Lessons learned about hypertension from renal denervation clinical trials

Renal denervation is being studied in clinical trials at a time when the community management of hypertension has fallen behind expectations. A major issue is poor adherence to medications. The DENER HTN trial of denervation used urine/plasma medication monitoring to confirm patient drug taking, but discovered that despite rigorous instructions to patients only 50% were taking drugs as prescribed, and 20% were taking no drugs at all. Similarly, the Spyral On Meds trial reported that only about 50% of patients took their medications consistently during the trial. But clinicians are also part of the problem: despite unrestricted access to drugs, long term follow-up of non-denervated patients in RDN trials has failed to achieve acceptable levels of BP control. On a positive note, the TRIO RDN trial in patients with uncontrolled hypertension despite multi-drug regimens observed that substitution by a single-pill 3-drug combination was remarkably effective in many patients. Guidelines recommend out-of-office BP measurements, and home BP is now used by many patients and is helpful in diagnosing hypertension. But HBP may be a two-edged sword. In the REQUIRE RDN trial, where patients routinely measured HBPs, an early significant BP-reduction advantage to RDN over sham progressively disappeared as some patients with lower BPs (mainly RDN patients) started reducing medications, and those with higher BPs (mainly sham) increased medications. Ambulatory BP monitoring is also recommended. Its data are reproducible over time for cohorts, but the Spyral Off-Meds trial demonstrated large fluctuations of BP, both upwards and downwards, in individuals in the control group, thus questioning the value of single ABPM procedures for diagnosing hypertension in clinical practice. Surveys of hypertensive patients attitudes regarding RDN in Japan and the United States have demonstrated a likely acceptance if it is needed to improve BP control. Interestingly, this occurred in patients who in many cases were not adherent to medications; but yet were concerned at the possible serious medical consequences of poorly controlled BP, thus illustrating a challenging clinical paradox. An important lesson from these observations in RDN studies is that there are limits to what can be achieved with conventional drug therapy in many people with hypertension, and that the clinical use of RDN may not just be appropriate for patients with true resistant hypertension, but might be of particular value in those who despite the well-intentioned prescription of medications remain with unacceptably high blood pressures.