AHA 2013: Mix of Positive, Negative Trials Help Guide Interventional Practice

Findings from a record number of late-breaking trials presented at the American Heart Association Scientific Sessions in Dallas, TX, November 16-20, 2013, provided a wealth of new information for attendees to digest and translate into clinical practice. 

As important as the clinical trial results, said Robert A Harrington, MD, of Stanford University School of Medicine (Stanford, CA), in an interview with TCTMD, was publication of a series of updated cardiovascular prevention guidelines timed to coincide with the meeting. “The message the guideline writers are trying to get through to the cardiovascular community is: We now really need to focus on patient risk and not just on individual factors like cholesterol,” he observed.

Revascularization: RAS No, PAD Yes

From an interventional standpoint, the renal stenting trial CORAL was “really important news,” Dr. Harrington said. “It took a long time to get done, and during that time [clinicians] were doing renal stenting with the hope that it would not just improve hypertension but perhaps even reduce the risk of developing chronic kidney disease. Well, in a very well done trial, we didn’t see that.”

In the study, led by Christopher J. Cooper, MD, of the University of Toledo (Toledo, OH), 947 patients with renal artery stenosis and either refractory systolic hypertension or chronic kidney disease were randomized to medical therapy with or without renal stenting. After a median follow-up of 43 months, the rates of a composite of death from cardiovascular or renal causes, MI, stroke, hospitalization for CHF, progressive renal insufficiency, or need for renal-replacement therapy (primary endpoint) were nearly identical for the stenting and nonstenting groups (35.1% vs. 35.8%; P = 0.58), although systolic BP was modestly reduced by stenting.

Another trial that, although small, may have an impact on practice, Dr. Harrington commented, is ERASE, in which 212 PAD patients with intermittent claudication were randomized to supervised exercise with or without endovascular revascularization. At 1, 3, and 12 months, the revascularized group was able to walk farther and with less pain than the exercise-alone group. “You get an early bump in improvement with the addition of revascularization,” said Dr. Harrington, “although that difference diminished somewhat over the course of a year, probably as people continue to exercise. That’s a good practical piece of data. If you have a patient able and willing to embark on an exercise training program and they have disease amenable to revascularization, [adding exercise] may be a reasonable thing to do to provide additional relief.”

Hypothermia Protocols Fail to Improve Cardiac Outcomes

Two studies of hypothermia for patients who survive cardiac arrest were also very important, Dr. Harrington said, in part because they demonstrate that large-scale trials can be accomplished in this population. “That’s a powerful message,” he observed. “A lot of decision making and health policy dealing with resuscitated patients [has been] based on relatively small numbers. Here we have 2 much larger, multicenter trials.”

One study asked whether rapid cooling by EMS personnel alters outcomes compared with waiting until hospital arrival. Investigators at the University of Washington (Seattle, WA) randomized 1,359 patients resuscitated after cardiac arrest to standard care with or without hypothermia as soon as possible after return of spontaneous circulation. Early intervention reduced the time to achieve a temperature of less than 34º C by about 1 hour. Nonetheless, rates of survival to hospital discharge and neurological status were similar between the study and control groups regardless of whether or not patients had experienced ventricular fibrillation (V-fib; table 1).

Table 1. Survival, Neurological Status at Hospital Discharge

 

Early Cooling
(n = 688)

Standard Care
(n = 671)

P Value

Survival to Hospital Discharge
V-fib
No V-fib

 
62.7%
19.2%

 
64.3%
16.3%

 
0.69
0.30

Full Neurological Recovery/Mild Impairment
V-fib
No V-fib

 
57.5%
14.4%

 
61.9%
13.4%

 
0.69
0.30


Dr. Harrington noted that early cooling not only did not improve survival but also worsened some outcomes, including heart failure, as indicated by greater use of diuretics in the early cooling group in the first 12 to 48 hours after hospital arrival (P = 0.01). “A large volume of saline was infused rapidly, and maybe other methods of out-of-hospital cooling would be beneficial,” he commented. “But at the current time, it doesn’t look like changing our EMS [protocol], at least by this mechanism, is beneficial.”

The second trial addressed the important question of what temperature to target with hypothermia. For the multicenter TTM trial, researchers led by Niklas Nielsen, MD, PhD, of Helsingborg Hospital (Helsingborg, Sweden), randomized 950 patients who were unconscious after out-of-hospital cardiac arrest to cooling to either 33º C or 36º C. After 180 days, there was no difference in mortality or neurological function between the 2 groups, and serious adverse events trended higher in patients cooled to the lower temperature (table 2).

 Table 2. Clinical Outcomes at 180 Days by Degree of Hypothermia

 

33º C
(n = 473)

36º C
(n = 466)

P Value

Mortality

50%

48%

0.51

Neurological Functiona

52%

52%

0.87

Serious Adverse Events

93%

90%

0.09

a Modified Rankin scale score 4-6.

Dr. Harrington emphasized that the current study “by no means refutes the notion that cooling in general is an important part of the treatment for this group of patients.” Holding patients at around 36º C is normal practice, he observed, because many patients develop febrile episodes after arrest, and in earlier studies, temperature started to rise to close to 38º C in uncooled patients.

‘Real World’ FFR-Guided Revascularization Safe

Results from the French FFR registry, R3F, presented by Eric Van Belle, MD, PhD, of Hôpital Cardiologique (Lille, France), are consistent with randomized data, Dr. Harrington observed. In the study, among 1,075 patients undergoing angiography, subsequent FFR led to reclassification of ischemic status and change in treatment strategy (medical therapy or revascularization) in 43% of cases. Yet at 1 year there was no difference in MACE rates between patients who were or were not reclassified (11.2% and 11.9%, respectively; P = 0.78).

While lauding FFR as an invaluable technology that enables more specific targeting of lesions that warrant revascularization, Dr. Harrington remarked that for him, a more interesting question is whether, as the technology moves toward incorporation into cardiac CT, FFR will offer a noninvasive way to determine ischemic burden.

Cell Therapy: Small Steps

Several presentations focused on cell therapy for patients with ischemic cardiomyopathy, an area that Dr. Harrington characterized as marked by small trials and a mix of promising and neutral results.

For example, a pilot trial tested the hypothesis that CD34+ bone marrow cells would be especially effective in inducing vascularization. But after injecting CD34+, CD34-, and bone marrow mononuclear cells as well as saline into separate areas of ischemic myocardium in 6 patients undergoing LVAD implantation, the investigators found no difference in endothelial density as a marker of vascular genesis.

In another study involving LVAD recipients, 30 patients were randomized 2:1 to intramyocardial injection of autologous mesenchymal precursor cells or a control medium. At 90 days there were no primary safety events, and half of study treatment patients tolerated temporary weaning from the LVAD compared with 20% of controls. According to lead researcher Debora D. Ascheim, MD, of Mount Sinai School of Medicine (New York, NY), mesenchymal precursor cells have many potential advantages for cell therapy, including off-the-shelf availability and possible immunologic privilege.

In the TAC-HFT trial, 65 patients with LV dysfunction were divided into 2 groups, 1 randomized to injection with autologous mesenchymal stem cells or placebo and the other to bone marrow mononuclear cells or placebo. There were no primary safety events over the first 90 days. At 1 year, patients who received either cell therapy experienced improvements in quality of life, while placebo-treated patients did not.

For the TIME trial, 120 patients who underwent primary PCI were given intracoronary infusions of autologous bone marrow cells or placebo. One group was treated at 3 days and the other at 7 days after STEMI. Cell therapy did not enhance recovery of LV function at either time point.

“Cell therapy research is headed in the right direction,” Dr. Harrington commented, “but there is still much work to be done.”

New Data on a Variety of Issues

Other studies of interest to the interventional community included:

  • CTSN SMR: Mitral valve repair resulted in 1-year rates of survival and LV reverse remodeling similar to those of valve replacement in patients with ischemic regurgitation, although replacement provided more durable correction of regurgitation.
  • STREAM: For STEMI patients, a strategy of prehospital fibrinolysis followed by timely angiography continued to show survival rates similar to primary PCI at 1 year.
  • STS/ACC TVT Registry: ‘Real world’ use of the transcatheter Edwards Sapien valve in 7,710 US patients with severe aortic stenosis showed safety and efficacy comparable to randomized trials and the global TAVR experience.
  • Symplicity HTN-2: Substantial reductions in systolic BP in refractory hypertension patients who underwent renal denervation persisted at 2 years and were matched by similar declines in control patients who crossed over to the procedure at 6 months.
  • RADAR-AF: In patients with paroxysmal A-fib, high-frequency source ablation of arrthythmia drivers did not show noninferiority to circumferential pulmonary vein isolation in terms of freedom from A-fib at 6 months, although it did achieve that status at 1 year. In patients with persistent A-fib, high-frequency source ablation did not add incremental benefit to circumferential pulmonary vein isolation alone and was associated with an increase in serious adverse events.
  • PROVE-IT-TIMI 22/A-to-Z: In ACS patients, high-potency statin therapy does not raise serum creatinine or the risk of kidney injury compared with a modest statin regimen, according to a pooled analysis of these 2 large randomized trials.
     


Sources:
Presentations at the American Heart Association Scientific Sessions; November 16-20, 2013; Dallas, TX.

 

 

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AHA 2013: Mix of Positive, Negative Trials Help Guide Interventional Practice

Findings from a record number of late-breaking trials presented at the American Heart Association Scientific Sessions in Dallas, TX, November 16-20, 2013, provided a wealth of new information for attendees to digest and translate into clinical practice.  As
Disclosures
  • Dr. Harrington reports no relevant conflicts of interest.

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