July 29th, 2013
Selections from Richard Lehman’s Literature Review: July 29th
CardioExchange is pleased to reprint selections from Dr. Richard Lehman’s weekly journal review blog at BMJ.com. Selected summaries are relevant to our audience, but we encourage members to engage with the entire blog.
NEJM 25 July 2013 Vol 369
Riociguat for the Treatment of Chronic Thromboembolic Pulmonary Hypertension and Pulmonary Arterial Hypertension (pages 319 and 330): There are still some life-shortening conditions where there are so few therapeutic options that everybody with them should be invited to take part in randomized trials of new interventions. One such is chronic thromboembolic pulmonary hypertension. Progression leads to reduced walking distance and ultimately to death, and is accompanied by an inexorable rise in B-type natriuretic peptide. So when a drug comes along that leads to an improvement in walking distance and a decrease in BNP over 16 weeks, it could mark a potential breakthrough, though we cannot be certain without longer trials. The drug is riociguat, a member of a new class of compounds, the soluble guanylate cyclase stimulators. The two trials reported here and here are very similar and encouraging. Yet the accompanying editorial contains a pretty explicit warning:
“Another caveat, which is not unique to PATENT-1 and CHEST-1, is the relationship to the sponsoring company. The study was supported by Bayer HealthCare, and although the manuscript was drafted by the first author, editorial assistance was provided by a company supported by the sponsor (Adelphi Communications). In addition, although the authors had access to the complete database, the statistician was employed by Bayer HealthCare. Riociguat is poised for examination by the Food and Drug Administration as a therapy for pulmonary hypertension and, if approved, has the potential to generate substantial revenue for the sponsor. In light of the financial stakes, both real and apparent investigator autonomy remain key to ensuring the delivery of new drugs for pulmonary hypertension for patients.” So where does the buck stop—with the NEJM which printed these studies, and will presumably get reprint income from Bayer, or with the FDA? Which impartial body is going to conduct the necessary replication studies and long-term mortality studies? Do we get to see the full data set?
Mechanisms of Hypoglycemia-Associated Autonomic Failure in Diabetes (pg. 362): This week’s NEJM review article is about hypoglycaemia—something that we all need to take more account of when piling on treatments for diabetes. This paper deals with the detail of autonomic regulation of hypoglycaemia awareness, and why awareness tends to diminish with each hypoglycaemic episode. The wider clinical relevance of hypoglycaemia is the subject of a brilliant article by Kasia Lipska and Victor Montori in this week’s JAMA Internal Medicine.
BMJ 27 July 2013 Vol 347
Renal Outcomes Associated with Invasive vs. Conservative Management of ACS: It’s the end of July and there is sleepiness in the air; even people who aren’t on holiday feel as if they should be; e-mails go unanswered, and jobs get postponed. Perhaps this accounts for the lack-lustre contents of the journals at this time of year too. A Canadian register was trawled for evidence that renal outcomes after acute coronary syndrome might be influenced by invasive versus conservative management: they found that early invasive management of acute coronary syndrome is associated with a small increase in risk of acute kidney injury, but not dialysis or long term progression to end stage renal disease.
JAMA Intern Med 22 July 2013 Vol 173
Association Between Hypoglycemia and Dementia in Older Adults with Diabetes Mellitus (pg. 1300): The more you look at what we are incentivized to do with elderly diabetic patients, the scarier it gets. Are we reducing beta-cell decline, or accelerating it? Are we reducing cardiovascular risk, or increasing it? When we tighten control, are we preventing cognitive decline or inducing it? For every treatment beyond metformin, we simply don’t know. But there is increasing evidence that by inducing hypoglycaemia, commonly with sulfonylurea drugs or insulin, we are in danger of damaging the elderly brain, and elderly people with dementia then become more prone to hypoglycaemia. It’s a bidirectional disaster area, as this study shows. In an elderly diabetic cohort followed for 12 years, “those who experienced a hypoglycaemic event had a 2-fold increased risk for developing dementia compared with those who did not have a hypoglycaemic event… Similarly, older adults with DM who developed dementia had a greater risk for having a subsequent hypoglycaemic event compared with participants who did not develop dementia.”
Statins and Musculoskeletal Conditions, Arthropathies, and Injuries (pg. 1318): Statins are great. And the initial randomized trials showed no increase in muscle aches in the treated group. Now that is really strange, because every GP has encountered many patients who are desperate to continue taking a statin but cannot because of muscle pains which recur whenever they do. Nor do we quite know the full range of muscle effects which statins can produce: this retrospective cohort study with propensity score matching concludes that “musculoskeletal conditions, arthropathies, injuries, and pain are more common among statin users than among similar nonusers.” But let’s not get carried away: the odds ratios in the study were pretty small (1.07-1.1).