July 2011 FAQs
July 2011 FAQs
What are the new recommendations for managing hypertension in the elderly?
What are the new recommendations for managing hypertension in the elderly?
With the aging of the population, the benefit and risk of lowering blood pressure (BP) in the elderly (≥ 65 years) is of particular interest. Although clinical trials include elderly patients, those aged 80 years and older (very old) are poorly represented. Recent data; however, has been published that has led to recommendations from the American Heart Association (AHA) and the American College of Cardiology Foundation (ACCF) for the management of hypertension (HTN) in the elderly and very old.1
A review of recent data in the very old is discussed as well as general recommendations for management of HTN in this particular age group. For detailed recommendations on management of patients with comorbid conditions and use of classes of antihypertensive agents, the consensus document should be reviewed.
The Hypertension in the Very Elderly Trial (HYVET) study compared the rate of fatal or nonfatal stroke in 3845 patients 80 years or older treated with indapamide 1.5 mg (n = 1933) or placebo (n = 1912) for HTN.2 The goal BP was <150/80 mm Hg. If needed, perindopril 2 or 4 mg or matching placebo was added to achieve the target BP. The mean age of patients was 83.6 years and mean sitting baseline BP was 173/90 mm Hg. With respect to comorbid conditions, 11.5% of patients had cardiovascular disease, 6.7% had previous stroke, about 3% had a previous myocardial infarction (MI) or heart failure, close to 7% had diabetes, and 6.5% were smokers. An interim analysis identified a significant reduction in the rate of death from any cause (relative risk [RR] 0.76, 95% confidence interval [CI] 0.62 to 0.93, p = 0.007) and in the rate of any stroke (RR 0.59, 95% CI 0.40 to 0.93, p = 0.009) with indapamide treatment compared with placebo which led to early termination of the study. After a mean treatment duration of 2 years, close to 50% of patients randomized to receive indapamide were receiving perindopril 4 mg. At 2 years, approximately 50% of patients receiving active treatment compared to about 20% of patients on placebo achieved the target BP. Although a 30% reduction in the rate of fatal or nonfatal stroke was observed (hazard ratio [HR] 0.70, 95% CI 0.49 to 1.01, p = 0.06) at the end of the study, the reduction was not statistically significant. Secondary outcomes of statistical significance included death from stroke (HR 0.61, 95% CI 0.38 to 0.88, p = 0.046), death from any cause (HR 0.79, 95% CI 0.65 to 0.95, p = 0.02), any heart failure (HR 0.36, 95% CI 0.22 to 0.58, p<0.001), and any cardiovascular event (HR 0.66, 95% CI 0.53 to 0.82, p<0.001). Interestingly, serious adverse events were significantly more frequent with placebo compared to treatment (448 vs. 358, p=0.001). This trial was the first to demonstrate a benefit in reducing BP in the very old without significant adverse reactions. However, the trial studied a healthy, elderly population from Europe and China and therefore, does not represent the typical elderly population observed in the US.
A substudy of the International Verapamil SR-Trandolapril (INVEST) trial evaluated the impact of controlling HTN on the primary endpoint of overall mortality, nonfatal MI, and nonfatal stroke in patients 80 years of age or older with coronary artery disease compared to younger patients in the larger trial.3 Target BP was <140/90 mm Hg or <130/85 mm Hg for patients with diabetes or renal dysfunction. Over 2000 patients were randomized to receive either atenolol or long-acting verapamil. If needed, further BP reduction could be achieved with the addition of trandolapril and hydrochlorothiazide. Over 60% of the patients were female with an average age of 83.8 years. At baseline, slightly over 10% of patients had heart failure and/or a previous stroke or transient ischemic attack, 23% had left ventricular hypertrophy, close to 4% were current smokers and 34% were past smokers, and 22% had diabetes. Compared to younger patients in the larger study, these older patients had higher systolic and lower diastolic BP at baseline and at 24 months. Although BP improved in all age groups, a fewer number of patients in this age group achieved goal BP. The primary outcome was observed at the highest rate (23.6%) in these older patients compared to other age groups with cardiovascular causes as the primary cause of death. No difference in outcomes were observed between treatment group. Analysis of the relationship between BP and the primary outcome led to the conclusion that the lowest risk of events occurred at a systolic BP of 140 mm Hg and a diastolic BP of 70 mm Hg in patients 80 years and older. For patients between 70 and 79 years of age, no benefit was observed with a systolic BP of < 135 mm Hg and diastolic BP < 75 mm Hg. The authors concluded that lowering blood pressure below 140/70 mm Hg in patients 80 years of age or older may not be beneficial.
Data from a 1999 meta-analysis demonstrated results in slight contrast to that observed in the HYVET trial in terms of mortality. The analysis evaluated the effect of antihypertensive treatment on fatal and nonfatal stroke in patients 80 years and older.4 This analysis included data from well-known trials such as the Systolic Hypertension in the Elderly Program (SHEP) trial and the Systolic Hypertension in Europe (Syst-Eur) trial. Outcomes on 874 patients receiving active treatment were compared to 796 patients on placebo from a total of 7 trials. Treatment was shown to reduce the occurrence of strokes by 34%, cardiovascular events by 22% and heart failure by 39%. However, a reduction in cardiovascular death was not observed and a relative increase (6%, p value not significant) in all-cause death occurred in patients receiving treatment. Although treatment of hypertension in older patients reduced stroke and other cardiovascular events, the meta-analysis was unable to find a benefit on overall mortality.
The general BP goal of <140/90 mm Hg applied to the very elderly has been based on expert opinion rather than evidence from clinical trials. 1 The ideal BP goal for patients 80 years and older with or without comorbid conditions has not been established.1,5 With information available from the above studies, the AHA/ACCF Expert Consensus Document suggests that systolic BP < 140 mm Hg is reasonable for most patients 79 years and younger. However, systolic BP between 140 and 145 mm Hg is acceptable, if tolerated for those 80 years and older. Lowering diastolic BP lower than 65 to 70 mm Hg appears to increase the risk of cardiovascular events and current recommendations suggest keeping diastolic BP over 65 mm Hg . Treatment can be considered for elderly patients with systolic BP over 150 mm Hg as this may reduce cardiovascular events and mortality. When BP is > 20/10 mm Hg of the goal, initiation of 2 antihypertensive agents may be considered. For patients that are unable to achieve a systolic BP < 150 mm Hg despite use of multiple agents or who experience intolerable adverse events, systolic BP should be maintained at the safest level over 150 mm Hg without lowering diastolic BP below 65 mm Hg. Treatment may be withheld in patients who are frail and otherwise medically unstable or who are approaching 90 years of age or older.
Prior to initiating drug therapy, the impact on cognitive function, general activity, adherence, sexual function as well as the risk of medication adverse events must be considered.1,5 Elderly patients are more likely to experience adverse events with use of medications because of altered drug disposition. Pharmacokinetic changes that occur due to aging include an increase in distribution of lipophilic drugs and a reduction in drug absorption, distribution of hydrophilic substances, hepatic metabolism, and renal clearance. Depending on the medication, its effects may be enhanced or reduced due to these age-related changes. To the extent possible, lifestyle modifications should be implemented. Initiating treatment with a thiazide diuretic, a long-acting dihydropyridine calcium antagonist, an angiotensin converting enzyme inhibitor (ACEI), or an angiotensin receptor blocker (ARB) for patients aged 80 years and older is recommended. However, concomitant diseases may require the use of other antihypertensives and are detailed further in the guideline. Treatment should be initiated at low doses and increased after close monitoring of both sitting and standing BP. As demonstrated in the HYVET trial, many elderly patients require at least 2 agents to reduce BP.2
Clinicians caring for octogenarians can refer to recent data and the AHA/ACCF consensus document suggesting that lowering BP can reduce cardiovascular events and possibly, death. The extent to which BP is lowered, however, may not need to be as low as for younger patients. Although a target BP for the very old has not been established, maintaining systolic BP between 140 and 145 mm Hg and diastolic BP over 65 mm Hg is acceptable. Additionally, BP values higher than this are also acceptable in certain elderly patients unable to achieve lower BPs.
1. Aronow WS, Fleg JL, Pepine CJ, et al. ACCF/AHA 2011 consensus document on hypertension in the elderly. J Am Coll Cardiol. 2011;57(20):2037-2114.
2. Beckett NS, Peters R, Fletcher AE, et al. Treatment of hypertension in patients 80 years of age or older. N Engl J Med. 2008;358(18):1887-1898.
3. Denardo SJ, Gong Y, Nichols WW, et al. Blood Pressure and outcomes in very old hypertensive coronary artery disease patients: an INVEST substudy. Am J Med. 2010;123(8):719-726.
4. Gueyffier F, Bulpitt C, Boissel JP, et al. Antihypertensive drugs in very old people: a subgroup meta-analysis of randomized controlled trials. Lancet. 1999;353(9155):793-796.
5. Cupp M. Hypertension in the elderly: pharmacotherapy focus. Pharmacist's Letter/Prescriber's Letter. June 2011: Detail Document #270601.
Why was the niacin AIM-HIGH trial stopped early?
Why was the niacin AIM-HIGH trial stopped early?
According to data from the National Health and Nutrition Examination Survey (NHANES 2005-2006), approximately 45% of Americans have high total cholesterol (>200 mg/dL), about 33% have elevated low-density lipoprotein cholesterol (≥130 mg/dL), and 15.5% have low high-density lipoprotein cholesterol (<40 mg/dL).1 The primary target for dyslipidemia management is LDL according to the third report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel [ATP] III).2 HMG-CoA reductase inhibitors, or statins, are the first-line agents for lowering LDL when drug therapy is indicated. Alternative agents to lower LDL include bile acid sequestrants and nicotinic acid (niacin).
Although LDL reduction is the primary treatment goal, some patients present with arthrogenic dyslipidemia ("lipid triad") characterized by low HDL levels, elevated triglycerides, and presence of small LDL particles.2 This triad commonly occurs as part of metabolic syndrome. Lifestyle modifications (weight reduction and increased exercise) are recommended as well as therapy with a statin, bile acid sequestrant, or niacin. The combination of a statin and niacin has been given to patients with elevated LDL and low HDL levels.
The Atherothrombosis Intervention in Metabolic Syndrome with Low HDL Cholesterol/High Triglyceride and Impact on Global Health Outcomes (AIM-HIGH) was designed to evaluate outcomes with extended-release niacin compared to placebo when added to statin therapy in patients with a history of cardiovascular disease (coronary artery, cerebrovascular, or peripheral vascular) and athrogenic dyslipidemia who had low HDL levels, high triglyceride levels, and well-controlled LDL levels.3-6 The trial, which has not been published in full, was conducted in the United States and Canada and involved 3414 subjects who were randomized to extended-release (ER) niacin target 1500 to 2000 mg/day or placebo in addition to simvastatin. 4-6 The simvastatin dose was initially 40 mg/day and could be increased or decreased (range 10 mg to 80 mg/day) during the first year to meet LDL goals (40 to 80 mg/dL). Ezetimibe 10 mg/day was another option for furthering LDL reduction.
The primary outcome measure was time to coronary heart disease death, nonfatal myocardial infarction (MI), ischemic stroke, acute coronary syndrome, or symptoms requiring coronary or cerebral revascularization.4,6 The data and safety monitoring board (DSMB) recommended that the AIM-HIGH trial should be stopped 18 months earlier than planned since preliminary results revealed that niacin ER did not offer any benefit over simvastatin alone in preventing cardiovascular-related complications.5 The DSMB further stated that the results for the primary outcome measure were unlikely to change if the trial were continued. Subjects who received niacin ER did achieve higher HDL levels and lower triglyceride levels compared to those receiving simvastatin alone. An increase in the rate of ischemic stroke was seen with active therapy, which also contributed to the DSMB's decision to terminate the trial. Twenty-eight (1.6%) strokes occurred in the niacin ER group compared to 12 (0.7%) in the placebo group. At this time, it is not clear whether niacin is associated with an increase in the incidence of stroke or if the findings were due to chance or some other reason. Nine of 28 strokes in the niacin ER group occurred in patients who were no longer receiving the drug for at least 2 months and up to 4 years before the stroke.
The Food and Drug Administration (FDA) is planning to conduct a review of the AIM-HIGH trial results once the data are fully available (expected fall 2011).5,6 At this time, FDA has not made any recommendations about niacin ER based on AIM-HIGH; however, the agency has alerted providers and the public about the trial termination and preliminary results.6
Investigators from the AIM-HIGH trial caution providers not to apply the results of the trial to patients in practice including those at higher risk or those with LDL levels not as controlled as participants in the trial.5 In addition, results from AIM-HIGH differ from previous literature, which has shown beneficial effects of niacin. The acting director of the National Heart, Lung, and Blood Institute (NHLBI), an agency that sponsored the trial along with contributions from Abbott and Merck, states that AIM-HIGH results apply to the specific population studied and there is no need for a change in the general way in which niacin is used in the practice for management of dyslipidemia.3 Another trial involving niacin ER, the Heart Protection Study 2 Treatment of HDL to Reduce the Incidence of Vascular Events is ongoing with results anticipated in 2013.
Simvastatin doses could be increased up to 80 mg/day in AIM-HIGH.4 On June 8, 2011, FDA recommended limiting the use of simvastatin 80 mg due to increased risk of myopathy.7 The agency recommends not to initiate 80 mg in new patients, and only continue 80 mg/day in patients who have taken been taking the dose for at least 12 months without signs of myopathy. The labeling for simvastatin has also been updated to reflect the dose limits and to strengthen information about the potential for drug-drug interactions, which may increase the risk for simvastatin-induced myopathy. Full details are available on FDA's website:
The AIM-HIGH trial was terminated early by the DSMB since the addition of niacin ER failed to significantly reduce the occurrence of cardiac complications compared to placebo in subjects receiving simvastatin. Subjects included in the trial had well-controlled LDL levels at baseline, prior to the addition of niacin ER. Results of this trial are in conflict with previous data demonstrating beneficial effects of niacin. Niacin ER was associated with a higher percentage of ischemic stroke compared to simvastatin alone; however, the causal relationship has been questioned. Clinicians should continue to maximize statin therapy as first-line treatment for dyslipidemia, with the caveat to limit the use of simvastatin 80 mg in accordance with the new FDA recommendations. Lifestyle modifications including diet and exercise are an effective option for raising HDL levels.
- Lloyd-Jones D, Adams R, Carnethon M, et al. Heart disease and stroke statistics-2009 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2009;119(3):e21-e181.
- National Heart Lung and Blood Institute. Third report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATP III final report). http://www.nhlbi.nih.gov/guidelines/cholesterol/atp3_rpt.htm. Accessed June 16, 2011.
- TheHeart.org. NIH pulls plug on AIM-HIGH trial with niacin. http://www.theheart.org/article/1231453.do. Accessed June 23, 2011.
- Pharmacist's Letter detail document. Niacin plus statin to reduce cardiovascular risk: AIM-HIGH study. Pharmacist's Letter/Prescriber's Letter. July 2011.
- U.S. Department of Health and Human Services. NIH News. National Institutes of Health. NIH stops clinical trial on combination cholesterol treatment. http://public.nhlbi.nih.gov/newsroom/home/GetPressRelease.aspx?id=2792 . Accessed June 9, 2011.
- U.S. Food and Drug Administration. FDA statement on the AIM-HIGH trial. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm256841.htm . Accessed June 9, 2011.
- U.S. Food and Drug Administration. FDA drug safety communication: new restrictions, contraindications, and dose limitations for Zocor (simvastatin) to reduce the risk of muscle injury. http://www.fda.gov/Drugs/DrugSafety/ucm256581.htm. Accessed June 16, 2011.
What are the new recommendations for pharmacological interventions used to conserve blood in cardiovascular procedures?
What are the new recommendations for pharmacological interventions used to conserve blood in cardiovascular procedures?
Blood conservation is a major concern in the management of patients undergoing surgical procedures, seeing as approximately 15 million units of packed red blood cells (PRBC) are transfused as a result of surgical procedures every year.1 Blood transfusion is associated with added costs to the procedure and significant risk to patients.2 Procedures involving cardiopulmonary bypass (CPB) and extracorporeal membrane oxygenation (ECMO) are of particular interest because they consume a large portion of the United States' blood supply. With the rate of transfusions increasing and the number of donors decreasing, measures must be taken to optimize blood conservation.
The Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists have recently updated their practice guidelines on blood conversation after cardiovascular procedures.3 Since the last blood conservation guidelines were published in 2007, multiple events have happened to either change practice or alter the way practitioners view blood conservation.3,4 In the 2011 updated guidelines, major revisions can be seen in:
- the management of dual antiplatelet therapy before surgery
- use of drugs that augment red blood cell volume or limit blood loss
- the use of blood derivatives (including fresh frozen plasma [FFP], Factor XIII, leukoreduced red blood cells, platelet plasmapheresis, recombinant Factor VIIa, antithrombin III, and Factor IX concentrates)
- changes in management of blood salvage
- the use of minimally invasive procedures to limit bleeding and transfusion
- ECMO and CPB recommendations
- the use of topical hemostatic agents
- value of team interventions for blood management.
This summary will focus on the recommendations for pharmacologic agents from these guidelines.3
Evidence Grading for Recommendations5
I: Conditions for which there is evidence and/or general agreement that a given procedure or treatment is useful and effective.
II: Conditions for which there is conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of a procedure or treatment.
- IIa: Weight of evidence/opinion is in favor of usefulness/efficacy
- IIb: Usefulness/efficacy is less well established by evidence/opinion
III: Conditions for which there is evidence and/or general agreement that the procedure/treatment is not useful/effective and in some cases may be harmful.
A: Data derived from multiple randomized clinical trials or meta-analyses.
B: Data derived from a single randomized trial or non-randomized studies.
C: Consensus opinion of experts, case studies, or standard of care.
Table. New Recommendations for Medications Used for Blood Conservation in Cardiac Procedures.3
Recommendation Comment Evidence Grading
P2Y12 inhibitors (clopidogrel and prasugrel) should be discontinued preoperatively if possible
- Time interval between drug discontinuation and procedure varies between agents
- The optimal duration of P2Y12 inhibitor discontinuation is unknown
- A period of 5 to 7 days has traditionally been recommended but recent evidence suggests 3 days may be appropriate in some cases 6,7
Point-of-care testing for ADP responsiveness may be reasonable to identify clopidogrel nonresponders
- Patients who are nonresponders may be candidates for early revascularization and may not require a waiting period prior to procedure
Addition of P2Y12 inhibitors to aspirin early after CABG is not indicated
- Except for those patients who qualify for ACC/AHA guideline-recommended dual antiplatelet therapy (e.g., patients presenting with ACS or those with drug-eluting coronary stents)
Preoperative EPO plus iron may be reasonable several days prior to cardiac surgery to increase RBC mass
- Patients with impaired renal function are at highest risk of diminished endogenous EPO production
- EPO may be useful for patients with preoperative anemia, those who refuse transfusions, and those at high-risk for postoperative anemia
- Necessary to begin therapy in advance of procedure
- Onset of action for EPO is 4 to 6 days
- Chronic use of EPO is associated with thrombotic cardiovascular events in renal failure patients
- Caution in patients with history of coronary revascularization and unstable symptoms
- No large-scale safety studies for patients having CV procedures
EPO may be used to restore RBC volume in patients also receiving autologous pre-operative blood donation before cardiac procedures
- No large safety trials have been conducted in cardiac surgical patients
- Goal Hgb levels are 11 to12 g/dL
- EPO therapy is costly and risk for thrombotic complications in this population are unknown
Intra-operative Blood Management
Lysine analogues (aminocaproic acid and tranexamic acid) are recommended for blood conservation
- Reduces total blood loss and decreases number of patients who require blood transfusions
- Aminocaproic acid has experienced some supply shortages due to American Regent manufacturing issues8
Aprotinin is not indicated for routine usea
- Risks outweigh benefits due to high-dose aprotinin associated with 49% to 53% increased risk of 30-day mortality and 47% increased risk of renal dysfunction in adult patients when compared to lysine analogues9
Antifibrinolytics applied to the surgical wound are reasonable options after CPB
- Topical tranexamic acid or aprotinin has been shown to reduce 24-hour chest drainage
Plasma transfusion may be used for patients with serious bleeding
- When safer fractionated products are unavailable
- Plasma transfusions carry many of the same risks as blood transfusion; due to these risks, avoidance of plasma and blood transfusions should be an objective of blood conservation management
- Guidelines for the precise use of plasma products are not currently available for the CV surgery population
PCC products are preferred for urgent warfarin reversal
- Contain little Factor VII; warfarin patients with severe bleeding may require plasma
- Contain high levels of factors II, IX, and X (with factor VII varying between products)
- Advantages to plasma: given in smaller volume and do not have to consider blood groups
Plasma transfusion may be part of a massive transfusion algorithm in bleeding patients
- In patients requiring substantial amounts of RBCs
- Plasma is not indicated for volume expansion, plasma exchange (possible exception in TTP), or correction of coagulopathy in absence of bleeding
Prophylactic use of plasma is not indicated
- In the absence of coagulopathy
- This practice does not reduce blood loss and exposes patients to the risks and complications of allogeneic blood transfusion
Plasma should not be used for warfarin reversal
- In the absence of bleeding
Factor XIII may be used for clot stabilization after cardiac procedures requiring CPB
- When other blood conservation measures are unavailable or unsatisfactory in bleeding patients
- No information on using in conjunction with antifibrinolytic drugs
- Factor XIII creates cross-links with fibrin
- Antifibrinolytics prevents these cross-links from being degraded
Recombinant Factor VIIa may be considered for intractable non-surgical bleeding
- For patients that are unresponsive to routine hemostatic therapy after CPB
- No large, randomized trials have been conducted
- Uncertain which populations in CV procedures would be ideal candidates for Factor VIIa
AT III concentrates indicated to reduce plasma transfusion
- For patients with AT III-mediated heparin resistance immediately before CPB
AT III concentrates are less well established as part of multi-disciplinary blood management protocols
- For high-risk patients who may have AT depletion or for those who refuse blood products for religious reasons
- For patients with hereditary AT III deficiency to prevent thrombotic complications
- For patients with heparin resistance – failure to achieve an ACT of at least 400 to 800 seconds after standard heparin dosing
Factor IX concentrates (or clotting factor combinations that include Factor IX) may be considered in patients with hemophilia B
- Can also be considered for patients who refuse blood transfusions for religious reasons
- Used for 4 situations in CV procedures
- Control of bleeding in patients with hemophilia B
- Prophylaxis in high-risk patients unable to accept transfusions for religious reasons
- As part of PCC for reversal of warfarin prior to procedure
- As part of factor VIII inhibitor bypassing activity in patients with factor VIII inhibitors requiring a procedure
a Aprotinin is no longer available in the United States.
Abbreviations: ACC/AHA, American College of Cardiology/American Heart Association; ACS, acute coronary syndrome; ACT, activated clotting time; ADP, adenosine diphosphate; AT III, antithrombin III; CABG, coronary artery bypass graft; CPB, cardiopulmonary bypass; CV, cardiovascular; EPO, erythropoietin; Hgb, hemoglobin; PCC, prothrombin complex concentrate; RBC, red blood cell; TTP, thrombotic thrombocytopenic purpura.
The new guidelines include recommendations for blood conservation from the 2007 guidelines with continued support in the literature.3 Use of 1-deamino-8-D-arginine (DDAVP) may still be used for excessive bleeding and transfusion prevention in patients with demonstrable and specific platelet dysfunction known to respond to DDAVP in the past. DDAVP may be valuable for patients with uremic platelet dysfunction, CPB-induced platelet dysfunction, or Type I von Willebrand's disease. After cardiac procedures using CPB, prophylactic use of DDAVP is not recommended to reduce bleeding or blood transfusion. Dipyridamole is another agent that has been previously used perioperatively in cardiovascular procedures to prevent postoperative bleeding. This agent is not indicated for this purpose and is unnecessary to prevent graft occlusion after CABG, while potentially increasing bleeding risk to the patient.3
The 2011 Blood Conservation Clinical Practice Guidelines by The Society of Thoracic Surgeons and Society of Cardiovascular Anesthesiologists have been updated from the 2007 edition. The recommendations are based on new clinical evidence and affect the practice of hospital pharmacists, especially those who work in the operating room and intensive care unit. These practitioners should become familiar with the new body of evidence regarding medications administered for blood conservation in cardiovascular procedures to improve patient safety. Of particular note is the removal of aprotinin from the US market due to increased mortality compared to lysine analogues for intra-operative blood management. Using sound clinical judgment and treating each patient individually should help guide recommendations for specific agents and blood products. These guidelines assist with the formation of blood conservation protocols at institutions performing cardiovascular procedures to preemptively reduce the risk of postoperative bleeding in patients receiving cardiovascular surgeries.
1. Sullivan MT, Cotten R, Read EJ, Wallace EL. Blood collection and transfusion in the United States. Transfusion. 2007;47(3):385-394.
2. Spiess BD. Blood transfusion: the silent epidemic. Ann Thorac Surg. 2001;72(5):S1832-S1837.
3. Society of Thoracic Surgeons Blood Conservation Guideline Task Force, Ferraris VA, Brown JR, Despotis GJ, et al; Society of Cardiovascular Anesthesiologists Special Task Force on Blood Transfusion, Shore-Lesserson LJ, Goodnough LT, Mazer CD, et al; International Consortium for Evidence Based Perfusion, Baker RA, Dickinson TA, FitzGerald DJ, et al. 2011 Update to the society of thoracic surgeons and the society of cardiovascular anesthesiologists blood conservation clinical practice guidelines. Ann Thorac Surg. 2011;91(3):944-982.
4. Society of Thoracic Surgeons Blood Conservation Guideline Task Force , Ferraris VA,Ferraris SP, Saha SP, et al; Society of Cardiovascular Anesthesiologists Special Task Force on Blood Transfusion , Spiess BD, Shore-Lesserson L, et al. Perioperative blood transfusion and blood conservation in cardiac surgery: The Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists clinical practice guideline. Ann Thorac Surg. 2007;83(5Suppl):S27-S86.
5. Methodology Manual for ACCF/AHA Guideline Writing Committee. January 2010. http://www.americanheart.org/downloadable/heart/
12604770597301209Methodology_Manual_for_ACC_AHA_Writing_Committees.pdf . Accessed June 14, 2011.
6. Haydar AA, Abchee AB, El-Hajj II, et al. Bleeding post coronary artery bypass surgery. Clopidogrel – cure or culprit? J Med Liban. 2006;54(1):11-16.
7. Maltais S, Perrault LP, Do QB. Effect of clopidogrel on bleeding and transfusions after off-pump coronary artery bypass graft surgery: impact of discontinuation prior to surgery. Eur J Cardiothorac Surg. 2008;34(1):127-131.
8. American Society of Health-System Pharmacists. ASHP Drug Shortage. http://www.ashp.org/DrugShortages/Current/Bulletin.aspx?id=789. Accessed May 27, 2011.
9. Fergusson DA, Hebert PC, Mazer CD, et al. A comparison of aprotinin and lysine analogues in high-risk cardiac surgery. N Engl J Med. 2008;358(22):2319-2331.
Prepared by: Mark Pangrazzi, PharmD