This year’s Cardiology Update focused on heart failure and the testing of new therapies for the acute form. However, there was also news in the area of lipid management in high-risk patients.
With 120,000 people affected in Switzerland alone, the disease has moved from being Cinderella to the center of cardiovascular disease. Demographic changes and therapies that allow us to grow old with heart disease indicate that the number of new diagnoses of 25000 cases per year in Switzerland will continue to increase.
Although great success has been achieved in the treatment of heart failure, the prognosis remains poor: 10% of those affected die within a year, and about 50% within five years. In recent years, progress has been made, especially in the field of non-drug therapies, such as device therapy (ICDs) and resynchronization therapy (CRT). The use of mechanical assist devices (VADs) in advanced heart failure is also becoming increasingly important.
For the first time, the current guidelines of the European Society of Cardiology (ESC) recommend the use of VADs, not only as a bridge to heart transplantation (Bridge to Transplantation), but also instead of heart transplantation (Class IIa, Level B) in highly selected patients due to the lack of transplantation [1]. In order to better meet the integrative therapy requirements, a new Center for Heart Failure has been established at the University Hospital Zurich. This will be part of the future heart center.
Serelaxin and Ularitide: new treatment options in acute heart failure.
A major problem in clinical practice is the treatment of acute heart failure. The disease is the most common reason for hospitalization in patients over 65 and is characterized by high mortality in addition to a high re-hospitalization rate.
There have been some setbacks in testing new drugs in recent years. Complicating matters further, there are no evidence-based guidelines for the management of acute heart failure. “The therapy recommendations are mainly based on expert opinions,” said Prof. Piotr Ponikowski, M.D., head of the Department of Cardiology at the Clinical Military Hospital Wroclav in Poland, at the press conference in Davos. There is general consensus that end-organ damage can be reduced by prompt initiation of treatment, which is beneficial to the prognosis of the disease.
With the results of the Pre-RELAX AHF and RELAX AHF trials [2, 3], data have now been shown for the first time that give hope for progress in the treatment of acute heart failure. The drug serelaxin (the recombinant form of human relaxin-2) studied in this study leads, among other things, to increased cardiac ejection fraction, a decrease in systemic vascular resistance, and an increase in renal blood flow.
The study results showed that early intravenous delivery (within 16 hours of hospitalization) of serelaxin persistently reduced the primary end point, dyspnea. Mortality was 37% lower in the Serelaxin group than in the placebo group six months after therapy. However, the re-hospitalization rate did not change with treatment. Since the study was not originally intended to examine mortality, the result should be viewed with caution, Prof. Ponikowski said.
The first study ever to investigate mortality in patients with acute heart failure in a prospective design is the newly launched Trial of Ularitide’s Efficacy and safety in patients with Acute Heart Failure (TRUE-AHF). The international, multicenter phase III study is designed to investigate whether the early use of urodilatin (Ularitide), a natriuretic peptide with a pronounced vasodilatory effect, can positively influence both the short-term symptoms and the long-term course of acute heart failure.
Lipid management in high-risk patients
News in the field of lipid management mainly concerned statin-supplementing therapies in high-risk cardiovascular patients. Available strategies include the use of ezetimibe (Ezetrol®) with the goal of further reducing LDL cholesterol by decreasing intestinal absorption. Whether this strategy also leads to improved cardiovascular outcomes is the subject of the IMPROVE-IT trial [4], the results of which are expected in 2014.
Another strategy is to increase HDL cholesterol by either nicotinic acid or CETP inhibitors. In conclusion, the increase in HDL-C shown in studies has not yet led to the hoped-for improvement in clinical outcome. For the time being, increased physical activity, abstinence from tobacco and a low-fat diet remain the only effective measures to positively influence HDL-C. The molecule PCSK9 represents an interesting new target in LDL therapy. Initial studies investigating an antibody against this molecule have shown a dramatic 60-70% reduction in LDL levels.
Spoilt for choice with the new anticoagulants
In Switzerland, three new anticoagulants, rivaroxaban (Xarelto®), dabigatran (Pradaxa®) and apixaban (Eliquis®), are approved for the treatment of thromboembolic events. The introduction of another substance in the next two years is considered likely. While these substances have been well studied in comparison with oral anticoagulants (OACs), it remains to be seen to what extent the effects of the three substances differ from each other and which is the best therapy in individual cases. “For a reliable assessment, the existing indirect comparisons are insufficient,” said Prof. John Camm, MD, of St.George’s Hospital in London. This would require large prospective comparative studies. “Until these are available, use must be based on practical considerations such as individual cardiovascular risk, patient age, renal function, and once- or twice-daily dosing.”
Source: Cardiology Update Davos, press conference on February 11, 2013.
Literature:
- McMurray JJ: ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012. Eur J Heart Fail 2012 Aug;14(8): 803-869.
- Teerlink JR, et al: Relaxin for the treatment of patients with acute heart failure (Pre-RELAX-AHF): a multicentre, randomised, placebo-controlled, parallel-group, dose-finding phase IIb study. Lancet 2009; 373 (9673): 1429-1439.
- Teerlink JR, et al; Serelaxin, recombinant human relaxin-2, for treatment of acute heart failure (RELAX-AHF): a randomised, placebo-controlled trial. Lancet 2013 Jan 5; 381 (9860): 29-39.
- Cannon CP, et al: Rationale and design of IMPROVE-IT (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial): comparison of ezetimbe/simvastatin versus simvastatin monotherapy on cardiovascular outcomes in patients with acute coronary syndromes. Am Heart J 2008 Nov; 156(5): 826-832.
