Ann Robinson’s weekly research reviews—5 November 2018

Ann Robinson reviews the latest research from the top medical journals

Another nail in warfarin’s coffin?

For more than 50 years, warfarin was the only option for stroke prevention. Since direct acting oral anticoagulants (DOACs) came on the scene in 2008, they’ve enjoyed a steady rise in popularity and now account for 31% of treated patients and around 93% of expenditure on anticoagulants. But which of the four DOACs commonly used is safest and most effective, and how do they each compare with warfarin? This review looks at 220 studies and found that all the DOACs are “at least as effective and safe as warfarin for patients with non-valvular atrial fibrillation (AF).” They have some minor differences: dabigatran and apixaban are better than rivaroxaban, edoxaban, and warfarin in stroke and embolism prevention. And apixaban and edoxaban are superior to rivaroxaban, dabigatran, and warfarin in terms of bleeding risk. Compared with warfarin, left atrial appendage closure is as effective at preventing stroke and all-cause mortality and it causes less major bleeding, but it has a higher (though still low overall) rate of adverse effects such as pericardial effusion. The authors say, “DOACs had similar benefits across several patient subgroups and seemed safe and efficacious for a wide range of patients with nonvalvular AF.” Is this study another nail in warfarin’s coffin?

Safety and effectiveness of bariatric surgery technique

Another treatment that has enjoyed a huge surge in popularity is bariatric surgery for obesity. A 10 year retrospective observational cohort study in the US looked at bariatric procedures and compared their long term effectiveness. The three procedures were Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy, and adjustable gastric banding. Rates of major adverse events in the first 30 days were 5.0% for RYGB, 2.6% for sleeve gastrectomy, and 2.9% for adjustable gastric banding, all of which presumably need to be weighed up against the risks of ongoing obesity. Some people were lost to follow-up, the study design was non-randomised, and the outcome data incomplete, but at five years the study had data on 84% of those with RYGB, 68% sleeve gastrectomy, and 69% adjustable gastric banding. The RYGB group lost an average of a quarter of their total body weight, the sleeve gastrectomy group just under a fifth, and the adjustable gastric banding group just over a tenth. Patients who were less likely to lose as much weight were older, diabetic, less obese (BMI <50 kg/m2), African American, and Hispanic. The more radical procedure, RYGB, is the most effective but also the riskiest.

Viagra: does it reach the parts that other drugs don’t?

In theory, sildenafil (Viagra) could help treat Raynaud’s phenomenon. It is sometimes prescribed off label for severe cases of the condition, but does it work? In this French study, on demand sildenafil was taken up to 90 minutes before conditions likely to trigger an attack, or within 5 minutes of the start of an attack and compared with placebo in a series of n-of-1 trials. The aggregated results did not show that on demand sildenafil was more effective than placebo from a clinical standpoint. The authors say “the use of n-of-1 trials allowed individual efficacy to be estimated, and on-demand sildenafil led to a clinically relevant benefit in a few patients. These findings may justify sildenafil use as a second-line treatment in patients who do not want daily, long-term therapy with calcium-channel blockers or PDE5 inhibitors and do not have digital ulcers.”

Does obesity kill you?

The rise in bariatric surgery for obesity implies that we are all convinced that obesity is bad for health. However, a UK population based cohort study of nearly 2 million people who had never smoked found that BMI had a J-shaped association with mortality. Lowest overall mortality, including deaths from cancer, cardiovascular diseases, and respiratory diseases occurred in those with a BMI of 21-25 kg/m2. Deaths from self-harm or interpersonal violence showed an inverse linear association; the thinnest people were most at risk. Being obese shortened life expectancy by 4.2 years in men and by 3.5 years in women over 40. Being underweight (BMI<18.5 kg/m2) was associated with a similar reduction in life expectancy.

Polycystic kidneysdesperately seeking a solution

Autosomal dominant polycystic kidney disease (ADPKD) is the most commonly inherited kidney disorder and affects 3-4/10000 people. It causes progressive cyst formation in both kidneys and loss of renal function, eventually leading to a need for kidney replacement therapy. There’s no definitive treatment, but a randomised clinical trial of 305 patients with later stage ADPKD were given the somatostatin analogue lanreotide to see whether it slowed the rate of decline in kidney function. Somatostatin—a peptide that is secreted by cells in the pancreas and thyroid—inhibits the enzyme that produces cyclic adenosine monophosphate (cAMP) in renal tubular cells. cAMP levels are raised in renal tubular cells in ADPKD, so the rationale behind this treatment is that somatostatin analogues may protect the kidneys. Alas, not all treatments that should work do, and this study couldn’t show any slowing down in the rate of decline of kidney function in these patients over a 2.5 year period.


Shingles—a new vaccine may be on the way

A quarter of the population is at risk of developing herpes zoster during their lifetime, two thirds of those who get it are over 50, and it hurts more and lasts longer, the older you are. There’s a live attenuated, injectable vaccine licensed for the over 50’s although the NHS programme limits shingles vaccination to people in their seventies. The vaccine becomes less effective over 70 and can’t be given to anyone who is immunosuppressed (because it’s a live vaccine.) Recently, a new adjuvant recombinant subunit vaccine against herpes zoster has been approved in Canada, the United States, Europe, and Japan. A systematic review and network meta-analysis compared the efficacy, effectiveness, and safety of the live attenuated herpes zoster vaccine with the adjuvant recombinant subunit vaccine, placebo, or no vaccine in those aged 50 years and older. The new vaccine appears to be better at preventing cases of shingles but caused more pain at the injection site.

Ann Robinson is an NHS GP and health writer/broadcaster. She works within her local community and is a trustee of the Anthony Nolan charity.

Competing interests: None declared.