Limited role and benefit of ivabradine in the treatment of angina and heart failure with reduced ejection fraction.

Ivabradine is an original drug that has been approved in two indications (systolic heart failure and angina). The aim of this short review is to draw the attention of clinician prescribers to the evidence base of ivabradine. Three large randomized trials testing ivabradine versus placebo have been performed. The BEAUTIFUL and SIGNIFY trials were in fact negative in the treatment of angina while the SHIFT trial found a marginal benefit of ivabradine over placebo in the treatment of heart failure. These important results are put into perspective in order to improve the assessment of risk-cost/benefit balances when ivabradine is considered. Ideally, a further clinical trial investigating the use of ivabradine in heart failure should be carried out with optimal treatment of the patient population in order to identify the subgroup of patients who respond to ivabradine.

What does it take to create a European Health Data Space? International commitments and national realities.

Public health concerns in Europe demonstrate the necessity of building a health policy that could contribute to the long-term sustainable development of the European Union (EU), as stated in the European Health Union (EHU) manifesto. The main desire to create an EHU is embodied in the launch of the European Health Data Space (EHDS). The EHDS seeks to foster a genuine single market for digital health services and products by, among other things, accelerating the uptake and implementation of harmonised and interoperable electronic health record (EHR) systems across the EU. In the context of primary and secondary use of EHR data, developments in Europe have thus far resulted in patchy and, in some places, non-interoperable solutions. Taking the gap between international ambitions and national realities as a starting point, this paper contends that both EU level and Member State level circumstances should be considered to make the EHDS a reality.

Outcome postponement as a potential patient centred measure of therapeutic benefit: examples in cardiovascular medicine.

Background: The impact of randomised controlled trials (RCTs) depends heavily on the presentation of the findings.Objective: Classically, RCT findings are presented in the form of absolute risk reduction (ARR), number needed to treat (NNT) to prevent one adverse outcome, and relative risk reduction (RRR) or hazard ratio (the most favourable means for drug marketing). However, the estimation of average survival gain (i.e. outcome postponement between a trial intervention and comparator) is an alternative and informative means of presenting the findings of RCTs.Study selection: Recent cardiovascular RCTs evaluating ezetimibe added to simvastatin, evolocumab, canakinumab, ticagrelor, rivaroxaban, ivabradine, LCZ 696 (sacubitril/valsartan), and transfemoral aortic valve replacement are analysed and discussed.Findings: The average survival gains ranged between 4.9 days on a composite end point with ticagrelor versus clopidogrel in randomised patients with acute coronary syndrome and 117 days of life expectancy obtained with TAVR versus standard therapy in patients with severe aortic stenosis deemed ineligible for surgery.Conclusions: Using outcome postponement as an additional measure of treatment effect is likely to be more easily understood than hazard ratio or RRR by both patients and physicians and could help when evaluating drugs.

From evidence-based medicine to personalized medicine, with particular emphasis on drug-safety monitoring.

Nowadays, guidelines are derived from the findings of randomized controlled therapeutic trials. However, an overall significant P value does not exclude that some patients may be harmed by or will not respond to the therapeutic agent being studied. Trials in patients with a low risk of events and/or a limited chance of providing significant differences in therapeutic effects require a large patient population to demonstrate a beneficial effect. Composite efficacy endpoints are often employed to obviate the need for a large patient population when low rates of events or limited therapeutic efficacy are anticipated. Results of randomized controlled therapeutic trials are commonly expressed in terms of relative risk reduction, whereas absolute risk reduction allows the calculation of the "number needed to treat" to prevent an adverse outcome. The number needed to treat is a far more clinically relevant variable than relative risk reduction. The clinician's mission is to match treatment to patient with the goal of achieving optimal therapeutic response. Drug-safety monitoring is also of major importance to avoid exposing patients to irreversible adverse effects. Unfortunately, drug-safety monitoring is often overlooked in routine clinical practice. Finally, the lack of long-term therapeutic data (>5-10 years) is an unsolved dilemma, as most trials are limited to a duration of a few months or years.