Summary 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.
Abstract Background Hypertension guidelines recommend the use of 2 agents with synergistic action when >1 agent is needed to achieve blood pressure goals. Newer antihypertensive treatment ...combinations include fixed-dose combinations of an angiotensin receptor blocker and a calcium channel blocker. Objective The I-COMBINE study aimed to determine whether the antihypertensive efficacy of the fixed-dose combination irbesartan 150 mg/amlodipine 5 mg (I150/A5) was superior to that of amlodipine 5 mg (A5) monotherapy in lowering home systolic blood pressure (HSBP) after 5 weeks' treatment. Methods The I-COMBINE study was a 10-week, multicenter, Phase III, prospective, randomized, parallel-group, open-label with blinded–endpoint study. The main inclusion criterion was essential uncontrolled hypertension (SBP ≥145 mm Hg at office, after at least 4 weeks of A5 monotherapy administered once daily). Patients continued to receive A5 for 7 to 10 days and were randomized to either monotherapy with A5 for 5 weeks then amlodipine 10 mg (A10) for the next 5 weeks or to a fixed-dose combination therapy (I150/A5 then I150/A10). Safety profile was assessed by recording adverse events reported by patients or observed by the investigator. Results Following enrollment, 290 patients were randomized to treatment, and 287 (mean SD age, 57.3 11.2 years; 48% male) were included in the intention-to-treat analysis: 144 patients treated with I150/A5 then I150/A10, and 143 patients treated with A5 then A10. At randomization, mean HSBP was similar in both groups: 148.5 (10.3) mm Hg in the I150/A5 group and 149.2 (9.7) mm Hg in the A5 group. At week 5, the adjusted mean difference in HSBP between groups was –6.2 (1.0) mm Hg ( P < 0.001). The proportion of controlled patients (mean home blood pressure <135 and 85 mm Hg) was significantly higher in the I150/A5 group than in the A5 group ( P < 0.001). Treatment-emergent adverse events were experienced by 13.8% of I150/A5-treated patients and 11.9% of A5-treated patients during the first 5-week period, and by 15.8% of I150/A10-treated patients and 17.0% of A10-treated patients during the second 5-week period. Two serious adverse events were reported with the fixed-dose combination; both patients recovered. Conclusions Data from this adult population with essential hypertension suggest greater efficacy with the fixed-dose combination I150/A5 over A5 monotherapy in lowering SBP after 5 weeks. Both treatment regimens were well tolerated throughout the study. ClinicalTrials.gov identifier: NCT00956644.
Abstract Background Hypertension guidelines recommend the use of 2 agents with synergistic action when >1 agent is needed to achieve blood pressure goals. Newer antihypertensive treatment ...combinations include fixed-dose combinations of an angiotensin receptor blocker and a calcium channel blocker. Objective The I-ADD study aimed to demonstrate whether the antihypertensive efficacy of fixed-dose combination irbesartan 300 mg/amlodipine 5 mg (I300/A5) was superior to that of irbesartan (I300) monotherapy in lowering home systolic blood pressure after 10 weeks' treatment. Methods The I-ADD study was a 10-week, multicenter, Phase III, prospective, randomized, parallel-group, open-label with blinded–end point study. The main inclusion criterion was essential uncontrolled hypertension (systolic blood pressure ≥145 mm Hg at office after at least 4 weeks of irbesartan 150 mg I150 monotherapy administered once daily). Patients continued to receive I150 for 7 to 10 days and were randomized to either monotherapy with I150 for 5 weeks then I300 for the next 5 weeks, or to a fixed-dose combination therapy (I150/A5, then I300/A5). Safety profile was assessed by recording adverse events reported by patients or observed by the investigator. Results Following enrollment, 325 patients were randomized to treatment, and 320 (mean SD age, 56.7 11.4 years; 41% male) were included in the intention-to-treat analysis: 155 patients treated with I150/A5 then I300/A5, and 165 patients treated with I150 then I300. At randomization, mean home systolic blood pressure was similar in both groups: 152.7 (11.8) mm Hg in the I150/A5 group and 150.4 (10.1) mm Hg in the I150 group. At week 10, the adjusted mean difference in home systolic blood pressure between groups was –8.8 (1.1) mm Hg ( P < 0.001). The percentage of controlled patients (mean home blood pressure <135 and 85 mm Hg) was nearly 2-fold higher in the I300/A5 group versus the I300 group ( P < 0.001). Treatment-emergent adverse events were experienced by 10.5% of I300/A5-treated patients and 6.6% of I300-treated patients during the second 5-week period. Three serious adverse events were reported; 2 with monotherapy (1 with I150 and 1 with I300) and 1 with fixed-dose combination I300/A5. All patients affected by serious adverse events made a full recovery. Conclusions These 10-week data from this patient population suggest a greater antihypertensive efficacy of the fixed-dose combination I300/A5 over I300 alone in lowering systolic blood pressure. Both treatments were well tolerated throughout the study. ClinicalTrials.gov identifier: NCT00957554.
Aims
Hypertension is a major contributor to cardiac diastolic dysfunction. Different therapeutics strategies have been proposed to control blood pressure (BP), but their independent impact on cardiac ...function remains undetermined. In patients with resistant hypertension, we compared the changes in cardiac parameters between two strategies based on sequential nephron blockade (NBD) with a combination of diuretics or sequential renin‐angiotensin system blockade (RASB).
Methods and results
After a 4‐week period where all patients received Irbesartan 300 mg/day + hydrochlorothiazide 12.5 mg/day + amlodipine 5 mg/day, 140 resistant hypertension patients (54.8 ± 11.1 years, 76% men, mean duration with hypertension: 13.1 ± 10.5 years, no previous history of heart failure or current symptoms of congestive heart failure) were randomized 1:1 to the NBD regimen or to the RASB regimen at week 0 (W0, baseline). Treatment intensity was increased at week 4, 8, or 10 if home BP was ≥135/85 mmHg, by sequentially adding 25 mg spironolactone, 20–40 mg furosemide, and 5 mg amiloride (NBD group) or 5–10 mg ramipril and 5–10 mg bisoprolol (RASB group). No other antihypertensive drug was allowed during the study. BP, BNP levels, and echocardiographic parameters were assessed at weeks 0 and 12.
The baseline characteristics, laboratory parameters, and plasma hormones (BNP, renin, and aldosterone) and cardiac echocardiographic parameters did not significantly differ between the NBD and the RASB groups. Over 12 weeks, BNP levels significantly decreased in NBD but increased in RASB (mean CI 95% change in log‐transformed BNP levels: −43% −67%; −23% vs. +55% 46%; 62% in NBD vs. RASB, respectively, P < 0.0001). Similarly, the proportion of patients presenting ≥2 echocardiographic criteria of diastolic dysfunction decreased between baseline and W12 from 31% to 3% in NBD but increased from 19% to 32% in RASB (P = 0.0048). As compared with RASB, NBD induced greater decrease in ambulatory systolic BP (P < 0.0001), pulse pressure (P < 0.0001), and systemic vascular resistance (P < 0.005). In multivariable linear regression analyses, NBD treatment was significantly associated with decreased BNP levels (adjusted ß: −46.41 ± 6.99, P < 0.0001) independent of age, gender, renal function, and changes in BPs or heart rate.
Conclusions
In patients with resistant hypertension, nephron blockade with a combination of diuretics significantly improves cardiac markers of diastolic dysfunction independently of BP lowering.
Prevalence of masked hypertension (MH) is far from negligible reaching 40% in some studies. The SHEAF study (Self measurement of blood pressure at Home in the Elderly: Assessment and Follow-Up) and ...others clearly showed that masked hypertension (MH) as detected by home blood pressure measurement (HBPM) is associated with poor cardiovascular prognosis.
Systematic HBPM to detect MH is not yet routine. The aim of this work is to better define the clinical profile of masked hypertensives within a population with controlled office blood pressure (BP) and the factors associated with a higher prevalence of MH.
BP was measured at the clinic by the doctor and at home by the patient himself. Risk factors for MH were analysed in a cohort of 1150 treated hypertensive patients over the age of 60 (mean age 70 +/- 6.5, 48.9% men) with controlled office BP. (SBP < 140 mmHg and DBP < 90 mmHg).
463 patients (40%) were masked hypertensives (SBP > or = 135 mmHg or DBP > or = 85 mmHg at home). Three parameters were associated with MH (odds ratio OR): office SBP (OR = 1.110), male gender (OR = 2.214) and age (OR = 1.031). Decision trees showed a 130 mmHg SBP was an efficient threshold to propose HBPM with a higher probability to detect MH. Subsequent variables were male gender and age over 70 in males.
To detect masked hypertension, it would be logical to first of all select patients whose office SBP is between 130 and 140 mmHg.
...36 of the 190 patients screened in the Symplicity HTN-2 (Renal Denervation in Patients With Uncontrolled Hypertension) trial (1) did not meet the BP criteria for inclusion, and 30 had a renal ...artery anatomy incompatible with RDN. ...we estimated the number of patients eligible for RDN by retrospectively reviewing the computerized medical records of all consecutive patients hospitalized for at least 1 day in 2011 at our tertiary hypertension center at a university hospital in Paris, France. ...the risk associated with this invasive procedure also depends on the careful selection of patients eligible for RDN as well as the experience of the radiologist/cardiologist conducting the intervention.
Phaeochromocytomas and paragangliomas (PPGL) can cause acute catecholamine cardiomyopathy (ACC). We assessed the prevalence of ACC and compared the presentation of cases with and without ACC in a ...large series of PPGL.
Single centre retrospective study.
Hypertension Unit, University Hospital, Paris.
140 consecutive patients with PPGL, referred from January 2003 to September 2012.
Left ventricular ejection fraction (LVEF), perioperative mortality.
Fifteen patients (11%) had suffered an ACC, occurring in 14 cases before the diagnosis of PPGL. Precipitating factors were identified in 11 cases. Twelve patients presented with acute pulmonary oedema, including 10 with cardiogenic shock, requiring life support in eight cases. Seven patients (five with pulmonary oedema) presented with acute chest pain and cardiac dysfunction. Electrocardiographic abnormalities were present in 14 cases: ST segment elevation or pathological Q waves, ST segment depression, and/or diffuse T wave inversion. Six patients displayed classical (apical ballooning) or inverted (basal/mid ventricular stunning) takotsubo-like cardiomyopathy. Coronary arteries were always normal on angiography. In patients with ACC, median LVEF rose from 30% (IQR 23-33%) during ACC to 71% (50-72%) before surgery (n=11, p<0.001). Median LVEF before PPGL surgery was 65% (51-72%) and 65% (60-70%) in patients with and without a history of ACC, respectively (not significant).
PPGL may present as ACC in 11% of cases, excluding patients dying from undiagnosed tumours. Left ventricular dysfunction is usually reversible before surgery. PPGL should be suspected in patients with acute heart failure without evidence of valvular or coronary artery disease.
Blood pressure (BP) measurement in clinicians' offices with a mercury sphygmomanometer has numerous drawbacks. In contrast, the use of home BP measurement improves measurement precision and ...reproducibility. However, data about its prognostic value are lacking.
To assess the prognostic value of home vs office BP measurement by general practitioners in a European population of elderly patients being treated for hypertension.
Office and home BP and cardiac risk factors were measured at baseline in a cohort of 4939 treated hypertensive patients (mean age, 70 SD, 6.5 years; 48.9% men) who were recruited and followed up by their usual general practitioners without specific recommendations about their management. The cohort was then followed up for a mean of 3.2 (SD, 0.5) years. The thresholds defining uncontrolled hypertension were at least 140/90 mm Hg for office BP and 135/85 mm Hg for home BP.
The primary end point was cardiovascular mortality. Secondary end points were total mortality and the combination of cardiovascular mortality, nonfatal myocardial infarction, nonfatal stroke, transient ischemic attack, hospitalization for angina or heart failure, percutaneous transluminal coronary angioplasty, or coronary artery bypass graft surgery.
At the end of follow-up, clinical status was known for 99.9% of patients. At least 1 cardiovascular event had occurred in 324 (incidence, 22.2/1000 patient-years). For BP self-measurement at home, each 10-mm Hg increase in systolic BP increased the risk of a cardiovascular event by 17.2% (95% confidence interval CI, 11.0%-23.8%) and each 5-mm Hg increase in diastolic BP increased that risk by 11.7% (95% CI, 5.7%-18.1%). Conversely, for the same increase in BP observed using office measurement, there was no significant increase in the risk of a cardiovascular event. In a multivariable model with patients having controlled hypertension (normal home and office BP) as the referent, the hazard ratio of cardiovascular events was 1.96 (95% CI, 1.27-3.02) in patients with uncontrolled hypertension (high BP with both measurement methods), 2.06 (95% CI, 1.22-3.47) in patients with normal office BP and elevated home BP, and 1.18 (95% CI, 0.67-2.10) in patients with elevated office BP and normal home BP.
Our findings suggest that home BP measurement has a better prognostic accuracy than office BP measurement. Blood pressure should systematically be measured at home in patients receiving treatment for hypertension.
The effect of renal artery angioplasty on blood pressure in patients with true resistant hypertension and atherosclerotic renal artery stenosis has not been fully investigated due to the exclusion of ...these patients from most trials. In this study, we assessed the benefits of renal angioplasty on daytime ambulatory blood pressure (dABP) in this subgroup of patients. Medical records of our hypertension department were retrospectively analyzed from 2000 to 2016. Seventy-two patients were identified with resistant hypertension (dABP >135 or 85 mm Hg despite at least 3 antihypertensive drugs, including a diuretic) and atherosclerotic renal artery stenosis treated by angioplasty. Atherosclerotic renal artery stenosis was unilateral in 57 patients and bilateral in 15 patients. The mean age of the patients was 67.8±11.2 years; dABP was 157±16/82±10 mm Hg despite 4.0±1.0 antihypertensive treatments; estimated glomerular filtration rate was 52 (41-63) mL/min. After renal angioplasty, dABPM decreased by 14.0±17.3/6.4±8.7 mm Hg (
<0.001 for both), and the number of antihypertensive treatments decreased to 3.6±1.4 (
=0.002) with no significant change in estimated glomerular filtration rate. A high baseline systolic dABP and a low body mass index were independent predictors of systolic dABP changes. The decrease in dABP was confirmed in a subgroup of patients at one and 3 years of follow-up (N=31 and N=18 respectively,
≤0.001 for systolic and diastolic blood pressure at both visits). In this retrospective uncontrolled single-center study, angioplasty in patients with atherosclerotic renal artery stenosis and with true resistant hypertension significantly decreased dABP, reducing the need for antihypertensive treatment with no change in estimated glomerular filtration rate.
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