Symplicity HTN-3是經皮腎動脈去神經術的序幕還是終點_West China Medical Journal

Authors：

 張鑫 ,  陳曉平

四川大學華西醫院心臟內科（成都 610041）;

Corresponding?author：

陳曉平, Email: 971979713@qq.com

Keywords：

難治性高血壓; 腎動脈去神經術; 血壓; 心血管風險

DOI：

10.7507/1002-0179.201600263

Video：

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難治性高血壓的發生會顯著增加患者發生心血管事件的風險。交感神經在高血壓的發病機制中至關重要，目前藥物以外的治療方法越來越得到重視，其中腎動脈去神經術（RDN）逐漸顯示出治療難治性高血壓的潛力，RDN 分為射頻消融、超聲系統、化學技術3 個方法。目前RDN 研究的熱點主要集中于經皮導管腎臟交感神經射頻消融術。前期的非隨機Symplicity HTN-1 實驗以及隨機非盲法Symplicity HTN-2 實驗顯示出了明顯的降壓效果。盡管后期嚴格設計、隨機、假手術對照的Symplicity HTN-3 研究未能達到主要療效終點，但這種藥物以外的治療方法值得進一步探討，現以RDN 為核心話題作一綜述。

Citation： 張鑫, 陳曉平. Symplicity HTN-3是經皮腎動脈去神經術的序幕還是終點. West China Medical Journal, 2016, 31(5): 972-977. doi: 10.7507/1002-0179.201600263 Copy

1.	Turnbull F, Blood Pressure Lowering Treatment Trialists’ Collaboration. Effects of different blood-pressure-lowering regimens on major cardiovascular events: results of prospectively-designed overviews of randomised trials[J]. Lancet, 2003, 362(9395): 1527- 1535.
2.	Calhoun DA, Jones D, Textor S, et al. Resistant hypertension: diagnosis, evaluation, and treatment: a scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research[J]. Circulation, 2008, 117 (25): e510-e526.
3.	The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major cardiovascular events in hypertensive patients randomized to doxazosin vs chlorthalidone: the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT). ALLHAT Collaborative Research Group[J]. Jama, 2000, 283(25): 1967-1975.
4.	Pepine CJ, Handberg EM, Cooper-DeHoff RM, et al. A calcium antagonist vs a non-calcium antagonist hypertension treatment strategy for patients with coronary artery disease. The International Verapamil-Trandolapril Study (INVEST): a randomized controlled trial[J]. JAMA, 2003, 290(21): 2805-2816.
5.	Jamerson K, Weber MA, Bakris GL, et al. Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients[J]. N Engl J Med, 2008, 359(23): 2417-2428.
6.	Dahlof B, Devereux RB, Kjeldsen SE, et al. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol[J]. Lancet, 2002, 359(9311): 995-1003.
7.	Judd E, Calhoun DA. Apparent and true resistant hypertension: definition, prevalence and outcomes[J]. J Hum Hypertens, 2014, 28(8): 463-468.
8.	Muntner P, Davis BR, Cushman WC, et al. Treatment-resistant hypertension and the incidence of cardiovascular disease and endstage renal disease: results from the Antihypertensive and Lipid- Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) [J]. Hypertension, 2014, 64(5): 1012-1021.
9.	Jung O, Gechter JL, Wunder C, et al. Resistant hypertension? Assessment of adherence by toxicological urine analysis[J]. J Hum Hypertens, 2013, 31(4): 766-774.
10.	Esler M, Jennings G, Lambert G, et al. Overflow of catecholamine neurotransmitters to the circulation: source, fate, and functions[J]. Physiol Rev, 1990, 70(4): 963-985.
11.	Grassi G, Vailati S, Bertinieri G, et al. Heart rate as marker of sympathetic activity[J]. J Hypertens, 1998, 16(11): 1635-1639.
12.	Grassi G, Mark A, Esler M. The sympathetic nervous system alterations in human hypertension[J]. Circ Res, 2015, 116(6): 976-990.
13.	Thomas P, Dasgupta I. The role of the kidney and the sympathetic nervous system in hypertension[J]. Pediatr Nephrol, 2015, 30(4): 549-560.
14.	Sakakura K, Ladich E, Cheng Q, et al. Anatomic assessment of sympathetic peri-arterial renal nerves in man[J]. J Am Coll Cardiol, 2014, 64(7): 635-643.
15.	DiBona GF, Kopp UC. Neural control of renal function[J]. Physiol Rev, 1997, 77(1): 75-197.
16.	DiBona GF. Sympathetic nervous system and the kidney in hypertension[J]. Curr Opin Nephrol Hypertens, 2002, 11(2): 197-200.
17.	Krum H, Schlaich M, Whitbourn R, et al. Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study[J]. Lancet, 2009, 373(9671): 1275-1281.
18.	Symplicity HTN-2 investigators, Esler MD, Krum H, et al. Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity HTN-2 Trial): a randomised controlled trial[J]. Lancet, 2010, 376(9756): 1903-1909.
19.	Bhatt DL, Kandzari DE, O’Neill WW, et al. A controlled trial of renal denervation for resistant hypertension[J]. N Eng J Med, 2014, 370(15): 1393-1401.
20.	Olsen LK, Kamper AL, Svendsen JH, et al. Renal denervation[J]. Eur J Int Med, 2015, 26(2): 95-105.
21.	Symplicity HTN-1 investigators. Catheter-based renal sympathetic denervation for resistant hypertension: durability of blood pressure reduction out to 24 months[J]. Hypertension, 2011, 57(5): 911-917.
22.	Krum H, Schlaich MP, Sobotka PA, et al. Percutaneous renal denervation in patients with treatment-resistant hypertension: final 3-year report of the Symplicity HTN-1 study[J]. Lancet, 2014, 383(9917): 622-629.
23.	Esler MD, Bohm M, Sievert H, et al. Catheter-based renal denervation for treatment of patients with treatment-resistant hypertension: 36 month results from the SYMPLICITY HTN-2 randomized clinical trial[J]. Eur Heart J, 2014, 35(26): 1752-1759.
24.	Bohm M, Mahfoud F, Ukena C, et al. First report of the Global SYMPLICITY Registry on the effect of renal artery denervation in patients with uncontrolled hypertension[J]. Hypertension, 2015, 65(4): 766-774.
25.	Mancia G, Mahfoud F, Narkiewicz K, et al. Long-term effects of renal artery denervation in real world patients with uncontrolled hypertension from the global symplicity registry[J]. J Hypertens, 2015, 33(Suppl 1): e49.
26.	Iliescu R, Lohmeier TE, Tudorancea I, et al. Renal denervation for the treatment of resistant hypertension: review and clinical perspective[J]. Am J Physiol Renal Physiol, 2015, 309(7): F583-F594.
27.	Lobo MD, de Belder MA, Cleveland T, et al. Joint UK societies’ 2014 consensus statement on renal denervation for resistant hypertension[J]. Heart, 2015, 101(1): 10-16.
28.	Kandzari DE, Bhatt DL, Brar S, et al. Predictors of blood pressure response in the SYMPLICITY HTN-3 trial[J]. Eur Heart J, 2015, 36(4): 219-227.
29.	Pekarskiy S, Baev A, Mordovin V, et al. Failure of renal denervation in Symplicity HTN-3 is a predictable result of anatomically inadequate operative technique and not the true limitations of the technology[J]. J Hypertens, 2015, 33(Suppl 1): e108.
30.	Kandzari DE, Bhatt DL, Brar S, et al. Predictors of blood pressure response in the Symplicity HTN-3 trial[J]. Eur Heart J, 2015, 36(4): 219-227.
31.	Tsioufis CP, Papademetriou V, Dimitriadis KS, et al. Catheter-based renal denervation for resistant hypertension: twenty-four month results of the EnligHTN Ⅰ first-in-human study using a multielectrode ablation system[J]. Int J Cardiol, 2015, 201(1): 345-350.
32.	Lobo M, Saxena M, Jain AJ, et al. Safety and performance of the enlightn renal denervation system in patients with severe uncontrolled hypertension: 12 month results from the Enlightn Ⅱ study[J]. J Hypertens, 2015, 33(Suppl 1): e51.
33.	Fadl Elmula FE, Jin Y, Yang WY, et al. Meta-analysis of randomized controlled trials of renal denervation in treatment-resistant hypertension[J]. Blood Press, 2015, 24(5): 263-274.

1. Turnbull F, Blood Pressure Lowering Treatment Trialists’ Collaboration. Effects of different blood-pressure-lowering regimens on major cardiovascular events: results of prospectively-designed overviews of randomised trials[J]. Lancet, 2003, 362(9395): 1527- 1535.
2. Calhoun DA, Jones D, Textor S, et al. Resistant hypertension: diagnosis, evaluation, and treatment: a scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research[J]. Circulation, 2008, 117 (25): e510-e526.
3. The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major cardiovascular events in hypertensive patients randomized to doxazosin vs chlorthalidone: the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT). ALLHAT Collaborative Research Group[J]. Jama, 2000, 283(25): 1967-1975.
4. Pepine CJ, Handberg EM, Cooper-DeHoff RM, et al. A calcium antagonist vs a non-calcium antagonist hypertension treatment strategy for patients with coronary artery disease. The International Verapamil-Trandolapril Study (INVEST): a randomized controlled trial[J]. JAMA, 2003, 290(21): 2805-2816.
5. Jamerson K, Weber MA, Bakris GL, et al. Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients[J]. N Engl J Med, 2008, 359(23): 2417-2428.
6. Dahlof B, Devereux RB, Kjeldsen SE, et al. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol[J]. Lancet, 2002, 359(9311): 995-1003.
7. Judd E, Calhoun DA. Apparent and true resistant hypertension: definition, prevalence and outcomes[J]. J Hum Hypertens, 2014, 28(8): 463-468.
8. Muntner P, Davis BR, Cushman WC, et al. Treatment-resistant hypertension and the incidence of cardiovascular disease and endstage renal disease: results from the Antihypertensive and Lipid- Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) [J]. Hypertension, 2014, 64(5): 1012-1021.
9. Jung O, Gechter JL, Wunder C, et al. Resistant hypertension? Assessment of adherence by toxicological urine analysis[J]. J Hum Hypertens, 2013, 31(4): 766-774.
10. Esler M, Jennings G, Lambert G, et al. Overflow of catecholamine neurotransmitters to the circulation: source, fate, and functions[J]. Physiol Rev, 1990, 70(4): 963-985.
11. Grassi G, Vailati S, Bertinieri G, et al. Heart rate as marker of sympathetic activity[J]. J Hypertens, 1998, 16(11): 1635-1639.
12. Grassi G, Mark A, Esler M. The sympathetic nervous system alterations in human hypertension[J]. Circ Res, 2015, 116(6): 976-990.
13. Thomas P, Dasgupta I. The role of the kidney and the sympathetic nervous system in hypertension[J]. Pediatr Nephrol, 2015, 30(4): 549-560.
14. Sakakura K, Ladich E, Cheng Q, et al. Anatomic assessment of sympathetic peri-arterial renal nerves in man[J]. J Am Coll Cardiol, 2014, 64(7): 635-643.
15. DiBona GF, Kopp UC. Neural control of renal function[J]. Physiol Rev, 1997, 77(1): 75-197.
16. DiBona GF. Sympathetic nervous system and the kidney in hypertension[J]. Curr Opin Nephrol Hypertens, 2002, 11(2): 197-200.
17. Krum H, Schlaich M, Whitbourn R, et al. Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study[J]. Lancet, 2009, 373(9671): 1275-1281.
18. Symplicity HTN-2 investigators, Esler MD, Krum H, et al. Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity HTN-2 Trial): a randomised controlled trial[J]. Lancet, 2010, 376(9756): 1903-1909.
19. Bhatt DL, Kandzari DE, O’Neill WW, et al. A controlled trial of renal denervation for resistant hypertension[J]. N Eng J Med, 2014, 370(15): 1393-1401.
20. Olsen LK, Kamper AL, Svendsen JH, et al. Renal denervation[J]. Eur J Int Med, 2015, 26(2): 95-105.
21. Symplicity HTN-1 investigators. Catheter-based renal sympathetic denervation for resistant hypertension: durability of blood pressure reduction out to 24 months[J]. Hypertension, 2011, 57(5): 911-917.
22. Krum H, Schlaich MP, Sobotka PA, et al. Percutaneous renal denervation in patients with treatment-resistant hypertension: final 3-year report of the Symplicity HTN-1 study[J]. Lancet, 2014, 383(9917): 622-629.
23. Esler MD, Bohm M, Sievert H, et al. Catheter-based renal denervation for treatment of patients with treatment-resistant hypertension: 36 month results from the SYMPLICITY HTN-2 randomized clinical trial[J]. Eur Heart J, 2014, 35(26): 1752-1759.
24. Bohm M, Mahfoud F, Ukena C, et al. First report of the Global SYMPLICITY Registry on the effect of renal artery denervation in patients with uncontrolled hypertension[J]. Hypertension, 2015, 65(4): 766-774.
25. Mancia G, Mahfoud F, Narkiewicz K, et al. Long-term effects of renal artery denervation in real world patients with uncontrolled hypertension from the global symplicity registry[J]. J Hypertens, 2015, 33(Suppl 1): e49.
26. Iliescu R, Lohmeier TE, Tudorancea I, et al. Renal denervation for the treatment of resistant hypertension: review and clinical perspective[J]. Am J Physiol Renal Physiol, 2015, 309(7): F583-F594.
27. Lobo MD, de Belder MA, Cleveland T, et al. Joint UK societies’ 2014 consensus statement on renal denervation for resistant hypertension[J]. Heart, 2015, 101(1): 10-16.
28. Kandzari DE, Bhatt DL, Brar S, et al. Predictors of blood pressure response in the SYMPLICITY HTN-3 trial[J]. Eur Heart J, 2015, 36(4): 219-227.
29. Pekarskiy S, Baev A, Mordovin V, et al. Failure of renal denervation in Symplicity HTN-3 is a predictable result of anatomically inadequate operative technique and not the true limitations of the technology[J]. J Hypertens, 2015, 33(Suppl 1): e108.
30. Kandzari DE, Bhatt DL, Brar S, et al. Predictors of blood pressure response in the Symplicity HTN-3 trial[J]. Eur Heart J, 2015, 36(4): 219-227.
31. Tsioufis CP, Papademetriou V, Dimitriadis KS, et al. Catheter-based renal denervation for resistant hypertension: twenty-four month results of the EnligHTN Ⅰ first-in-human study using a multielectrode ablation system[J]. Int J Cardiol, 2015, 201(1): 345-350.
32. Lobo M, Saxena M, Jain AJ, et al. Safety and performance of the enlightn renal denervation system in patients with severe uncontrolled hypertension: 12 month results from the Enlightn Ⅱ study[J]. J Hypertens, 2015, 33(Suppl 1): e51.
33. Fadl Elmula FE, Jin Y, Yang WY, et al. Meta-analysis of randomized controlled trials of renal denervation in treatment-resistant hypertension[J]. Blood Press, 2015, 24(5): 263-274.

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Symplicity HTN-3是經皮腎動脈去神經術的序幕還是終點

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