Medicine JournalFeeds

Underestimated and under-recognized: the late consequences of acute coronary syndrome (GRACE UK-Belgian Study).

Eur Heart J. 2010 Aug 30;

Authors: Fox KA, Carruthers KF, Dunbar DR, Graham C, Manning JR, De Raedt H, Buysschaert I, Lambrechts D, Van de Werf F

Aim To define the long-term outcome of patients presenting with acute coronary syndrome [ST-segment elevation myocardial infarction (STEMI), and non-STEMI and unstable angina acute coronary syndrome (ACS) without biomarker elevation] and to test the hypothesis that the GRACE (Global Registry of Acute Coronary Events) risk score predicts mortality and death/MI at 5 years. Methods and results In the GRACE long-term study, UK and Belgian centres prospectively recruited and followed ACS patients for a median of 5 years (1797 days). Primary outcome events: deaths, cardiovascular deaths (CVDs) and MIs. Secondary events: stroke and re-hospitalization for ACS. There were 736 deaths, 19.8% (482 CVDs, 13%) and 347 (9.3%) MIs (>24 h), 261 strokes (7.7%), and 452 (17%) subsequent revascularizations. Rehospitalization was common: average 1.6 per patient; 31.2% had >1 admission, 9.2% had 5+ admissions. These events were despite high rates of guideline indicated therapies. The GRACE score was highly predictive of all-cause death, CVD, and CVD/MI at 5 years (death: chi(2) likelihood ratio 632; Wald 709.9, P< 0.0001, C-statistic 0.77; for CVD C-statistic 0.75, P< 0.0001; CVD/MI C-statistic 0.70, P< 0.0001). Compared with the low-risk GRACE stratum (ESC Guideline criteria), those with intermediate [hazard ratio (HR) 2.14, 95% CI 1.63, 2.81] and those with high-risk (HR 6.36, 95% CI 4.95, 8.16) had two- and six-fold higher risk of later death (Cox proportional hazard). A landmark analysis after 6 months confirmed that the GRACE score predicted long-term death (chi(2) likelihood ratio 265.4; Wald 289.5, P< 0.0001). Although in-hospital rates of death and MI are higher following STEMI, the cumulative rates of death (and CVD) were not different, by class of ACS, over the duration of follow-up (Wilcoxon = 1.5597, df = 1, P= 0.21). At 5 years after STEMI 269/1403 (19%) died; after non-STEMI 262/1170 (22%) after unstable angina (UA) 149/850 (17%). Two-thirds (68%) of STEMI deaths occurred after initial hospital discharge, but this was 86% for non-STEMI and 97% for UA. Conclusion The GRACE risk score predicts early and 5 year death and CVD/MI. Five year morbidity and mortality are as high in patients following non-ST MI and UA as seen following STEMI. Their morbidity burden is high (MI, stroke, readmissions) and the substantial late mortality in non-STE ACS is under-recognized. The findings highlight the importance of pursuing novel approaches to diminish long-term risk.

PMID: 20805110 [PubMed - as supplied by publisher]

Reperfusion strategy in Europe: temporal trends in performance measures for reperfusion therapy in ST-elevation myocardial infarction.

Eur Heart J. 2010 Aug 30;

Authors: Schiele F, Hochadel M, Tubaro M, Meneveau N, Wojakowski W, Gierlotka M, Polonski L, Bassand JP, Fox KA, Gitt AK

Aims The rate and type of reperfusion, as well as time delays to reperfusion are directly associated with mortality and are established as performance measures (PMs) in the treatment of ST elevation myocardial infarction (STEMI). To date, little information exists about PMs for reperfusion in clinical practice in Europe and their temporal changes. Methods and results Using the Euro Heart Survey ACS-III data set (2 years of inclusions between 2006 and 2008, 138 centres in 21 countries), we selected patients with STEMI eligible for reperfusion therapy. Recorded variables corresponded to the CARDS data set. The rate and type of reperfusion, as well as door to needle and door to artery times were assessed and compared between periods. Timely reperfusion was defined as a door to needle time <30 min, or a door to artery time <90 min. We assessed changes in PMs for reperfusion over the 2 years of recruitment. Among 19 205 patients included in the registry, 7655 had STEMI, and 6481 were admitted within the first 12 h and eligible for reperfusion. The rate of patients who underwent reperfusion increased from 77.2 to 81.3%, with an increase in the use of primary percutaneous coronary intervention (P-PCI). The door to needle and door to artery times decreased significantly during the study period, from 20 to 15 min (P = 0.0011) and from 60 to 45 min (P < 0.0001) respectively. As a result, the number of eligible patients receiving reperfusion therapy in a timely manner increased from 53.1 to 63.5% (P < 0.0001). In parallel, over the 2-year period, in-hospital mortality decreased from 8.1 to 6.6% (P = 0.047). Conclusion In centres participating in the Euro Heart Survey ACS III, PMs for reperfusion in STEMI improved significantly between 2006 and 2008, with greater use of PCI. Similarly, the rate of patients reperfused in a timely manner also increased, with a significant reduction in door to needle and door to artery times.

PMID: 20805111 [PubMed - as supplied by publisher]

COlchicine for the Prevention of the Post-pericardiotomy Syndrome (COPPS): a multicentre, randomized, double-blind, placebo-controlled trial.

Eur Heart J. 2010 Aug 30;

Authors: Imazio M, Trinchero R, Brucato A, Rovere ME, Gandino A, Cemin R, Ferrua S, Maestroni S, Zingarelli E, Barosi A, Simon C, Sansone F, Patrini D, Vitali E, Ferrazzi P, Spodick DH, Adler Y,

Aims No drug has been proven efficacious to prevent the post-pericardiotomy syndrome (PPS), but colchicine seems safe and effective for the treatment and prevention of pericarditis. The aim of the COlchicine for the Prevention of the Post-pericardiotomy Syndrome (COPPS) trial is to test the efficacy and safety of colchicine for the primary prevention of the PPS. Methods and results The COPPS study is a multicentre, double-blind, randomized trial. On the third post-operative day, 360 patients (mean age 65.7 +/- 12.3 years, 66% males), 180 in each treatment arm, were randomized to receive placebo or colchicine (1.0 mg twice daily for the first day followed by a maintenance dose of 0.5 mg twice daily for 1 month in patients >/=70 kg, and halved doses for patients <70 kg or intolerant to the highest dose). The primary efficacy endpoint was the incidence of PPS at 12 months. Secondary endpoint was the combined rate of disease-related hospitalization, cardiac tamponade, constrictive pericarditis, and relapses. Baseline characteristics were well balanced between the study groups. Colchicine significantly reduced the incidence of the PPS at 12 months compared with placebo (respectively, 8.9 vs. 21.1%; P = 0.002; number needed to treat = 8). Colchicine also reduced the secondary endpoint (respectively, 0.6 vs. 5.0%; P = 0.024). The rate of side effects (mainly related to gastrointestinal intolerance) was similar in the colchicine and placebo groups (respectively, 8.9 vs. 5.0%; P = 0.212). Conclusion Colchicine is safe and efficacious in the prevention of the PPS and its related complications and may halve the risk of developing the syndrome following cardiac surgery. ClinicalTrials.gov number, NCT00128427.

PMID: 20805112 [PubMed - as supplied by publisher]

ISAR-REACT 3A: a study of reduced dose of unfractionated heparin in biomarker negative patients undergoing percutaneous coronary intervention.

Eur Heart J. 2010 Aug 30;

Authors: Schulz S, Mehilli J, Neumann FJ, Schuster T, Massberg S, Valina C, Seyfarth M, Pache J, Laugwitz KL, Büttner HJ, Ndrepepa G, Schömig A, Kastrati A,

Aims Although a 140 U/kg dose of unfractionated heparin (UFH) was comparable with bivalirudin in terms of net clinical outcome in the Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment (ISAR-REACT) 3 trial, it was associated with a higher risk of bleeding. We designed this study to assess whether a reduction in the UFH dose from 140 to 100 U/kg is associated with improved net clinical outcome. Methods and results A total of 2505 biomarker negative patients undergoing percutaneous coronary intervention (PCI) after clopidogrel pre-treatment received a single bolus of 100 U/kg UFH. The primary endpoint was net clinical outcome-a quadruple endpoint of death, myocardial infarction, urgent target-vessel revascularization within 30 days, or in-hospital REPLACE 2 defined major bleeding. The primary comparison was with the historical UFH group of ISAR-REACT 3 (2281 patients). In a second analysis, we checked for non-inferiority against the historical bivalirudin arm of ISAR-REACT 3 (2289 patients). The incidence of the primary endpoint was 7.3% in the lower UFH dose group compared with 8.7% in the higher UFH dose group [hazard ratio (HR) 0.81; 95% confidence interval (CI) 0.67-1.00; P = 0.045]. The incidence of major bleeding was 3.6% in the lower UFH dose group and 4.6% in the higher UFH dose group (HR 0.79; 95% CI 0.59-1.05; P = 0.11). The lower UFH dose met the criterion of non-inferiority compared with bivalirudin (P < 0.001). Conclusion In biomarker negative patients undergoing PCI after clopidogrel loading, a reduced dose of 100 U/kg UFH provided net clinical benefit compared with the historical control of 140 U/kg UFH in the ISAR-REACT 3 trial. The benefit was mostly driven by reduction in bleeding. Clinical trial registration information URL www.clinicaltrials.gov; Unique identifier NCT00735280.

PMID: 20805113 [PubMed - as supplied by publisher]

Thrombin receptor antagonists may become an important antiplatelet therapy for coronary artery disease.

Eur Heart J. 2010 Aug 30;

Authors: Van de Werf F

PMID: 20805114 [PubMed - as supplied by publisher]

Double-blind, placebo-controlled Phase II studies of the protease-activated receptor 1 antagonist E5555 (atopaxar) in Japanese patients with acute coronary syndrome or high-risk coronary artery disease.

Eur Heart J. 2010 Aug 30;

Authors: Goto S, Ogawa H, Takeuchi M, Flather MD, Bhatt DL,

Aims Two multicentre, randomized, double-blind, placebo-controlled Phase II studies assessed the safety and efficacy of the oral protease-activated receptor 1 (PAR-1) antagonist E5555 in addition to standard therapy in Japanese patients with acute coronary syndrome (ACS) or high-risk coronary artery disease (CAD). Methods and results Patients with ACS (n = 241) or high-risk CAD (n = 263) received E5555 (50, 100, or 200 mg) or placebo once daily for 12 (ACS patients) or 24 weeks (CAD patients). The incidence of TIMI major, minor, and minimal bleeds requiring medical attention was similar in the placebo and combined E5555 (atopaxar) groups (ACS: 6.6% placebo vs. 5.0% E5555; CAD: 1.5% placebo vs. 1.5% E5555). There were no TIMI major bleeds and three CURE major bleeds (two with placebo; one with 100 mg E5555). There was a numerical increase in ‘any’ TIMI bleeding with the E5555 200 mg dose (ACS: 16.4% placebo vs. 23.0% E5555, P = 0.398; CAD: 4.5% placebo vs. 13.2% E5555, P = 0.081). The rate of major cardiovascular adverse events in the combined E5555 group was not different from placebo (ACS: 6.6% placebo vs. 5.0% E5555, P = 0.73; CAD: 4.5% placebo vs. 1.0% E5555, P = 0.066). There was a statistically significant dose-dependent increase in liver function abnormalities and QTcF with E5555. At trough dosing levels in both populations, mean inhibition of platelet aggregation was >90% with 100 and 200 mg E5555, and 20-60% with 50 mg E5555. Conclusion E5555 (50, 100, and 200 mg) did not increase clinically significant bleeding, although there was a higher rate of any TIMI bleeding with the highest two doses. All doses tested achieved a significant level of platelet inhibition. There was a significant dose-dependent increase in liver function abnormalities and QTcF. Although further study is needed, PAR-1 antagonism may have the potential to be a novel pathway for platelet inhibition to add on to the current standard of care therapy.

PMID: 20805115 [PubMed - as supplied by publisher]

Randomized trial to compare bilateral vs. single internal mammary coronary artery bypass grafting: 1-year results of the Arterial Revascularisation Trial (ART).

Eur Heart J. 2010 Aug 30;

Authors: Taggart DP, Altman DG, Gray AM, Lees B, Nugara F, Yu LM, Campbell H, Flather M,

Aims Observational data suggest that the use of bilateral internal mammary arteries (BIMA) during coronary artery bypass graft surgery provides superior revascularization to a single internal mammary artery (SIMA), but concerns about safety have prevented the widespread use of BIMA. The Arterial Revascularisation Trial (ART) is a randomized trial of BIMA vs. SIMA, with a primary outcome of survival at 10 years. This paper reports mortality, morbidity, and resource use data at 1 year. Methods and results Coronary artery bypass graft patients were enrolled in 28 hospitals in seven countries. Three thousand one hundred and two patients were randomly assigned to SIMA (n = 1554) or BIMA (n = 1548). The mean number of grafts was 3 for both groups. Forty per cent of the SIMA procedures and 42% of the BIMA were performed off-pump. Mortality at 30 days was 18 of 1548 (1.2%) for SIMA and 19 of 1537 (1.2%) for BIMA, and at 1 year was 36 of 1540 (2.3%) and 38 of 1529 (2.5%), respectively. The rates of stroke, myocardial infarction, and repeat revascularization were all </=2% at 1 year and similar between the two groups. Sternal wound reconstruction was required in 0.6 and 1.9% of the SIMA and BIMA groups, respectively. Conclusion Data from ART demonstrate similar clinical outcomes for SIMA and BIMA at 1 year but BIMA grafts are associated with a small absolute increase (1.3%) in the need for sternal wound reconstruction. The results suggest that the use of BIMA grafts is feasible on a routine basis. The 10-year results of the ART will confirm whether BIMA grafting results in lower mortality and the need for repeat intervention. Trial registration: Controlled-trials.com (ISRCTN46552265).

PMID: 20805116 [PubMed - as supplied by publisher]