COW Week 8

A 60 yo male is admitted  for his 3rd episode of diverticular lower GI bleeding. Surgery evaluates him for hemicolectomy. He has ETOH cirrhosis and his last drink was 1 week ago. His Child-Pugh class is C and MELD score is 23. He denies chest pain or DOE. Exercise tolerance is 8 Mets and his ECHO shows an EF of 65%. You are asked for a preoperative evaluation.

Which of the following is the best recommendation for his elective surgery?
a. Delay surgery 7-10 days
b. Delay surgery indefinitely until risk improves
c. Proceed with surgery without further risk stratification
d. Recommend against elective surgery

While this patient has no active cardiac conditions and a fair-moderate exercise tolerance, he is still a poor surgical candiate in terms of his liver disease and elective surgery should be avoided. Child-Turcotte-Pugh class A, B, anc C have a 10%, 30%, and 80% postoperative mortality respectively. Patients with MELD score greater then15 are also considered to be at greater risk for postoperative mortality. Other risk factors in cirrhotic patients include age greater then 70yrs, obstructive jaundice,and  portal hypertension. Therefore, elective surgeries are avoided in these patients.

Risk Factors for Mortality After Surgery in Patients With Cirrhosis: Gastroenterology. 2007; 132(4):1261-1269

COW Week 7

A 58 yo post-menopausal female presents for F/U. She is concerned about her risk for breast cancer and wants to know if there is preventative therapy. She is uptodate on mammogram screening with normal results. Her sister was diagnosed with breast cancer at age 65. She has no children and menarche was at age 11. What should you do?

a. half-yearly mammograms

b. reassurance

c. discuss tamoxifen  (correct answer)

d. prophylactic mastectomies

According to the Gail model or Breast Cancer Risk Assessment Tool (BCRAT),  this patient has a 3.1% risk of developing breast cancer in the next 5 years. The Gail model is a clinical tool to help physicians calculate a woman’s individual risk of developing breast cancer over the next five years based on current age, age of menarche, age of first live birth, first degree relatives with breast cancer, prior breast biopsies, and race. The tool was created based on the Care Trial (looking specifically at African Americans) and Breast Cancer Detection Demonstration Project. The tool is not intended for women with a history suggesting inherited breast cancer.

The SERMs tamoxifen and raloxifene reduce the risk for new breast cancer by as much as 50%. For premenopausal women, tamoxifen is the only Food and Drug Administration–approved SERM for breast cancer prevention. For postmenopausal women, both tamoxifen and raloxifene are Food and Drug Administration–approved therapies. Use of these agents is approved for women with Gail model scores of greater than 1.7% for the risk of breast cancer over the next 5 years. Side effect profiles dictate whether tamoxifen or raloxifene should be used. Both the American Society of Clinical Oncology and USPSTF recommend discussing the risks/benefts of breast cancer prevention with these high risk women and starting a SERM if benefits outweigh risks. There are many risks to these therapies which would warrant not starting medication including but not limited to uterine cancer. Models have been developed to estimate the risk/benefit ratio of raloxifene and tamoxifen for postmenopausal women based upon their risk factors and can assist in risk discussions

The American Breast Cancer Prevention Trial sponsored by the National Surgical Adjuvant Breast and Bowel Project (NSABP) first showed the benefits of tamoxifen for breast cancer prevention. Women were eligible for the NSABP trial if they were considered to be "at increased risk" for breast cancer (age;60yrs or age 35-59 with a Gail score of at least 1.66%) and randomized to receive tamoxifen 20mg/daily vs. placebo. The study was stopped early after a median follow-up of 48 months when an interim analysis found that the benefit of tamoxifen was already statistically significant showing a relative risk reduction of 43% (2.5% vs. 4.3%) of invasive breast cancer and 37% for non-invasive breast cancer. The reduction was entirely by a decrease in ER-positive tumors and thus there was no significant change in occurrence of ER-negative tumors. Older women were found to have derived the most benefit. However, there was no difference in overall or breast cancer specific-survival between those receiving tamoxifen versus those receiving placebo

COW week 6

35 yo F w/ SLE and HTN has 1 month of worsening dull substernal CP associated w/ nausea and SOB. Episodes lasts  less than 15 minutes She takes prednisone 10mg, ASA & lisinopril. Vitals & PE are normal. EKG: NSR, TWI leads V1- V3. the first troponin is less than 0.04. What do you do?

Answer:

B.  CCU: heparin/Diagnostic Cath

This young female has HTN but no other traditional or "Framingham " Risk factors for CAD, but has autoimmune inflammatory disease. The proposed mechanism for increased risk of premature CAD is endothelial injury.  CAD is a major cause of death in patients with SLE so they should be considered high risk. Given this history plus ASA use,  worsening Angina, and T wave inversions, this patient should be treated as a "High TIMI" equivelent Unstable Angina/NSTEMI and be triaged to early  coronary angiography (within 48-72 hours).  Heparin or LMWH can be considered along with NTG sublingual or gtt  and Beta-blocker for HR control.

One study found that  "after controlling for common risk factors at baseline, the increase in relative risk for these outcomes was 10.1 for nonfatal MI (95% CI 5.8-15.6), 17.0 for death due to CHD (95% CI 8.1-29.7), 7.5 for overall CHD (95% CI 5.1-10.4), and 7.9 for stroke (95% CI 4.0-13.6)."

Stress test is unlikely to be helpful as this patient is high risk rather than intermediate risk.  The patient's CV exam is normal, which is unlikely in pericarditis or pericardial effusion with tamponade (would be significant for friction rub, Elevated JVP and Pulsus Pardoxus) though this can happen in SLE. In addition low voltage and electrical alternans would likely be present on EKG, no TWI.

Observation Unit would not be appropriate as this patient is high risk. D/C home would not be appropriate.   The patient has SLE so her HSCRP would be unhelpful (likely high due to systemic disease.

See the references below:

Esdaile JM, Abrahamowicz M, Grodzicky T, etal Traditional Framingham risk factors fail to fully account for accelerated atherosclerosis in systemic lupus erythematosus. Arthritis Rheum. 2001 Oct;44(10):2331-7

Bessant R,  Hingorani A, Patel L, et al Risk of coronary heart disease and stroke in a large British cohort of patients with systemic lupus erythematosus Rheumatology (2004) 43 (7): 924-929.

COW Week 5 Answer

COW#5

You are a resident in the ICU. You admit a 57y/o male for a COPD exacerbation. When would prophylactic PPI not be indicated with the following additional history?

Answer D: The patient is started on solumedrol 40mg IV daily.

Data from large prospective observational studies have found that ICU patients who have coagulopathy or respiratory failure requiring mechanical ventilation have a substantially higher risk of clinically important bleeding.  A prospective multicenter cohort study evaluated potential risk factors for stress ulceration in patients admitted to ICUs (Cook et al, Risk Factors for gastrointestinal bleeding in critically ill patients, NEJM 1994). Of 2252 patients, 33 (1.5%) had clinically important bleeding. Two strong independent risk factors for bleeding were identified: respiratory failure requiring ventilation x 48 hours (odds ratio [OR] 15.6) and coagulopathy (OR 4.3) defined as Plt<50 inr="inr">1.5 or PTT>2x control. Of 847 patients who had one or both of these risk factors, 31(3.7%) had clinically important bleeding. Of 1405 patients without these risk factors, 2 (0.1%) had clinically important bleeding. Of note, some potential risk factors for bleeding have not been adequately studied and it is unclear if they are independent predictors of bleeding. A majority of investigations excluded patients with a history of ulcers or GI bleed as well as long term NSAID use. Additionally, it was found that as minor risk factors build up, there is a higher risk for GI bleed. In 1999, the American Society of Health-System Pharmaciests (ASHP) released guidelines for stress ulcer prophylaxis. The recommendations are as follows:

1) Prophylaxis is recommended in patients with coagulopathy or patients requiring mechanical ventilation for more than 48 hours. (Strength of evidence = C= Non randomized cohort studies)

2) Prophylaxis is also recommended in patients with a history of GI ulceration or bleeding within one year before admission(Strength of evidence = D = Expert Opinion)

3) Prophylaxis is also recommended in patients with at least TWO of the following risk factors: sepsis, ICU stay of more than one week, occult bleeding lasting six days or more, and use of high-dose corticosteroids (>250 mg per day of hydrocortisone or the equivalent). (Strength of evidence = D = Expert Opinion)

4) Many clinicians also recommend prophylaxis for patients with traumatic brain injury, traumatic spinal cord injury, or thermal injury (>35 percent of the body surface area), as these special populations are generally excluded from studies given their high risk of stress ulcers.

5) Lastly, it is recommended to continue a PPI for a patient already on a PPI as there is a risk for rebound gastric acid hypersecretion.

TAKE HOME POINT: The two biggest risk factors for GI bleeding in the ICU is coagulopathy and intubation! 

Click on the link below for a good summary

Stress Induced Ulcer PPX Summary 

Also below are the 1999 guidelines. Its pretty long but read the portion on stress ulcer ppx. They have nice summaries in italics after each section:

ASHP Therapeutic Guidelines on Stress Ulcer Prophylaxis. ASHP Commission on Therapeutics and approved by the ASHP Board of Directors on November 14, 1998 Am J Health Syst Pharm February 1, 1999 56:347-379

COW Week 4 Answer

This patient should have been started on argatroban 2 days ago when HIT was suspected and should stay in the hospital for minimum 2 weeks on an argatroban drip. Fonadaprinux can be used off-label for outpatient management but this is not FDA approved. Coumadin is not appropriate as HIT is a very hypercoagulable state requiring a “true” anticoagulant. Coumadin does not inhibit activated clotting factors and has also been associated with a purpura fulminans kind of syndrome in this setting. Up to 50% of patients with HIT develop thrombosis.

Words of Wisdom from Dr. Rosove:

This patient has heparin induced thrombocytopenia (HIT). HIT develops anywhere from day 4 to 14 of de novo therapy. It takes that long for IgG antibodies to the heparin-platelet factor 4 complex to develop. Thrombocytopenia can occur earlier than day 4, even immediately, upon exposure to unfractionated heparin (UFH) if there has been a recent exposure to any glycosaminoglycan anticoagulant, GAG, (UFH, LMWH, or fondaparinux) such that antibodies are already present. This patient was exposed to heparin recently which is why her platelets dropped so quickly.

HIT patients must be anticoagulated for a minimum of two weeks (3 months per Board Review), even if there is full recovery of the platelet count, no evident thrombosis, and no need for longer-term anticoagulation. By two weeks, nearly all of the acute risk has passed. If there is evidence of thrombosis then one must be anti-coagulated for 3-6months. The only FDA-approved anticoagulants for HIT are argatroban, bivalirudin, and lepirudin (the first two are on our formulary), but these are IV infusions, thus requiring inpatient care. Therefore fondaparinux SQ is often given off-label to allow outpatient management. Fondaprinux may perpetuate antibody formation but is virtually incapable of causing HIT. Rivaroxaban or dabigatran could also serve in the same capacity since they are not GAGs, but neither have been tested and thus should not be used at this time.

HIT is a preventable problem. By far it occurs more frequently with UFH than LMWH, and HIT due to fondaparinux is practically reportable. Therefore, whenever there is a reasonable choice of which anticoagulant to use, UFH is best avoided altogether. In the case of unstable angina and percutaneous coronary interventions, there are legitimate alternatives to UFH.

A positive HAPA, no matter how strongly positive, only permits a diagnosis of HIT, it does not make a diagnosis since the majority of patients who are antibody positive do not have HIT. However, the negative predictive value of HAPA is nearly perfect.

ACCP 2012 Guidelines: HIT 

HIT Clinical Review 

COW Week 3 Answer

Answer: 1 and 3

ALLHAT was a double blind RCT evaluating adults with HTN and at least one cardiac risk factor (prior MI, CVA, LVH, DM, Tob, low HDL, known atherosclerosis) and randomized them to 3 groups: Amlodipine vs Chlorthalidone vs Lisinopril. After 5 years, 68% of patients in the Chlorthalidone group achieved the blood pressure goal (less than140/90) vs 66% in the Amlodipine group and 61% in the Lisinopril group. There was no difference in all cause mortality or fatal coronary heart disease and nonfatal MIs. However, the Chlorthalidone group did have a significant decrease in Heart failure and stroke when compared to Lisinopril. Based on ALLHAT, a thiazide diuretic, chlorthalidone, is at least as effective if not better than several other medications as first line therapy in high risk patients with hypertension and it is definitely cheaper. For this reason, the JNC 7 recommends thiazides as first line agents for hypertension in most patients.

In this vignette, the patient has diabetic nephropathy due to his proteinuria. In such patients, JNC 7 recommends an ACE/ARB as first line treatment rather than a thiazide. However, the patient has stage II hypertension for which JNC recommends 2 medications as initial therapy. Thus, this patient should be started on both a Thiazide and ACE/ARB.

Lastly, the ACCOMPLISH trial compared HCTZ and Benazepril vs Amlodipine and Benazepril in patients with HTN and high cardiovascular risk and showed Amlodipine to be superior by decreasing cardiovascular events. Some experts believe this is due to HCTZ being a less potent Thiazide than Chlorthalidone. Stay tuned to the upcoming JNC 8 to see if the recommendations change!! Click on the link below to see the articles.

 ALLHAT
ACCOMPLISH

COW Week 2 Answer

The AIM-HIGH Study (N Engl J Med 2011; 365:2255-2267) looked at patients with established cardiovascular disease already on appropriate statin therapy who had low LDL and low HDL. They were randomized to statin alone or statin plus niacin. There was no incremental clinical benefit from the addition of niacin to statin therapy during a 36-month follow-up period, despite significant improvements in HDL cholesterol and triglyceride levels.

The ACCORD Trial (N Engl J Med 2010; 362:1563-1574) looked at combination lipid therapy in type 2 diabetes and found no difference in cardiovascular outcomes between statin alone and statin plus fenofibrate. However, a subgroup analysis of patients with low HDL and triglycerides above 200 did show improved outcomes. Based on this subgroup, a new clinical trial is currently underway to study whether addition of fibrates to patients on optimal statin therapy (ie: LDL less than 70) with low HDL and high triglycerides reduces cardiovascular mortality. 

So niacin is out, but the the utility of fibrates is yet to be determined.

Remember: just because the numbers look good doesn't mean it has any clinical significance!

NEJM Article: AIM-HIGH

NEJM Article: ACCORD