Adherence to Antihypertensive Treatment and the Blood Pressure-Lowering Effects of Renal Denervation in the Renal Denervation for Hypertension (DENERHTN) Trial.

BACKGROUND: The DENERHTN trial (Renal Denervation for Hypertension) confirmed the blood pressure-lowering efficacy of renal denervation added to a standardized stepped-care antihypertensive treatment for resistant hypertension at 6 months. We report the influence of adherence to antihypertensive treatment on blood pressure control. METHODS: One hundred six patients with hypertension resistant to 4 weeks of treatment with indapamide 1.5 mg/d, ramipril 10 mg/d (or irbesartan 300 mg/d), and amlodipine 10 mg/d were randomly assigned to renal denervation plus standardized stepped-care antihypertensive treatment, or the same antihypertensive treatment alone. For standardized stepped-care antihypertensive treatment, spironolactone 25 mg/d, bisoprolol 10 mg/d, prazosin 5 mg/d, and rilmenidine 1 mg/d were sequentially added at monthly visits if home blood pressure was ≥135/85 mm Hg after randomization. We assessed adherence to antihypertensive treatment at 6 months by drug screening in urine/plasma samples from 85 patients. RESULTS: The numbers of fully adherent (20/40 versus 21/45), partially nonadherent (13/40 versus 20/45), or completely nonadherent patients (7/40 versus 4/45) to antihypertensive treatment were not different in the renal denervation and the control groups, respectively (P=0.3605). The difference in the change in daytime ambulatory systolic blood pressure from baseline to 6 months between the 2 groups was -6.7 mm Hg (P=0.0461) in fully adherent and -7.8 mm Hg (P=0.0996) in nonadherent (partially nonadherent plus completely nonadherent) patients. The between-patient variability of daytime ambulatory systolic blood pressure was greater for nonadherent than for fully adherent patients. CONCLUSIONS: In the DENERHTN trial, the prevalence of nonadherence to antihypertensive drugs at 6 months was high (≈50%) but not different in the renal denervation and control groups. Regardless of adherence to treatment, renal denervation plus standardized stepped-care antihypertensive treatment resulted in a greater decrease in blood pressure than standardized stepped-care antihypertensive treatment alone. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01570777.

Optimum and stepped care standardised antihypertensive treatment with or without renal denervation for resistant hypertension (DENERHTN): a multicentre, open-label, randomised controlled trial.

BACKGROUND: Conflicting blood pressure-lowering effects of catheter-based renal artery denervation have been reported in patients with resistant hypertension. We compared the ambulatory blood pressure-lowering efficacy and safety of radiofrequency-based renal denervation added to a standardised stepped-care antihypertensive treatment (SSAHT) with the same SSAHT alone in patients with resistant hypertension. METHODS: The Renal Denervation for Hypertension (DENERHTN) trial was a prospective, open-label randomised controlled trial with blinded endpoint evaluation in patients with resistant hypertension, done in 15 French tertiary care centres specialised in hypertension management. Eligible patients aged 18-75 years received indapamide 1·5 mg, ramipril 10 mg (or irbesartan 300 mg), and amlodipine 10 mg daily for 4 weeks to confirm treatment resistance by ambulatory blood pressure monitoring before randomisation. Patients were then randomly assigned (1:1) to receive either renal denervation plus an SSAHT regimen (renal denervation group) or the same SSAHT alone (control group). The randomisation sequence was generated by computer, and stratified by centres. For SSAHT, after randomisation, spironolactone 25 mg per day, bisoprolol 10 mg per day, prazosin 5 mg per day, and rilmenidine 1 mg per day were sequentially added from months two to five in both groups if home blood pressure was more than or equal to 135/85 mm Hg. The primary endpoint was the mean change in daytime systolic blood pressure from baseline to 6 months as assessed by ambulatory blood pressure monitoring. The primary endpoint was analysed blindly. The safety outcomes were the incidence of acute adverse events of the renal denervation procedure and the change in estimated glomerular filtration rate from baseline to 6 months. This trial is registered with ClinicalTrials.gov, number NCT01570777. FINDINGS: Between May 22, 2012, and Oct 14, 2013, 1416 patients were screened for eligibility, 106 of those were randomly assigned to treatment (53 patients in each group, intention-to-treat population) and 101 analysed because of patients with missing endpoints (48 in the renal denervation group, 53 in the control group, modified intention-to-treat population). The mean change in daytime ambulatory systolic blood pressure at 6 months was -15·8 mm Hg (95% CI -19·7 to -11·9) in the renal denervation group and -9·9 mm Hg (-13·6 to -6·2) in the group receiving SSAHT alone, a baseline-adjusted difference of -5·9 mm Hg (-11·3 to -0·5; p=0·0329). The number of antihypertensive drugs and drug-adherence at 6 months were similar between the two groups. Three minor renal denervation-related adverse events were noted (lumbar pain in two patients and mild groin haematoma in one patient). A mild and similar decrease in estimated glomerular filtration rate from baseline to 6 months was observed in both groups. INTERPRETATION: In patients with well defined resistant hypertension, renal denervation plus an SSAHT decreases ambulatory blood pressure more than the same SSAHT alone at 6 months. This additional blood pressure lowering effect may contribute to a reduction in cardiovascular morbidity if maintained in the long term after renal denervation. FUNDING: French Ministry of Health.

Is home blood pressure monitoring feasible and well accepted in nephrectomized patients for renal cancer? (STAFF study).

AIMS: Few studies have looked at blood pressure (BP) evolution after nephrectomy, except for in living kidney donors with no clinical relevant modifications. STAFF is a pilot, open-label, observational study to evaluate the feasibility of following BP by home blood pressure monitoring (HBPM) after nephrectomy for cancer. MAJOR FINDINGS: 56 patients (66.1% previously treated for hypertension) were included between November 1, 2011, and December 31, 2012; 95.8% of the patients realized five of six primary end-points in HBPM, but the last monitoring session at 6 months was often lacking (60%) probably because of a lack of understanding. When BP was controlled before surgery, 36% of the patients underwent new hypertension or hypertension dysregulation, without any correlating factor found; 33% of the patients presented the presence of proteinuria or an increase during the follow-up. Previous hypertension or high body mass index were risk factors for proteinuria increase (p = 0.036 and 0.032) but not treatment by an renin-angiotensin system blocker. There was no statistical link between HTA control and proteinuria. CONCLUSION: Our study shows that most patients undergoing nephrectomy for cancer are able to follow HBPM. It should be encouraged for detecting high BP or proteinuria, especially if antiangiogenic therapies are envisaged because of the supplementary risk of hypertension and proteinuria induced by these treatments.

Impact of miscuffing during home blood pressure measurement on the prevalence of masked hypertension.

BACKGROUND: Masked hypertension has been associated with obesity. However, because most studies do not mention the specific cuff size used for home measurements, masked hypertension prevalence may have been overestimated in obese patients because of undersized cuffs. In this prospective, observational study, the effect of miscuffing on hypertension status was evaluated in patients with large arms. METHODS: Fifty-three patients with an upper-arm circumference >33cm, undergoing treatment for mild-to-moderate hypertension, took 2 sets of home blood pressure (BP) measurements (standard vs. large cuff) using the validated Microlife BP A100 Plus automated device. RESULTS: Mean BP was 143/85mm Hg at the office using a large cuff, 141/84mm Hg at home using a standard cuff, and 134/80mm Hg at home using a large cuff. Standard vs. large cuff home BP mean differences were 6.9mm Hg (95% confidence interval (CI) = 4.7-9.2; P < 0.0001) for systolic BP and 4.0mm Hg (95% CI = 2.4-5.5; P < 0.0001) for diastolic BP. Hypertension status differed significantly between standard vs. large cuffs: sustained hypertension (56.6% vs. 41.5%, respectively; P = 0.002), controlled hypertension (20.8% vs. 28.3%, respectively; P = 0.04), white coat hypertension (7.5% vs. 22.6%, respectively; P = 0.002), masked hypertension (15.1% vs. 7.5%, respectively; P = 0.04). CONCLUSIONS: In patients with large arms, use of an appropriately sized large cuff for home BP measurements led to a 2-fold reduction in masked hypertension. Regarding clinical and epidemiological implications, future studies investigating masked hypertension should specify cuff size for home BP measurements. The low market availability and increased cost of large cuffs should also be addressed.