Influence of functional deficiency of complement mannose-binding lectin on outcome of patients with acute ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention

Aims Experimental data point towards a favourable effect of low serum concentrations of complement mannose-binding lectin (MBL) on myocardial ischaemia/reperfusion (I/R) injury. As comparable data on the role of MBL in human I/R injury is lacking, we investigated the influence of low serum MBL concentrations on mortality of patients with acute ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Methods and results Mannose-binding lectin was determined in 890 acute STEMI patients that were prospectively recruited in the APEX-AMI trial. This trial had a primary endpoint of death through Day 30 and secondary endpoints of death through Day 90 and the composite of death, cardiogenic shock, or congestive heart failure (CHF) through Days 30 and 90. Samples were taken immediately before PCI and the analysis of MBL limited to patients having received placebo. Patients with serum MBL levels of or below 100 ng/mL were considered to be functionally deficient. Of the 890 patients, 127 had functional MBL deficiency (14.3%). Characteristics of patients with MBL deficiency and those with MBL levels >100 ng/mL did not differ. In patients with MBL deficiency, there was 1 death (0.79%) compared with 42 deaths (5.51%) in patients with MBL levels >100 ng/mL (P = 0.0233) representing an absolute and relative lower mortality in MBL deficient patients of 4.7 and 85%, respectively. Functional MBL deficiency, however, was not associated with decreased risk of the combined endpoints of death and shock or death, shock, and CHF, respectively. Conclusion Functional deficiency of complement MBL is associated with reduced mortality in patients with STEMI undergoing PCI. This unique finding suggests that a component of the innate immune system affects mortality in STEMI patients undergoing primary PCI. Trial Registration: clinicaltrials.gov, Identifier: NCT0009163

The authors' reply [to: Effects of glycoprotein IIb/IIIa blockers / Kalyanasndaram, Berger and Kastrati]

We thank Drs Kalyanasundaram, Kastrati and Berger for their interesting comments about our article.Patients included in our subgroup meta-analysis were not routinely scheduled for an early coronary revascularisation, so our results are not directly comparable with the ISAR trials. Patients did not receive clopidogrel as background medication at the time of admission, but almost all received dual antiplatelet treatment at the time of percutaneous coronary intervention (PCI). We agree that clopidogrel is recommended in patients with non-ST segment elevation ACS (NSTEACS) whether or not an invasive approach is planned. The concern, however, is the timing of clopidogrel administration, which continues to be debated, with many cardiologists electing to withhold clopidogrel until angiography because of concerns about bleeding with bypass surgery. This approach is consistent with the treatment strategy applied in the trials included in our meta-analysis.We agree that troponin-negative patients with moderate-to-high risk NSTEACS seem to have less benefit than troponin-positive patients, as we have shown in a previous post hoc subgroup analysis from our dataset. We acknowledge, however, [...

The authors' reply [to: Effects of glycoprotein IIb/IIIa blockers / Kalyanasndaram, Berger and Kastrati]

We thank Drs Kalyanasundaram, Kastrati and Berger for their interesting comments about our article.Patients included in our subgroup meta-analysis were not routinely scheduled for an early coronary revascularisation, so our results are not directly comparable with the ISAR trials. Patients did not receive clopidogrel as background medication at the time of admission, but almost all received dual antiplatelet treatment at the time of percutaneous coronary intervention (PCI). We agree that clopidogrel is recommended in patients with non-ST segment elevation ACS (NSTEACS) whether or not an invasive approach is planned. The concern, however, is the timing of clopidogrel administration, which continues to be debated, with many cardiologists electing to withhold clopidogrel until angiography because of concerns about bleeding with bypass surgery. This approach is consistent with the treatment strategy applied in the trials included in our meta-analysis.We agree that troponin-negative patients with moderate-to-high risk NSTEACS seem to have less benefit than troponin-positive patients, as we have shown in a previous post hoc subgroup analysis from our dataset. We acknowledge, however, [...

The authors' reply [to: Effects of glycoprotein IIb/IIIa blockers / Kalyanasndaram, Berger and Kastrati]

We thank Drs Kalyanasundaram, Kastrati and Berger for their interesting comments about our article.Patients included in our subgroup meta-analysis were not routinely scheduled for an early coronary revascularisation, so our results are not directly comparable with the ISAR trials. Patients did not receive clopidogrel as background medication at the time of admission, but almost all received dual antiplatelet treatment at the time of percutaneous coronary intervention (PCI). We agree that clopidogrel is recommended in patients with non-ST segment elevation ACS (NSTEACS) whether or not an invasive approach is planned. The concern, however, is the timing of clopidogrel administration, which continues to be debated, with many cardiologists electing to withhold clopidogrel until angiography because of concerns about bleeding with bypass surgery. This approach is consistent with the treatment strategy applied in the trials included in our meta-analysis.We agree that troponin-negative patients with moderate-to-high risk NSTEACS seem to have less benefit than troponin-positive patients, as we have shown in a previous post hoc subgroup analysis from our dataset. We acknowledge, however, [...

ACC/AHA guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction - 2002: Summary article: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients with Unstable Angina)

The American College of Cardiology (ACC)/American Heart Association (AHA) guidelines for the management of unstable angina and non–ST-segment elevation myocardial infarction (UA/NSTEMI) were published in September 2000.1 Since then, a number of clinical trials and observational studies have been published or presented that, when taken together, alter significantly the recommendations made in that document. Therefore, the ACC/AHA Committee on the Management of Patients With Unstable Angina, with the concurrence of the ACC/AHA Task Force on Practice Guidelines, revised these guidelines. These revisions were prepared in December 2001, reviewed and approved, and then published on the ACC World Wide Web site (www.acc.org) and AHA World Wide Web site (www.americanheart.org) on March 15, 2002. The present article describes these revisions and provides further updates in this rapidly moving field. Minor clarifications in the wording of three recommendations that now appear differently from those that were previously published on the ACC and AHA Web sites are noted in footnotes

ACC/AHA Guidelines for the Management of Patients With Unstable Angina and Non–ST-Segment Elevation Myocardial Infarction: Executive Summary and Recommendations: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Unstable Angina)

The American College of Cardiology (ACC)/American Heart Association (AHA) Task Force on Practice Guidelines was formed to make recommendations regarding the diagnosis and treatment of patients with known or suspected cardiovascular disease. Coronary artery disease (CAD) is the leading cause of death in the United States. Unstable angina (UA) and the closely related condition non–ST-segment elevation myocardial infarction (NSTEMI) are very common manifestations of this disease. These life-threatening disorders are a major cause of emergency medical care and hospitalizations in the United States. In 1996, the National Center for Health Statistics reported 1 433 000 hospitalizations for UA or NSTEMI. In recognition of the importance of the management of this common entity and of the rapid advances in the management of this condition, the need to revise guidelines published by the Agency for Health Care Policy and Research (AHCPR) and the National Heart, Lung and Blood Institute in 1994 was evident. This Task Force therefore formed the current committee to develop guidelines for the management of UA and NSTEMI. The present guidelines supersede the 1994 guidelines

ACC/AHA guidelines for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the management of patients with unstable angina)

The ACC/AHA Task Force on Practice Guidelines was formed to make recommendations regarding the diagnosis and treatment of patients with known or suspected cardiovascular disease. Coronary artery disease (CAD) is the leading cause of death in the United States. Unstable angina (UA) and the closely related condition non–ST-segment elevation myocardial infarction (NSTEMI) are very common manifestations of this disease. In recognition of the importance of the management of this common entity and of the rapid advances in the management of this condition, the need to revise guidelines published by the Agency for Health Care Policy and Research (AHCPR) and the National Heart, Lung, and Blood Institute (NHLBI) in 1994 (1) was evident. This Task Force therefore formed the current committee to develop guidelines for the management of UA and NSTEMI, supported by the Agency for Healthcare Research and Quality’s USCF-Stanford Evidence-Based Practice Center. This document should serve as a useful successor to the 1994 AHCPR guideline

ACC/AHA 2007 guidelines for the management of patients with unstable angina/non ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non ST-Elevation Myocardial Infarction)

"The ACC/AHA Task Force on Practice Guidelines was formed to make recommendations regarding the diagnosis and treatment of patients with known or suspected cardiovascular disease (CVD). Coronary artery disease (CAD) is the leading cause of death in the United States. Unstable angina (UA) and the closely related condition of non–ST-segment elevation myocardial infarction (NSTEMI) are very common manifestations of this disease. The committee members reviewed and compiled published reports through a series of computerized literature searches of the English-language literature since 2002 and a final manual search of selected articles. Details of the specific searches conducted for particular sections are provided when appropriate. Detailed evidence tables were developed whenever necessary with the specific criteria outlined in the individual sections. The recommendations made were based primarily on these published data. The weight of the evidence was ranked highest (A) to lowest (C). The final recommendations for indications for a diagnostic procedure, a particular therapy, or an intervention in patients with UA/NSTEMI summarize both clinical evidence and expert opinion.

ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction)

"The ACC/AHA Task Force on Practice Guidelines was formed to make recommendations regarding the diagnosis and treatment of patients with known or suspected cardiovascular disease (CVD). Coronary artery disease (CAD) is the leading cause of death in the United States. Unstable angina (UA) and the closely related condition of non–ST-segment elevation myocardial infarction (NSTEMI) are very common manifestations of this disease. The committee members reviewed and compiled published reports through a series of computerized literature searches of the English-language literature since 2002 and a final manual search of selected articles. Details of the specific searches conducted for particular sections are provided when appropriate. Detailed evidence tables were developed whenever necessary with the specific criteria outlined in the individual sections. The recommendations made were based primarily on these published data. The weight of the evidence was ranked highest (A) to lowest (C). The final recommendations for indications for a diagnostic procedure, a particular therapy, or an intervention in patients with UA/NSTEMI summarize both clinical evidence and expert opinion.

Impact of Diabetes Mellitus and Chronic Kidney Disease on Cardiovascular Outcomes and Platelet P2Y(12) Receptor Antagonist Effects in Patients With Acute Coronary Syndromes : Insights From the PLATO Trial

Background-There are limited data on how the combination of diabetes mellitus (DM) and chronic kidney disease (CKD) affects cardiovascular outcomes as well as response to different P2Y(12) receptor antagonists, which represented the aim of the present investigation. Methods and Results-In this post hoc analysis of the PLATO (Platelet Inhibition and Patient Outcomes) trial, which randomized acute coronary syndrome patients to ticagrelor versus clopidogrel, patients (n=15 108) with available DM and CKD status were classified into 4 groups: DM+/CKD+ (n=1058), DM+/CKD- (n=2748), DM-/CKD+ (n=2160), and DM-/CKD- (n=9142). The primary efficacy end point was a composite of cardiovascular death, myocardial infarction, or stroke at 12 months. The primary safety end point was PLATO major bleeding. DM+/CKD+ patients had a higher incidence of the primary end point compared with DM-/CKD- patients (23.3% versus 7.1%; adjusted hazard ratio 2.22; 95% CI 1.88-2.63; P Conclusions-In acute coronary syndrome patients, a gradient of risk was observed according to the presence or absence of DM and CKD, with patients having both risk factors at the highest risk. Although the ischemic benefit of ticagrelor over clopidogrel was consistent in all subgroups, the absolute risk reduction was greatest in patients with both DM and CKD.Peer reviewe