New research presented at last week’s European Society of Cardiology (ESC) Congress ranged from informative updates on innovative percutaneous procedures to results on the use of drugs or technology that foiled expectations and seemed to question conventional wisdom.

In a broad sense, the meeting was distinctive in that unlike many others, it included a number of trials with positive results, commented Ted Feldman, MD, of Evanston Hospital (Evanston, IL), in an interview with TCTMD. Moreover, several trials “will make us think about changing practice and may set us on the way to revising some guidelines.”

Possible STEMI Shake-up

The PRAMI trial, which randomized 465 STEMI patients with multivessel disease to primary PCI of the infarct-related vessel with or without immediate revascularization of other obstructed vessels, was halted early after complete revascularization showed a clear advantage for the primary endpoint of death, MI, and refractory angina.

At first glance, this seems like a “complete turnaround” from previous negative experience and contradicts current guidelines, Dr. Feldman noted. But a closer look shows that the randomized patients represent only a fraction of the STEMI pool at the investigators’ institutions, he pointed out. “I get the impression that these are highly selected patients, and it takes a lot of judgment to decide whether the additional vessel [intervention] is a plus [when weighed against the need for] a heavier contrast load,” he said. “We rarely know [a patient’s] renal function going into primary PCI, and the liability of the contrast load is great. Also, the potential for getting into a protracted procedure in a patient with compromised LVEF has to be carefully balanced against going after another vessel.” A large upcoming Canadian randomized trial should shed further light on this issue, he added.

Noting that even negative trials often help inform practice, Dr. Feldman cited findings from the TASTE trial. In this randomized study of more than 7,000 STEMI patents, routine manual thrombectomy did not reduce early mortality beyond the benefit provided by primary PCI. But importantly, thrombus aspiration did not cause harm, he noted, “so in my mind that relegates [thrombectomy] to an as-needed, operator-judgment procedure that we can now perform with greater confidence that there isn’t a downside.” Moreover, longer-term follow-up may yet show benefits such as improved LV recovery, he added.

Dr. Feldman noted that the study also created buzz with regard to its design, which integrated randomization into a comprehensive online registry. Randomized trials guide practice but are expensive, difficult to execute, and provide data on only a narrow slice of the patients, while registry studies are broader but carry multiple limitations, he said. “But this seems to be a little bit of the best of both worlds,” he said. “It is really a landmark for pioneering a new way to do randomized trials in a registry setting.”

Additionally, the IABP-SHOCK II trial appeared to undercut current guidelines with the finding that among patients undergoing early revascularization for MI complicated by cardiogenic shock, use of an intra-aortic balloon pump does not reduce mortality at 30 days (the primary endpoint) and yields similar mortality and quality of life at 1 year.

Optimizing Adjunctive Pharmacology

Other studies assessed the potential benefit of various adjunctive drugs in the PCI setting. For example, in the randomized PROMISE trial, early administration of intracoronary adenosine in STEMI patients improved functional recovery and reduced infarct mass in those with ischemic times below 200 minutes. And a meta-analysis of the CHAMPION trials suggested that IV cangrelor decreases ischemic events compared with clopidogrel at the cost of only mild bleeding.

The randomized ACCOAST trial explored prasugrel preloading in NSTE-ACS patients. The study was stopped early because the strategy not only failed to reduce ischemic events at 30 days but also increased major bleeding. According to Dr. Feldman, the negative finding is helpful insofar as “it reassures us that loading on the table at the time of PCI gives the same benefit as we might get from preloading—without [unnecessarily] exposing all the patients who might end up on medical therapy or going to surgery [instead of PCI].”

Updated results from the PARIS registry showed that the clinical impact of DAPT cessation on post-PCI patients varies depending on the reason for stopping. While the risk of MACE and stent thrombosis from unplanned disruption of therapy due to bleeding or noncompliance is substantial, brief, physician-guided interruption for surgery and simple discontinuation based on physician judgment are largely benign. A key message, Dr. Feldman said, is that “with our current knowledge base, [clinicians] generally make good decisions about stopping antiplatelet therapy.” However, he added, the fact that most thromboembolic events occurred while patients were on DAPT underlines the need for better antiplatelet therapy.

Exploring the Scope of the New Anticoagulants

Several studies provided data to help guide use of the new oral anticoagulants in a variety of high-risk patients and settings. For example, a subanalysis of the ROCKET AF trial focusing on A-fib patients who also have PAD showed that rates of stroke/systemic embolism as well as major or non-major clinically relevant bleeding were similar for rivaroxaban and warfarin. And in a substudy of the ARISTOTLE trial, apixaban was superior to warfarin for stroke protection as well as reduction of bleeding and all-cause mortality among A-fib patients who also have valvular heart disease. Meanwhile, in the Hokusai-VTE study the new oral factor Xa inhibitor edoxaban matched warfarin in efficacy while reducing major bleeding across a spectrum of patients with venous thromboembolism.

On a cautionary note, however, a dose-validation study comparing dabigatran vs. warfarin in patients with mechanical heart valves was halted prematurely when the new agent was linked with higher rates of stroke and major bleeding. This negative finding, though important, is probably not the end of the story, Dr. Feldman said, noting that about four-fifths of the patients were newly implanted and so likely presented a highly thrombotic milieu. Antithrombotic requirements may differ in the chronic setting, he added.

Meanwhile, the safety of a percutaneous option for stroke protection in A-fib patients was bolstered by pooled 5-year data (3,503 patient-years) from the PROTECT AF trial and Continued Access Protocol registry. Over time, patients whose LAA was closed with the Watchman device experienced progressively fewer procedure-related complications. 

Positive Data Grow for TAVR, Renal Denervation 

TAVR continued to gain ground as a post-hoc analysis from Cohort A of the PARTNER trial showed that the procedure is a safe and effective option for high-risk diabetic patients, reducing mortality compared with surgery without increasing stroke risk at 1 year. Meanwhile, data from the FRANCE 2 registry found that postprocedural aortic regurgitation is the strongest predictor of 1-year mortality.

Renal denervation as percutaneous therapy for treatment-resistant hypertension also moved forward. An update of the Symplicity HTN-1 trial showed persistent blood pressure reductions out to 3 years, while the Global Symplicity Registry confirmed the safety and efficacy of renal denervation in more than 1,000 real-world patients.

In addition, new data appeared to extend the clinical usefulness of functional ischemia testing to the field of surgery. In a registry study of patients with intermediate stenosis, adding FFR to angiography to guide CABG surgery was associated with fewer grafts and less use of on-pump procedures. 

Additional reports yielded the following results:

• At 6 months, RVX-208, a novel compound that induces synthesis of Apo-A1, failed to reduce atherosclerosis in CAD patients with low HDL more than placebo.
• In NSTE-ACS patients, the novel injectable anticoagulant otamixiban was no better than unfractionated heparin plus eptifibatide at protecting against postprocedural death or MI and doubled bleeding risk.
• The renin inhibitor aliskiren failed to stop atherosclerosis progression in prehypertensive patients with CAD, although it appeared to reduce 2-year MACE.
• Analysis of female patients of 26 randomized trials from 2002 to 2013 showed that DES (especially second-generation devices) are as safe as BMS.
• The biomarker copeptin can be safely used to manage low-to-intermediate risk chest pain patients who are troponin-negative.
• In comatose patients resuscitated after out-of-hospital cardiac arrest, emergency angiography and/or PCI in combination with therapeutic hypothermia proved feasible and safe.

Related Stories:

• ESC Congress 2012: Diverse Lineup of Practice-Changing Presentations
• ESC Congress 2011: Drugs, Devices Work Together
• ESC Congress 2010: Pharmacology Trials Take Center Stage