A controlled trial of renal denervation for resistant hypertension
Deepak L Bhatt, David E Kandzari, William W O'Neill, Ralph D'Agostino, John M Flack, Barry T Katzen, Martin B Leon, Minglei Liu, Laura Mauri, Manuela Negoita, Sidney A Cohen, Suzanne Oparil, Krishna Rocha-Singh, Raymond R Townsend, George L Bakris, SYMPLICITY HTN-3 Investigators, George Bakris, Deepak L Bhatt, Sidney A Cohen, Ralph D'Agostino, Murray Esler, John Flack, David Kandzari, Barry Katzen, Martin Leon, Laura Mauri, Manuela Negoita, Suzanne Oparil, Krishna Rocha-Singh, Ray Townsend, Paul Sobotka, Clive Rosendorff, Ladan Golestaneh, Steven Marx, Michele H Mokrzycki, Joel Neugarten, Sorin Brener, Roxana Mehran, Bernard J Gersh, John A Ambrose, Phyllis August, Glenn M Chertow, Stuart Pocock, Joseph Massaro, Michael Jaff, Jeffrey J Popma, Tania Cochran, Milind Y Desai, Ziad Abbud, Joseph Albanese, Tayo Addo, Wanpen Vongpatanasin, David Anderson, Mark Segal, John Angle, Dearing Johns, Herbert Aronow, Ahmed Rehan, Anvar Babaev, Eugenia Gianos, Keith Benzuly, James Paparello, Somjot Brar, Colin Watanabe, David Brown, Scott Biedermann, David Calhoun, Silvio Papapietro, Paul Casale, James Groff, Sheldon Chaffer, Timothy Mixon, James Choi, Cara East, Eugene Chung, Dean Kereiakes, Debbie L Cohen, Robert Wilensky, Mark Creager, Piotr Sobieszczyk, George Dangas, Lawrence Krakoff, Harold Dauerman, Richard Solomon, Shukri David, Susan Steigerwalt, Mark Davies, Kathleen Wyne, Eduardo de Marchena, Leopoldo Raij, Ali Emin Denktas, Brett Stephens, Chandan Devireddy, Janice Lea, William Downey, Richard Browne, Mark Dunlap, Sanjay Gandhi, Daniel Fisher, Rebecca Takis-Smith, John Flack, Theodore Schreiber, Magdi Ghali, Randolph Rough, Eric Gnall, Geoffrey Teehan, Raghava Gollapudi, Ronald Miller, Mark Goodwin, Joseph Marek, Nilesh Goswami, Richard Katholi, Luis Gruberg, Nand Wadhwa, Rajiv Gulati, Gary Schwartz, Anuj Gupta, Elijah Saunders, Anjan Gupta, V Shrinivas Murthy, Hitinder Gurm, J Brian Byrd, Jeffrey Hastings, Subhash Banerjee, David Kandzari, Dariush Bahrami, Scott Kinlay, Robert Hamburger, Robert Kipperman, Maurice Buchbinder, Paul Fine, Ajay Kirtane, Giora Weisz, Richard Kovach, David His, David Lee, Adrian Ma, Samuel Mann, S Chiu Wong, Steven Marso, Fadi Matar, John Thompson Sullebarger, Ernest Mazzaferri, Christopher Valentine, Farrell Mendelsohn, Alain Bouchard, Issam Moussa, Peter Fitzpatrick, Timothy Murphy, Douglas Shemin, Sandeep Nathan, George Bakris, Brian Negus, Claude Galphin, Sahil Parikh, Jackson Wright, Manesh Patel, Laura Svetkey, Kiritkumar Patel, Michele DeGregorio, Basil Paulus, Frank McGrew, George Petrossian, Richard Shlofmitz, Alex Powell, David Hoffman, Jacek Preibisz, Salvatore Sclafani, Florian Rader, Raj Makkar, Otelio Randall, Prithviraj Rai, Mahmood Razavi, Lawrence Santora, John Reilly, Richard Re, Jonathan Reiner, Manuel Velasquez, Michael Ring, Katherine Tuttle, Mark Robbins, Jay Gainer, Kevin Rogers, Stuart Linas, Nicolas Ruggiero, Edward Filippone, Renato Santos, William Little, Amret Hawfield, John Schindler, James Johnston, Thomas Scott, William Difilippo, Thomas Shimshak, Pankaj Dhingra, Mehdi Shishehbor, George Thomas, Mitchell Silver, Elizabeth Rave, Jasvindar Singh, Angela Brown, Kanwar Singh, William White, David Slovut, Maria Coco, Rick George Stouffer, Alan Hinderliter, Paul Teirstein, Andrew King, Thomas Todoran, Michael Zile, George Vetrovec, Domenic Sica, Ron Waksman, Judith Veis, Yale Wang, Nedaa Skeik, Sergio Waxman, Thomas Piemonte, Robert Wilkins, Byran Batson, Khaled Ziada, Thomas Whayne, Frank Zidar, Robert Hootkins, Deepak L Bhatt, David E Kandzari, William W O'Neill, Ralph D'Agostino, John M Flack, Barry T Katzen, Martin B Leon, Minglei Liu, Laura Mauri, Manuela Negoita, Sidney A Cohen, Suzanne Oparil, Krishna Rocha-Singh, Raymond R Townsend, George L Bakris, SYMPLICITY HTN-3 Investigators, George Bakris, Deepak L Bhatt, Sidney A Cohen, Ralph D'Agostino, Murray Esler, John Flack, David Kandzari, Barry Katzen, Martin Leon, Laura Mauri, Manuela Negoita, Suzanne Oparil, Krishna Rocha-Singh, Ray Townsend, Paul Sobotka, Clive Rosendorff, Ladan Golestaneh, Steven Marx, Michele H Mokrzycki, Joel Neugarten, Sorin Brener, Roxana Mehran, Bernard J Gersh, John A Ambrose, Phyllis August, Glenn M Chertow, Stuart Pocock, Joseph Massaro, Michael Jaff, Jeffrey J Popma, Tania Cochran, Milind Y Desai, Ziad Abbud, Joseph Albanese, Tayo Addo, Wanpen Vongpatanasin, David Anderson, Mark Segal, John Angle, Dearing Johns, Herbert Aronow, Ahmed Rehan, Anvar Babaev, Eugenia Gianos, Keith Benzuly, James Paparello, Somjot Brar, Colin Watanabe, David Brown, Scott Biedermann, David Calhoun, Silvio Papapietro, Paul Casale, James Groff, Sheldon Chaffer, Timothy Mixon, James Choi, Cara East, Eugene Chung, Dean Kereiakes, Debbie L Cohen, Robert Wilensky, Mark Creager, Piotr Sobieszczyk, George Dangas, Lawrence Krakoff, Harold Dauerman, Richard Solomon, Shukri David, Susan Steigerwalt, Mark Davies, Kathleen Wyne, Eduardo de Marchena, Leopoldo Raij, Ali Emin Denktas, Brett Stephens, Chandan Devireddy, Janice Lea, William Downey, Richard Browne, Mark Dunlap, Sanjay Gandhi, Daniel Fisher, Rebecca Takis-Smith, John Flack, Theodore Schreiber, Magdi Ghali, Randolph Rough, Eric Gnall, Geoffrey Teehan, Raghava Gollapudi, Ronald Miller, Mark Goodwin, Joseph Marek, Nilesh Goswami, Richard Katholi, Luis Gruberg, Nand Wadhwa, Rajiv Gulati, Gary Schwartz, Anuj Gupta, Elijah Saunders, Anjan Gupta, V Shrinivas Murthy, Hitinder Gurm, J Brian Byrd, Jeffrey Hastings, Subhash Banerjee, David Kandzari, Dariush Bahrami, Scott Kinlay, Robert Hamburger, Robert Kipperman, Maurice Buchbinder, Paul Fine, Ajay Kirtane, Giora Weisz, Richard Kovach, David His, David Lee, Adrian Ma, Samuel Mann, S Chiu Wong, Steven Marso, Fadi Matar, John Thompson Sullebarger, Ernest Mazzaferri, Christopher Valentine, Farrell Mendelsohn, Alain Bouchard, Issam Moussa, Peter Fitzpatrick, Timothy Murphy, Douglas Shemin, Sandeep Nathan, George Bakris, Brian Negus, Claude Galphin, Sahil Parikh, Jackson Wright, Manesh Patel, Laura Svetkey, Kiritkumar Patel, Michele DeGregorio, Basil Paulus, Frank McGrew, George Petrossian, Richard Shlofmitz, Alex Powell, David Hoffman, Jacek Preibisz, Salvatore Sclafani, Florian Rader, Raj Makkar, Otelio Randall, Prithviraj Rai, Mahmood Razavi, Lawrence Santora, John Reilly, Richard Re, Jonathan Reiner, Manuel Velasquez, Michael Ring, Katherine Tuttle, Mark Robbins, Jay Gainer, Kevin Rogers, Stuart Linas, Nicolas Ruggiero, Edward Filippone, Renato Santos, William Little, Amret Hawfield, John Schindler, James Johnston, Thomas Scott, William Difilippo, Thomas Shimshak, Pankaj Dhingra, Mehdi Shishehbor, George Thomas, Mitchell Silver, Elizabeth Rave, Jasvindar Singh, Angela Brown, Kanwar Singh, William White, David Slovut, Maria Coco, Rick George Stouffer, Alan Hinderliter, Paul Teirstein, Andrew King, Thomas Todoran, Michael Zile, George Vetrovec, Domenic Sica, Ron Waksman, Judith Veis, Yale Wang, Nedaa Skeik, Sergio Waxman, Thomas Piemonte, Robert Wilkins, Byran Batson, Khaled Ziada, Thomas Whayne, Frank Zidar, Robert Hootkins
Abstract
Background: Prior unblinded studies have suggested that catheter-based renal-artery denervation reduces blood pressure in patients with resistant hypertension.
Methods: We designed a prospective, single-blind, randomized, sham-controlled trial. Patients with severe resistant hypertension were randomly assigned in a 2:1 ratio to undergo renal denervation or a sham procedure. Before randomization, patients were receiving a stable antihypertensive regimen involving maximally tolerated doses of at least three drugs, including a diuretic. The primary efficacy end point was the change in office systolic blood pressure at 6 months; a secondary efficacy end point was the change in mean 24-hour ambulatory systolic blood pressure. The primary safety end point was a composite of death, end-stage renal disease, embolic events resulting in end-organ damage, renovascular complications, or hypertensive crisis at 1 month or new renal-artery stenosis of more than 70% at 6 months.
Results: A total of 535 patients underwent randomization. The mean (±SD) change in systolic blood pressure at 6 months was -14.13±23.93 mm Hg in the denervation group as compared with -11.74±25.94 mm Hg in the sham-procedure group (P<0.001 for both comparisons of the change from baseline), for a difference of -2.39 mm Hg (95% confidence interval [CI], -6.89 to 2.12; P=0.26 for superiority with a margin of 5 mm Hg). The change in 24-hour ambulatory systolic blood pressure was -6.75±15.11 mm Hg in the denervation group and -4.79±17.25 mm Hg in the sham-procedure group, for a difference of -1.96 mm Hg (95% CI, -4.97 to 1.06; P=0.98 for superiority with a margin of 2 mm Hg). There were no significant differences in safety between the two groups.
Conclusions: This blinded trial did not show a significant reduction of systolic blood pressure in patients with resistant hypertension 6 months after renal-artery denervation as compared with a sham control. (Funded by Medtronic; SYMPLICITY HTN-3 ClinicalTrials.gov number, NCT01418261.).
Source: PubMed