ESC Congress 2015: Presentations Sift Clinical Wheat From Chaff
LONDON, England—Last week’s European Society of Cardiology (ESC) Congress, held August 29 through September 2, 2015, featured a wealth of findings that are likely to influence cardiologists’ everyday decision making. Studies offered insight into which patients need urgent revascularization and which none at all, what medications can be safely prescribed for diabetics, and when the duration of dual antiplatelet therapy should be individualized.
Overall, the studies showed mixed results, with many failing to prove their hypotheses. But as Spencer B. King III, MD, of Emory University School of Medicine (Atlanta, GA), editor-in-chief of JACC: Cardiovascular Interventions, reminded in an on-site interview with TCTMD, “The value of negative trials is often underappreciated. It’s just as valuable to know what we shouldn’t be doing as it is to find out what we should be doing.”
Hits, Misses for MI Management
Two presentations assessed the potential role of high-sensitivity troponin in evaluating symptomatic patients. In the BACC study, an algorithm based on troponin I safely ruled out acute MI within 1 hour of patient presentation vs the ESC guideline-recommended 3 hours. In addition, data from the SWEDEHEART registry showed that adoption of a troponin T assay for triaging patients with suspected ACS did not lead to overuse of diagnostic procedures and treatments.
High-sensitivity troponin “looks pretty accurate” and should be very useful in busy emergency departments—if it is approved and reimbursed, Dr. King commented. However, “it will be important for physicians to use it to rule out an acute event but not to rule out heart disease,” he cautioned.
In what may mark the end of a proposed adjunctive therapy, the multicenter PRomPT trial found that pacing of the peri-infarct zone in patients with a large MI does not attenuate cardiac remodeling or improve quality of life. And in the randomized, controlled PRESERVATION I trial, use of a novel bioabsorbable cardiac matrix (Bellerophon Therapeutics; Hampton, NJ) did not prevent LV remodeling in patients with large infarcts.
Additionally, several drugs failed to live up to their early hope for alleviating the impact of MI. In the randomized ALBATROSS study, aldosterone antagonists provided no benefit for acute MI patients without heart failure, although a survival advantage was seen in the STEMI subgroup. Meanwhile, in the randomized CIRCUS trial, administration of cyclosporine—hypothesized to protect against reperfusion injury—before revascularization did not improve outcomes in patients with anterior STEMI. Moreover, data from the ATLANTIC trial showed that giving ticagrelor (Brilinta; AstraZeneca) to STEMI patients en route to the hospital does not reduce ischemic events in the 24 hours after primary PCI.
Novel Drugs Safe for Diabetics
New analyses of randomized trials offered reassurance about the cardiac safety of 2 novel glucose-lowering drugs. A substudy of the ELIXA trial extended previous findings by showing no adverse impact of lixisenatide (Lyxumia; Sanofi) on MACE or heart failure among type-2 diabetics with a history of ACS. Similarly, a subanalysis of the TECOS trial found that adding sitagliptin (Januvia; Merck) to usual diabetes care does not increase the risk of recurrent hospitalization among patients with heart failure.
Sitagliptin’s safety is reassuring in light of previous trials suggesting substantial cardiac side effects for some glucose-lowering drugs, said former American College of Cardiology President W. Douglas Weaver, MD, of Henry Ford Hospital (Detroit, MI), in an on-site interview with TCTMD. Other drugs of the same class will likely need similar safety trials, and “that’s an awesome job,” he noted, adding that Europe has been “smarter” by allowing postmarketing safety studies.
In addition, a subanalysis of the IMPROVE-IT trial showed that adding the novel cholesterol-lowering drug ezetimibe (Zetia; Merck) to statins reduces LDL and improves outcomes better in diabetics than in nondiabetics. Another analysis from the same trial in patients with new-onset diabetes failed to show the same advantage, although use of ezetimibe was safe.
The combination of statins and ezetimibe “certainly makes sense in a high-risk population,” and is also appropriate for nondiabetics, said Dr. Weaver, who suggested that the PCSK9 drugs might be even more potent.
Finally, a substudy of the FREEDOM trial comparing revascularization strategies in diabetics with multivessel disease found that CABG held an edge over PCI primarily among patients with moderately elevated blood pressure (140-160 mm Hg), with no difference between the approaches for those with higher or lower levels. The findings prompted the presenter to suggest that recommendations to target blood pressure below 140 mm Hg should be tailored to the mode of revascularization.
Bioresorbable Scaffolds Show Progress
Two presentations added to the evidentiary momentum behind the everolimus-eluting Absorb BVS bioresorbable scaffold ( Abbott Vascular). In the randomized ABSORB Japan trial involving ischemic patients, the scaffold proved noninferior to second-generation metallic EES for target lesion failure (cardiac death, target vessel MI, or ischemia-driven TLR) at 1 year. In ABSORB TROFI II, it matched EES in STEMI patients, showing noninferior arterial healing at 6 months.
New Data on FFR
The survival benefit of FFR vs angiographic guidance in patients with multivessel disease undergoing PCI with DES holds up long term, according 5-year follow-up of FAME.
“The FAME trial changed the way we do things—treating only the lesions that need treating,” Dr. King said, noting that the key finding here is the absence of late catchup for FFR. But he cautioned against becoming “addicted” to FFR results. Just because a patient has a negative FFR, “that isn’t necessarily the end of the story” with regard to evaluation of stable ischemic heart disease, he remarked.
In the randomized PLATFORM study, CT-based FFR (HeartFlow; Redwood City, CA) compared with invasive angiography substantially reduced the likelihood of finding obstructive CAD among intermediate-risk patients with chest pain and no history of CAD who were scheduled for an invasive strategy. As a result, invasive procedures were cancelled in 61% of patients, with no adverse effects.
Mixed DAPT Results Suggest Need to Customize Duration
Three trials added intriguing new data to the vexed issue of the optimal duration of dual antiplatelet therapy.
In the multicenter OPTIDUAL trial, 1,385 patients who were free of MACCE and bleeding 1 year after DES implantation were randomized to DAPT continuation or aspirin only for the next 36 months. At follow-up, there were no differences between the arms in either ischemic or bleeding events, leading the presenter to conclude that the length of dual antiplatelet therapy should be decided on a “case-by-case basis.”
OPTIDUAL showed “trends that [prolonged] DAPT was an advantage, while other small studies say with today’s stents you don’t need as much,” Dr. Weaver commented. “What we learned from the DAPT Study is that dual antiplatelet therapy was very effective not only at preventing stent thrombosis but also in preventing a lot of heart attacks that weren’t due to stent thrombosis…. So in my mind the wealth of evidence says, unless someone has bleeding and complications, it’s very reasonable from a prevention standpoint to continue them on dual treatment.”
In fact, meta-analysis of 33,435 patients with a history of MI culled from 6 trials showed that those who received DAPT beyond 1 year reaped lower rates of cardiovascular death, MI, or stroke than those on aspirin alone, albeit at the price of increased major bleeding. It is important to identify which “high-risk patients at low risk of bleeding” will benefit from prolonged dual therapy, the presenter concluded.
Meanwhile, a bit of reassurance came from DAPT Study data suggesting that the 0.5% higher rate of all-cause death among patients continuing thienopyridines beyond 12 months may be attributable to cancer rather than to bleeding. Moreover, the fact that at the time of enrollment cancer cases already trended higher in the continued dual antiplatelet arm suggests that the mortality difference could be a chance finding.
Additional reports provided insights into a variety of cardiovascular issues:
- In a Danish registry study, the CHA2DS2-VASc score appeared to predict the risk of ischemic stroke in heart failure patients regardless of whether they had A-fib.
- In 5-year follow-up of the EXAMINATION trial, second-generation EES remained superior to BMS for STEMI patients.
- A UK registry study suggested that lower hospital PCI volume does not adversely affect 30-day mortality.
- Data from RE-LY show that A-fib patients on warfarin or dabigatran (Pradaxa; Boehringer Ingelheim) are more likely to bleed and be hospitalized if they are also taking an nonsteroidal anti-inflammatory drug.
- According to the MATRIX Antithrombin study, in ACS patients undergoing PCI, bivalirudin (Angiomax; The Medicines Company) reduces major bleeding and mortality but not net adverse clinical events.
- In the EVEREST II REALISM registry study, patients treated with MitraClip (Abbott Vascular) achieved similar improvements in mitral regurgitation and quality of life regardless of whether they were at high surgical risk.
- A BASKET-PROVE II subanalysis showed that prasugrel (Effient; Eli Lilly/Daiichi Sankyo) does not increase major non-CABG-related bleeding in stable vs ACS patients or in comparison with clopidogrel in stable patients.
Presentations at: European Society of Cardiology Congress; August 30-September 2, 2015; London, England.
- ESC Congress 2014: Positive, Negative Findings Come on Background of Improving Outcomes Overall
- ESC Congress 2013: Mix of Trials with Potential to Reshape Practice
- ESC Congress 2012: Diverse Lineup of Practice-Changing Presentations