Blood pressure control during pregnancy

During pregnancy there are limited or no benefit of treating blood pressure below 169/109. This meta-analysis of 49 randomized control trials including 4723 women found that antihypertensive therapy was not associated with a lower risk of preeclampsia (RR 0.93; 95% CI 0.80 to 1.08), fetal demise (RR 0.71; 95% CI 0.49 to 1.02), pre-term birth (RR 0.96; 95% CI 0.85 to 1.10) or a small for gestational age baby (RR 0.97; 95% CI 0.80 to 1.17). Antihypertensive therapy decreased the risk of severe hypertension (RR 0.49; 95% CI 0.40 to 0.60).

Most clinicians would prescribe antihypertensive pharmacotherapy to a pregnant woman with a blood pressure of 165/105 and clinical practice guidelines support treatment. This study indicates we should carefully consider the anticipated benefits of antihypertensive therapy for mild hypertension during pregnancy. Treatment reduced progression to severe hypertension which is not in itself a clinically meaningful outcome, and there was a trend towards a lower risk of fetal demise. No other benefits were even suggested by the data.

Source

Abalos E, Duley L, Steyn DW. Antihypertensive drug therapy for mild to moderate hypertension during pregnancy. Cochrane Database Syst Rev. 2014 Feb 6;2:CD002252.

Via EvidenceUPDATES

Bisphosphonates and a-fib

Bisphosphonates increase the risk of atrial fibrillation. This meta-analysis of 6 RCTs (N = 41 375) and 6 observational studies (N = 149 856) found an increased risk of atrial fibrillation (1.40, 95%CI 1.02-1.93 and 1.27, 95%CI 1.16-1.39). There was no increased stroke incidence or cardiovascular mortality.

It seems that bisphosphonates cause atrial fibrillation since the effect was present both in RCTs and observational studies. The effect is not very large but the risk might affect a patient’s decision about whether to take a bisphosphate, especially if risk factors for atrial fibrillation (e.g. hypertension) are present or if there is only a questionable expected benefit from the bisphosphonate.

Source

Sharma A, Chatterjee S, Arbab-Zadeh A, et al. Risk of Serious Atrial Fibrillation and Stroke With Use of Bisphosphonates: Evidence From a Meta-analysis. Chest. 2013 Oct;144(4):1311-22. doi: 10.1378/chest.13-0675.

Via EvidenceUPDATES

Dabigitran versus warfarin for mechanical heart valve

Dabigitran caused excess strokes when compared with warfarin in patients with mechanical heart valves. This RCT was stopped early after 252 were enrolled because of excess strokes in the dabigitran group (9 patients or 5 % in the dabigitran group versus none in the warfarin group). Valve thrombosis, major bleeds, any bleeds and myocardial infarctions all occurred more often in the dabigitran group (although only one patient had a myocardial infarction). 

Ironically even though the main benefit to patients of dabigitran over warfarin is avoiding blood work and dose adjustments, the authours of the paper point to problems with the dabigitran dosing as the likely explanation for the excess risk. In the study dabigitran was dosed based on renal function and adjusted based on blood levels which is more cautious than usual clinical practice. (Meanwhile warfarin was dosed as it usually is.) So the risks of dabigitran may be greater in clinical practice compared with in the study. 

The results of this study must be considered along side those from trials of dabigitran (and other new oral anticoagulants) versus warfarin for atrial fibrillation which make the newer agents look better. If the excess events in this trial really were caused by improper dabigitran dosing, there may be some patients with atrial fibrillation receiving the wrong dose of dabigitran. 

Source

Eikelboom JW, Connolly SJ, Brueckmann M, Granger CB, Kappetein AP, Mack MJ, Blatchford J, Devenny K, Friedman J, Guiver K, Harper R, Khder Y, Lobmeyer MT, Maas H, Voigt JU, Simoons ML, Van de Werf F; RE-ALIGN Investigators. Dabigatran versus warfarin in patients with mechanical heart valves. N Engl J Med. 2013 Sep 26;369(13):1206-14.

Via InfoPOEM

Agomelatine and depression

Agomelatine, a melatonin receptor agonist, is not an efficacious treatment of depression.This meta-analysis of 13 RCTs involving 2947 patients found a statistically significant difference in patient reported symptoms (-1.51 Hamilton Depression scale versus placebo) but there was not a clinically significant improvement (greater than 3 points clinically significant). Among the 13 included RCTs were 7 negative trials that were unpublished.

The unpublished studies seem not to have been considered in previous reviews that came to more positive conclusions about agomelatine. Kudos to the authors of the meta-analysis for tracking down and then bringing to light the unpublished data that might save patients from being exposed to this seemingly useless depression treatment. The European Medicines Agency should also be recognized for making the data available even though the EMA approved the medication over objections that:

“licensing should not be granted until robust efficacy has been demonstrated”.

Source

Koesters M, Guaiana G, Cipriani A, Becker T, Barbui C. Agomelatine efficacy and acceptability revisited: systematic review and meta-analysis of published and unpublished randomised trials. Br J Psychiatry. 2013 Sep;203:179-87. doi: 10.1192/bjp.bp.112.120196. PubMed PMID: 23999482.

Via EvidenceUPDATES

Risperidone and OCD

Adding psychological interventions such as exposure therapy to an SSRI is better than adding risperidone. This RCT of 100 adults found that reported symptoms at 8 weeks were better with psychological interventions than risperidone which was no better than placebo. 

Antipsychotics seem to be prescribed for almost any indication from “agitation” to insomnia, so it is helpful to have a reminder that there are more effective alternatives with fewer adverse effects. We should ensure that our patients have access to the best treatment modalities rather than prescribing potentially hazardous medications that are no more helpful than sugar pills.

Source

Simpson HB, Foa EB, Liebowitz MR, Huppert JD, Cahill S, Maher MJ, McLean CP, Bender J Jr, Marcus SM, Williams MT, Weaver J, Vermes D, Van Meter PE, Rodriguez CI, Powers M, Pinto A, Imms P, Hahn CG, Campeas R. Cognitive-Behavioral Therapy
vs Risperidone for Augmenting Serotonin Reuptake Inhibitors in Obsessive-Compulsive Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2013 Nov 1;70(11):1190-9.

Via EvidenceUPDATES

Telemonitoring and COPD

Telemonitoring (completing a daily questionnaire about symptoms and taking an oxygen saturation level) of COPD patients did not reduce hospital admissions for exacerbations. This RCT of 256 Scottish patients found no difference in admission rates (Hazard ration 0.98, 95% confidence interval 0.66 to 1.44) after one year. There was no benefit with respect to other outcomes such as quality of life, and a subgroup analysis actually indicated that there were more admissions in patients with mild disease. 

Some previous trials of telemonitoring have suggested benefits for patients with diabetes, heart failure and COPD. The apparent discrepancy in results might reflect differences in the control interventions which might (appropriately) increase admission rates. This illustrates a general problem with using admission to hospital as an outcome in these types of trials: admission to hospital is not necessarily a bad thing. Also, COPD patients seem to worry more about their declining ability to do things that they want to do without being desperately out of breath (not to mention dying) than they worry about being admitted to hospital. Yet most trials of interventions for COPD focus on admission to hospital. This might be because the various puffers used for COPD predominantly effect admissions to hospital as opposed to exercise capacity or mortality. So this negative result with respect to hospital admission might be even more negative than it seems.

Source

Pinnock H, Hanley J, McCloughan L, Todd A, Krishan A, Lewis S, Stoddart A, van der Pol M, Macnee W, Sheikh A, Pagliari C, McKinstry B. Effectiveness of telemonitoring integrated into existing clinical services on hospital admission
for exacerbation of chronic obstructive pulmonary disease: researcher blind, multicentre, randomised controlled trial. BMJ. 2013 Oct 17;347:f6070. doi: 10.1136/bmj.f6070.

Via Richard Lehman’s journal review—18 November 2013

Screening echocardiograms

Screening echocardiograms in unselected middle aged people conferred no benefit. A Norwegian RCT of 6861 with 15 years(!) of follow up found no mortality benefit (hazard ratio 0.97; 95%CI 0.89 to 1.06). There was also no difference in the secondary outcomes of myocardial infarction or stroke.

At least screening echocardiograms do not cause harm like exercise stress tests in asymptomatic patients. But the screening echocardiogram is included in some “executive” or VIP physicals even though it seems to be useless.

Source

Lindekleiv H, L?chen ML, Mathiesen EB, Nj?lstad I, Wilsgaard T, Schirmer H. Echocardiographic screening of the general population and long-term survival. A randomized clinical study. JAMA Intern Med 2013;173(17):1592-1598.

Via InfoPOEM

Blood pressure target in diabetes

A lower blood pressure targets (e.g. 130/80) in patients with diabetes does not reduce overall mortality compared with the standard target (e.g. 140/90) used for those who do not have diabetes. This meta-analysis of five RCTs including 7314 participants based its main finding on the ACCORD trial 4734 patients. There was no significant effect on mortality (RR 1.05, 95%CI 0.84 to 1.30) and reduction in risk of stroke (RR 0.58, 95%CI 0.39 to 0.88) was offset by an increased risk of serious adverse effects (RR 2.58, 95%CI 1.70 to 3.91). There was a trend toward benefit for the lower diastolic blood pressure (80) target (RR 0.73, 95%CI 0.53 to 1.01) that interestingly seems to be driven by lower non-cardiovascular mortality. 

Combining these findings with those from studies of blood pressure targets in patients with renal disease, the management of blood pressure seems to be getting simpler: target 140/90.

Source

Arguedas JA, Leiva V, Wright JM. Blood pressure targets for hypertension in people with diabetes mellitus. Cochrane Database Syst Rev. 2013 Oct 30;10:CD008277. doi: 10.1002/14651858.CD008277.pub2.

Via EvidenceUPDATES

Bone density testing for elderly patients

Repeat bone mineral density imaging does not improve fracture prediction in elderly (75 year old) men and women. This cohort study of 310 men and 492 women indicates that patients who were not treated for osteoporosis after an initial bone mineral density scan would not benefit from a repeat scan because it does not add predictive value.

Yet some older adults who are not being treated for osteoporosis have BMDs repeated every few years, partly because some concerned patients ask for it to be done even more frequently. The value of even the first BMD is questionable in men. 

It is often difficult to know how often to repeat tests. So it is useful to have a study the helps to guide this decision, even if the study is small and the data is a bit stale (patients were followed between 1987-1999).

Source

Berry SD, Samelson EJ, Pencina MJ, et al. Repeat bone mineral density screening and prediction of hip and major osteoporotic fracture. JAMA 2013;310(12):1256-1262.

Via InfoPOEMS

Nebulisers and asthma

Nebulisers provide do not improve the effect of beta-agonists in the treatment of asthma in adults and children. This systematic review included 1897 children and 729 adults who participated in 33 RCTs and found no benefit of nebulisers versus inhalers. Hospital admission rates, length of stay in emergency rooms and peak flow rates were all similar between the groups.

This study provides clear confirmation that nebulisers don’t help. Interestingly children randomized to receive beta-agonist therapy via the nebuliser actually stayed in the emergency room longer. So nebulisers might be one of those unhelpful interventions that actually makes patients feel a little more sick. 

Source

Cates CJ, Welsh EJ, Rowe BH. Holding chambers (spacers) versus nebulisers for beta-agonist treatment of acute asthma. Cochrane Database Syst Rev. 2013 Sep 13;9:CD000052. 

 

Via EvidenceUPDATES