Cardiac complications in Duchenne and Becker muscular dystrophy and X‐linked dilated cardiomyopathy

Review question

What are the effects of treatments used to prevent or treat heart complications in Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), and X‐linked dilated cardiomyopathy (XLDCM)?

Cochrane Review; five trials (205 participants).

Key results and certainty of the evidence

Early treatment with ACE inhibitors or angiotensin receptor blockers (ARBs) may help people with DMD. In boys with early heart involvement, the effect of ACE inhibitor and ARB may be equivalent; however, the evidence is very uncertain. Findings from non‐randomised studies, some of which have been long term, have led to the use of these drugs in daily clinical practice. Very low‐certainty evidence indicates that adding eplerenone might give additional benefit in DMD when early cardiomyopathy is detected. No clinically meaningful effect for growth hormone or idebenone in the studies examined was found, although the certainty of the evidence was also very low. The trials provided only low or very low‐certainty evidence on side effects.
Overall, the numbers of patients in each of these studies was small, and some studies had limitations that might have affected the results, so we are very uncertain about the results.

Read the full Cochrane Review

Review question

We determined how renin inhibitors (RIs) compared with angiotensin converting enzyme (ACE) inhibitors for treating hypertension.

Background

Hypertension is a worldwide public‐health challenge associated with high levels of occurrence and risks of circulatory and kidney disease. RIs were introduced into clinical use for hypertension in 2007. ACE inhibitors are widely prescribed for hypertension. However, the comparative effectiveness and safety of RIs and ACE inhibitors is not known.

Search date

We searched for evidence up to August 2020.

Study characteristics

We included randomized, active‐controlled, double‐blinded studies (RCTs) for this review. We include 11 RCTs involving 13,627 participants, with an average age from 51 to 74 years. Length of follow‐up ranged from four weeks to 36 months.

Key results and certainty of evidence

Low‐certainty evidence showed no difference between RIs and ACE inhibitors for deaths from any cause, for heart attacks, for serious side effects or for leaving the study because of side effects. Low‐certainty evidence suggested that RIs reduce blood pressure more than ACE inhibitors do, but this could have been due to bias in the design and conduct of the studies. More independent RCTs are needed to assess illnesses and deaths, and to see if the difference in blood pressure‐lowering is real.

Review question

Does respiratory muscle training have beneficial effects for children and adults with neuromuscular disease?

Background

Neuromuscular disease is a very broad term that covers many diseases that either directly or indirectly affect muscles or nerves. Children and adults with neuromuscular diseases can present with muscle weakness, loss of movement control, and muscle wasting. Some neuromuscular diseases cause weakness of respiratory muscles (diaphragm and accessory muscles of respiration). The decline of respiratory muscle function in these diseases affects activities of daily living and quality of life. Respiratory muscle training could potentially be considered as an extra therapy for people with suspected or confirmed respiratory muscle weakness.

Study characteristics

This review included 11 studies with a total of 250 randomized participants with neuromuscular disease. Six studies included 112 young males (including children) with Duchenne muscular dystrophy, which is an inherited muscle disease. One trial involved 23 adults with other muscle diseases (Becker muscular dystrophy and limb‐girdle muscular dystrophy). Three trials involved 88 people with amyotrophic lateral sclerosis, a progressive condition that affects the nerves controlling movement. One trial involved 27 people with myasthenia gravis, a condition that affects the signals between nerves and muscles.

Key results

The studies showed that respiratory muscle training may result in some improvements in lung function for people with amyotrophic lateral sclerosis and Duchenne muscular dystrophy. However, this finding was not consistent between studies. Physical function and quality of life were only assessed in one amyotrophic lateral sclerosis trial, which indicated that RMT may have no clear effect. One trial reported on adverse events, but the certainty of evidence was too low for conclusions to be drawn. The studies did not report the number of unscheduled hospitalisations for sudden infection or worsening of chronic respiratory failure.

Certainty of the evidence

The certainty of the evidence examined as part of this review was low or very low. Low‐certainty evidence means that our confidence in the effect of respiratory muscle training is limited, and the true effect may be substantially different. When the evidence is of very low‐certainty, the true effect is likely to be substantially different. Given the low or very low‐certainty of the evidence presented in the studies, we believe that there is a need for more well‐conducted studies in order to assess the efficacy of respiratory muscle training in people with NMD. The evidence is current to November 2018.

Review question

To determine the effectiveness and safety of hormone replacement therapy (HRT) in women who have been treated for endometrial cancer.

Cochrane Review; one study (1236 participants) that randomly allocated women to receive either HRT or a placebo.

Key findings

The single trial found no difference in the likelihood of the cancer regrowth between the two groups. They showed that HRT may or may not increase the risk of recurrence of developing a new cancer. They did not provide any information on survival or symptom relief. However, the study was not completed due to poor recruitment into the clinical trial, so was not large enough to definitively say whether the use of HRT could be recommended after treatment for early endometrial cancer.

Quality of the evidence

It is uncertain whether HRT increases the risk of recurrence after a diagnosis of endometrial cancer, as the certainty of the current evidence was very low. This trial had areas of potential bias that reduced our certainty in the results.

What were the conclusions?

Limited, very-low certainty evidence suggests that HRT may have little or no effect on the risk of endometrial cancer returning for women who have been treated surgically for an early-stage endometrial cancer. There were no data to say whether HRT had an effect on overall survival after hysterectomy for endometrial cancer.

Early administration of angiotensin converting enzyme inhibitors (ACEI - Enalapril Maleate)

may delay the progression of myocardial fibrosis in young men with Duchenne muscular dystrophy (DMD) or Becker muscular dystrophy (BMD), according to the results of a clinical trial. The Brazilian group of the University of São Paulo conducted a randomized study in two centers in which 76 male patients (mean age at start of study: 13.1 years) were recruited between June 2009 and June 2012. All patients performed magnetic resonance imaging at the start of the study and at two years of follow-up. According to the group the early onset of the treatment with convertase inhibitor, before the cardiovascular magnetic resonance reveals myocardial fibrosis, benefits the patients with DMD or BMD. The researchers believe that the data will have some impact on the therapeutic guidelines for DMD and BMD, indicating earlier initiation of treatment with angiotensin-converting enzyme inhibitors, different from current practice, in which the use of convertase inhibitors is only initiated when the left ventricular ejection fraction is below normal.