European Society of Cardiology 2011 Congress
he European Society of Cardiology (ESC) meeting is the largest cardiology meeting in the world. This year more than 30,800 registrants from 154 countries gathered to hear presentations of findings from more than 4,200 studies. This Meeting Report will cover 5 studies presented at ESC: ARISTOTLE, RUBY-1, EXAMINATION, PRODIGY, and CRISP-AMI.
Apixaban Superior to Warfarin in Preventing Stroke in AF Patients
pixaban outperformed warfarin in prevention of stroke and systemic embolism in patients with AF, and was associated with less bleeding and lower mortality rates, according to a presentation by the authors of the ARISTOTLE study.
The trial randomized 18,201 patients in 1,034 medical centers in 39 countries to double-blind, double-dummy treatment with apixaban 5 mg twice daily versus warfarin, with a target International Normalized Ratio (INR) between 2.0 and 3.0. INR was monitored at least monthly by an encrypted point-of-care device. Time in therapeutic range (TTR) for each medical center was calculated using the Rosen—daal method as the median of all individuals’ TTRs in the warfarin-treated patients.
Results at a median duration of follow-up of 1.8 years showed primary outcomes (ischemic or hemorrhagic stroke or systemic embolism) in 1.27% of patients in the apixaban group and 1.60% in the warfarin group. The rate of death from any cause was 3.52% in the apixaban group and 3.94% in the warfarin group (HR 0.89; 95% CI, 0.80-0.99; P = 0.047).
Apixaban was associated with a 21% reduction in the risk of stroke or systemic embolism, a 31% reduction in bleeding, and an 11% reduction in all-cause mortality. For every 1,000 patients treated for 1.8 years, apixaban, as compared with warfarin, prevented a stroke in 6 patients, major bleeding in 15 patients, and death in 8 patients.
Median TTR was 65.7% (interquartile limits, 58.0% and 72.2%). Across the TTR quartiles there were consistently lower rates of stroke, systemic embolism, and major bleeding with apixaban than were seen with warfarin.
Study author Christopher Granger, MD, of Duke University, noted that the ARISTOTLE trial “has really hit the ‘sweet spot’ in terms of dose.” The researchers concluded that the benefit of apixaban over warfarin was observed independent of time in therapeutic range (TTR) i.e quality of INR control.
The RUBY-1 Trial: Further Study Needed
arexaban, another new oral Factor Xa inhibitor, was found to be associated with a dose-dependent 2- to 4-fold increase in bleeding when added to dual antiplatelet therapy in patients following an acute coronary syndrome (ACS).
RUBY-1 was a Phase II multicenter trial of darexaban, which aimed to explore the safety, tolerability, and optimal dosing regimen in the secondary prevention of ischemic vascular events in subjects with recent ACS.
In this trial, 1,279 patients with recent high-risk non-ST segment elevation and ST-segment elevation ACS after discontinuation of parenteral antithrombotic therapy received one of six darexban regimens: 5 mg twice daily, 10 mg once daily, 15 mg bid, 3 mg qd, 30 mg bid, or 60 mg qd, or placebo, in addition to dual antiplatelet treatment for 24 weeks.
Gabriel Steg, of the Hôpital Bichat in Paris, who presented the results of RUBY-1, said the study produced no other safety concerns and that a large Phase III study for this indication was needed to establish the role of low-dose darexaban in preventing major cardiac events after ACS. While additional studies may provide further insight on whether darexaban may achieve better clinical efficacy on top of dual antiplatelet therapy without an unacceptable increase in the risk of bleeding, it should be noted that prior studies with other agents have failed to show superior efficacy with triple antithrombotic agent therapy.
The RUBY 1 study was published online in the European Heart Journal.
The EXAMINATION Trial: Lower Rate of Stent Thrombosis With Second-Generation DES
second-generation drug-eluting stent (DES)—the Xience V—performs well in patients having primary PCI for ST elevation myocardial infarction (MI), and it has a better safety profile than that of bare-metal stents.
EXAMINATION was a randomized controlled trial with an “all-comers” design that evaluated the Xience V stent in the setting of STEMI. This design is a change from studies of the first-generation DESs, which had been evaluated in randomized, controlled trials in the setting of STEMI, leading to positive results overall. According to investigator Manuel Sabate, MD, of Barcelona, Spain, most of these trials lacked generalizability to real-world circumstances, and there had been no safety and efficacy data for the new-generation DESs in this high-risk group of patients with STEMI. Patients included in the EXAMINATION trial represented up to 70% of all STEMI patients being attended in the medical centers during recruitment, reflecting the realworld nature of the study design.
EXAMINATION involved 1,498 STEMI patients randomized to either a Xience V stent (everolimus-eluting) or cobalt chromium bare-metal stent.
After 1 year of follow-up, there was a nonsignificant trend toward benefit with the Xience V stent by virtue of a lower rate of new revascularizations during follow-up as compared with the bare-metal stents. The rates of definite and definite/probable stent thrombosis at 1-year follow-up were significantly lower with the Xience V stent compared with the bare-metal stents.
Two Years of Dual Antiplatelet Therapy Is No Better than 6 Months
randomized multicenter open-label study, (PRODIGY), evaluating the efficacy and safety of prolonged antiplatelet therapy in patients with coronary disease, found that 24 months of dual antiplatelet therapy (DAPT) is no better than 6 months DAPT in preventing adverse cardiac events. PRODIGY also found a consistently greater risk of hemorrhage in the 24-month dual therapy group. The need for transfusion was also increased in the longer treatment group.
Among patients receiving a bare-metal stent or one of the three DESs, the rate of all-cause death, MI, or stroke was not significantly different in patients treated with an antiplatelet agent plus aspirin for 6 months, compared with those who continued DAPT for 24 months: 10% vs 10.1%.
Investigator Marco Valgimigli, MD, PhD, from the University Hospital of Ferrara, Italy, said the results bring into question the validity of current guideline recommendations, which were based on registry data, that at least 12 months of DAPT should be pursued after implantation of a DES.
IABC Doesn’t Reduce Infarct Size in Patients With STEMI Without Shock
n the CRISP-AMI study, a multicenter prospective, randomized trial in patients with acute ST segment elevation MI without shock, patients were recruited within 6 hours of chest pain onset and planned primary PCI. Of the 337 patients enrolled, 161 were randomized to receive intra-aortic balloon counterpulsation (IABC) prior to primary PCI and 176 to standard care (SOC, primary PCI without IABC support).
The primary efficacy end point was infarct size at 3 to 5 days post-PCI; the secondary end point was the composite of major adverse clinical events including death, reinfarction, and heart failure at 6 months.
Mean infarct size was not significantly different between the IABC and SOC groups. At 30 days, major bleeding or transfusion had occurred in 5 IABC patients and 2 SOC patients. Death occurred in 3 patients of the IABC group and 9 of the SOC group by 6 months. Thus, routine use of IABC in patients with STEMI without cardiogenic shock did not lead to a reduction in infarct size or to better clinical outcome in 6 months.
While the study did not meet its primary end point, investigator Manesh Patel, MD, of Duke University, said the results offer an insight into treatment of STEMI patients. “The most striking observation is the excellent overall outcome for the highest risk patients within the context of the trial,” he said.