LIVE: Late-breaker coverage from STREAM, VISTA-16, ERASE and CORAL

DALLAS — Healio.com/Cardiology is reporting live from Late Breaking Clinical Trials session number 4, which focuses on therapeutic advances in coronary and peripheral vascular disease.

5:12 p.m. Session concludes.

5:11 p.m.  Panel discussed patients lost to follow-up. Cooper responded: I am delighted to say that the rate of loss to follow-up was very low.

5:08 p.m. Cooper: We will have pressure gradient data we will analyze. This issue about hemodynamic significance should be addressable.

5:07 p.m. Cooper: During CORAL, design had diverse group of investigators in a room debating what the inclusion criteria should be. Based on that discussion is how the CORAL criteria were created.

5:07 p.m. Panel discussed CORAL data.

5:04 p.m. Zeller: Determination of significance of RAS is not trivial.

5:03 p.m. Zeller: Major flaw of study is liberal inclusion criteria regarding severity of renal artery stenosis.

5:02 p.m. Zeller: I congratulate the investigators having been able to finish the trial despite publication of ASTRAL trial at the beginning of enrollment of this trial.

5:01 p.m. Thomas Zeller, MD, of Bad Krozingen, Germany, discussed the CORAL findings.

4:59 p.m. In conclusion, renal artery stenting did not confer a benefit to the prevention of clinical events when added to comprehensive multifactorial medical therapy.

4:58 p.m. Cooper: Early after randomization by 3 months, we achieved significant reductions in systolic BP. We noted a consistent, significant reduction in BP favoring the stent arm, about 2.5 mm Hg. That difference in BP did not translate into difference in clinical events.

Primary endpoint: First major CV or renal event at 3 years (stent plus medical therapy, 35.1%; medical therapy, 35.8%; HR=0.94; 95% CI, 0.76-1.17; P=.58). Stenting when added to medical therapy did not reduce the rate of clinical events. No difference in CV or renal death; stroke; MI; occurrence of hospitalization for HF; progressive renal insufficiency; or need for renal replacement therapy. Data were consistent across all subgroups.

4:57 p.m. Cooper: Periprocedural clinical complications infrequent. No patient required dialysis within 30 days of randomization. One stroke occurred resulting in death on the day of randomization in medical therapy group.

4:56 p.m. Results of stent treatment by angiographic core lab stenosis: stenosis reduced to about 16%. Stenting was also relatively safe.

4:55 p.m. Cooper: No significant differences in clinical and angiography characteristics. Approximately 20% had global ischemia. Stenosis severity was similar to FDA-approved trials.

4:53 p.m. Cooper: 5,322 patients screened; 947 randomized. Stent plus medical therapy (n=467); medical therapy only (n =480).

4:50 p.m. Cooper: CORAL was an open label, randomized, international, multicenter, controlled clinical trial that enrolled people with atherosclerotic RAS and elevated BP or CKD. Inclusion criteria included hypertension with two or more antihypertensive medications and renal dysfunction defined as stage 3 or greater CKD as well as renal artery stenosis. Primary endpoint analyzed as time to the first primary endpoint event on an intent-to-treat basis. Sixteen participants were excluded from a single site, where scientific issues identified and the data was administratively withdrawn. Sample size selected to provide 90% power to test hypothesis that stenting reduced the incidence of the primary endpoint by 25%.

4:49 p.m. Christopher J. Cooper, MD, professor and chairman of the department of medicine at University of Toledo, presented results of the randomized, multicenter CORAL study.

4:45 p.m. Fakhry responds: More patients in the combination therapy group did not require secondary interventions during follow-up (92% vs. 77%).

4:44 p.m. McDermott: Most people in the United States do not have access to supervised exercise. Medical insurance does not pay for supervised exercise and frequent travel to supervised exercise is burdensome for the elderly. Future studies should identify exercise programs for PAD that overcome these barriers.

4:41 p.m. McDermott: Treadmill walking outcome has limitations. Six-minute walk is a more objective measure. AHA/ACC clinical practice guidelines recommend supervised treadmill exercise three times per week. Dose of exercise in ERASE is less than that currently recommended by clinical practice guidelines.

4:39 p.m. Mary McGrae McDermott, MD, professor of medicine and preventive medicine at Northwestern University Feinberg School of Medicine, discussed the ERASE data in detail.

4:38 p.m. To summarize, in patients with intermittent claudication combination therapy significantly improved functional performance and quality of life compared with standard of care of supervised exercise only.

4:38 p.m. Fakhry: A cost-effectiveness analysis is planned.

4:38 p.m. Pain-free walking distance was another endpoint: Combination therapy group able to walk 408 meters further.

4:37 p.m. Maximum walking distance was the primary endpoint: Mean difference at 12 months was 282 meters favoring the combination therapy group (P<.001).

4:36 p.m. Average of 30 sessions in SET group; 44% followed more than 26 sessions.

4:35 p.m. Fakhry: Follow-up at 1, 6 and 12 months. Deaths: SET, three; EVR-SET, one.

4:33 p.m. Patients’ average age was 65 years. 106 patients assigned combination therapy and 106 assigned supervised exercise therapy only. Primary endpoint was maximum walking distance, assessed on graded treadmill test.

4:32 p.m. ERASE trial goal was to compare the clinical effectiveness of endovascular revascularization plus supervised exercise therapy (EVR-SET) vs. standard care of SET only in patients with intermittent claudication.

4:30 p.m. Fakhry: Combination therapy of endovascular revascularization and exercise is promising. Supervised exercise therapy is first-line treatment. Endovascular revascularization is increasingly performed.

4:29 p.m. Farzin Fakhry, a PhD candidate at Erasmus Medical Center in The Netherlands, provided audience with findings from the ERASE trial.

4:28 p.m. Nicholls: I don’t think this compound has a future.

4:26 p.m. Nicholls: Patients who received varespladib were significantly more likely to have a recurrent MI (3.4%) than those who received placebo (2.2 %).

4:23 p.m. Steg: Two trials of darapladib ongoing. One week ago, it was announced that one of these trials, STABILITY, did not reach primary endpoint. More information forthcoming.

4:23 p.m. Steg: Does this trial have implications of Lp-PLA2 inhibition trial with darapladib?

4:23 p.m. Steg: Can’t definitively conclude on mechanism for increased risk of MI.

4:22 p.m. Steg: Delayed access to the data from the sponsor and the incomplete ascertainment of the 6-month data.

4:22 p.m. Steg: The trial may have been underpowered or undersized.

4:22 p.m. Steg: Power of study was 80%.

4:22 p.m. Steg: This was an ambitious trial.

4:21 p.m. Discussant Steg: Premature discontinuation was justified.

4:20 p.m. P. Gabriel Steg of Hôpital Bichat, Paris, served as a discussant for VISTA-16.

4:20 p.m. In March 2012, a prespecified interim analysis including 212 or 55% of the projected primary endpoint events, the Data and Safety Monitoring Board recommended termination of the trial. Despite being prespecified by the protocol, the sponsor collected 6-month survival data in only 31% of patients.

4:18 p.m. Nicholls: More varespladib patients discontinued study drug due to adverse events.

4:16 p.m. 66% increased risk of MI with varespladib.

4:15 p.m. Primary endpoint occurred in 5.1% of placebo vs. 6.1% in varespladib group. Difference did not meet statistical significance (P=.08). Secondary efficacy endpoints: Greater rate of CV death, MI, stroke were observed in the varespladib group.

4:15 p.m. Nicholls: Primary outcome was composite CV death, nonfatal MI, nonfatal stroke and hospitalization for unstable angina.

4:13 p.m. Nicholls: 5,391 patients screened and 5,145 patients treated at 353 centers in Europe, Australia, New Zealand, India and North America. Patients had one additional risk factor for adverse CV events and were randomly assigned to varespladib 500 mg daily or matching placebo for 16 weeks in addition to atorvastatin and established medical therapies.

4:11 p.m. Nicholls: The impact of varespladib on CV events is not known. VISTA-16 included 6,500 patients within 96 hours of an ACS. Objective was to determine effect of varespladib on CV outcomes in patients treated for the first 16 weeks following an ACS.

4:11 p.m. Nicholls: Secretory phospholipase A2 is a circulating family of enzymes which generates bioactive lipid species implicated in inflammatory pathways. Study examined varespladib.

4:11 p.m. Nicholls: Despite current evidenced-based treatment, CV risk remains high following ACS.

4:10 p.m. Stephen J. Nicholls, MBBS, PhD, deputy director of the South Australian Health and Medical Research Institute in Adelaide, Australia, reported new data from the VISTA-16 study.

4:09 p.m. Panelist: The greatest need of pharmaco-invasive treatment is in the developing world.

4:08 p.m. Sinnaeve: Cardiac death at 1 year was 4% with pharmaco-invasive strategy vs. 4.1% with primary PCI (P=.93)

4:08 p.m. Sinnaeve: Primary combined endpoint was 14.3% with primary PCI vs. 12.4% with pharmaco-invasive strategy (P=.21)

4:05 p.m. Sinnaeve: STREAM 1-year results should change the guidelines. They support the emphasis of primary PCI. But primary PCI is not possible everywhere in the world due to distance, infrastructure and finances. This supports use of pharmaco-invasive or pharmalytic therapy in a large proportion of patients presenting with STEMI.

4:03 p.m. Dauerman: In summary, the STREAM protocol amendment should have an immediate impact on STEMI algorithms. And it is reasonable to use a half-dose of fibrinolysis.

4:00 p.m. Dauerman: Overall conclusion of the trial was that a pharmaco-invasive strategy is similar to a primary PCI strategy for STEMI PCI.

3:58 p.m. Dauerman: Intracranial bleeding was higher with pharmaco-invasive strategy (P=.03)

3:57 p.m. Harold L. Dauerman, MD, professor of medicine at University of Vermont College of Medicine, provided discussion of the STREAM data.

3:57 p.m. Sinnaeve: All-cause mortality and cardiac morality at 1 year were similar irrespective of the treatment strategy. After the amendment mortality rates in both arms converged. While the amendment likely played a role, we cannot exclude the play of chance. Taken together these 1-year results indicate that the pharmaco-invasive strategy used the trial were similar to primary PCI.

3:56 p.m. All-cause and cardiac mortality at 1 year similar irrespective of treatment strategy.

3:54 p.m. 6.7% rate in pharmaco-invasive group vs. 5.9% in primary PCI group (RR=1.13; 95% CI, 0.77-1.67).

3:52 p.m. Sinnaeve: 6.7% death in the pharmaco-invasive group at 1 year vs. 5.9% rate in the primary PCI group.

3:51 p.m. Pharmaco-invasive group group had a higher rate of hemorrhagic stroke vs. the primary PCI group.

3:49 p.m. Sinnaeve: One-year results of the STREAM trial. STREAM patients were randomized to primary PCI or pharmaco-invasive strategies. Also targeted patients 3 hours after symptoms onset.

3:46 p.m. Peter Sinnaeve, MD, PhD, assistant professor of cardiology at University of Leuven in Belgium, presented 1-year results of the STREAM trial.

3:45 p.m. Session begins. John J. Harold and Mark A. Creager are moderating. Harold opens session.

– by Katie Kalvaitis, Joan-Marie Stiglich and Melissa Foster