- Email: [email protected]
Individual-Patient Meta-Analysis of Three Randomized Trials Comparing Endovascular Versus Open Repair for Ruptured Abdominal Aortic Aneurysm
260 Abstracts
embolism is the most common cause of RAO, RAO patients should have immediate brain imaging and work up for possible treatable etiologies of their RAO. Family History of Atherosclerotic Vascular Disease Is Associated With the Presence of Abdominal Aortic Aneurysm Ye Z, Bailey KR, Austin E, et al. Vasc Med 2016;21:41-6. Conclusions: There are shared environmental and genetic factors mediating susceptibility to AAA and atherosclerotic cardiovascular disease (ASCVD). Summary: Family history can be a useful tool for risk assessment for vascular disease. It is used as a proxy for genetic predisposition as well as for shared environmental factors that contribute to disease development. A positive family history is a risk factor for coronary heart disease, cerebrovascular disease and peripheral arterial disease. AAA has a significant genetic component. However, it is unknown whether a family history of ASCVD is associated with the presence of AAA. In this study, the authors hypothesized that a family history of ASCVD would be a risk factor for AAA. They investigated the association of family history of ASCVD with the presence of AAA in a case control study of patients referred to the Mayo Clinic. A secondary aim was to assess whether family history of different subtypes of ASCVD and parental vs sibling history were differentially associated with the presence of AAA. There were 696 patients with AAA (70 6 8.8 years; 84% men) and 2886 controls (68 6 10 years; 61% men) recruited from the noninvasive vascular and stress electrocardiogram laboratories at the Mayo Clinic. AAA was defined as a transverse diameter $3 cm, or a history of AAA repair. Controls were not known to have AAA. Family history was defined as having at least one first degree relative with aortic aneurysm or onset of ASCVD (coronary, cerebral, or peripheral artery disease) before 65 years of age. Family history of aortic aneurysm or ASCVD were each associated with the presence of AAA after adjustment for age, sex, conventional risk factors, and ASCVD (adjusted OR, 2.17; 95% CI, 1.66-2.83; P < .001; and OR, 1.31; 95% CI, 1.08-1.59; P < .001, respectively). Family history of ASCVD remained associated with AAA after additional adjustment for family history of aortic aneurysm (adjusted OR 1.27; 95% CI, 1.05-1.55; P ¼ .01). Family history of ASCVD in multiple arterial locations was associated with higher odds of having AAA: adjusted odds were 1.23 times higher for each individual additionally located arterial location reported in the family history (95% CI, 1.08-1.40; P ¼ .01). Comment: The major finding in this study is that a family history of ASCVD is associated with the presence of AAA independent of conventional cardiovascular risk factors and a family history of aortic aneurysm. In addition, sibling history of ASCVD had a stronger association with AAA than parental history. A family history of ASCVD in multiple arterial locations also increases risk odds of having AAA. Clearly there are genetic and environmental factors that increase susceptibility to AAA. These factors appear to be associated with ASCVD as well. A family history of ASCVD, therefore, may be an important consideration in determining or recommending screening for AAA. Additional studies will be needed to determine whether risk is equal in men and women and whether it applies equally to different ethnic groups.
Pioglitazone After Ischemic Stroke or Transient Ischemic Attack Kernan WN, Viscoli CM, Furie KL, et al. N Engl J Med 2016;374:1321-31. Conclusions: In patients without diabetes but who have insulin resistance along with a recent history of ischemic stroke or TIA, the risk of stroke or myocardial infarction was lower among those patients who received pioglitazone than among those who received placebo. Summary: Insulin resistance is nearly universal in patients with type 2 diabetes but is also present in more than 50% of patients without diabetes who have had an ischemic stroke or TIA (Kernan WN et al, Neurology 2003;60:1447-51). Insulin resistance increases risk of vascular disease likely because of associated hypertension, hyperglycemia, hyperinsulinemia, dyslipidemia, endothelial dysfunction, hypercoagulability, inflammation, and increased platelet reactivity. This suggests treatment of insulin resistance could be a potential new preventative strategy that may be added to standard care after ischemic stroke or TIA. In this multicenter, double-blind trial, the authors randomly assigned 3876 patients who had a recent ischemic stroke or TIA to either receive pioglitazone (target dose, 45 mg daily, an insulin sensitizing drug) or a placebo. Patients did not have diabetes or were found to have insulin resistance on the basis of a score of more than 3.0 on the homeostasis model assessment of insulin resistance
JOURNAL OF VASCULAR SURGERY July 2016
(HOMA-IR) index. The HOMA-IR value is calculated as the level of fasting glucose (measured in mL per liter) the level of fasting insulin (measured in micro units per mL) O by 22.5 (Matthews DR et al, Diabetologia 1985;28:412-9). The index threshold of 3.0 was chosen as it identifies the highest quartile among populations without diabetes. Blood tests were conducted 14 days after the index event as insulin sensitivity may be transiently impaired after an acute stroke. Primary outcomes in this study were fatal or nonfatal stroke or myocardial infarction. By 4.8 years, a primary outcome had occurred in 175 of 1939 patients (9%) in the pioglitazone group and 228 of 1937 (11.8%) in the placebo group (HR in the pioglitazone group, 0.76; 95% CI, 0.62-0.93; P ¼ .007). Diabetes developed in 73 patients (3.8%) and in 149 patients (7.7%) respectively (HR, 0.48; 95% CI, 0.33-0.69; P < .001). There was no significant between group difference in all-cause mortality (HR, 0.93; 95% CI, 0.73-1.77; P ¼ .52). Pioglitazone was associated with a greater frequency of weight gain exceeding 4.5 kilograms than was placebo (52.2% vs 33.7%; P < .001), edema (35.6% vs 24.9%; P < .001), and bone fracture requiring surgery or hospitalization (5.1% vs 3.2%; P ¼ .003). Comment: Results of this study are in contrast to the findings of two trials previously involving type 2 diabetes. In the PRO-Active trial, rate of primary outcome of death, myocardial infarction, stroke, acute coronary syndrome, and vascular surgery amputation was not different among those patients in the pioglitazone group than the placebo group. The BARI-2D trial rate of primary outcome of death, stroke, or myocardial infarction was not significantly lower among patients receiving rosiglitazone and metformin vs those receiving insulin and sulfonylurea therapy (Wilcox R et al, Stroke 2007;38:865-73, and BARI-2D Study Group, N Eng J Med 2009;360:2503-15). However, the results of the PRO-Active trial indicated rates of death, myocardial infarction, or stroke were lower with pioglitazone than with placebo (Nissen SE et al, JAMA 2008;299:1561-73). Overall, the data regarding treatment of insulin resistance as an adjunct to reduce vascular events in patients with stroke or TIA seem a bit mixed and the potentially useful therapy may come at the expense of weight gain, edema, and serious fractures. Individual patient preference will require careful consideration with regard to the use of insulin sensitizing therapy in patients with TIA or stroke.
Individual-Patient Meta-Analysis of Three Randomized Trials Comparing Endovascular Versus Open Repair for Ruptured Abdominal Aortic Aneurysm Sweeting MJ, Balm R, Desgranges P, et al. BJS 2015;102:1229-39. Conclusions: Survival to 90 days following endovascular or open repair strategy for ruptured abdominal aortic aneurysm (rAAA) is similar for all patients and for the restricted population anatomically suitable for endovascular repair. However, women may benefit more from endovascular strategy than men and patients, on average, are discharged sooner after endovascular repair. Summary: Benefits of endovascular repair of rAAA are controversial and there is no level-one evidence indicating advantages in specific subgroups. The authors’ analysis was designed to test the hypothesis that particularly for patients anatomically suitable for EVAR, endovascular repair offers an improved 90-day survival and earlier hospital discharge compared with open repair for rAAA. They also sought to identify whether specific subgroup analyses by age, sex, and Hardman index, a morbidity score for rAAA (Hardman DT et al, J Vasc Surg 1996;23:123-9) had better 90-day survival with EVAR. This was an individual patient data metaanalysis of three recent randomized trials of endovascular vs open repair of rAAA and was conducted according to a prespecified analysis plan reporting results to 90 days after the index event. The trials included a total of 836 patients. Mortality rate across the three trials at 30 days was 31.3% with patients randomized in the endovascular vascular repair strategy and 34.0% for those randomized to open repair (pooled OR, 0.88; 95% CI, 0.66-1.18) and 34.3 and 38.0%, respectively, at 90 days (pooled OR, 0.85; 95% CI, 0.64-1.13). There was no evidence of significant heterogeneity in the odds ratios between trials. Mean (s.d.) of aneurysm diameter was 8.2 (1.9) cm and overall in-hospital mortality rate was 34.8%. There was no significant effect modification with age or Hardman index, but there was an indication of an early benefit from endovascular strategy for women. Discharge from hospital was faster after endovascular repair (HR, 1.24; 95% CI, 1.04-1.47). For open repair, 30-day mortality diminished with increasing aneurysm length (adjusted OR, 0.69; 95% CI, 0.53-0.89) per 15 mm, but aortic diameter was not associated with mortality for either type of repair. Comment: Despite proclamations by enthusiasts, it remains maddeningly difficult to prove, with level-one evidence, that there is a dramatic
JOURNAL OF VASCULAR SURGERY Volume 64, Number 1
Abstracts 261
improvement in outcomes using EVAR vs open repair for rAAA. Nevertheless, EVAR for rAAA is here to stay and certainly should be considered in appropriate patients, as it appears to reduce hospital length of stay and therefore likely perioperative morbidity and may have advantages in women.
of surgical patients indicating adverse effects of transfusion. Attempts to minimize transfusion through the use of strict transfusion requirements and perhaps tourniquets for below-knee amputation should be encouraged for the amputation patient.
Blood Transfusion Is Associated With Increased Risk of Perioperative Complications and Prolonged Hospital Duration of Stay Among Patients Undergoing Amputation Tan TW, Eslami M, Rybin D, et al. Surgery 2015;158:1609-16.
Antiplatelet Effects of Aspirin in Chronic Kidney Disease Patients Polzin A, Dannenberg L, Sansone R, et al. J Throm Haemost 2016;14:375-80.
Conclusions: Patients undergoing lower extremity amputation with perioperative transfusion have greater risk for perioperative pneumonia, thromboembolism, and prolonged hospital length of stay. Summary: Patients undergoing major amputations secondary to vascular conditions are projected to increase from <1 million to >2.3 million by 2050 (Ziegler-Graham K et al, Arch Phys Med Rehabil 2008;89:422-9). Perioperative transfusion with packed red blood cells (PRBCs) is administered in up to 27% of patients with vascular disease. The effect of transfusion in this patient population is poorly understood (O’Keefe SD et al, J Vasc Surg 2010;51:616-21). The authors evaluated the risk of blood transfusion during lower extremity amputation using the American College of Surgeons National Surgical Quality Initiative Program (ACS-NSQIP) database. They sought to examine an association with preoperative, intraoperative, and postoperative transfusion and outcomes of patients undergoing major amputation. Using the NSQIP database from 2005-2011, they examined 5739 above-knee and 6725 below-knee amputations. Patients were stratified by perioperative, preoperative, intraoperative, and postoperative blood transfusions. Outcomes included perioperative mortality, myocardial infarction, thromboembolism, and hospital length of stay. Adjusted comparisons of outcomes between transfusion and nontransfused patients were performed by matching the two groups for age, smoking, diabetes, renal failure, coronary artery disease, and classification by the American Society of Anesthesiologists, as well as functional status and procedure type. Of the 12,464 amputations in this study cohort, 2133 (17%) required transfusion. The majority of cases were performed for critical ischemia (66%) and overall 30-day mortality was 9%. In both crude and matched cohorts, perioperative mortality and cardiac complication rates were similar and transfusion was associated with a greater incidence of pneumonia (crude, 6.1% vs 3%; P < .001; matched, 5.9% vs 3.7%; P < .001), thromboembolism (2.5% vs 1.6%, P ¼ .003; 2.5% vs 1.4%; P ¼ .002) and longer length of stay (18 6 19 vs 13.6 6 14.3 days; P < .001; 17.8 6 18.4 vs 14.2 6 14.5 days; P < .001). Multivariable adjustment for confounding variables in the crude cohort demonstrated transfusion was independently associated with greater odds of perioperative pneumonia (OR, 1.6; 95% CI, 1.3-2; P < .001), thromboembolism (OR, 1.3; 95% CI, 1.0-1.9; P ¼ .09) and longer length of stay (OR, 1.1; 95% CI, 1.1-1.6; P ¼ .006). Comment: There are, of course, many potential confounding variables unaccounted for with the use of an administrative database such as NSQIP. Clinical indications for transfusion were not delineated in this study and exact number of units of PRBCs transfused is not available in the NSQIP database. However, the data are consistent with many other studies
Conclusions: Patients with chronic kidney disease (CKD) have an increased risk of impaired antiplatelet effects of aspirin. Summary: The pharmacologic response to aspirin varies substantially between individuals. Insufficient antiplatelet effects are referred to as high on-treatment platelet reactivity (HTPR; formally known as “resistance”). HTPR to antiplatelet medication is associated with increased mortality and an increased incidence of stent thrombosis in patients with coronary artery disease and also increases the severity of stroke in patients with cerebrovascular events. HTPR to aspirin has many potential etiologies including genetic factors, chronic inflammation, noncompliance, and analgesic cold medications. It is known to impair renal function and is associated with increased mortality and incidence of cardiovascular events. Insufficient P2Y12 inhibition to clopidogrel is also more frequent in patients with chronic kidney disease (Gremmel T et al, Nephrol Dial Transplant 2013;28:211622). The authors hypothesize in this study that HTPR to aspirin is associated with chronic kidney disease. Therefore, they investigated the pharmacodynamic response to aspirin in patients with CKD. This was a cross-sectional study of 116 patients on permanent aspirin medication. The pharmacodynamic response to aspirin was determined by arachidonic acid-induced thromboxane formation. Overall, HTPR to aspirin was more frequent in patients with impaired renal function (47% vs 22%; OR, 3.16; 95% CI, 1.34-7.41; P ¼ .008). The pharmacodynamic response to aspirin was impaired in patients with moderate to severe CKD, with moderate CKD defined as a glomerular filtration rate (GFR) between 30 and 59 mL min1 and CKD IV defined as GFR below 30 mL min1. Bivariate Pearson analysis also showed residual thromboxane formation to be correlated with GFR (R ¼ 0.303; R2 ¼ 0.0092; P ¼ .001). Patients with CKD were older and more frequently female. Multivariate linear regression analysis indicated the correlation was independent of age (R ¼ 0.314; R2 ¼ 0.082; P ¼.002) and gender (R ¼ 0.305; R2 ¼ 0.077; P ¼ .006). Comment: Results indicate that antiplatelet effects of aspirin are correlated with kidney function and that CKD is associated with an impaired pharmacodynamic response to aspirin. This may serve as at least a partial explanation for the enhanced incidence of cardiovascular events in CKD patients. Optimal antithrombotic regimes in patients with CKD may require protocols different than those for patients with normal renal function. Determining whether or not this is true will require large-scale clinical trials, but given the adverse cardiovascular event rate in patients with CKD, such clinical trials, while likely difficult and expensive to perform, might potentially have a large impact on the medical and postsurgical management of patients with chronic kidney disease.
embolism is the most common cause of RAO, RAO patients should have immediate brain imaging and work up for possible treatable etiologies of their RAO. Family History of Atherosclerotic Vascular Disease Is Associated With the Presence of Abdominal Aortic Aneurysm Ye Z, Bailey KR, Austin E, et al. Vasc Med 2016;21:41-6. Conclusions: There are shared environmental and genetic factors mediating susceptibility to AAA and atherosclerotic cardiovascular disease (ASCVD). Summary: Family history can be a useful tool for risk assessment for vascular disease. It is used as a proxy for genetic predisposition as well as for shared environmental factors that contribute to disease development. A positive family history is a risk factor for coronary heart disease, cerebrovascular disease and peripheral arterial disease. AAA has a significant genetic component. However, it is unknown whether a family history of ASCVD is associated with the presence of AAA. In this study, the authors hypothesized that a family history of ASCVD would be a risk factor for AAA. They investigated the association of family history of ASCVD with the presence of AAA in a case control study of patients referred to the Mayo Clinic. A secondary aim was to assess whether family history of different subtypes of ASCVD and parental vs sibling history were differentially associated with the presence of AAA. There were 696 patients with AAA (70 6 8.8 years; 84% men) and 2886 controls (68 6 10 years; 61% men) recruited from the noninvasive vascular and stress electrocardiogram laboratories at the Mayo Clinic. AAA was defined as a transverse diameter $3 cm, or a history of AAA repair. Controls were not known to have AAA. Family history was defined as having at least one first degree relative with aortic aneurysm or onset of ASCVD (coronary, cerebral, or peripheral artery disease) before 65 years of age. Family history of aortic aneurysm or ASCVD were each associated with the presence of AAA after adjustment for age, sex, conventional risk factors, and ASCVD (adjusted OR, 2.17; 95% CI, 1.66-2.83; P < .001; and OR, 1.31; 95% CI, 1.08-1.59; P < .001, respectively). Family history of ASCVD remained associated with AAA after additional adjustment for family history of aortic aneurysm (adjusted OR 1.27; 95% CI, 1.05-1.55; P ¼ .01). Family history of ASCVD in multiple arterial locations was associated with higher odds of having AAA: adjusted odds were 1.23 times higher for each individual additionally located arterial location reported in the family history (95% CI, 1.08-1.40; P ¼ .01). Comment: The major finding in this study is that a family history of ASCVD is associated with the presence of AAA independent of conventional cardiovascular risk factors and a family history of aortic aneurysm. In addition, sibling history of ASCVD had a stronger association with AAA than parental history. A family history of ASCVD in multiple arterial locations also increases risk odds of having AAA. Clearly there are genetic and environmental factors that increase susceptibility to AAA. These factors appear to be associated with ASCVD as well. A family history of ASCVD, therefore, may be an important consideration in determining or recommending screening for AAA. Additional studies will be needed to determine whether risk is equal in men and women and whether it applies equally to different ethnic groups.
Pioglitazone After Ischemic Stroke or Transient Ischemic Attack Kernan WN, Viscoli CM, Furie KL, et al. N Engl J Med 2016;374:1321-31. Conclusions: In patients without diabetes but who have insulin resistance along with a recent history of ischemic stroke or TIA, the risk of stroke or myocardial infarction was lower among those patients who received pioglitazone than among those who received placebo. Summary: Insulin resistance is nearly universal in patients with type 2 diabetes but is also present in more than 50% of patients without diabetes who have had an ischemic stroke or TIA (Kernan WN et al, Neurology 2003;60:1447-51). Insulin resistance increases risk of vascular disease likely because of associated hypertension, hyperglycemia, hyperinsulinemia, dyslipidemia, endothelial dysfunction, hypercoagulability, inflammation, and increased platelet reactivity. This suggests treatment of insulin resistance could be a potential new preventative strategy that may be added to standard care after ischemic stroke or TIA. In this multicenter, double-blind trial, the authors randomly assigned 3876 patients who had a recent ischemic stroke or TIA to either receive pioglitazone (target dose, 45 mg daily, an insulin sensitizing drug) or a placebo. Patients did not have diabetes or were found to have insulin resistance on the basis of a score of more than 3.0 on the homeostasis model assessment of insulin resistance
JOURNAL OF VASCULAR SURGERY July 2016
(HOMA-IR) index. The HOMA-IR value is calculated as the level of fasting glucose (measured in mL per liter) the level of fasting insulin (measured in micro units per mL) O by 22.5 (Matthews DR et al, Diabetologia 1985;28:412-9). The index threshold of 3.0 was chosen as it identifies the highest quartile among populations without diabetes. Blood tests were conducted 14 days after the index event as insulin sensitivity may be transiently impaired after an acute stroke. Primary outcomes in this study were fatal or nonfatal stroke or myocardial infarction. By 4.8 years, a primary outcome had occurred in 175 of 1939 patients (9%) in the pioglitazone group and 228 of 1937 (11.8%) in the placebo group (HR in the pioglitazone group, 0.76; 95% CI, 0.62-0.93; P ¼ .007). Diabetes developed in 73 patients (3.8%) and in 149 patients (7.7%) respectively (HR, 0.48; 95% CI, 0.33-0.69; P < .001). There was no significant between group difference in all-cause mortality (HR, 0.93; 95% CI, 0.73-1.77; P ¼ .52). Pioglitazone was associated with a greater frequency of weight gain exceeding 4.5 kilograms than was placebo (52.2% vs 33.7%; P < .001), edema (35.6% vs 24.9%; P < .001), and bone fracture requiring surgery or hospitalization (5.1% vs 3.2%; P ¼ .003). Comment: Results of this study are in contrast to the findings of two trials previously involving type 2 diabetes. In the PRO-Active trial, rate of primary outcome of death, myocardial infarction, stroke, acute coronary syndrome, and vascular surgery amputation was not different among those patients in the pioglitazone group than the placebo group. The BARI-2D trial rate of primary outcome of death, stroke, or myocardial infarction was not significantly lower among patients receiving rosiglitazone and metformin vs those receiving insulin and sulfonylurea therapy (Wilcox R et al, Stroke 2007;38:865-73, and BARI-2D Study Group, N Eng J Med 2009;360:2503-15). However, the results of the PRO-Active trial indicated rates of death, myocardial infarction, or stroke were lower with pioglitazone than with placebo (Nissen SE et al, JAMA 2008;299:1561-73). Overall, the data regarding treatment of insulin resistance as an adjunct to reduce vascular events in patients with stroke or TIA seem a bit mixed and the potentially useful therapy may come at the expense of weight gain, edema, and serious fractures. Individual patient preference will require careful consideration with regard to the use of insulin sensitizing therapy in patients with TIA or stroke.
Individual-Patient Meta-Analysis of Three Randomized Trials Comparing Endovascular Versus Open Repair for Ruptured Abdominal Aortic Aneurysm Sweeting MJ, Balm R, Desgranges P, et al. BJS 2015;102:1229-39. Conclusions: Survival to 90 days following endovascular or open repair strategy for ruptured abdominal aortic aneurysm (rAAA) is similar for all patients and for the restricted population anatomically suitable for endovascular repair. However, women may benefit more from endovascular strategy than men and patients, on average, are discharged sooner after endovascular repair. Summary: Benefits of endovascular repair of rAAA are controversial and there is no level-one evidence indicating advantages in specific subgroups. The authors’ analysis was designed to test the hypothesis that particularly for patients anatomically suitable for EVAR, endovascular repair offers an improved 90-day survival and earlier hospital discharge compared with open repair for rAAA. They also sought to identify whether specific subgroup analyses by age, sex, and Hardman index, a morbidity score for rAAA (Hardman DT et al, J Vasc Surg 1996;23:123-9) had better 90-day survival with EVAR. This was an individual patient data metaanalysis of three recent randomized trials of endovascular vs open repair of rAAA and was conducted according to a prespecified analysis plan reporting results to 90 days after the index event. The trials included a total of 836 patients. Mortality rate across the three trials at 30 days was 31.3% with patients randomized in the endovascular vascular repair strategy and 34.0% for those randomized to open repair (pooled OR, 0.88; 95% CI, 0.66-1.18) and 34.3 and 38.0%, respectively, at 90 days (pooled OR, 0.85; 95% CI, 0.64-1.13). There was no evidence of significant heterogeneity in the odds ratios between trials. Mean (s.d.) of aneurysm diameter was 8.2 (1.9) cm and overall in-hospital mortality rate was 34.8%. There was no significant effect modification with age or Hardman index, but there was an indication of an early benefit from endovascular strategy for women. Discharge from hospital was faster after endovascular repair (HR, 1.24; 95% CI, 1.04-1.47). For open repair, 30-day mortality diminished with increasing aneurysm length (adjusted OR, 0.69; 95% CI, 0.53-0.89) per 15 mm, but aortic diameter was not associated with mortality for either type of repair. Comment: Despite proclamations by enthusiasts, it remains maddeningly difficult to prove, with level-one evidence, that there is a dramatic
JOURNAL OF VASCULAR SURGERY Volume 64, Number 1
Abstracts 261
improvement in outcomes using EVAR vs open repair for rAAA. Nevertheless, EVAR for rAAA is here to stay and certainly should be considered in appropriate patients, as it appears to reduce hospital length of stay and therefore likely perioperative morbidity and may have advantages in women.
of surgical patients indicating adverse effects of transfusion. Attempts to minimize transfusion through the use of strict transfusion requirements and perhaps tourniquets for below-knee amputation should be encouraged for the amputation patient.
Blood Transfusion Is Associated With Increased Risk of Perioperative Complications and Prolonged Hospital Duration of Stay Among Patients Undergoing Amputation Tan TW, Eslami M, Rybin D, et al. Surgery 2015;158:1609-16.
Antiplatelet Effects of Aspirin in Chronic Kidney Disease Patients Polzin A, Dannenberg L, Sansone R, et al. J Throm Haemost 2016;14:375-80.
Conclusions: Patients undergoing lower extremity amputation with perioperative transfusion have greater risk for perioperative pneumonia, thromboembolism, and prolonged hospital length of stay. Summary: Patients undergoing major amputations secondary to vascular conditions are projected to increase from <1 million to >2.3 million by 2050 (Ziegler-Graham K et al, Arch Phys Med Rehabil 2008;89:422-9). Perioperative transfusion with packed red blood cells (PRBCs) is administered in up to 27% of patients with vascular disease. The effect of transfusion in this patient population is poorly understood (O’Keefe SD et al, J Vasc Surg 2010;51:616-21). The authors evaluated the risk of blood transfusion during lower extremity amputation using the American College of Surgeons National Surgical Quality Initiative Program (ACS-NSQIP) database. They sought to examine an association with preoperative, intraoperative, and postoperative transfusion and outcomes of patients undergoing major amputation. Using the NSQIP database from 2005-2011, they examined 5739 above-knee and 6725 below-knee amputations. Patients were stratified by perioperative, preoperative, intraoperative, and postoperative blood transfusions. Outcomes included perioperative mortality, myocardial infarction, thromboembolism, and hospital length of stay. Adjusted comparisons of outcomes between transfusion and nontransfused patients were performed by matching the two groups for age, smoking, diabetes, renal failure, coronary artery disease, and classification by the American Society of Anesthesiologists, as well as functional status and procedure type. Of the 12,464 amputations in this study cohort, 2133 (17%) required transfusion. The majority of cases were performed for critical ischemia (66%) and overall 30-day mortality was 9%. In both crude and matched cohorts, perioperative mortality and cardiac complication rates were similar and transfusion was associated with a greater incidence of pneumonia (crude, 6.1% vs 3%; P < .001; matched, 5.9% vs 3.7%; P < .001), thromboembolism (2.5% vs 1.6%, P ¼ .003; 2.5% vs 1.4%; P ¼ .002) and longer length of stay (18 6 19 vs 13.6 6 14.3 days; P < .001; 17.8 6 18.4 vs 14.2 6 14.5 days; P < .001). Multivariable adjustment for confounding variables in the crude cohort demonstrated transfusion was independently associated with greater odds of perioperative pneumonia (OR, 1.6; 95% CI, 1.3-2; P < .001), thromboembolism (OR, 1.3; 95% CI, 1.0-1.9; P ¼ .09) and longer length of stay (OR, 1.1; 95% CI, 1.1-1.6; P ¼ .006). Comment: There are, of course, many potential confounding variables unaccounted for with the use of an administrative database such as NSQIP. Clinical indications for transfusion were not delineated in this study and exact number of units of PRBCs transfused is not available in the NSQIP database. However, the data are consistent with many other studies
Conclusions: Patients with chronic kidney disease (CKD) have an increased risk of impaired antiplatelet effects of aspirin. Summary: The pharmacologic response to aspirin varies substantially between individuals. Insufficient antiplatelet effects are referred to as high on-treatment platelet reactivity (HTPR; formally known as “resistance”). HTPR to antiplatelet medication is associated with increased mortality and an increased incidence of stent thrombosis in patients with coronary artery disease and also increases the severity of stroke in patients with cerebrovascular events. HTPR to aspirin has many potential etiologies including genetic factors, chronic inflammation, noncompliance, and analgesic cold medications. It is known to impair renal function and is associated with increased mortality and incidence of cardiovascular events. Insufficient P2Y12 inhibition to clopidogrel is also more frequent in patients with chronic kidney disease (Gremmel T et al, Nephrol Dial Transplant 2013;28:211622). The authors hypothesize in this study that HTPR to aspirin is associated with chronic kidney disease. Therefore, they investigated the pharmacodynamic response to aspirin in patients with CKD. This was a cross-sectional study of 116 patients on permanent aspirin medication. The pharmacodynamic response to aspirin was determined by arachidonic acid-induced thromboxane formation. Overall, HTPR to aspirin was more frequent in patients with impaired renal function (47% vs 22%; OR, 3.16; 95% CI, 1.34-7.41; P ¼ .008). The pharmacodynamic response to aspirin was impaired in patients with moderate to severe CKD, with moderate CKD defined as a glomerular filtration rate (GFR) between 30 and 59 mL min1 and CKD IV defined as GFR below 30 mL min1. Bivariate Pearson analysis also showed residual thromboxane formation to be correlated with GFR (R ¼ 0.303; R2 ¼ 0.0092; P ¼ .001). Patients with CKD were older and more frequently female. Multivariate linear regression analysis indicated the correlation was independent of age (R ¼ 0.314; R2 ¼ 0.082; P ¼.002) and gender (R ¼ 0.305; R2 ¼ 0.077; P ¼ .006). Comment: Results indicate that antiplatelet effects of aspirin are correlated with kidney function and that CKD is associated with an impaired pharmacodynamic response to aspirin. This may serve as at least a partial explanation for the enhanced incidence of cardiovascular events in CKD patients. Optimal antithrombotic regimes in patients with CKD may require protocols different than those for patients with normal renal function. Determining whether or not this is true will require large-scale clinical trials, but given the adverse cardiovascular event rate in patients with CKD, such clinical trials, while likely difficult and expensive to perform, might potentially have a large impact on the medical and postsurgical management of patients with chronic kidney disease.