ACC-i2 Scientific Session 2012: Cooperation Key as Practice Changing Results Released
CHICAGO, IL—A strong focus on new therapeutic options was seen at this year’s American College of Cardiology/i2 Annual Scientific Session, held March 24-27, 2012. New and follow-up results also were presented in a wide variety of specialties, with both interventionalists and surgeons working together to improve clinical outcomes.
CABG and PCI, at It Again
Much anticipated results of the ASCERT trial showed that for older patients with multivessel disease, PCI and CABG yield equivalent mortality at 1 year, but CABG patients fare better in the longer-term.
At 1 year, both groups saw death rates of slightly over 6%. However, at 4 years, mortality was higher after PCI than after CABG (20.8% vs. 16.4%; adjusted RR 0.79, 95% CI 0.76-0.82). The 4-year risk ratios showed a benefit of CABG across subgroups defined according to sex, age, diabetic status, body-mass index, presence or absence of chronic lung disease, ejection fraction, and glomerular filtration rate irrespective of patient risk.
Despite recent reports showing worse results with off-pump—with the heart still beating— CABG as opposed to on-pump, results from CORONARY, the largest prospective randomized trial to date comparing the two surgical techniques, shows that they achieve similar outcomes at 30 days. At 1 month, the composite of death, nonfatal stroke, nonfatal MI, or new renal failure requiring dialysis was equivalent in both groups, as were each of the component endpoints.
In addition, results of the CPORT-E trial showed that PCI outcomes at hospitals without surgical backup were noninferior to those at hospitals with surgical capabilities with regard to MACE, though no differences were detected in all-cause mortality or MI.
Adjunctive Therapies Examined
Late-breaking data from the INFUSE-AMI trial showed that intracoronary delivery of a bolus dose of the glycoprotein IIb/IIIa inhibitor abciximab reduces infarct size in patients receiving primary PCI for STEMI. Unfortunately, manual aspiration thrombectomy provides no such benefits.
Neither abciximab nor thrombus aspiration made a difference in markers of reperfusion post PCI, such as corrected TIMI frame counts, myocardial blush grade, or ST-segment resolution at 60 minutes. At 30 days, patients receiving abciximab had smaller infarct size (% of total LV mass) on cardiac MRI than did those not given the drug. Other outcomes such as total LV mass and LVEF were equivalent.
Contrary to shorter-term results, new findings from the BCIS-1 trial showed that elective intra-aortic balloon pump therapy in high-risk PCI patients reduces mortality by roughly a third in follow-up beyond 4 years.
TAVR Pushes Ahead
The PARTNER trial also released up-to-date findings. Two-year data from cohort A showed that TAVR with the Edwards Sapien device (Edwards Lifesciences, Irvine, CA) matches the mortality rate of surgical valve repair in high-risk patients with aortic stenosis who are considered eligible for either procedure. As with the 1-year results, major strokes trended higher for TAVR patients but the difference only reached significance when considering the composite of stroke/transient ischemic attack. Though major vascular complications were increased with TAVR, this difference was balanced by decreases in major bleeding and MI.
The prospective ADVANCE trial found that in high-risk, inoperable patients, TAVR with the CoreValve device is safe and associated with an improvement in aortic valve function and low stroke and mortality rates at 6 months. The study is the first to evaluate the safety and efficacy of TAVR per the Valve Academic Research Consortium (VARC) standards for defining adverse events.
And another study showed that in high-risk or inoperable patients who undergo TAVR, two-thirds of late deaths are noncardiac, with mortality mostly predicted by comorbidities. At a median follow-up of 3 years, mortality was 43.1%, with no difference between transfemoral and transapical patients.
New Options in Medical Therapy Explored
Potentially opening doors for patients who need to stop dual antiplatelet therapy early after DES implantation, a new study found that 3 months of dual therapy in those receiving Endeavor zotarolimus-eluting stents (Medtronic, Santa Rosa, CA) can match the clinical outcomes achieved by a full year of aspirin and clopidogrel in patients who receive other DES. The primary composite of cardiovascular death, MI, Academic Research Consortium-defined stent thrombosis, TVR, or TIMI major or minor bleeding was 4.7% in each group (P < 0.01 for noninferiority).
Another study showed that prasugrel effectively decreases platelet reactivity at 15 days compared with double-dose clopidogrel in stable patients who respond poorly to the older antiplatelet agent after PCI.
In patients undergoing PCI with BMS, meanwhile, the anti-inflammatory bindarit was shown to significantly reduce in-stent late loss at 6 months compared with placebo. However, there was no difference in MACE.
The large, multinational TRA 2P-TIMI 50 trial showed that vorapaxar, the first of a new class of investigational antithrombotic agents, reduces the risk of cardiovascular death, MI, or stroke in patients with atherosclerosis at 3 years when added to aspirin therapy. However, the drug also increased the risk of moderate or severe bleeding, including intracranial hemorrhage.
Thirty-day results of the HOST-ASSURE trial confirmed that the addition of cilostazol to standard dual antiplatelet therapy in patients receiving second-generation DES (Promus Element; Boston Scientific, Natick, MA or Endeavor Resolute; Medtronic, Santa Rosa, CA) is noninferior to doubling the dose of clopidogrel. The cumulative incidence of cardiac death, nonfatal MI, definite or probable stent thrombosis, stroke, and PLATO major bleeding was 1.4% in the dual therapy group and 1.2% in the triple therapy group (P for noninferiority < 0.001).
Another study showed that a fixed dose of the oral factor X inhibitor rivaroxaban is noninferior to standard therapy with enoxaparin and a vitamin K antagonist in patients with acute symptomatic pulmonary embolism with or without DVT. Researchers said the twice-daily therapy could potentially help simplify treatment and reduce length of stay.
The EXOME trial used whole exome analysis, which involves sequencing all protein coding regions of the human genome, to identify new and previously known variants downstream of clopidogrel metabolism that appear to influence on-treatment reactivity after PCI. While ATP2B2 and TIAM2 were linked to on-treatment reactivity at baseline, only the CYP2C18/19 locus was the primary protein-coding determinant of clopidogrel response variability at 30 days.
Delving into Devices
Biodegradable-polymer sirolimus-eluting stents showed promising safety and efficacy compared with permanent-polymer DES, according to 2 separate presentations.
In the first study, individual patient data was pooled from 3 large-scale multicenter randomized clinical trials (ISAR-TEST 3, ISAR-TEST 4, and LEADERS) that compared biodegradable polymer drug-eluting stents (sirolimus-eluting and biolimus-eluting) with durable polymer sirolimus-eluting stents and assessed clinical outcomes during follow-up through 4 years. The biodegradable polymer DES reduced the 4-year rates of clinically indicated TLR and definite stent thrombosis, mainly driven by a lower risk of very late stent thrombosis.
And in the EVOLUTION trial, patients with de novo coronary artery lesions were randomized to treatment with either a sirolimus-eluting stent (SES) with a biodegradable polymer (Excel, JW Medical System, Weihai, China) or an SES with a durable polymer (Cypher Select, Cordis Corporation, Miami Lakes, FL). At 12 months, the biodegradable-polymer SES were noninferior to durable-polymer SES for ischemia-driven target vessel failure within 12 months (composite of cardiac death, MI, and ischemia-driven TVR).
Two-year results of the RESOLUTE US trial showed that the zotarolimus-eluting Resolute Integrity stent (Medtronic), approved by the US Food and Drug Administration in February 2012, continues to promote low restenosis rates and demonstrate clinical safety. Target lesion failure (composite of cardiac death, MI, and clinically-driven TLR) was 5.9% for Resolute and 8.1% for historical controls (P < 0.001 for noninferiority).
CTA Comes Out Ahead
Coronary computed tomographic angiography (CTA) was shown to be an effective screening tool for patients in the emergency department with suspected ACS, capable of safely ruling out many who would otherwise be admitted with conventional testing strategies. After randomization to CTA or traditional care, both groups showed the same rate of cardiac catheterization (4%). In the CTA group, 76% of these patients were found to have coronary stenosis of 50% or more, while this rate was 44% in the traditional care group.
Moreover, ROMICAT II (Rule-Out Myocardial Ischemia/Infarction using Computer Assisted Tomography) showed that incorporating cardiac CTA early in the evaluation of patients presenting to emergency departments with chest pain can improve triage and clinical decision making compared with standard evaluation. The study found length of hospital stay, the primary endpoint, to be significantly lower in the cardiac CTA group compared with the standard evaluation group.
Radial vs. Femoral Debate Continues
Not only does using the transradial approach for PCI result in less bleeding compared with the transfemoral approach, but new data suggest that it also saves health-care dollars—about $553 per case—particularly for those at highest bleeding risk. Comparing actual hospital costs in the United States for transradial and transfemoral PCI, researchers used an inpatient administrative database that included approximately one-sixth of all US hospitalizations to identify PCI patients treated from 2004 to 2009.
Another study showed that PCI performed via transradial access may result in fewer blood transfusions and even lower mortality compared with transfemoral access, but only at higher volume centers. The top quartile of propensity-matched centers performing transradial PCI showed a lower risk of transfusion with radial vs. femoral access (P = 0.03). In the same propensity matched cohort, patients treated at centers in the top quartile of sites performing radial PCI showed a lower mortality risk with radial vs. transfemoral procedures at 30 days (HR 0.6; 95% CI 0.4-0.9).
Renal Denervation the Next Frontier?
For patients with refractory hypertension, catheter-based renal denervation by radiofrequency ablation continues to result in safe and durable blood pressure reductions without serious adverse events, according to 2 separate presentations.
Three-year data from the Symplicity HTN-1 trial included an expanded cohort from 19 sites in the United States, Europe, and Australia. One-hundred percent of patients were considered responders, defined as experiencing a ≥ 10 mm Hg reduction in systolic blood pressure at 3 years, including each of the 45 late responders who did not originally respond at 1 month.
One-year results of the Symplicity HTN-2 trial focused on 35 of the 54 patients originally assigned to the control group who were allowed to cross over to treatment at 6 months. These subjects saw substantial reductions in blood pressure similar to those of patients who originally received treatment (-23.7 ± 27.5 mm Hg systolic; P < 0001 vs. baseline; -8.4 ± 12.1 mm Hg diastolic; P < 0.001 vs. baseline). Long-term safety was established with no deaths and only 3 hypertensive events reported in 2 crossover patients.
Odds and Ends
Other important trials at ACC/i2 included FOCUS-CCTRN, which failed to show any benefit from bone marrow stem cell therapy in patients with chronic heart disease and LV dysfunction, and BRIDGE-ACS, which showed the benefit of a simple, hospital-based education initiative in improving care for ACS patients.
Source:Presentations at: American College of Cardiology/i2 61st Annual Scientific Session; March 24-27, 2012; Chicago, IL.
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Yael L. Maxwell is Senior Medical Journalist for TCTMD and Section Editor of TCTMD's Fellows Forum. She served as the inaugural…
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