France
France (La France)
The French enter the NephroWorldCup confident that they can win. Why? The French are team taking direct aim at the achilles-heel of dialysis patients: the absence of high-quality medical care to reduce cardiovascular mortality (Table 1). Despite statins and other lipid-lowering medications, the overwhelming benefit in cardiovascular prevention seen in the non-dialysis population hasn't translated to patients in the spectrum of kidney disease (Figure 1).
Some argue that the type of lipid lowering agent may be irrelevant and that other factors mitigate their beneficial effects. Recently the notion that untreated hyperphosphatemia could play an instrumental role in minimizing the benefits of statin therapy in ESRD patients.
Figure 1: General principles of lipid management in CKD and ESRD patients | Presented at the Phillipine Society of Nephrology Conference | Courtesy of Dr. Edgar Lerma
It is no surprise, however, that the French have turned their attention from statins to a new agent: Icosapent Ethyl. Representing the France in the NephroWorldCup is the REDUCE-IT RENAL study. Researchers randomized 8179 patients with a median eGFR of 75 ml/min/1.73 square-meter, but it was the subgroup of patients with eGFR <60 ml/min who had the largest decrease in relative risk reduction. Compared to placebo, icosapent ethyl showed a 21.8% reduction in the composite primary outcome of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina (versus 28.9% in the placebo arm). That's a hazard ratio (HR) of 0.71 [95% CI, 0.59–0.85]; P=0.0002.
Audio 1: France's World Cup victory song in 2018
In fact, the reduction of the single-endpoint of cardiovascular mortality was significantly better in the icosapent ethyl group (7.6% versus 10.6%; HR, 0.70 [95% CI, 0.51–0.95]; P=0.02).
With any winning strategy there are also potential downsides, as no strategy is 100% perfect. Didier Deschamps may disagree with this, he's the current coach of the French team for the 2022 FIFA World Cup. Dechamps knows a thing-or-two about winning: he was the captain of the 1998 World Cup winners: France's first championship. Twenty years later, Les Bleus did it again (Audio 1).
Icosapent ethyl is not void of side effects. In REDUCE-IT RENAL a subset of patients in the intervention arm had higher rates of atrial fibrillation/flutter (icosapent ethyl: 4.2%; placebo 3.0%; HR 1.42 [95% CI, 0.86–2.32]; P=0.17) and serious bleeding (icosapent ethyl: 5.4%; placebo 3.6%; HR, 1.40 [95% CI, 0.90–2.18]; P=0.13). These are concerning findings given that they were independent of eGFR.
Where does that place REDUCE-IT RENAL and France in the NephroWorldCup? The findings of are really important because cardiovascular mortality in advanced CKD and dialysis patients remains a big problem that needs a solution. Icosapent ethyl may be a winning strategy recommended by an increasing number of hypertriglyciridemia experts and whose side effects may be a necessary evil that we must accept (Video 1).
Video 1: Icosapent Ethyl and the REDUCE-IT and REDUCE-IT RENAL studies by Dr. Pierre Sabouret
France continues to advance in science and sport, but it won't meet easy challenges. Other teams have placed their scientific eyes on the ultimate prize. Can France duplicate its on-pitch successes of 1998 and 2018 on the field of science in 2022?