6% 0.21 NS

Thanks Dr. Dan DresslerEmory University

• Thrombectomy window now proven beyond 16 hours and up to 24 hours

• Benefits seen in functional independence and disability• Ask your neurology colleagues if the deficit is out of proportion to radiographic findings

• Ask your neurology colleagues what is stroke volume and ischemia to infarct ratio


Take Home Points for Acute Ischemic CVA after 6 hours

I WAS BORN TO BE WILD…..BUT ONLY UNTIL ABOUT 9 PM OR SO!!

Case Presentation

Your 70 yo patient is admitted with CHF exacerbation. Per CT surgery, it is not amenable to surgery‐ too high risk.The echo report says EF 25%, global left ventricular dilatation with severe functional mitral insufficiency. Your patient has been on maximal doses of guideline directed medical therapy‐beta blocker, sacubitril/valsartan, spironolactone, and furosemide. Unfortunately, functional capacity is at NYHA Class III….EKG shows sinus rhythm, QRS 95 msec….

What can you offer your patient?

A. Cardiac resynchronizationB. HospiceC. Transcatheter Mitral Valve RepairB. Cardiac transplant

Transcatheter Mitral‐Valve Repair in Patients with Heart Failure:COAPT Study

Background: Among patients with heart failure who have mitral regurgitation due to left ventricular dysfunction, the prognosis is poor. Transcatheter mitral‐valve repair may improve their clinical outcomes. Research Question: What is the impact of transcatheter mitral valve repair in symptomatic patients with moderate to severe secondary mitral regurgitation despite guideline directed medical therapy?Design: Randomized Clinical N=614Device therapy versus medical managementPrimary Efficacy Outcome: All hospitalizations for heart failure over 2 yearsPrimary Safety Outcome: Freedom from device related complications x 1 year

Stone N Engl J Med 2018;379:2307‐18

Transcatheter Mitral‐Valve Repair in Patients with Heart Failure:

CHF Readmissions over 2 years dropped in Device group: COAPT

Device group is be er to ↓ CHF readmissions!


Safety at acceptable levels!

Improved survival in device cohort!


COAPT Take Home Points

In patients with severe mitral regurgitation and heart failure:• Optimize guideline directed medical therapy at aggressive doses as tolerable

• Consider cardiac synchronization therapy if evidence of dys‐synchrony: LBBB, QRS > 150 msec, and NYHA > 2 on GDMT

• Refer for minimally invasive mitral valve repair to reduce heart failure admissions, reduce mortality, improve functional capacity, and improve quality of life at a very low risk of complications related to device therapy.

Case Presentation

You have a 75 yo lady with CHADS 2 score of 4 and atrial fibrillation going for colorectal surgery resection in a week. No prior Hx of CVA.Creatinine clearance is 50 ml/min.

What do you do with her Apixaban perioperatively? A. Stop it 5 days before surgery and restart POD 2B. Stop it 4 days before surgery and start LMWH 3 days before surgery

and last dose the day before surgery. Restart Apixaban POD 2C. Stop it 2 days before surgery and restart it POD 2D. Stop it 1 days before surgery and resume POD 1E. Call Hematology

PAUSE Trial Background: The management of atrial fibrillation on DOACs perioperatively is unclear.Research Question: What is the safety of a standard protocol managing DOACs perioperativelyMethods: Prospective Cohort Study N=3,007 patients 23 centers Canada, US and Europe on Apixaban, Rivaroxaban, and Dabigatran for atrial fibrillationOutcomes: Arterial thromboembolism, bleed, and % patients with undetectable or minimal residual anticoagulant levels (< 50 ng/ml) on Day of Surgery

Douketis J JAMA Intern Med Online August 5, 2019

DOAC Interruption Protocol




Perioperative Emboli < 1%Perioperative Bleed ~ 1 %Although not powered, but CHADS SCORE was not associated with either outcome


PAUSE: Take Home Points

• DO NOT BRIDGE DOACS!!!• Most cases hold 2 days preop and restart POD 2 unless Creatinine Clearance < 50 ml/min.

• Data not shown, but minimal or undetectable residual anticoagulant levels were > 95%, so anticoagulant was OFF during surgery


What we covered

• Preoperative Risk Assessment• VTE Treatment and Prevention with Active Cancer• C Difficile Risk Prediction • Complex Orthopedic Infections• Treatment of Endocarditis • Treatment of Bacteremia• Diagnosis and Treatment of Stroke• Heart Failure and Valves• Perioperative DOAC management

Take home points

• MD subjective assessment of patient’s functional capacity prior to noncardiac surgery is flawed

• Consider administering Duke Activity Status Index or ordering N‐Terminal B‐type Natriuretic Peptide for an objective assessment

• Edoxaban joins Rivaroxaban as options for monotherapy for cancer‐associated VTE events pending Apixaban approval

• Remember to check your Eosinophil count on admission CBC for C Difficile Colitis patients

Take home points

• Consider stepdown therapy from IV antibiotics to oral for the following indications, assuming functional gut:

• Enterobacteriaceae bacteremia if source control by day 5, but caution in ICU patients

• Endocarditis by day 10, assuming patient is over the initial high risk phase, but caution in IVDA’s

• Complex orthopedic infections

Take home points

• Start ASA plus load with clopidogrel followed by maintenance DAPT for at least 2‐3 months in high risk TIA or low risk ischemic CVA to reduce ischemic CVA in the short term

• For acute ischemic CVA from 6 ‐ 24 hours, refer for mechanical thrombectomy

• For systolic CHF and severe MR or secondary functional MR, referred for transcatheter mitral valve repair

• Periop DOACs, do not bridge‐ most cases hold 2 days preop and restart POD 2 if Creatinine Clearance ≥ 50 ml/min

Thank You!

Documents

Update in Hospital Medicine - Internal Medicine | ACP · For treatment of her DVT, she refuses to inject herself with low molecular weight heparin shots. ... Research Question: What