Motivation: Last weekend, I was flipping through an old issue of TIME magazine when I noticed an article with large picture of pink kidneys. Wondering why TIME magazine would be concerned with urine production, I read a little more and learnt about a "revolutionary" new treatment for hypertension discovered in England in 2010. The article refers to amazing results published in a trial in Lancet in 2010 from renal sympathetic ablation. Throughout intern year, we had never seriously considered this therapy. Why? How good is the data?
Paper: Symplicity HTN-2 Investigators. "Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity HTN-2 Trial): a randomised controlled trial" Lancet (2010); 376: 1903-09.
Methods: Multicenter randomized unblinded trial of renal denervation with treatment resistant hypertension, defined as SBP > 160 mmHg (SBP > 150 with DM2) despite compliance on 3 or more anti-hypertensives. Important exclusion criteria were GFR < 45 and history of MI, unstable angina, or stroke. Study conducted at Europe, Australia, and New Zealand. Patients randomized to renal denervation had endovascular catheter directed radioablation through renal artery access. Primary endpoint was change in average office-based SBP from baseline to 6 months.
Results:
Cohort: In total, 52 patients were randomized to renal denervation while 54 were in the control group. The two groups were overall similar except for differences in gender (35% female in intervention vs. 50% in control group) and difference in baseline GFR (77 ml/min in intervention vs. 86 in control group). Three patients were lost to follow-up in each group.
Efficacy: In per-protocol analysis, at six-months, renal denervation resulted in mean decrease in BP of 33/11 mmHg compared to no changed in the control group. The baseline was 178/96 in the intervention group and the same in the control group. The result is statistically significant, p < 0.0001. Similar changes were noted in BP measurements at home-based and 24 hour ambulatory measurements. At least 84% of patients in intervention group had >10 mmHg decrease in SBP at 6 months.
Secondary End Points: There were no differences in serum creatinine, eGFR, and cystatin C between baseline and 6 months in both groups. There were no differences in composite cardiovascular between the two groups.
Safety: No serious procedure-related or device related complications noted in the six month follow-up.
Discussion: In this preliminary phase trial of renal denervation, the procedure appears remarkably efficacious. The degree of BP measurement is clearly better than any other current medicinal or lifestyle approach. Yet, before adopting this intervention, the paper has multiple limitations that need to be clarified. First, the control and intervention groups were different some important baseline parameters such as gender distribution and GFR. Second, there were no hard endpoints used in the paper such as MI or long-term cardiovascular outcomes. It is unclear whether renal denervation has any long-term risks that may outweigh short-term benefits in BP reduction. Finally, this entire study was funded, designed, and analyzed by Ardian, the maker of the denervation catheter. The data would gain more integrity if the trial was designed and analyzed independently. Thus, this therapy is promising but needs a larger follow-up trial before widespread use.
Paper: Symplicity HTN-2 Investigators. "Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity HTN-2 Trial): a randomised controlled trial" Lancet (2010); 376: 1903-09.
Methods: Multicenter randomized unblinded trial of renal denervation with treatment resistant hypertension, defined as SBP > 160 mmHg (SBP > 150 with DM2) despite compliance on 3 or more anti-hypertensives. Important exclusion criteria were GFR < 45 and history of MI, unstable angina, or stroke. Study conducted at Europe, Australia, and New Zealand. Patients randomized to renal denervation had endovascular catheter directed radioablation through renal artery access. Primary endpoint was change in average office-based SBP from baseline to 6 months.
Results:
Cohort: In total, 52 patients were randomized to renal denervation while 54 were in the control group. The two groups were overall similar except for differences in gender (35% female in intervention vs. 50% in control group) and difference in baseline GFR (77 ml/min in intervention vs. 86 in control group). Three patients were lost to follow-up in each group.
Efficacy: In per-protocol analysis, at six-months, renal denervation resulted in mean decrease in BP of 33/11 mmHg compared to no changed in the control group. The baseline was 178/96 in the intervention group and the same in the control group. The result is statistically significant, p < 0.0001. Similar changes were noted in BP measurements at home-based and 24 hour ambulatory measurements. At least 84% of patients in intervention group had >10 mmHg decrease in SBP at 6 months.
Secondary End Points: There were no differences in serum creatinine, eGFR, and cystatin C between baseline and 6 months in both groups. There were no differences in composite cardiovascular between the two groups.
Safety: No serious procedure-related or device related complications noted in the six month follow-up.
Discussion: In this preliminary phase trial of renal denervation, the procedure appears remarkably efficacious. The degree of BP measurement is clearly better than any other current medicinal or lifestyle approach. Yet, before adopting this intervention, the paper has multiple limitations that need to be clarified. First, the control and intervention groups were different some important baseline parameters such as gender distribution and GFR. Second, there were no hard endpoints used in the paper such as MI or long-term cardiovascular outcomes. It is unclear whether renal denervation has any long-term risks that may outweigh short-term benefits in BP reduction. Finally, this entire study was funded, designed, and analyzed by Ardian, the maker of the denervation catheter. The data would gain more integrity if the trial was designed and analyzed independently. Thus, this therapy is promising but needs a larger follow-up trial before widespread use.
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