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Our goal is to reduce the burden in cardiovascular disease in Europe through percutaneous cardiovascular interventions.
Our Mission is "to improve the quality of life of the population by reducing the impact of cardiac rhythm disturbances and reduce sudden cardiac death"
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OUR MISSION: TO REDUCE THE BURDEN OF CARDIOVASCULAR DISEASE
Dr. Simon Gibbs,
Clinicians who treat pulmonary arterial hypertension (PAH) are turning to combining disease-targeted therapies when monotherapy fails to improve their patients or deterioration occurs, despite the fact that combination therapy is not fully tested. Notwithstanding the scientific rationale for combination therapy in PAH and the increasing use of combination therapy in clinical practice, clinical trials remain a step behind.
PAH is a lethal disease. Proliferation within the pulmonary arterial wall causing luminal obstruction is a fundamental feature of all forms of PAH. This leads to a rise in pulmonary vascular resistance and hence pulmonary hypertension. This proliferative phenotype is a consequence of numerous changes which include alterations in endothelin, serotonin, growth factors, ion channels and the TGFbeta superfamily which governs apoptosis. Professor Lewis Rubin argued that it is unlikely that any one of these pathways will turn out to be of over-riding importance. Treating PAH requires targeting multiple pathways.
At present combinations of endothelin receptor antagonists, phosphodiesterase inhibitors and prostanoids are used. Of 3 randomised controlled trials presented, one (BREATHE-2 with 33 patients) had a negative outcome and two (STEP-1 with 67 patients and PACES-1 with 267 patients) have demonstrated beneficial outcomes.
The limited evidence for combination therapy comes as a major challenge for revising the ESC guidelines for PAH. Professor Nazzareno Galie emphasised the need for a better definition of disease severity than NYHA functional class, and for a well-designed follow-up strategy for patients on therapy.
Combination therapy can be expected to become the standard of care in the future but there are many hurdles to overcome: What are the best molecular targets? When should combination therapy be started? Can the first drug be withdrawn after the second drug is started? Can combination therapy improve cost-effectiveness? While we await the results of more trials, those who fund healthcare in many European countries remain reluctant to pay for a combination of drugs which are already individually expensive. Therein lies another costly challenge!
Modern therapy in pulmonary arterial hypertension Symposium
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