Renal Denervation Cost-Effective for Resistant Hypertension in SYMPLICITY HTN-2

Reed Miller

September 13, 2012

September 12, 2012 (Menlo Park, California) – A complex analysis of the SYMPLICITY HTN 2 trial, first presented at the American College of Cardiology 2012 Scientific Sessions, suggests that renal denervation is a cost-effective therapy for resistant hypertension [1]. A cost-effectiveness study of the trial by Dr Benjamin Geisler (Wing Tech Inc, Menlo Park, CA) and colleagues, is now published online September 12, 2012 in the Journal of the American College of Cardiology.

The analysis shows that catheter-based renal denervation "might be cost-effective when compared with other, well-accepted medical treatments, with an incremental cost-effectiveness ratio that is markedly below the commonly accepted threshold of $50 000 per quality-adjusted life-year," Geisler and colleagues conclude. The study also shows that the therapy may actually save money directly in about 20% of patients. "Although renal-denervation therapy represents an additional cost at time of treatment, it seems to offer great value over time."

As reported by heartwire , 18-month results of SYMPLICITY HTN 2 presented at the European Society of Cardiology 2012 Congress last month show that ablating the renal nerves with the Symplicity radiofrequency catheter system (Medtronic) improves pulse pressure and stabilizes the heart rate in patients with otherwise uncontrollable hypertension. So far, the SYMPLICITY HTN 2 patients have not shown any serious device-related adverse events.

Based on the SYMPLICITY HTN 2 data, cardiovascular-event probabilities derived from the Framingham Study and the Prospective Cardiovascular Muenster Heart Study, and lipid-level data from the National Health and Nutrition Examination Survey, Geisler et al calculated that renal denervation substantially reduces the 10-year and lifetime probability of adverse events compared with standard medical therapy for hypertension.

According to the study, renal denervation reduced cardiovascular mortality by 30% and all-cause mortality by 15% compared with standard therapy over 10 years while increasing median survival from 17.07 to 18.37 years and quality-adjusted life expectancy from 12.07 to 13.17 quality-adjusted life-years.

Long-Term Relative Risk of Adverse Events With Renal Denervation vs Standard of Care

Event 10-y relative risk Lifetime relative risk
Stroke 0.70 0.83
MI 0.68 0.85
All coronary disease 0.78 0.90
Heart failure 0.79 0.92
End-stage renal disease 0.72 0.81

The statistical model assumed that the renal-denervation procedure cost $12 500 and that hypertension management costs an average of $868 annually. The model shows the renal denervation reduced undiscounted costs by $1769; over a lifetime it increased discounted costs by $2013, reflecting the fact that the costs of the procedure are incurred up front while the resulting savings are reaped over a lifetime. The discounted lifetime incremental cost-effectiveness ratio (incremental direct medical costs of treatment and consequences divided by the incremental health benefits in quality-adjusted life-years) for renal denervation were $2715 per life-year gained and $3071 per quality-adjusted life-year.

Commenting on the study, Dr David Cohen (St Luke's Mid America Heart Institute, Kansas City, MO), who has led many studies of the cost-effectiveness of new therapies, told heartwire that the methods used by Geisler et al "are quite reasonable when you have a treatment with a benefit so far off into the future that you have to model it using epidemiological equations rather than actually doing a study to measure the benefits. It would be hard to measure the benefits of renal denervation on reduction of hypertension in a shorter-term trial." He added that the methods the investigators used to develop their model appear to be "reasonable."

The Goal Should Be to Move Patients Closer to Ideal BP Range

The co–primary investigator of the SYMPLICITY HTN 3 trial, hypertension specialist Dr George Bakris (University of Chicago, IL) told heartwire that the results of the cost-effectiveness analysis were expected, based on the impressive reductions in blood pressure shown in the SYMPLICITY HTN 2 trial.

"This is all about the pressure load to arteries. The arteries see the pressure second by second 24/7," he said. "So if we can reduce the total pressure burden on the vessel such that it puts the pressure in a range epidemiologically that we know is associated with lower cardiovascular events, and there's no significant adverse events associated with the procedure, I can't imagine, if you look at it on a population basis, that it would not be cost-effective.

"If there were a high incidence of renal-artery stenosis or any surgical intervention, it would be a totally different story, but in this situation, based on the available data, I think it is a no-brainer," he said.

The study shows that renal denervation is most cost-effective in patients with the worst baseline hypertension, so it remains unclear whether or not this therapy will benefit patients with less severe hypertension. Bakris estimates that the current resistant-hypertension population is only about 8% of hypertension patients, but the therapy may also benefit relatively young patients with normal systolic pressures but elevated diastolic pressure that has not responded to medication. This small group of patients do not yet currently meet the indication for renal denervation but represent an important unmet need, he said.

Cohen told heartwire , "It's a good piece of work. It's helpful, and it will be interesting to see how, just like with other treatments rolling out now like [transcatheter aortic-valve replacement] TAVR, how strictly the payers decide to enforce the label. The potential population of patients that theoretically could receive this treatment is far greater than what they've proved in this study."

Small Study Finds Renal Denervation Reduces AF

Renal-artery denervation can help to reduce the recurrence of atrial fibrillation in concert with pulmonary-vein isolation (PVI) in patients with drug-resistant hypertension, results of a small study show [2].

Dr Evgeny Pokushalov (State Research Institute of Circulation Pathology, Novosibirsk, Russia) and colleagues randomized 27 patients with a history of symptomatic paroxysmal or persistent AF refractory to two antiarrhythmic drugs or systolic blood pressure of at least 160 mm Hg despite triple drug therapy to either PVI ablation only or PVI plus renal-artery denervation. Results of the study are published online September 5, 2012 in the Journal of the American College of Cardiology.

The 13 patients who got both procedures showed significant reductions in average systolic pressure (from 181 to 156 mm Hg, p<0.001) and diastolic blood pressure (from 97 to 87 mm Hg, p<0.001), while there was no significant blood-pressure improvement in the PVI-only group. Nine of the 13 patients (69%) treated with both procedures were completely AF-free at the one-year postablation follow-up examination vs only four of the 14 patients (29%) in the PVI-only group (p=0.033).

In an accompanying editorial [3], Dr Ralph Verdino (University of Pennsylvania, Philadelphia) suggests that the study by Pokushalov et al raises the possibility that renal-artery denervation may someday be an alternative to PVI for AF, although he cautions that much more research will be needed to know that. "Have we been targeting the wrong organ? This study also allows one to wonder whether improved pharmacologic control of hypertension can decrease AF recurrences after catheter ablation of AF or even instead of performing this procedure," he writes. "Maybe with better control of hypertension, however we physiologically achieve it, we can indeed improve the success rates of catheter ablation of the atria or decrease the need to ever perform this procedure in many patients."

Geisler's company, Wing Tech, provided consulting services for Medtronic Ardian to construct the health-economic model. Disclosures for the coauthors are listed in the paper. Pokushalov has no conflicts of interest. Disclosures for the coauthors are listed in the paper. Verdino has reported that he has no relationships relevant to the contents of this paper to disclose. The SYMPLICITY HTN-3 trial is sponsored by Medtronic.