On The Pulse - 20th April 2012
New antiplatelet drug disappoints
The TRA 2P-TIMI trial , reported in the NEJM, randomizes over 26,000 patients with prior myocardial infarction, ischaemic stroke or peripheral artery disease to the novel PAR-1 inhibitor vorapaxar or placebo. Almost all were taking aspirin, and many were also on a second drug. At 2 years, treatment was discontinued on safety grounds in patients with a history of stroke, complicating interpretation. At 3 years, vorapaxar slightly improved a composite outcome of cardiovascular death, myocardial infarction or stroke (9.3% vs 10.5%), but at the cost of an increased risk of moderate or severe bleeding (4.2% vs 2.5%) and intracranial haemorrhage (1.0% vs 0.5%).
Which Angiotensin Receptor Blocker?
People with heart failure who can’t tolerate ACE inhibitors should get angiotensin receptor blockers instead. Both candesartan and valsartan have been shown to reduce morbidity and mortality in placebo-controlled trials but there has been no head-to-head comparison yet. A Danish registry-based study in JAMA tracks new users of these drugs and finds no differences between them when given at full dose although, hardly surprisingly, low and medium doses of losartan weren’t as effective as high doses of candesartan.
Ruling out acute coronary syndromes
Great numbers of patients find their way to hospital with acute chest pain, but few have acute coronary syndromes. A study in the NEJM randomizes 908 low-to-intermediate-risk patients to coronary CT angiography (CCTA) and 462 to traditional care. CCTA had a higher rate of detecting coronary disease (9.0% vs 3.5%), no patient with negative findings died or had a myocardial infarction within 30 days, and 50% of the CCTA group were discharged home from the emergency department vs only 23% of controls. While avoiding unnecessary hospital admission is obviously desirable, the authors also hope that earlier diagnosis will improve outcomes in the remainder.
Statins for healthy men
Should a 55-year-old man with a systolic blood pressure of 110 mmHg and total cholesterol 6.5 mmol/l be given a statin if he has no family history of cardiovascular disease and currently feels well? Since his 10-year risk of developing CVD is around 10%, some would argue that he should. On the other hand, his level of risk is determined more by his age than his cholesterol level, and any benefits of statins might be outweighed by their potential effects on diabetes, cognition and muscle. Read a nuanced discussion of the pros and cons in JAMA.
Neuropathic back pain carries a huge economic burden, but its optimal management remains uncertain. A trial in Annals of Internal Medicine randomizes 84 adults with lumbosacral radiculopathy of less than 6 months' duration to two epidural injections of steroids, etanercept, or saline, mixed with bupivacaine and separated by 2 weeks. The steroid group reported less leg pain at 1 month, but the effect was fairly modest and not statistically significant, as were differences in back pain and functioning. The authors think that larger trials are indicated, but it’s unclear that the effect would be clinically useful even if confirmed in a larger sample.
A recent Practice article in the BMJ briefly reviews the causes and treatment of epistaxis . It’s useful to distinguish between the common anterior bleeds (blood running out of the nose, usually one nostril) and the rarer posterior bleeds (blood running into the throat or from both nostrils), because the latter won’t respond to pressure on the soft part of the nose. And don’t forget to check pulse, blood pressure and capillary filling – surprisingly large volumes of blood can be lost. An additional simple treatmen t suggested in a Rapid Response is getting the patient to suck ice, which reduces nasal blood flow considerably and helps stop both anterior and posterior bleeds.
Hormone replacement after myocardial infarction
Hormone replacement therapy hasn’t been recommended for the prevention of cardiovascular disease since the Women’s Health Initiative trial was stopped early when it found that the risk was actually increased. But does that mean that HRT should be withdrawn if a women taking it for menopausal symptoms has a myocardial infarction? An observational study from Denmark in the BMJ finds no significant differences in rates of reinfarction or death between women who discontinued HRT after an infarction and those who persisted with the treatment. Unfortunately, the hazard ratios couldn’t be measured precisely enough to give a definitive answer.
Off-label prescribing in Quebec
A study in Archives of Internal Medicine used an electronic health record network in Quebec to examine off-label prescribing in primary care. The overall prevalence was a substantial 11%, and the authors reckon that nearly 80% of these prescriptions lacked strong supporting scientific evidence. Off-label prescribing was also more common for patients without comorbidities, with older drugs, and with drugs with only one or two approved indications. An accompanying Editorial considers the meaning of off-label prescribing, and concludes that what we really need is better information about how medicines are prescribed and why.