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2012 European HF Guidelines Cover New Ground: TAVI, Ivabradine Make Debuts

Steve Stiles*

May 21, 2012 (Belgrade, Serbia) — Four years and at least 19 major trials after its last such effort, the European Society of Cardiology (ESC) has unveiled new formal guidelines for the management of heart failure [1]. It gives sometimes-enthusiastic, sometimes-cautious seals of approval to a new treatment target, the inaugural appearances of some drugs, the rising status of others, and the mainstreaming of some devices after decades of development.

Compared with the ESC’s 2008 guidelines, the new document calls for “a more liberal use of mineralocorticoid-receptor antagonists” (MRAs)–that is, aldosterone antagonists–in heart failure using some of the strongest terms yet, observed Dr John JV McMurray (University of Glasgow, Scotland), who chaired the society’s guidelines-preparing task force. MRAs are now recommended for most patients who remain symptomatic despite treatment with both ACE inhibitors and beta blockers. “They really replace angiotensin-receptor blockers [ARBs] as one of the three pivotal neurohormonal blockers for almost all patients with symptomatic systolic heart failure.”

The 2012 guidelines were unveiled here at the Heart Failure Congress 2012 sessions of the ESC Heart Failure Association and simultaneously published online in the European Heart Journal.

McMurray told heartwire he was “pleasantly surprised” that there was little controversy at committee and document-reviewer discussions about the guidelines’ new recommendations for drug therapy. “There might have been, for example, some concern about our extrapolation a bit beyond the evidence for MRAs, because the new trial, EMPHASIS-HF, had fairly restrictive inclusion criteria.” It entered NYHA class 2 patients with an LVEF <35%.

“Our recommendation goes beyond the actual inclusion criteria for the trial. We felt that was justified because we’ve obviously now got three large studies with mineralocorticoid-receptor antagonists [also including EPHESUS and RALES] all showing improvement in survival, covering really the whole spectrum from postinfarction heart failure all the way to end-stage heart failure. So the reviewers seemed to accept that.”

The new document also gives new weight to heart-rate (HR) reduction as a specific treatment target by adding ivabradine (Procoralan, Servier) if the rate remains 70 bpm or higher despite triple-drug therapy: optimized beta blockers, ACE inhibitors, and MRAs. Ivabradine was approved in the European Union earlier this year but has yet to be decided by regulators in Canada and the US.

Guidelines reviewers had queries for the writing task force about why ivabradine entered the guidelines at such a prominent position, higher than digoxin, “which in some ways has broadly similar effects,” after only one major heart-failure trial, McMurray noted for heartwire. SHIFT entered patients in NYHA class 2–4 heart failure, an LVEF <35%, and a resting heart rate >70 bpm without atrial fibrillation and saw ivabradine associated with significant 18% to 26% declines in end points such as CV death and HF hospitalization.

Two reasons, he thinks: SHIFT “was done in the modern era of therapeutics, so ivabradine was added to an ACE inhibitor, added to a beta blocker, and added to a mineralocorticoid-receptor antagonist in the majority of patients. Second–there was an ivabradine trial in postinfarction patients with reduced systole function. That trial [BEAUTIFUL] did not show an improvement in outcome, but what it did do was give us an enormous safety data set in very similar patients: all with reduced systole function, all with coronary artery disease. So we felt we had a very good comfort level in terms of safety.”

Other Drug-Therapy Recommendations

Also in the new guidelines, according to Dr Aldo Pietro Maggioni (Italian Association of Hospital Cardiologists Research Center, Firenze, Italy), who formally presented the pharmacologic therapy recommendations: drugs that should not be given specifically for heart failure include statins and oral anticoagulants, except in patients with atrial fibrillation. Drugs that may actually be harmful in heart failure include thiazolidinediones and calcium-channel blockers that are negatively inotropic–that is, most of them.

In patients with atrial fibrillation, Maggioni said, “it is possible of course to use the new anticoagulants [oral direct thrombin inhibitors and oral factor Xa inhibitors] that now are available, but it’s very important to remember that these drugs are contraindicated in severe renal impairment–and a lot of patients with heart failure, as we know, have this condition.”

Cardiac Resynchronization Therapy (CRT)

“There is little doubt that patients expected to survive with good functional status for more than one year should receive CRT if they are in sinus rhythm, their LVEF is low (<30%), and QRS duration is markedly prolonged irrespective of symptom severity,” the guidelines document states.

Application to NYHA class 2 heart failure is what’s new since the last set of guidelines, based on the MADIT-CRT and RAFT trials, in addition to reduced certainty that CRT will benefit patients with a right-bundle-branch-block QRS morphology or atrial fibrillation, said Dr Kenneth Dickstein (University of Bergen, Stavanger University Hospital, Norway) when presenting the new guidelines.

They give a strong recommendation for CRT in patients with NYHA class 2 with a QRS duration >130 ms with a left-bundle-branch-block (LBBB) morphology and LVEF <30%. “And for non-LBBB morphology, we ask for a QRS width of >150 ms, and that gets a class IIa [‘should be considered’] recommendation,” Dickstein said.

Questions the clinician might want to ask when considering CRT in NYHA class 2 patients within the QRS-duration window of 120 ms to 150 ms, he noted: “Do you see strong convincing evidence of mechanical dyssynchrony with an imaging technique? Is there left ventricular dilatation? Is there left bundle branch block? Has the patient recently been more symptomatic?”

Ventricular Assist Devices, Other Surgery

As described at the presentation by Dr Stamatis Adamopoulos (Onassis Cardiac Surgery Center, Athens, Greece), recommendations for use of CABG in heart failure have broadened as a result of the STICH trial, which saw benefits from the surgery in patients with systolic heart failure but only mild angina. It didn’t lower the primary end point of all-cause mortality, Adamopoulos said, but there were significant effects on cardiovascular death and the composite of all-cause death/CV hospitalization.

Also, as a result of the PARTNER trials, transcatheter aortic-valve implantation (TAVI) enters the guidelines, although it is not deeply discussed. Nonetheless, as Adamopoulos noted, it “should be considered” in patients with aortic stenosis who aren’t appropriate candidates for conventional surgery.

And left ventricular assist devices (LVADs) have come of age since the 2008 guidelines, he observed, as smaller continuous-flow devices, exemplified by the HeartMate II, have since emerged. They are now “recommended” in patients who are also candidates for transplantation and have “should-be-considered” status for destination therapy.

The new document also embraces the idea that LVADs may be increasingly used in selected patients with less severe disease than end stage, “before right-ventricular or multiorgan failure develops,” Adamopoulos said.

“This is our prophesy, that the ventricular assist devices may ultimately become a more general alternative therapy to transplantation, because the current two- to three-year survival rates with continuous-flow devices seem superior not only to medical therapy but also to pulsatile-flow devices.”

Away With “Artificial” Recommendations

Another major difference between the new document and the 2008 guidelines, according to McMurray, is a much smaller presence of recommendations relating to lifestyle changes. “We decided that we probably had been artificially giving recommendations for lifestyle advice really on the basis of no good evidence. So with only two exceptions, you will not see in the new guidelines any recommendation in relation to lifestyle.”

The exceptions, both class IA recommendations: “Regular aerobic exercise is encouraged in patients with heart failure to improve functional capacity and symptoms,” and patients are advised to enroll in a “multidisciplinary-care management program” to lower the risk of heart-failure hospitalization.

For task-force member and reviewer disclosures, the guidelines document refers readers to www.escardio.org/guidelines.

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References

1. McMurray JJV, Adamopoulos S, Anker SD, et al. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur Heart J 2012; DOI:10.1093/eurheartj/ehs104. Available here.

Heartwire © 2012 Medscape, LLC

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*Steve Stiles

Steve Stiles is a journalist for Medscape. He has been reporting on cardiovascular medicine since 1984 and for the past 3 years has been a journalist for theheart.org, part of the WebMD Professional Network. Steve is a graduate of Kenyon College and has an MS from the journalism department at Boston University. He can be contacted at [email protected].