The High Hanging Fruit: Treatment for Non-Obstructive HCM – Commentary by Dr. Sharlene Day

A recent study conducted in the U.K. evaluated whether the anti-anginal drug trimetazidine would improve symptoms and exercise capacity for those patients with non-obstructive hypertrophic cardiomyopathy. 

Unfortunately, this study which was conducted by Dr. Perry Elliott and his colleagues at University College London, found that trimetatazidine did not improve exercise capacity in these patients. Following the results of this study, trimetazidine will now join ranolazine and spironolactone in the compost heap of drugs which tried and failed to improve HCM symptoms.  While a third drug, perhexiline, was found to improve symptoms for non-obstructive HCM, its limitations, including potentially serious side effects, stand in the way of its common usage.

In a companion editorial to this study entitled “Non-Obstructive Hypertrophic Cardiomyopathy-the High Hanging Fruit,” Dr. Sharlene Day of the University of Michigan’s HCM Center discusses the difficulties seen in drug trials related to non-obstructive HCM.

Though seemingly a more benign form of the disease, in fact, patients with non-obstructive HCM share a similar risk of sudden death and heart failure with their obstructed counterparts.  Because treatments available to treat non-obstructive disease have been largely limited to beta blockers, calcium channel blockers and diuretics, there is a great need for new medications directed at this problem.

The problem with setting up HCM Drug trials is complicated by several factors:

  1. Different Types of HCM:  There appear to be multiple kinds of HCM. Some are genetic and some are not. We are now at a place where treatments for HCM should become more individualized.
  2. Difficulty in Recruitment:   It is difficult to recruit enough patients to take part in these trials. Patients often travel considerable distances for care at dedicated HCM Centers. Multi-center trials provide a potential way to get around this issue.
  3. Duration of HCM:  HCM is a disease process which takes place over decades which is not easily studied in a clinical trial of limited duration.
  4. The Unknown:  Timing of interventions may be critical, and it is hard to know the proper window of time to target. The bottom line is that there is still so much that is unknown, HCM researchers much continually adapt as knowledge of the disease process unfolds.

In conclusion, Dr. Day suggests that while medical researchers continue to test new drugs and push forward studies of HCM, physicians should counsel their patients that in addition to medication, lifestyle choices like proper nutrition and exercise will improve their clinical course and the overall outlook for HCM patients.

Restyle HCM Study: Ranolazine Doesn’t Improve HOCM Heart Failure Symptoms

Dr. Iacopo Olivotto and a team of Italian researchers conducted a recent multi-center trial of the late sodium channel blocker ranolazine.  The results of the trial showed that the drug failed to improve functional capacity, diastolic function, quality of life or brain natriuretic peptide (BNP) levels in 80 non-obstructive HCM patients.

Nevertheless, the researchers found that ranolazine is a very safe drug which may still be useful in the treatment of HCM by reducing arrhythmias and improving angina.

A companion editorial by Dr. Perry Elliot from the U.K. shed light on the difficulties inherent in designing clinical trials for HCM.  Dr. Elliot noted that Restyle HCM was the third unsuccessful attempt at finding a new drug for HCM in the past year since a study on  eleclazine, a drug with similar properties, and another for the drug perhexilene were both halted last year due to lack of efficacy.

Regardless, Dr. Elliot stated that increasing worldwide collaboration between HCM centers and expanding knowledge of certain sub-types of HCM treatable with specifically targeted therapies substantially improve the outlook for upcoming HCM drug trials.

End of the Road for Eleclazine and Liberty HCM Study

 Eleclazine:  The Liberty HCM Trial

It appears to be the end of the road for the Gilead drug eleclazine, a late sodium channel inhibitor previously known as GS-6615.  Eleclazine, with properties similar to the anti-angina drug ranolazine (which was approved by the FDA in 2006), was the subject of a recently terminated HCM clinical trial known as Liberty-HCM.  The HCM eleclazine study focused on whether the drug would improve symptoms and exercise capacity in patients with HCM by increasing their peak oxygen uptake, resulting in improved VO2 max readings on exercise testing.  The HCM study began enrolling patients in February 2015. Data collection had been scheduled to continue through June 2017. Continue reading “End of the Road for Eleclazine and Liberty HCM Study”