An opinionated take on NEJM highlights for July 2017


Taking stock: two decades of progress in heart failure:

Here comes a clever study using existing clinical trial data to assess progress in standard of care over time for heart failure. For each trial, the authors assessed the rate of sudden cardiac death during the early part of the study (excluding patients with ICDs), and it appears that between 1995 and 2014, it decreased by nearly half.  As always, in observational retrospective studies, one has to worry about systematic biases around the population that are included (i.e. are they really the same over time?), but there is a likely a message here: we indeed have come a long way in the last two decades. Declining Risk of Sudden Death in Heart Failure (subscriber access)


One more way to keep the pipes clean:

Population based genome wide association studies have identified a substantial number of genetic variants with impact on lipid metabolism and cardiovascular disease which have been turned in drug discovery targets. The latest of those is ANGPLT3, for which early clinical results are the topic of two articles, one letter, and one editorial this month. ANGPLT3 is an inhibitor of lipoprotein lipase (LPL) an important player in lipid processing. In people with mutations causing loss of function of ANGPLT3 decreased lipid levels are observed (likely due to increased activity of LPL) and they seem less prone to cardiovascular disease, something confirmed in mouse models. Two companies are targeting ANGPLT3 in different ways: one through an antibody (evinacumab, Regeneron), and the other through an antisense RNA (ANGPTL3-LRX), Akcea), and getting results in volunteers that at first blush appear similar. Large decreases in triglycerides, moderate decreases in LDL and HDL. Common wisdom says that the level of triglycerides play a relatively smaller role in CV disease, and that decreasing HDL is a bad thing, but the recent failure of evacetrabip despite perfect biomarker impact should make one cautious about such inferences. Finally, a letter about encouraging experience with evinacumab in homozygous familial hypercholesterolemia patients who suffer from hugely elevated lipid levels, very early cardiovascular disease and unlike the heterozygous group, for whom the therapeutic effect of statins and/or PCSK9 inhibitors can be blunted by the underlying genetic defect. Genetic and Pharmacologic Inactivation of ANGPTL3 and Cardiovascular Disease; Cardiovascular and Metabolic Effects of ANGPTL3 Antisense Oligonucleotides; Increasing Lipolysis and Reducing Atherosclerosis (subscriber access); ANGPTL3 Inhibition in Homozygous Familial Hypercholesterolemia (free access)


The need for decision making models for prostate cancer:

Decision making around prostate cancer has been tricky for a long time: questions about when to screen, when/whether to treat, and how to treat are all legitimately open for discussion. In this month’s issues, a couple more data points to further muddy the waters. First a very long term study comparing two approaches to early prostate cancer showing that at 20 years, there is a slight mortality advantage for upfront surgery vs. watchful waiting, but somewhat more urological side effects. Then a couple papers showing remarkable impact of abiraterone (Zytiga, Janssen) in randomized trials of men with advanced prostate cancer, with a median survival advantage which if one eyeballs the curves looks to be at least 1 year if not 2.  Obviously this would change the calculus of the first study because deciding what to do in early prostate cancer should take into account what could happen 10 years down the line in the eventuality of an advanced cancer process. What we really need is a comprehensive quantitative model of prostate cancer therapeutics to which new data could be fed as it becomes available, allowing informed decision making (and also enabling value-based care since the two are intimately related) – sort of like the New York Times Rent vs. Buy model. Regrettably, such approaches are still very rare.  Follow-up of Prostatectomy versus Observation for Early Prostate Cancer ; Abiraterone for Prostate Cancer Not Previously Treated with Hormone Therapy; Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer; Improved Outcomes in Men with Advanced Prostate Cancer (subscriber access)


Wise words on Value Based Payments

An excellent review (and it’s really too bad that it is behind the paywall) on value based payment mechanisms and how they affect physician payments. Core to the story is the fact that despite the emphasis on value mechanisms, the system remains firmly anchored in the FFS approach for two reasons. First, VBP is usually implemented as adjustments on top of a FFS reimbursement scheme, not as the core basis of payment. Second, baselining heavily relies on FFS experience.   This reliance on FFS then give a disproportionate importance to the definition of RVUs which have remained heavily weighted toward procedures vs. patient management, in a way that is antithetical to a focus on population health.  Physician Payment Reform — Progress to Date (subscriber access)


The New England Journal of Medicine is a premier weekly medical journal covering many topics of interest to the health sector. In this monthly series we offer an opinionated perspective on selected highlights that might be of interest to our clients and others.