Impact on Mortality and Major Bleeding of Radial Versus Femoral Artery Access for Coronary Angiography or Percutaneous Coronary Intervention: a Meta-analysis of Individual Patient Data from Seven Multicenter Randomized Clinical Trials
Gargiulo G, Giacoppo D, Jolly SS, Cairns J, Le May M, Bernat I, Romagnoli E, Rao SV, van Leeuwen MAH, Mehta SR, et al
BACKGROUND In some randomized controlled trials (RCTs), transradial (TRA) compared with transfemoral access (TFA) was associated with lower mortality in coronary artery disease patients undergoing invasive management. We analyzed the effects of TRA versus TFA across multicenter RCTs and whether these associations are modified by patient or operator characteristics. METHODS We performed an individual patient data meta-analysis of multicenter RCTs comparing TRA versus TFA among patients undergoing coronary angiography with or without percutaneous coronary intervention (PCI) (PROSPERO; CRD42018109664). The primary outcome was all-cause mortality and the co-primary outcome was major bleeding at 30 days. The primary analysis was conducted by one-stage mixed-effects models based on the intention-to-treat cohort. The impact of access-site on mortality and major bleeding was further assessed by multivariable analysis. The relationship among access-site, bleeding, and mortality was investigated by natural effect model mediation analysis with multivariable adjustment. RESULTS A total of 21,600 patients (TRA=10,775 vs. TFA=10,825) from 7 RCTs were included. Median age was 63.9 years, 31.9% were female, 95% presented with acute coronary syndrome (ACS), and 75.2% underwent PCI. All-cause mortality (1.6% vs. 2.1%; HR 0.77, 95% CI 0.63-0.95, p=0.012) and major bleeding (1.5% vs. 2.7%; OR 0.55, 95% CI 0.45- 0.67, p<0.001) were lower with TRA. Subgroup analyses for mortality showed consistent results, except for baseline hemoglobin ((pinteraction)=0.033), indicating that the benefit of TRA was substantial in patients with significant anemia, while it was not significant in patients with milder or no baseline anemia. After adjustment, TRA remained associated with 24% and 51% relative risk reduction of all-cause mortality and major bleeding. A mediation analysis showed that the benefit of TRA on mortality was only partially driven by major bleeding prevention, and ancillary mechanisms are required to fully explain the causal association. CONCLUSIONS TRA is associated with lower all-cause mortality and major bleeding at 30 days, compared with TFA. The effect on mortality was driven by patients with anemia. The reduction in major bleeding only partially explains the mortality benefit.
A multicenter randomized controlled trial to assess the feasibility of testing modified ultrafiltration as a blood conservation technology in cardiac surgery
Boodhwani M, Hamilton A, de Varennes B, Mesana T, Williams K, Wells GA, Nathan H, Dupuis JY, Babaev A, Wells P, et al
The Journal of Thoracic and Cardiovascular Surgery. 2010;139((3):):701-6.
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OBJECTIVES Modified ultrafiltration is a technique after cardiopulmonary bypass whereby blood withdrawn from the aortic cannula is passed across a semipermeable membrane to hemoconcentrate. Unblinded trials have suggested that modified ultrafiltration is efficacious for blood conservation. The objective of this trial was to assess the feasibility of a model testing modified ultrafiltration in which all members of the surgical team were blinded to the intervention. METHODS Patients (<65kg) undergoing procedures involving cardiopulmonary bypass were randomized to undergo either modified ultrafiltration (n=29) or sham (circulation without an interposed filter, n=36) for 15 minutes. The circuit was shielded from all members of the team except the perfusionist. A questionnaire was administered to determine the blinding success. RESULTS Modified ultrafiltration resulted in a removal of 1000+/-251mL of fluid and a reduction in the pump balance (1025+/-807 vs 1804+/-838; P < . 001) with an increase in hemoglobin immediately after intervention (increase of 7. 7+/-8. 8g/L in modified ultrafiltration vs 3. 8+/-5. 1g/L in sham; P=. 04). Introduction or increase in dose of vasopressors was more frequent in the modified ultrafiltration group (52% vs 28%; P=. 048). Differences in red cell transfusion rates between groups did not reach statistical significance (P=. 59). Blinding was successful for the anesthetist (blinding index 0. 13 [95% confidence interval, 0. 11-0. 38] and the intensivist (blinding index, 0. 09 [95% confidence interval, 0. 14-0. 31]) but not for the surgeon (blinding index, 0. 24 [95% confidence interval, 0. 05-0. 42]). The compliance rate for the transfusion protocol was greater than 90%. CONCLUSIONS Modified ultrafiltration was effective for hemoconcentration after cardiopulmonary bypass in patients of low body weight, but it is associated with an increased need for vasopressor support. The anesthetist and intensivist were successfully blinded to the intervention.
Effect of hemoglobin levels in hemodialysis patients with asymptomatic cardiomyopathy
Foley RN, Parfrey PS, Morgan J, Barre PE, Campbell P, Cartier P, Coyle D, Fine A, Handa P, Kingma I, et al
Kidney International. 2000;58((3):):1325-35.
BACKGROUND Hemoglobin levels below 10 g/dL lead to left ventricular (LV) hypertrophy, LV dilation, a lower quality of life, higher cardiac morbidity, and a higher mortality rate in end-stage renal disease. The benefits and risks of normalizing hemoglobin levels in hemodialysis patients without symptomatic cardiac disease are unknown. METHODS One hundred forty-six hemodialysis patients with either concentric LV hypertrophy or LV dilation were randomly assigned to receive doses of epoetin alpha designed to achieve hemoglobin levels of 10 or 13.5 g/dL. The study duration was 48 weeks. The primary outcomes were the change in LV mass index in those with concentric LV hypertrophy and the change in cavity volume index in those with LV dilation. RESULTS In patients with concentric LV hypertrophy, the changes in LV mass index were similar in the normal and low target hemoglobin groups. The changes in cavity volume index were similar in both targets in the LV dilation group. Treatment-received analysis of the concentric LV hypertrophy group showed no correlation between the change in mass index and a correlation between the change in LV volume index and mean hemoglobin level achieved (8 mL/m2 per 1 g/dL hemoglobin decrement, P = 0.009). Mean hemoglobin levels and the changes in LV mass and cavity volume index were not correlated in patients with LV dilation. Normalization of hemoglobin led to improvements in fatigue (P = 0.009), depression (P = 0.02), and relationships (P = 0.004). CONCLUSIONS Normalization of hemoglobin does not lead to regression of established concentric LV hypertrophy or LV dilation. It may, however, prevent the development of LV dilation, and it leads to improved quality of life.
Does acute normovolemic hemodilution reduce perioperative allogeneic transfusion? A meta-analysis. The International Study of Perioperative Transfusion
Bryson GL, Laupacis A, Wells GA
Anesthesia & Analgesia. 1998;86((1):):9-15.
The objective of this study was to systematically review the literature and to statistically summarize the evidence evaluating acute normovolemic hemodilution (ANH). Prospective, randomized, controlled trials of ANH that reported either the proportion of patients exposed to allogeneic blood or the units of allogeneic blood transfused were included. All types and languages of publication were eligible. Of 1573 identified publications, 24 trials (containing a total of 1218 patients) were included in the meta-analysis. When all trials were pooled, ANH reduced the likelihood of exposure to allogeneic blood (odds ratio [OR] 0.31, 95% confidence interval [CI] 0.15, 0.62) and the total units of allogeneic blood transfused (weighted mean difference [WMD] -2.22 U, 95% CI -3.57, -0.86). However, there was marked heterogeneity of the results. In trials using a protocol to guide perioperative transfusion, ANH failed to reduce either the likelihood of transfusion (OR 0.64, 95% CI 0.31, 1.31) or the units administered (WMD -0.25 U, 95% CI -0.60, 0.10). Adverse events were incompletely reported. It is possible that biased experimental design is, in part, responsible for the reported efficacy of this technique. IMPLICATIONS after a systematic literature review, 24 randomized trials examining the role of acute normovolemic hemodilution were identified, pooled, and summarized using statistical techniques. Many studies reported an impressive reduction in blood transfused. Closer examination suggests that these reductions in blood exposure may be due to flawed study design.