Top News From ACC 2013: Slideshow

The American College of Cardiology (ACC) 2013 Scientific Sessions took place in San Francisco, California, on March 9-11.

Key trials presented at the sessions include:

CHAMPION-PHOENIX: Cangrelor cuts complications at PCI vs clopidogrel; bleeding a caution

STREAM: First success for fibrinolysis before transport to PCI

PARTNER A: Equal outcomes, many dead for both TAVI and SAVR arms

HPS2-THRIVE: Niacin/laropiprant plus statin did not reduce the risk for major vascular events in patients with well-controlled LDL cholesterol

TERISA: A unique benefit of ranolazine in diabetic angina?

PREVAIL: Yanked from ACC program; Watchman device meets safety endpoint

PEITHO: Persuasive for thrombolysis in PE?

OFF-PUMP/ON-PUMP CABG: GOPCABE, CORONARY, PRAGUE-6

RELAX: Sildenafil falls short in preserved-EF heart failure

SELECT-ACS: Hints of myocardial sparing with inclacumab in NSTEMI

MASS COM: Elective PCI safely performed without surgical back-up

CHAMPION-PHOENIX: Cangrelor cuts complications at PCI vs clopidogrel; bleeding a caution

Results: CHAMPION-PHOENIX, a randomized trial of over 11,000 patients, found that intravenous cangrelor cut the risk for periprocedural complications at all kinds of PCI compared with taking a pill of clopidogrel. Cangrelor's benefit of a 22% drop in a composite efficacy endpoint was driven by reductions in MI and stent thrombosis and was not associated with an increase in bleeding complications as they were prospectively defined. There were cautions, however, when bleeding complications were defined using other accepted criteria: Some kinds of bleeding were more common with cangrelor.

"And that to us seemed to strike a nice balance," said Dr. Robert Harrington (Stanford University, California), co-principal investigator for the CHAMPION-PHOENIX trial. "You see a bleeding effect suggesting that the drug is in fact a more potent antithrombotic than the comparator, yet you're not seeing the kind of bad bleeding that would be worrisome when adding another drug into the medical regimen. There's no question that intravenous administration of cangrelor provides a more predictable level of platelet inhibition than you see with the oral administration of clopidogrel."

STREAM: First success for fibrinolysis before transport to PCI

Results: In the STREAM trial, fibrinolysis with tenecteplase and contemporary antithrombotic therapy given before transport to a PCI-capable hospital, coupled with timely coronary angiography, is as effective as primary PCI in STEMI patients presenting within 3 hours of symptom onset who cannot undergo primary PCI within 1 hour of first medical contact.

There was a significant increase in intracranial hemorrhage in the fibrinolysis group, which led to the dose of tenecteplase being halved in people aged 75 years or older fairly early on in the course of the trial, after which the intracranial hemorrhage rate in the fibrinolysis group was reduced to 0.5%, which was not significantly different from the PCI group.

"The results provide the opportunity for a measured approach to invasive coronary interventions, circumventing an urgent procedure in about two thirds of fibrinolytic-treated STEMI patients," said Dr. Frans Van de Werf (University of Leuven, Belgium). "Drug therapy before transfer is at least as effective as PCI, and an urgent catheterization was avoided in two thirds of patients. This gives clinicians time to consider other options, such as CABG and medical therapy."

PARTNER A: Equal outcomes, many dead for both TAVI and SAVR arms

Results: Good news and bad news accompany the 3-year follow-up from the PARTNER A trial, comparing transcatheter aortic-valve implantation/replacement (TAVI/TAVR) with open surgical aortic-valve replacement (SAVR) in high-risk patients with severe aortic stenosis. The good news is that rates of both stroke and all-cause mortality were similar between both groups of patients 3 years out. The bad news is that more than 2 out of every 5 patients had died. The rates of clinical outcomes between the TAVR and surgical groups were similar. Periprocedural stroke concerns have diminished over time, and valve hemodynamics for the new device have remained stable, even though paravalvular (PV) regurgitation, or "leaks," have proved persistent and lethal.

"Future efforts should be directed toward reducing TAVR procedure-related complications, including strokes, vascular events, and paravalvular regurgitation," said Dr. Vinod Thourani (Emory University School of Medicine, Atlanta, Georgia). "What we're seeing at 1, 2, and 3 years is that [stroke] is not an issue, [patients are] not continuing to have strokes, even though the majority of us take our patients off of [clopidogrel] after 6 months, although they are on lifelong aspirin for the most part. The PV leaks that were happening early on are not increasing. So, once you get that PV leak at the index operation, there is some improvement, but for the most part they are staying stable and not getting worse, and that's something we can count on."

HPS2-THRIVE: Niacin/laropiprant plus statin did not reduce the risk for major vascular events in patients with well-controlled LDL cholesterol

Results: HPS2-THRIVE is a large, randomized trial testing the use of extended-release niacin and the antiflushing agent laropiprant for the reduction of major vascular events.

The combination of niacin and laropiprant in addition to statin therapy did not significantly reduce the risk for major vascular events in patients with well-controlled LDL-cholesterol levels. The failure of niacin in the 25,673-patient study was first announced in late December by Merck, which stated that it no longer had any plans to take the drug before the US FDA to gain approval.

Results of the study are clear, and according to lead investigator Dr. Jane Armitage (Oxford University, United Kingdom), "In light of these findings, the role of extended-release niacin for the prevention of cardiovascular disease should be reconsidered." She added that a negative study, even a large and expensive study such as HPS2-THRIVE, is beneficial, because it is just as important to find out whether a drug doesn't work.

TERISA: A unique benefit of ranolazine in diabetic angina?

Results: The first prospective, international, randomized controlled study focusing specifically on angina in patients with diabetes has shown that ranolazine is an effective treatment in this patient population. Ranolazine reduced episodes of stable angina in diabetes patients already receiving 1 or 2 antianginal drugs and led to less use of sublingual nitroglycerin. The benefits appeared more prominent in patients with higher rather than lower A1c levels.

"The results were modest but clinically meaningful. The efficacy of ranolazine was demonstrated on top of a profound placebo effect," said Dr. Mikhail Kosiborod (Saint Luke's Mid America Heart Institute, Kansas City, Missouri). "TERISA is the first in a line of trials that will establish ranolazine's role in diabetic patients with chronic angina; this study shows that ranolazine clearly does what it's supposed to do as an antianginal agent in patients with diabetes."

PREVAIL yanked from ACC program; Watchman device meets safety endpoint

Results: Preliminary data from the PREVAIL study of the Watchman device for the prevention of stroke and systemic embolism in patients with nonvalvular AF appear to give some reassurance on safety issues raised previously. But the trial has been surrounded by much controversy, with reports of endpoints being changed, attempts to present not all of the data, and finally an embargo break by the sponsor, leading the ACC to cancel the presentation completely. The slides, however, were made available to the media, although the data therein, particularly the efficacy results, appear to have many issues.

"Many people cannot take oral anticoagulants because they are at high bleeding risk, and others don't like the inconvenience of warfarin monitoring and the nuisance bleeding with any of the anticoagulant drugs. The Watchman device offers them the alternative of undergoing 1 procedure instead of taking lifelong anticoagulant therapy," said Dr. David Holmes (Mayo Clinic, Rochester, Minnesota). "Despite inclusion of higher-risk patients in PREVAIL than in the previous study, there were fewer complications, and results show that the device can be safely implanted by new operators. The Watchman device is therefore a real step forward, in that it offers an alternative to oral anticoagulation therapy for thromboembolic prevention in patients with nonvalvular atrial fibrillation."

PEITHO: Persuasive for thrombolysis in pulmonary embolism?

Results: The addition of the thrombolytic agent tenecteplase to standard treatment with heparin in patients with intermediate-risk pulmonary embolism significantly reduced the primary endpoint of death or hemodynamic collapse within 7 days of randomization in PEITHO. However, the benefits of thrombolysis came at the cost of a significantly increased risk for major hemorrhage.

"There is a price to pay, and we would not say that everybody in this group should receive thrombolysis," said Dr. Stavros Konstantinides (Center for Thrombosis and Hemostasis, University of Mainz, Germany). "Overall, the study strongly supports the concept that risk stratification of patients makes sense and that these patients need something to prevent deterioration. Patients who were less than 75 years old had most of the benefit and a tendency toward fewer hemorrhagic strokes. The dose of the drug that we used could be lowered in older patients, and alternative methods of delivering thrombolytics could be explored."

GOPCABE, CORONARY, PRAGUE-6: Off-pump/on-pump CABG: Still no consensus

Results: New results from 3 trials comparing off-pump and on-pump CABG have not been able to make a definitive case that off-pump is better for high-risk patients, despite that still being the belief of all of the surgeons leading the studies. First results from GOPCABE and 12-month results from the CORONARY study showed similar findings, with nonsignificant differences between the 2 procedures at 30 days and 12 months. A third, much smaller, single-center Czech study -- PRAGUE-6 -- did show a benefit of off-pump, but with only 200 patients it is difficult to draw conclusions from these data.

"Despite all of this experience with 2 very large studies, no clear benefit has been shown with off-pump," said Dr. Michael Mack (Baylor Health Care System, Dallas, Texas). Noting that the main criticism of previous studies was that they included too many low-risk patients, making it difficult to show differences, he added, "These trials selected higher-risk patients, but still no major differences have been found."

RELAX: Sildenafil falls short in preserved-EF heart failure

Results: In the RELAX trial, patients with preserved-EF heart failure (HF-PEF) (LVEF ≥ 50%) in NYHA class II-III were randomly assigned to sildenafil, a phosphodiesterase-5 (PDE-5) inhibitor, to investigate improvement in exercise capacity and clinical outcomes. The trial showed no improvements in patients (n = 113) who received the drug at 20 mg 3 times daily for 3 months, followed by 60 mg 3 times daily for another 3 months, compared with a placebo control group (n = 103). The trial's median patient age was 69 years.

"Unfortunately, there was absolutely no signal of benefit with this drug, and quite disappointingly so," said Dr. Margaret Redfield (Mayo Clinic, Rochester, Minnesota). "It may be that the primary therapeutic effects of PDE-5 inhibitors in heart failure involve the drugs' ability to dilate the pulmonary vascular bed, enhance right ventricular contractility, and reduce ventricular interdependence, and that pulmonary arterial hypertension and right ventricular failure must be significant in order to observe clinical benefit in HF-PEF."

SELECT-ACS: Hints of myocardial sparing with inclacumab in NSTEMI

Results: A small, phase 2 study, SELECT-ACS, with a biomarker test for its primary endpoint, offers some encouraging hints that the P-selectin antagonist inclacumab may be able to reduce myocardial damage in patients undergoing PCI for NSTEMI. P-selectin is a cell-adhesion molecule expressed on endothelial cells and platelets and is known to play a role in leukocyte and platelet "rolling." Animal studies have suggested that inhibition of this molecule may limit macrophage accumulation and neointimal formation after injury by decreasing neutrophil and platelet adhesion.

"We think that this consistent signal favoring inclacumab should lead us to perform additional studies in phase 3," said Dr. Jean-Claude Tardif (Montreal Heart Institute, Montreal, Quebec, Canada). "Further clinical investigation will be required to determine the clinical value -- benefit or harm -- of inclacumab in patients presenting with myocardial infarction, whether or not they undergo PCI."

MASS COMM: Elective PCI safely performed without surgical back-up

Results: The MASS COMM study showed that nonemergent PCI can be safely performed in community hospitals without on-site cardiac surgery, with Massachusetts investigators reporting that there was no difference in major adverse cardiac events (MACE) at 30 days and 12 months when these patients were compared with those treated at hospitals with surgical capability.

"We know that emergency coronary bypass surgery following PCI has become a rare event," said lead investigator Dr. Alice Jacobs (Boston University School of Medicine, Boston, Massachusetts). "So it raises the question of whether cardiac surgery on site is still necessary for the safe and effective performance of PCI. Moreover, the need for timely access to primary PCI has justified the expansion of PCI to hospitals without on-site cardiac surgery, but controversy exists as to whether there should be a further expansion for nonemergent PCI to these hospitals where the risk-benefit ratio might be different and the need for timely access is less important to cardiovascular outcomes."

For more information:

Complete ACC news coverage on Medscape

ACC 2013 Scientific Sessions

American College of Cardiology