Need for new therapies to treat Hypertension
A very tight control of blood pressure is required to produce reduction in risk of developing complications especially in patients with comorbidities like Diabetes Mellitus which tend to accelerate the development of complications. Difficult to treat hypertension is a commonly observed problem world-wide.

Hypertension is classified as resistant if the blood pressure is ≥140/90 mm Hg and they reported using antihypertensive medications from 3 different drug classes or drugs from ≥4 antihypertensive drug classes regardless of blood pressure. Among US adults on antihypertensive therapy with drugs, 12.8% of the hypertensives had resistant hypertension as per above criteria [1].

Since multiple factors contribute to hypertension, achieving control using a single agent acting via one single path may not always be successful. Though single drug treatment may be effective in some, more than 50% will require more than one drug for appropriate control of their BP [2]. It is very common to see regimens with Fixed Dose Combinations (FDCs) or drugs being added sequentially.

The challenge of multidrug regimens is getting the patient to adhere to it; since for the patients the condition is largely asymptomatic and the perceived value of being on continuing long term therapy is low. Researchers have been focusing on innovative treatment modalities which can produce long lasting results while keeping it easy on compliance terms and low on side effects.
Novel Device based therapies on the anvil

Renal Denervation
It is a percutaneous, catheter-based radiofrequency ablation for renal sympathetic denervation.

Mechanism:

By applying radiofrequency pulses to the renal arteries, the nerves in the vascular wall (adventitia layer) can be denervated. This causes reduction of renal sympathetic afferent and efferent activity and blood pressure can be decreased [3].



Simplicity HTN1 Trials [4]:
  • Single Arm with extended cohort
  • 45-treated patients with treatment resistant hypertension (baseline BP of 177 /101 mmHg; +/- 20/15 ).
  • Mean office BPs after the procedure were reduced by -27/-17 at 12 months
  • Responder rates (defined as a >10 mm Hg reduction) among patients completing follow–up is 69 percent at one month to 82 percent at 24 months.
Simplicity HTN2 Trials [5]:
  • Randomized controlled trial
  • 106 patients with resistant hypertension (baseline BP of 178/96 mm)
  • Mean blood-pressure reductions of -32/-12 mm Hg six months [n=49] after the procedure in patients with drug-resistant hypertension as against controls where the change was +1/0(n=51) (p<0.0001).
  • The percentage of patients with at least 10 mm Hg drop in systolic blood pressure from the baseline following the procedure was 84%.
Chronic Baroreflex activation

It requires surgical implantation of a device, with leads that electrically stimulate the carotid baroreceptors in the carotid sinus. It is implanted just below the clavicle and delivers four to six volts to the carotid arteries, mimicking the carotid baroreflex, which prompts a fall in blood pressure.

Mechanism:
  • It activates the baroreceptors located in the carotid sinus
  • Activation provides a signal to medullary brain centers that blood pressure is elevated
  • This triggers a reduction in sympathetic activation and promotes parasympathetic activation





    Rheos DEBuT-HT trial [6]
    • 45 patients from 4 European centers
    • 16 patients completed the 2-year follow-up
    N=16 Baseline 1 year 2 year 3 year
    Systolic BP (mmHg) 190 ± 30 -38 ± 8 -34 ± 8 -37 ± 10
    Diastolic BP (mmHg) 111 ± 22 -25 ± 5 -20 ± 6 -23 ± 7

     
    Pivotal Trials [7]
    • Prospective randomized double-blind trial
    • 322 patients at 49 sites
    • 55 roll-in patients / 265 randomized (2:1)
    • The average SBP drop at 12 months among responders was 44 mmHg
    • 81% of patients were responders (SBP ≥ 10 mmHg relative to preimplant)
     
     

    [1] Persell SD.; Prevalence of resistant hypertension in the United States, 2003-2008: Hypertension. 2011 Jun;57(6):1076-80. doi: 10.1161/HYPERTENSIONAHA.111.170308. Epub 2011 Apr 18.
    [2] Sanjay Kalra, Bharti Kalra and Navneet Agrawal- Combination therapy in hypertension: An update
    [3] Esler, MC; Krum, H, Sobotka, PA, Schlaich, MP, Schmieder, RE, Böhm, M (2010 Dec 4). "Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity HTN-2 Trian): a randomized controlled trial.". Lancet 376 (9756): 1903-9
    [4] Simplicity HTN1 Trials
    [5] Thomas Unger, Ludovit Paulis, and Domenic A. Sica; Therapeutic perspectives in hypertension: novel means for renin–angiotensin–aldosterone system modulation and emerging device-based approaches
    [6] C Venkat S Ram; Baroreceptor activation therapy for treating resistant hypertension : a status report
    [7]http://my.americanheart.org/idc/groups/ahamah-public/@wcm/@sop/@scon/documents/downloadable/ucm_425401.pdf


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    1 Comments

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