A symple lesson?

Hypertension is a huge public health problem, and contributes significantly to the development of cardiovascular disease. The mainstays of treatment are lifestyle measures and a range of common pharmacological agents such as ACE inhibitors, calcium channel blockers and diuretics. The general approach to managing hypertension is, the lower the blood pressure, the better. However, a significant number of patients experience what is known as resistant hypertension. These individuals may be in receipt of as many as 7 different antihypertensive agents, but their blood pressure remains stubbornly high.

So imagine the excitement when a proof-of-principle study was published in the Lancet in 2009, where patients with resistant hypertension received treatment using a novel catheter inserted into the renal artery utilising high-frequency radio waves to disrupt the renal sympathetic nervous supply. The results? Patients receiving the treatment had a massive blood pressure drop of 27/12mmHg over a 12-month period, unheard of using conventional treatments. The SYMPLICITY HTN- 1 trial was a victory for man over blood pressure. A steady stream of patients attended hypertension clinics with cut-outs from the Daily Mail detailing these findings for the edification of their consultant physicians. And a steady stream of consultants from said clinics bought large supplies of catheters, excited by the prospect of lucrative private practice. Cynical doctors pointed out that this was not a randomised trial. Yeah, yeah. Whatever.

Then the SYMPLICITY HTN-2 trial came long. Published again in the Lancet, patients were randomised to catheter renal denervation, or usual treatment. Blood pressure was reduced by 32/12mmHg at 6 months. Proof at last. Another victory for medical science. Cue more Daily Mail articles and more catheter sales. Various UK centres got excited about commissioning the service for the NHS. The European Society of Cardiology published supportive guidelines. The American Heart Association highlighted this as one of the top advances in cardiology in 2012. The same cynical doctors pointed out that there was no blinding – no sham intervention for the control group. Get a life. This is the future.

SYMPLICITY HTN-3 was next. A rigorously designed double-blinded randomised trial, with a sham intervention control and robustly measured ambulatory blood pressure, this was the study that would once and for all silence the doubters. On 9 January 2014, Medtronic (manufacturer of the Symplicity catheter used in the trial) issued a press release. There were no safety concerns, but the trial had failed to meet its primary efficacy endpoint, a reduction in blood pressure at 6 months.

The results are not as yet published, and some experts appear to be hanging on to some tiny strand of optimism that maybe things aren’t all that bad. Yet I suspect they are. I confess that I was one of those cynical doctors, and I confess I probably did allow myself a smug “told you so” smile on hearing the news. But I am also annoyed that we could let the hype from the early, inferior research cloud rational decision making, potentially resulting in wasted resources, false hopes and unnecessary treatments. And I am disappointed for the patients for whom we still have no effective way of treating resistant hypertension. This is an important and sobering lesson to clinicians and researchers alike; let us learn from it, and not make the same mistakes again.

This entry was posted in Blog and tagged . Group: . Bookmark the permalink. Both comments and trackbacks are currently closed.
  • The Cambridge Centre for Health Services Research (CCHSR) is a thriving collaboration between the University of Cambridge and RAND Europe. We aim to inform health policy and practice by conducting research and evaluation studies of organisation and delivery of healthcare, including safety, effectiveness, efficiency and patient experience.