After committing the 2008 guidelines to heart and four years of reverence as my holy book, the time has come to toss out the old and move onto the new; CHEST 2012 is here.
Its absolutely amazing how much additional evidence has become available in four years and to see just how much has changed. Although my work cut out for me, in reviewing the guidelines, it makes it easier to review what the experts recommend, rather than trying to go through all the trials and piece together recommendations myself. When guidelines wait too long to provide updates, in the end, they end up discrediting themselves *cough* JNC7 *cough*
Less than a year out a pharmacy school, I still have trouble wrapping my head around some of these recommendations. Have I become this set in my ways?
Let's look at CHEST.
Warfarin:
Warfarin can be initiated the same day that LMWH/fondaparinux/UFH is started for the treatment of VTE . Pharmacy school hammered into my head the mantra "no loading dose, no loading dose, no loading dose" however new recommendations suggest that patients should be given 10mg of warfarin for the first two days, then dosing after that should be based off the change seen in the INR. This recommendation seems to apply for any indication for warfarin start. This will push the patient into range faster, examples given showed patients more likely to get to range a day ahead of patients dosed conventionally.
Rebuttal: First and foremost, I would have to review the individual trials to see if patients were dichotomized by age, but it is unclear if the guidelines are recommending 10mg for two days across the board, including our 80 year old grandmas. I would like to see data specific to the elderly before following along.
Secondly, irregular dosing makes it more difficult to establish a starting weekly dose outpatient. From my brief experiences in managing patients in an outpatient warfarin clinic, I have had the most difficulty dosing patients who received highly variable dosing in the hospital, which can end up meaning overshooting or undershooting their INR.
Despite this recommendation by the consensus guideline, I doubt that many of the anticoagulation pharmacists at my facility will buy into it. The Navajo tend to be slower to respond to warfarin but much more sensitive. For anticoagulation pharmacists across the Navajo Nation, it is hypothesized that there may be a gene that contributes to this, but we have no way of knowing which patients will be more likely to respond in certain ways. Despite how slowly the INR budges in the first few days, some of the patients end up shooting up to incredibly high INRs in the second week. Very little medical research is done on Native Americans (it doesn't take a rocket scientist to figure out why they may be adverse to the idea considering the history with white America) so again, I have no data to support this, but using a loading dose in this population may be more dangerous than using it in other populations.
Dabigatran.
Dabigatran 150mg twice daily is recommended over warfarin for patients with atrial fibrillation with a CHADS score of one or higher.
Dabigatran was approved for atrial fibrillation based off the results from the RE-LY trial, which only looked at 110mg twice daily or 150mg twice daily and excluded patients with a creatinine clearance less than 30mL/min.
I am so excited about the new anticoagulants, and if you understand warfarin, its not difficult to understand why. Warfarin is a difficult drug. But the fact of the matter is, these new drugs are relatively unknown. It is difficult for me to consider recommending an expensive, new drug that has been studied limitedly over the gold standard of anti-coagulation that has been proven effective time and again in clinical trials. Am I afraid of the unknown? To be honest, yes. I know what to expect from warfarin, but I'm not entirely sure of all the risks I bestow on a patient by recommending dabigatran.
Furthermore, it is interesting that the guidelines specifically recommend only the 150mg twice daily dosing for patients with "good" renal function. The 75mg twice daily dose was never studied in clinical trials and many of the new precautions with bleeding are specific to patients with impaired renal function, despite being on the lower dose. A New Zealand study published in the New England Journal examined a series of case reports regarding bleeding with dabigatran showed that patients with low body weight, low renal function, and older age were at greater risk. Furthermore, the makers of dabigatran recommend that the INR fall below 2.0 for patients previously on warfarin before starting, which may not always be adhered to.
"But dabigatran did not have that caveat; I think the government wanted it be used. They saw it as a good replacement forwarfarin and wanted as many people as possible to switch. The uptake was very quick—too quick. Doctors were very keen to prescribe it, and everyone got carried away." Dr. Harper, the primary investigator, tells HeartWire (www.theheart.org).
To my knowledge, only two patients are taking dabigatran at my facility but are taking the 75mg twice daily dose (not according to my recommendation). One of the patients was switched as a result of variable INR due to non-compliance. This patient is not going to be anti-coagulated if she is non-compliant with her dabigatran, the difference is that we may not know the difference until she strokes out.
To summarize, I disagree with CHEST's "blanket-statement" recommendation and think that dabigatran should be recommended on a case-to-case basis and the greatest folly I see in the recommendation of the switch to dabigatran is to recommend it in patients who are non-compliant with warfarin. Patients that refuse to take their anticoagulants will not be anti-coagulated.
Aspirin.
I have a couple of beefs with recommendations regarding aspirin in the new guidelines.
For patients that have undergone hip fracture surgery, there is a strong recommendation for clot prevention therapy for at least 10-14 days, out to 30 days. Patients can use LMWH, UFH, fondaparinux, warfarin or... aspirin? really? aspirin? It almost seems hypocritical especially because aspirin has not been recommended as sufficient clot prophylaxis in other scenarios. LMWH is still recommended first line, and honestly I would need to see the full length VTE prophylaxis guideline to fully file my complaint on this one, but... really? aspirin?
Aspirin is recommended for anyone over the age of 50 WITHOUT symptomatic cardiovascular disease. Aspirin is cheap and prevents clots. In the early years of pharmacy school, I was told to give aspirin to anyone over the age of 50 AND to anyone with diabetes, regardless of age. However, after presenting on the ADA/AHA/ACCF 2010 and U.S. Preventive Service Task Force 2009 guidelines, I began to change my mind.
The majority of trials looking at aspirin for primary prevention did not reach statistical significance additionally, practitioners are beginning to think twice about using aspirin because there absolutely is an increased risk of bleed associated with its use. Both guidelines focus on weighing the risk of bleed against the risk of having an event. The Task Forces break down the recommendation by age, and recommend aspirin for age cohorts based on the man's risk of CHD and the woman's risk of stroke. Check the document for the specific recommendation, but to ball-park it, use aspirin in patients ages 60-79 when man's risk of CHD is greater or equal to 10% or woman's risk of stroke is greater of equal to 10% (recommendation for use in patients ages 50-59 starts at a lower risk level ~5%). The Task Forces do not make a specific recommendation for ages of either gender above the age of 80 due to significantly increased risk of bleed.
ADA is easier to follow but can only apply to patients with diabetes. For men over 50 and women over 60 with an additional risk factor (smoking, hypertension, hyperlipidemia, family history premature CVD, or albuminuria) low dose aspirin is recommended. Controlled risk factors are not counted.
The CHEST 2012 recommendation to use aspirin in any patient over 50 almost seems archaic in light of recommendations made recently by other major medical organizations. The ADA and Task Force guidelines are fairly similar; the CHEST recommendation creates a major discrepancy among other major guidelines.
So
I may not agree with everything in the new guidelines, I may be wary to change my ways, but the great thing about the medical field is that is always changing. A professor told me that she had been taught NEVER to use a beta-blocker in any patient with heart failure, now it is the standard of care. These discoveries that completely change clinical practice occur on a year to year basis. I think the best we can do is educate ourselves, read the literature, and keep an open mind. Despite my complaints/rebuttals, I love my new CHEST which if filled with a plethora of fabulous recommendations and will help us to guide therapy to improve patient care.
References:
pending (please excuse my unprofessionalism), CHEST exec summary, Chest Anticoagulants, CHEST therapy for VTE disease, USPSTF 2009, ADA/AHA/ACCF 2010, http://www.theheart.org/article/1363757.do
Its absolutely amazing how much additional evidence has become available in four years and to see just how much has changed. Although my work cut out for me, in reviewing the guidelines, it makes it easier to review what the experts recommend, rather than trying to go through all the trials and piece together recommendations myself. When guidelines wait too long to provide updates, in the end, they end up discrediting themselves *cough* JNC7 *cough*
Less than a year out a pharmacy school, I still have trouble wrapping my head around some of these recommendations. Have I become this set in my ways?
Warfarin:
Warfarin can be initiated the same day that LMWH/fondaparinux/UFH is started for the treatment of VTE . Pharmacy school hammered into my head the mantra "no loading dose, no loading dose, no loading dose" however new recommendations suggest that patients should be given 10mg of warfarin for the first two days, then dosing after that should be based off the change seen in the INR. This recommendation seems to apply for any indication for warfarin start. This will push the patient into range faster, examples given showed patients more likely to get to range a day ahead of patients dosed conventionally.
Rebuttal: First and foremost, I would have to review the individual trials to see if patients were dichotomized by age, but it is unclear if the guidelines are recommending 10mg for two days across the board, including our 80 year old grandmas. I would like to see data specific to the elderly before following along.
Secondly, irregular dosing makes it more difficult to establish a starting weekly dose outpatient. From my brief experiences in managing patients in an outpatient warfarin clinic, I have had the most difficulty dosing patients who received highly variable dosing in the hospital, which can end up meaning overshooting or undershooting their INR.
Despite this recommendation by the consensus guideline, I doubt that many of the anticoagulation pharmacists at my facility will buy into it. The Navajo tend to be slower to respond to warfarin but much more sensitive. For anticoagulation pharmacists across the Navajo Nation, it is hypothesized that there may be a gene that contributes to this, but we have no way of knowing which patients will be more likely to respond in certain ways. Despite how slowly the INR budges in the first few days, some of the patients end up shooting up to incredibly high INRs in the second week. Very little medical research is done on Native Americans (it doesn't take a rocket scientist to figure out why they may be adverse to the idea considering the history with white America) so again, I have no data to support this, but using a loading dose in this population may be more dangerous than using it in other populations.
Dabigatran.
Dabigatran 150mg twice daily is recommended over warfarin for patients with atrial fibrillation with a CHADS score of one or higher.
Dabigatran was approved for atrial fibrillation based off the results from the RE-LY trial, which only looked at 110mg twice daily or 150mg twice daily and excluded patients with a creatinine clearance less than 30mL/min.
I am so excited about the new anticoagulants, and if you understand warfarin, its not difficult to understand why. Warfarin is a difficult drug. But the fact of the matter is, these new drugs are relatively unknown. It is difficult for me to consider recommending an expensive, new drug that has been studied limitedly over the gold standard of anti-coagulation that has been proven effective time and again in clinical trials. Am I afraid of the unknown? To be honest, yes. I know what to expect from warfarin, but I'm not entirely sure of all the risks I bestow on a patient by recommending dabigatran.
Furthermore, it is interesting that the guidelines specifically recommend only the 150mg twice daily dosing for patients with "good" renal function. The 75mg twice daily dose was never studied in clinical trials and many of the new precautions with bleeding are specific to patients with impaired renal function, despite being on the lower dose. A New Zealand study published in the New England Journal examined a series of case reports regarding bleeding with dabigatran showed that patients with low body weight, low renal function, and older age were at greater risk. Furthermore, the makers of dabigatran recommend that the INR fall below 2.0 for patients previously on warfarin before starting, which may not always be adhered to.
"But dabigatran did not have that caveat; I think the government wanted it be used. They saw it as a good replacement forwarfarin and wanted as many people as possible to switch. The uptake was very quick—too quick. Doctors were very keen to prescribe it, and everyone got carried away." Dr. Harper, the primary investigator, tells HeartWire (www.theheart.org).
To my knowledge, only two patients are taking dabigatran at my facility but are taking the 75mg twice daily dose (not according to my recommendation). One of the patients was switched as a result of variable INR due to non-compliance. This patient is not going to be anti-coagulated if she is non-compliant with her dabigatran, the difference is that we may not know the difference until she strokes out.
To summarize, I disagree with CHEST's "blanket-statement" recommendation and think that dabigatran should be recommended on a case-to-case basis and the greatest folly I see in the recommendation of the switch to dabigatran is to recommend it in patients who are non-compliant with warfarin. Patients that refuse to take their anticoagulants will not be anti-coagulated.
I have a couple of beefs with recommendations regarding aspirin in the new guidelines.
For patients that have undergone hip fracture surgery, there is a strong recommendation for clot prevention therapy for at least 10-14 days, out to 30 days. Patients can use LMWH, UFH, fondaparinux, warfarin or... aspirin? really? aspirin? It almost seems hypocritical especially because aspirin has not been recommended as sufficient clot prophylaxis in other scenarios. LMWH is still recommended first line, and honestly I would need to see the full length VTE prophylaxis guideline to fully file my complaint on this one, but... really? aspirin?
Aspirin is recommended for anyone over the age of 50 WITHOUT symptomatic cardiovascular disease. Aspirin is cheap and prevents clots. In the early years of pharmacy school, I was told to give aspirin to anyone over the age of 50 AND to anyone with diabetes, regardless of age. However, after presenting on the ADA/AHA/ACCF 2010 and U.S. Preventive Service Task Force 2009 guidelines, I began to change my mind.
The majority of trials looking at aspirin for primary prevention did not reach statistical significance additionally, practitioners are beginning to think twice about using aspirin because there absolutely is an increased risk of bleed associated with its use. Both guidelines focus on weighing the risk of bleed against the risk of having an event. The Task Forces break down the recommendation by age, and recommend aspirin for age cohorts based on the man's risk of CHD and the woman's risk of stroke. Check the document for the specific recommendation, but to ball-park it, use aspirin in patients ages 60-79 when man's risk of CHD is greater or equal to 10% or woman's risk of stroke is greater of equal to 10% (recommendation for use in patients ages 50-59 starts at a lower risk level ~5%). The Task Forces do not make a specific recommendation for ages of either gender above the age of 80 due to significantly increased risk of bleed.
ADA is easier to follow but can only apply to patients with diabetes. For men over 50 and women over 60 with an additional risk factor (smoking, hypertension, hyperlipidemia, family history premature CVD, or albuminuria) low dose aspirin is recommended. Controlled risk factors are not counted.
The CHEST 2012 recommendation to use aspirin in any patient over 50 almost seems archaic in light of recommendations made recently by other major medical organizations. The ADA and Task Force guidelines are fairly similar; the CHEST recommendation creates a major discrepancy among other major guidelines.
So
I may not agree with everything in the new guidelines, I may be wary to change my ways, but the great thing about the medical field is that is always changing. A professor told me that she had been taught NEVER to use a beta-blocker in any patient with heart failure, now it is the standard of care. These discoveries that completely change clinical practice occur on a year to year basis. I think the best we can do is educate ourselves, read the literature, and keep an open mind. Despite my complaints/rebuttals, I love my new CHEST which if filled with a plethora of fabulous recommendations and will help us to guide therapy to improve patient care.
References:
pending (please excuse my unprofessionalism), CHEST exec summary, Chest Anticoagulants, CHEST therapy for VTE disease, USPSTF 2009, ADA/AHA/ACCF 2010, http://www.theheart.org/article/1363757.do
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