In a new consensus statement, the Joint UK Societies claim that the negative results of SYMPLICITY HTN-3 should not be used as a “rationale for abandoning” renal denervation as a “novel therapeutic development” for resistant hypertension because they claim more clinical trials are needed to evaluate the safety and efficacy of the therapy.
Writing in Heart, on behalf of the Joint UK Societies, Melvin Lobo (William Harvey Centre, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, UK) and others state that although SYMPLICITY HTN-3 did not show a significant benefit of Medtronic’s Symplicity renal denervation system compared with a sham procedure, the study had several limitations.
They add that the results conflict with previous studies that do show a benefit of renal denervation (albeit not in a comparison with a sham procedure). Therefore, they say further studies to assess the safety and efficacy of renal denervation are needed.
According to Lobo et al, the design and execution of such studies should take account of the “important lessons” about how to (and how not to) conduct clinical trials that can be learned from SYMPLICITY HTN-3. For example, because hypertension specialists were not involved in most of the centres participating in SYMPLICITY HTN-3, future studies should ensure the “routine use of multidisciplinary teams led by accredited hypertension specialists”.
The authors also highlight the relative lack of experience with performing renal denervation procedures of some of the operators in the study and, therefore, all future renal denervation trials should assume “a learning curve of at least 10 procedures with each renal denervation system”. Another “important lesson” is the need for stability of medication for at least eight weeks’ prior to the study entry, with Lobo et al noting that “as many as 20% of patients were not on stable medication within six weeks of inclusion”.
In the discussion section of the statement, the authors comment “Despite the negative results from SYMPLICITY HTN-3, it is too early to decide that renal denervation therapy is a failed treatment strategy.” They add that “now is the time” to focus on improved study design and “meticulous execution” of clinical trials of renal denervation, claiming that the UK is “ready to contribute to further study the place of this therapy in the management of resistant hypertension”.
However while keen that further studies should continue, Lobo et al are clear that renal denervation—“until we have better evidence of clinical efficacy in well-conducted trials”—should not be used in routine care of patients with resistant hypertension in the UK. This is a continuation of the “temporary moratorium” on renal denervation procedures that the Joint UK Societies recommended when Medtronic first revealed that SYMPLICITY HTN-3 had not met its primary efficacy endpoint (January 2014).
Furthermore, the authors note that “With the current uncertainties, it would not be reasonable to expect commissioners to meet the costs of treatment in newly designed postmarketing studies. Industry will need to meet the costs of industry-sponsored studies, although we hope that commissioners will support the clinical costs of National Institute for Health Research-funded studies.”
Lobo told Cardiovascular News: “Our statement is the first of its kind in the aftermath of HTN-3, but I do believe that other European authorities are likely to concur with our views. I believe that, in general, the international community wishes to see further randomised controlled trials of renal denervation but also accept that it is hard to justify its use in routine clinical care similar to what we have stated in the Joint UK Societies statement.”