NEJM Highlights for June 2015: the flavor of the month is distinctly cardiovascular

Interventionalist treatment for stroke:

In the 80s and 90s, treatment of myocardial infraction was greatly advanced by the introduction of systemic clot busting drugs (t-PA and others); further advance occurred in the 90s when it was shown that immediate cardiac catheterization produced even better results. Acute embolic stroke has followed the same path – in the 90s, it was shown that t-PA treatment within 3 hours of onset of symptoms was beneficial, and ever since there has been a move toward treatment modalities where an interventional radiologist acts on the clot directly. Two randomized controlled studies now show unambiguously that intervention (using the Solitaire device from Covidien) within 6 hours of symptoms in patients selected by imaging studies improves outcome.  Look for more 24/7 regional stroke centers supplied with patients by helicopters from large geographical areas. Stent-Retriever Thrombectomy after Intravenous t-PA vs. t-PA Alone in Stroke; Thrombectomy within 8 Hours after Symptom Onset in Ischemic Stroke; Endovascular Therapy for Stroke — It’s about Time (subscription access)


Uber CPR:

First a retrospective observational study from Sweden including thirty thousand witnessed out-of-hospital cardiac arrest shows that 30-day survival doubles (to about 10%) when CPR is initiated by by-standers before the arrival of EMS (even though EMS took longer to reach the patient in the early CPR group).  Then, in a separate prospective randomized study conducted in Stockholm, nearly 10,000 volunteers trained in CPR were enrolled and their cell phones registered in a positioning system. A report of a cardiac arrest would then alert volunteers within 500 m depending on the randomization of the event, and this showed a higher level of early CPR initiation in the intervention group than in the control group. What’s next – self driving cars showing up with AEDs?    Early Cardiopulmonary Resuscitation in Out-of-Hospital Cardiac Arrest; Mobile-Phone Dispatch of Laypersons for CPR in Out-of-Hospital Cardiac Arrest; Bystander-Initiated CPR by Design, Not by Chance (subscription access)


Lower LDL, better hearts:

The observation that cardiovascular risk decreases in individuals with low LDL cholesterol and high HDL cholesterol is long standing, but the question of whether lowering LDL or increasing HDL with drugs improves cardiovascular risk has not been so obvious. By and large drugs that increase HDL have not proven effective to reduce cardiovascular events. For statins that lower LDL, the impact on cardiovascular health has been clear but the suspicion has long been that perhaps this was due to a different concomitant effect. Now come the results of a 6-year study of ezetimibe (Zetia, Merck), a drug that lowers LDL by a mechanism completely different from statins. These show that indeed, in high risk patients, ezetimibe lowers the risk of cardiovascular events. The clinical effect was moderate to say the least: an absolute risk decrease by about 0.3%/year in the treatment arm. Since treatment costs about $3000/year (in the US), this translates to a cost of approximately $1,000,000 per MI/revascularization/stroke/death avoided. Given that the early read on the PCSK9 inhibitors is for a risk reduction of about 1%/year, a cost of treatment that is around $10,000 would be internally consistent with that pricing. Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes; Proof That Lower Is Better — LDL Cholesterol and IMPROVE-IT (free access)


Stopping the bleeding:

Atrial fibrillation and deep venous thrombosis affect millions who require anticoagulation to avoid strokes or pulmonary emboli. For many years, the treatment was warfarin (Coumadin aka rat poison) with difficult management requiring frequent testing and dose adjustment. Over the past few years several oral agents that do not require close monitoring have been developed and approved: the thrombin inhibitor dabigatran (Pradaxa, Boehringer Ingelheim – BI), and several factor Xa inhibitors.  Despite success of these therapies, one major issues has been the absence of reversal agents in case patients bleed or must urgently have surgery (e.g. after trauma).  BI has been developing such an agent in the form of an antibody fragment (idarucizumab) and in this issue of the journal, reports great success in restoring normal coagulation in 68 patients at immediate risk for severe bleeding. Idarucizumab has been submitted for regulatory approval and will almost certainly get it, but an interesting question is what BI will charge for it. It could be advantageous to price at cost or even as a loss leader as a way to encourage uptake of Pradaxa. On the other hand, Perosphere has been developing PER977 as a broad reversal agent applicable to the factor Xa inhibitors marketed by Daichi, BMS, Pfizer, and Bayer – and if it is approved, what will these companies do? Idarucizumab for Dabigatran Reversal; Targeted Anti-Anticoagulants; Acutely Injured Patients on Dabigatran; Use of PER977 to Reverse the Anticoagulant Effect of Edoxaban (free access)


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