Copy

March 11th, 2016

PILLBOX

THE STORY

Sitting pretty on a promising weight loss drug must be nice. So how did Orexigen Pharamaceuticals blow up its Phase 3b cardiovascular safety study for Contrave (naltrexone / buproprion)?

THE BASICS

After safety issues sank anti-obesity drugs in the 90's, a new generation of pills has come of age fast. The big players are 2012's Belviq (lorcaserin, 3.6 kg average weight loss at 1 year), 2012's Qsymia (phenteramine/topiramate, 6.6 kg), 2014's Saxenda (liraglutide, 5.8 kg), and 2014's Contrave (naltrexone/buproprion, 3.9 kg). But you have to pick your side effects: from flatulence to dysgeusia, to an increased risk of pancreatitis and more, weight loss meds can be a wild ride for patients. And different drugs seem to work for different people, meaning a lot of trial and error when writing prescriptions.

THE SNAFU

Contrave demonstrated weight loss benefit in 2010, but because the medication was found to increase blood pressure and heart rate, the FDA insisted that the sponsor tack on a cardiovascular safety study prior to approval. The drug was approved in 2014 after an interim analysis of the study did not suggest cardiovascular safety issues. This week, the second part of the safety trial was cancelled because Orexigen, the trial's sponsor, released some of the data early and filed claims about the results in its drug patent. Oops. Orexigen got a big scolding from its academic research partners, and the price of a new trial could be up to $200 mil. For what it's worth, the unfinished study did not show evidence of increased cardiovascular risk in patients on naltrexone/buproprion.
JAMA 

THE TAKEAWAY

Pharmaceutical companies seem a bit too anxious to make a buck with weight loss drugs. Despite progress in the field, be wary, as there are still a lot of unanswered questions.

SAY IT ON ROUNDS

WHEN YOUR STEPSISTER'S UNCLE ASKS YOU FOR A KIDNEY

You're more on the hook than you think. Anti-HLA antibodies are associated with hyperacute rejection in renal transplant and have for years prevented transplants between incompatible donors. Desensitization protocols use plasmapheresis to filter these antibodies and allow for HLA-incompatible transplants. Single center trials have supported the use of desensitization since 2009, and a 22-center study published this week demonstrated that non-HLA matched live kidney donor recipients had a survival benefit at 1, 5, and 8 years over matched controls on a waitlist and those who received deceased-donor kidneys. The results are good news for the 32,000 patients in the US with anti-HLA antibodies awaiting kidney transplant.
NEJM

WHEN THAT 6'6" DUDE SHOWS UP AT YOUR FELLOWSHIP INTERVIEWS

Don't sweat it. But know that a new study from the UK Biobank showed that height correlated with income in men, and BMI correlated with income in women. The catch is that researchers looked at panels of genes that predicted these factors, rather than actual population data. The authors say that looking at genes removes socioeconomic contributors to the relationship, since poverty is independently correlated with short height and high BMI. Two and half inches of height was worth $1,600 a year in income for men, while in women, 5 extra points of BMI meant a decrease in annual income of more than $4,000. 
BMJ

WHEN MOSQUITO BITES MEAN MORE THAN THE ARRIVAL OF SUMMER

In endemic regions, malaria in pregnancy can lead to fetal loss or maternal death. The WHO recommends artemisinin based treatments for pregnant women, but their guidelines lacked supporting evidence. The PREGACT trial enrolled over 3,400 pregnant women in four African countries and established the safety and efficacy of four different artemisinin based treatments. Cure rates were 94 - 99%. Dihydroartemisinin–piperaquine appears to be the treatment of choice, as it had the best efficacy, a good safety profile, and a long post-treatment prophylactic effect
NEJM

WHEN THE SIGHT OF THE OB WARD SPIKES YOUR BLOOD PRESSURE

New onset hypertension in pregnancy is known to lead to a greater chance of cardiovascular disease later in life. Researchers in Denmark used the national registry to assess rates of cardiomyopathy more than 5 months after delivery in women who were normotensive versus those with gestational hypertension. They found that the hypertension group had a small increased risk of cardiomyopathy more than 5 years postpartum. The underlying pathophysiology remains unknown. 
JAMA

BRUSH UP

HOW IT WORKS

Intra-aortic balloon pumps are inserted into the aorta to augment cardiac output. The balloon inflates to fill the aorta during diastole, which increases blood flow to the coronary arteries. During systole, the balloon deflates, which reduces pressure in the aorta and decreases afterload. The actions combine to increase myocardial oxygen supply and decrease myocardial oxygen demand. 

WHAT'S THE EVIDENCE

For intra-aortic ballon pumps (IABP)? Use IABP for failure to come off bypass following surgery or for low-output states that prompt cardiogenic shock (think: broken valves in need of repair, Class D heart failure awaiting transplant). Small trials show benefit, or no other options are available. But 2012's IABP-SHOCK II called into question one of IABP's traditional uses: cardiogenic shock from acute myocardial infraction prior to revascularization. IABP did not increase 30-day mortality among participants.

WHAT YOUR DERM FRIENDS ARE TALKING ABOUT

Dermatologist Samantha Lee (@drpimplepopper) has more Instagram followers than you. Her fame comes from popping gross pimples to carefully chosen soundtracks. It's a specialty-taste kind of thing. Right?

Spread the word

  

Not a subscriber? Sign up at MedicineScope.com
Copyright © 2016 Medicine Scope. All rights reserved.