Antihypertensive effect of barnidipine 10 mg or amlodipine 5 to 10 mg once daily in treatment-naive patients with essential hypertension: A 24-week, randomized, open-label, pilot study

Background: Dihydropyridine calcium antagonists are largely employed for the treatment of hypertension, coronary heart disease, and heart failure.Objective: The aim of our study was to compare the antihypertensive effect of the dihydropyridine calcium antagonists barnidipine and amlodipine.Methods: This was a 24-week, randomized, open-label, pilot study. Consecutive treatment-naive patients with grade I or II essential hypertension (office sitting systolic blood pressure [BP] of 140-179 mm Hg and diastolic BP of 90-109 mm Hg) were enrolled. The primary end points were the effect of treatment with either barnidipine 10 mg or amlodipine 5 mg once daily on office and ambulatory BP, left ventricular mass index (LVMI), and markers of cardiac damage, serum procollagen type I C-terminal propeptide, and plasma amino-terminal pro-B-type natriuretic peptide concentrations. Patients were assessed at enrollment, and 12 and 24 weeks. During each visit, the prevalence of adverse events (AEs) was also monitored using spontaneous reporting, patient interview, and physical examination, the relationship to study drug being determined by the investigators. Compliance with treatment was assessed at each study visit by counting returned tablets.Results: Thirty eligible patients (20 men, 10 women; mean [SD] age, 47 [12] years) were included in the study; all patients completed the 24 weeks of study treatment. Twelve weeks after randomization, 6 patients in the amlodipine group had their dose doubled to 10 mg due to inadequate BP control. Mean BP reductions at study end were not significantly different between the barnidipine and amlodipine groups (office BP, −10.3/−9.4 vs −16.6/−9.1 mm Hg; ambulatory BP, 9.4/6.4 vs 8.1/5.1 mm Hg). Reductions in LVMI and markers of cardiac damage were not significantly different between the 2 groups. Significantly more patients in the amlodipine group reported drug-related AEs compared with those in the barnidipine group (9 [60%] vs 2 [13%]; P < 0.05).Conclusion: In this small sample of treatment-naive hypertensive patients, the antihypertensive effect of barnidipine 10 mg once daily was not significantly different from that of amlodipine 5 to 10 mg once daily.     

Effects of the fixed combination of manidipine plus delapril in the treatment of hypertension inadequately controlled by monotherapy with either component: a phase III, multicenter, open-label, clinical trial

Background: Failure to achieve good blood pressure (BP) control is probably the most important reason for high rates of morbidity and mortality in patients with hypertension. Combination therapy has been shown to increase the percentage of patients in whom BP control is achieved. One combination is a calcium channel blocker (CCB) and an angiotensin-converting enzyme inhibitor (ACE-I).Objective: The aim of this study was to assess the effects of the fixed combination of the CCB manidipine and the ACE-I delapril in the treatment of hypertensive patients already given monotherapy with either component but with poor results (ie, insufficient BP control or adverse events [AEs]).Methods: In this Phase III, multicenter, open-label, clinical trial, patients with mild to moderate hypertension were assigned to 1 of 2 groups. Group 1 comprised patients whose diastolic BP (DBP) was >90 mm Hg or who experienced AEs with manidipine 20 mg once daily. Group 2 comprised patients who had a DBP >90 mm Hg or who experienced AEs with delapril 30 mg BID. In both groups, patients aged <65 years were to be treated with a fixed combination of manidipine 10 mg plus delapril 30 mg once daily for 12 weeks, whereas patients aged ≥65 years were to be treated with manidipine 5 mg plus delapril 15 mg once daily for 2 weeks and then manidipine 10 mg plus delapril 30 mg once daily for 10 weeks. Patients were assessed at baseline and at 2, 4, 8, and 12 weeks of treatment. At each visit, systolic blood pressure (SBP), DBP, and heart rate were measured 24 hours after dosing, and AEs were recorded.Results: Group 1 included 154 patients (80 men, 74 women; mean [SD] age, 55 [6] years); group 2 included 158 patients (79 men, 79 women; mean [SD] age, 56 [5] years). Mean BP decreased significantly in both groups (P<0.01). Compared with baseline values, mean SBP/DBP decreased 16.2 (3.8)/10.1 (1.9) mm Hg in group 1 and 15.8 (3.1)/11.0 (1.5) mm Hg in group 2 at the last visit. The success rate—rate of normalized DBP (≤90 mm Hg) and responder rate (DBP reduction ≥10 mm Hg)—was 79% in group 1 and 82% in group 2. The rates of treatment-related AEs were 11% in group 1 and 8% in group 2. In group 1, heart rate significantly increased from baseline only at 2 weeks (P<0.05); in group 2, at each visit (P<0.05) except at week 12. However, none of these differences were clinically significant.Conclusion: In this study population of patients whose BP was not adequately controlled by monotherapy, the fixed combination of manidipine 10 mg plus delapril 30 mg, once daily, was effective and well tolerated.     

Efficacy and tolerability of nebivolol monotherapy by baseline systolic blood pressure: A retrospective analysis of pooled data from two multicenter, 12-week,randomized, double-blind,placebo-controlled,parallel-group,dose-ranging studies in patients with mild to moderate essential hypertension

Background: In clinical studies, nebivolol at doses of 2.5 to 40 mg once daily was associated with significant decreases in systolic blood pressure (SBP) and diastolic BP (DBP) in patients with hypertension and was well tolerated.Objectives: This post hoc analysis of pooled data from 2 previously published registration studies was conducted to further evaluate the antihypertensive efficacy and tolerability of nebivolol in patients with mild to moderate (stage 1–2) hypertension.Methods: The 2 trials were similarly designed multicenter, 12-week, randomized, double-blind, placebocontrolled, parallel-group, dose-ranging studies in patients 18 years of age and older with stage 1 or 2 hypertension (SBP 140–159 mm Hg and/or DBP 90–99 mm Hg [stage 1] or SBP ≥ 160 mm Hg and/or DBP ≥ 100 mm Hg [stage 2]). The primary efficacy end point of the 2 studies was the change from baseline in mean trough SiDBP at week 12. A secondary end point was the change from baseline to week 12 in mean trough sitting SBP (SiSBP). The present analysis included only patients who received nebivolol 5, 10, or 20 mg (the doses were common to both studies) or placebo, including analyses stratified by baseline SBP, although DBP represented a criterion for entry into the studies. Baseline SBP stratification levels were 140 to 149 mm Hg, 150 to 159 mm Hg, 160 to 169 mm Hg, and 170 to 179 mm Hg. For the tolerability analysis, the prevalences of treatment-emergent adverse events (AEs) were compared between the 3 nebivolol dose groups and the placebo group.Results: Of the 1716 randomized patients who received study medication in the 2 trials, data from 1385 patients were included in this pooled analysis (759 men, 626 women; median age, ~54 years; 13.6% black). Mean (SD) baseline SiSBP and SiDBP values were 151.9 to 152.7 and 99.2 to 99.5 mm Hg, respectively. Reductions from baseline in trough SiSBP were ?10.8 (13.5), ?10.7 (14.7), and ?12.4 (15.5) mm Hg with nebivolol 5, 10, and 20 mg, respectively, compared with ?4.5 (13.4) mm Hg with placebo (all, P < 0.001). Reductions from baseline in trough SiDBP (the primary end point) were ?9.8 (7.9), ?10.5 (8.2), and ?11.1 (8.6) mm Hg with nebivolol 5, 10, and 20 mg, respectively, compared with ?5.1 (8.1) mm Hg with placebo (all, P < 0.001). In a subgroup of 1227 patients stratified by baseline SBP, the reductions in SBP and DBP were significantly greater (P < 0.03 and P < 0.001, respectively) with nebivolol at each dose compared with placebo in those with baseline SBP of 140 to 149 mm Hg and 150 to 159 mm Hg (the lowest 2 baseline strata); in the highest 2 baseline strata (SBP 160–169 and 170–179 mm Hg), the reductions in SBP with nebivolol 5 mg and nebivolol 20 mg in the 160 to 169-mm Hg baseline SBP stratum and in DBP with nebivolol 20 mg in the 170 to 179-mm Hg baseline stratum were significantly greater (P < 0.03) compared with placebo. The most common AE in the nebivolol 5?, 10?, and 20-mg groups and the placebo group was headache (36/409 [8.8%], 25/410 [6.1%], 27/410 [6.6%], and 10/156 [6.4], respectively), fol-lowed by fatigue (9/409 [2.2%], 10/410 [2.4%], 25/410 [6.1%], and 3/156 [1.9%]) and dizziness (6/409 [1.5%], 9/410 [2.2%], 15/410 [3.7%], and 4/156 [2.6%]).Conclusion: The present analysis of pooled data from 2 previously published registration studies found that nebivolol was associated with significant reductions in BP compared with placebo in these patients with stage 1 or 2 hypertension, with a tolerability similar to that of placebo.     

Efficacy and tolerability of two formulations of ramipril in Korean adults with mild to moderate essential hypertension: An 8-week,multicenter, prospective,randomized, open-label,parallel-group noninferiority trial

Objective: This study was designed to compare the efficacy and tolerability of a new generic formulation of ramipril (test) and the branded formulation of ramipril (reference) to satisfy regulatory requirements for marketing of the generic product for use in Korean patients with mild to moderate hypertension.Methods: This was an 8-week, multicenter, prospective, randomized, open-label, parallel-group non-inferiority trial in adult patients (age > 18 years) with mild to moderate essential hypertension (sitting dia-stolic blood pressure [SiDBP] 90–109 mm Hg). After a 2-week washout of previous antihypertensive medications, eligible patients were randomized to receive either ramipril 5 mg/d in the morning (low-dose group: baseline SiDBP 90–99 mm Hg) or ramipril 10 mg/d (high-dose group: baseline SiDBP 100–109 mm Hg) for the first 4 weeks. If SiDBP was ≥ 90 mm Hg after 4 weeks of treatment, the dose was increased to 10 mg/d for the remaining 4 weeks in the low-dose group, and hydrochlorothiazide 12.5 mg was added to the regimen for the remaining 4 weeks in the high-dose group. The primary end point was the change in SiDBP from baseline to week 8. Secondary end points included a noninferiority analysis of the test and reference formulations with respect to the change in mean sitting systolic blood pressure (SiSBP) from baseline to week 8; SiDBP and SiSBP response rates (proportion of patients achieving an SiDBP < 90 mm Hg and SiSBP < 140 mm Hg, respectively) at 8 weeks; and changes from baseline in SiSBP, pulse wave velocity (PWV), exercise capacity, left-ventricular diastolic function (LVDF), and levels of brain natriuretic peptide (BNP) and high-sensitivity C-reactive protein (hs-CRP). Laboratory and clinical adverse events (AEs) were monitored at each study visit (4 and 8 weeks).Results: The modified intent-to-treat population consisted of 89 patients (45 test, 44 reference; 60 men, 29 women; mean age, 49.7 years; mean weight, 69.9 kg). At week 8, mean (SD) SiSBP and SiDBP were significantly decreased from baseline in both groups (test: from 145.0 [9.7]/98.1 [5.3] mm Hg to 132.2 [11.1]/ 91.8 [7.1] mm Hg [P < 0.001]; reference: from 145.1 [11.4]/98.0 [5.7] mm Hg to 134.0 [14.6]/92.5 [7.9] mm Hg [P < 0.001]). The changes in blood pressure at week 8 did not differ significantly between the test and reference groups or between the low- and highdose groups in a subgroup analysis. Blood pressure response rates at 8 weeks did not differ significantly between the groups receiving the test and reference formulations (SiDBP: 26.7% and 31.8%, respectively; SiSBP: 37.8% and 40.9%). In addition, there were no significant between-group differences in the change in PWV (?63.8 and ?38.7 cm/sec), LVDF at rest or after exercise, or levels of BNP or hs-CRP. The incidence of AEs was 64.4% in the test formulation group and 68.2% in the reference group formulation (P = NS). The most common AE in both groups was cough (10/45 [22.2%] and 10/44 [22.7%]).Conclusions: There were no significant differences in the efficacy and tolerability of the test and reference formulations of ramipril in these Korean adults with mild to moderate hypertension. The new generic formulation was noninferior to the reference formulation in terms of the change in SiDBP at week 8.     

Effects of barnidipine on blood pressure and left ventricular diastolic function in patients with hypertension and metabolic syndrome: A 12-week, open-label noncomparison study

Background: Barnidipine is one of a new generation of dihydropyridine calcium-channel blockers. Despite evidence of favorable effects on blood pressure (BP) and insulin sensitivity, this drug has rarely been tested in hypertensive patients with metabolic syndrome (MS).Objective: The aim of this study was to evaluate the effects of barnidipine on BP and left ventricular (LV) diastolic function in patients with hypertension and MS.Methods: Consecutive subjects aged 18 to 75 years with systolic BP (SBP) of 140 to 179 mm Hg and/or diastolic BP (DBP) of 90 to 109 mm Hg and MS (based on Adult Treatment Panel III criteria) were assessed for inclusion in the study. Lifestyle changes according to current guidelines were recommended and barnidipine monotherapy 10 mg daily was initiated. All patients entered a 2-week run-in period. After a 6-week treatment period, the daily dosage was doubled for the remainder of the study in patients whose BP remained uncontrolled (≥140/≥90 mm Hg). We assessed the glycolipidic profile and LV structure and function using standard Doppler and tissue Doppler imaging (TDI) echocardiography before and after 12 weeks of treatment. Ambulatory BP records and electrocardiographic and echocardiographic tracings were coded and shipped to a central laboratory for blinded analysis. Possible adverse events (AEs) were recorded at predetermined intervals throughout the follow-up period and at unplanned intervals whenever an AE became known to the investigators.Results: Thirty-four consecutive patients were assessed for inclusion. Thirty consecutive patients (20 men, 10 women; mean {SD| age, 55.9 {10.3| years; 5 current smokers) were included in the study. At study entry, mean office SBP was 146 mm Hg, DBP was 87 mm Hg, and heart rate was 72 beats/min. At the study end, mean office SBP/DBP was <140/90 mm Hg in 20 patients (66.7%). From baseline to study end, 24-hour ambulatory BP decreased significantly by 12 and 8 mm Hg for SBP and DBP, respectively (both, P = 0.001). The smoothness index was 0.92 for SBP and 0.82 for DBP. Fasting plasma glucose concentration decreased significantly from 110 to 104 mg/dL (P = 0.001). Total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol concentrations did not change significantly. From baseline to study end, there were no significant changes in LV structure or systolic function (LV mass, 50.7 vs 50.6 g/ht^2.7; LV diastolic/systolic diameters, 47.50/29.80 vs 48.40/30.76 mm; wall motion score index, 1.0 vs 1.0; ejection fraction, 61% vs 60%), while the peak E/A velocity ratio on TDI increased from 1.078 to 1.245 (P = 0.009). No AEs (including AEs reflected by chemistry values) either unrelated or related to treatment were noted during the 12-week duration of the study.Conclusions: In these hypertensive patients with MS, a 12-week treatment period with barnidipine in addition to lifestyle modifications was associated with significant reductions in 24-hour BP and BP variability, reduction in plasma glucose concentration, and improvement in LV diastolic relaxation. No significant changes in lipid concentrations, LV structure, or systolic function were found.     

Effects of valsartan treatment on indicators of cardiovascular damage in newly diagnosed hypertensive patients: A prospective, twelve-month, open-label, pilot study

Background: Myocardial fibrosis and dysfunction can be detected in the early phases of organ damage associated with hypertension. Valsartan, an angiotensin-II receptor blocker, is efficacious in lowering blood pressure (BP) and reducing left ventricular mass in patients with hypertension. Levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and procollagen type I carboxy-terminal propeptide (PICP) are correlated with organ damage in patients with overt congestive heart failure; however, few data are available in patients with hypertension.Objective: The aim of this study was to assess the effects of 12 months of valsartan treatment on echocardiographic measures and indices of organ damage (NT-proBNP and PICP) in newly diagnosed patients with hypertension.Methods: This was a prospective, open-label, single-center, exploratory study. Patients with newly diagnosed, previously untreated hypertension were treated for 12 months with valsartan 160 mg/d and compared with an equal number of healthy, untreated control subjects. Baseline and follow-up visits at 3, 6, and 12 months included physical examination, systolic BP (SBP) and diastolic BP (DBP) measurements, ECG, echocardiography, and NT-proBNP and PICP determination.Results: A total of 20 patients (mean [SD] age, 48.05 [7.29] years) were enrolled and compared with 20 healthy controls (age, 49-6 [6.95] years). Compared with baseline, valsartan was associated with reduced BP in the group with hypertension after 12 months of treatment (mean SBP, 150.05 [11.15] vs 120.00 [8.43] mm Hg, P < 0.001; DBP, 97.80 [8.36] vs 79-50 [4.26] mm Hg, P < 0.001). Compared with the control group, at baseline, the group with hypertension had significantly higher mean left ventricular mass index (LVMI) (119.88 [22.86] vs 87.31 [15.77] g/m²; P < 0.001), relative wall thickness (thickness/radius [h/r] ratio: 0.45 [0.08] vs 0.35 [0.07]; P = 0.001), and NT-proBNP (50.00 [32.01] vs 25.47 [9.69] pg/dL; P = 0.002). PICP was higher, but the difference was not statistically significant (46.10 [15.69] vs 37.50 [7.20] μg/L). After 12 months, treatment with valsartan was associated with significant reductions in all measured parameters compared with baseline (LVMI, 106.51 [17.12] g/m², P = 0.004; h/r, 0.41 [0.07], P = 0.026; NT-proBNP, 22.55 [13.52] pg/dL, P = 0.001; PICP, 35.20 [9-19] μg/L, P < 0.008). At 12 months, patients with hypertension treated with valsartan achieved NT-proBNP and PICP levels not statistically different from those of the healthy controls (NT-proBNP, 22.55 [13-52] vs 25.24 [8.43] pg/dL; PICP, 35.20 [9.19] vs 36.90 [6.41] μg/L).Conclusion: Patients treated with valsartan for 12 months had significant reductions in BP, LVMI, and indices of subclinical organ damage (NT-proBNP and PICP) compared with baseline.     

Efficacy and Tolerability of Nilvadipine in Combination with an Angiotensin II Receptor Antagonist in Patients with Essential Hypertension: A Multicenter, Open-Label, Uncontrolled Study

Background: Combination therapy with different classes of antihypertensive drugs often is needed to achieve controlled blood pressure (BP). The combination of an angiotensin II receptor antagonist (AIIA) and a calcium antagonist is a preferred option for reducing uncontrolled BP.Objective: The aim of this study was to assess the clinical efficacy and tolerability of nilvadipine, a dihydropyridine calcium antagonist, in combination with an AIIA.Methods: Patients with essential hypertension whose BP was not controlled by an AIIA alone were eligible for this multicenter, open-label, uncontrolled study. One of 3 AIIAs (candesartan cilexetil, losartan potassium, or valsartan) was given for at least 10 weeks before the addition of nilvadipine (daily dose, 4 or 8 mg orally). This combination therapy was given for 8 weeks. BP and heart rate were measured between 2 and 4 weeks before and 0, 4, and 8 weeks after the start of combination therapy. Adverse events were monitored at each visit.Results: Thirty-one patients (18 women [58.1%], 13 men [41.9%]; mean [SD] age, 58.5 [10.5] years) were enrolled. At weeks 4 and 8 of combination therapy, mean systolic BP (SBP) and diastolic BP (DBP) were significantly decreased (P<0.01) (at week 8, by 22.0 mm Hg and 12.5 mm Hg, respectively). The mean BP-lowering effect did not differ significantly between the 3 AIIAs tested. Pulse pressure also decreased significantly at week 8, by 9.6 mm Hg (P<0.01). The responder rate (ie, the percentage of patients with DBP <90 mm Hg or a decrease in DBP ≥10 mm Hg) was 72.0% at week 8. Three patients experienced a total of 4 adverse events: mild or severe flushing, mild headache, and mild palpitation. All of these symptoms resolved after nilvadipine treatment was discontinued.Conclusions: Nilvadipine in combination with an AIIA showed good antihypertensive efficacy and was well tolerated in the hypertensive patients in this study. This combination also significantly decreased pulse pressure, suggesting that this combination therapy also may have a beneficial effect in elderly patients with isolated systolic hypertension.     

Effects of amlodipine and candesartan on arterial stiffness estimated by cardio-ankle vascular index in patients with essential hypertension: A 24-week study

Background: Aortic stiffness assessed by brachio-ankle pulse wave velocity (baPWV) can be used to predict cardiovascular events. However, baPWV is dependent on blood pressure. Antihypertensive drugs have been reported to reduce baPWV; but it is difficult to determine if this effect is associated with lowered blood pressure or reduced arterial stiffness.Objectives: The primary end point of this study was to assess whether antihypertensive drugs reduce arterial stiffness as estimated by cardio-ankle vascular index (CAVI). The secondary end point was to compare the effects of 2 widely used drugs, the calcium-channel blocker amlodipine and the angiotensin II receptor blocker candesartan, on arterial stiffness.Methods: Between October 2005 and September 2006, consecutive Japanese outpatients with essential hypertension (EHT) (defined as using antihypertensive drugs at screening, systolic blood pressure [SBP] > 140 mm Hg, or diastolic BP [DBP] >90 mm Hg) were assigned to treatment for 24 weeks with either amlodipine (5-10 mg/d) or candesartan (8-12 mg/d). Arterial stiffness was evaluated with CAVI before and after 24 weeks of treatment. Relative change in arterial stiffness from baseline was also compared. The evaluator was blinded to treatment.Results: Twenty patients (11 men, 9 women; mean [SD] age, 62 [10] years) were included in the study. There were no significant differences in clinical characteristics between the 2 groups. At baseline, mean (SD) CAVI was not significantly different in the amlodipine group compared with the candesartan group (8.93 [0.93] vs 8.46 [1.34], respectively). During the 24-week treatment period, mean SBP and DBP decreased significantly in both the amlodipine (14/10 mm Hg; P = 0.006 and P = 0.005) and the candesartan groups (13/11 mm Hg; P = 0.033 and P = 0.005). Amlodipine was associated with a significant change in CAVI from baseline (8.93 [0.93] vs 8.60 [1.50]; P = 0.017), whereas candesartan was not (8.46 [1.34] vs 8.81 [1.20]). The percentage change in CAVI was significantly different in the amlodipine group compared with the candesartan group (−7.14 [8.83] vs 5.85 [16.0], respectively; P = 0.038). After 24 weeks of treatment, the CAVI of the amlodipine group was still numerically larger than baseline CAVI of the candesartan group, although the difference was not statistically significant. Furthermore, there was no significant difference in absolute CAVI between the 2 groups after 24 weeks, but the relative change from baseline was significant in favor of amlodipine. Logistic regression analysis revealed that amlodipine improved CAVI independent of its antihypertensive effect.Conclusion: These data suggest that amlodipine and candesartan had different effects on aortic stiffness estimated by CAVI, despite similar effects on brachial blood pressure after 24 weeks of treatment in these Japanese patients with EHT.     

Irbesartan monotherapy in systemic hypertension: An open-label, uncontrolled trial

Background: Irbesartan is an orally active, specific blocker of the AT₁ receptor of angiotensin II that produces insurmountable antagonism. Irbesartan's plasma half-life of 11 to 15 hours and higher affinity for the AT₁ receptor versus other angiotensin II receptor subtypes may make it a suitable choice for once-daily treatment of hypertension. Few studies have examined the efficacy of this agent in Asian patients.Objective: The purpose of this open-label, uncontrolled study was to assess the 24-hour efficacy of irbesartan once-daily monotherapy in Chinese outpatients with mild to moderate hypertension.Methods: Patients with stage I or stage II hypertension (as defined by the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure) were treated with irbesartan once daily for 6 to 8 weeks. The dose of irbesartan was titrated from an initial dose of 150 mg to 275 mg or 300 mg if adequate blood pressure (BP) control was not achieved by week 3 or 4; doses were taken once daily between 8 am and 9 am. For each patient, 24-hour ambulatory BP monitoring was performed twice, once before and once after 6 to 8 weeks of treatment.Results: A total of 25 patients (mean age, 54 years) were enrolled; 24 completed the study. Mean 24-hour systolic/diastolic BP after irbesartan treatment was significantly decreased compared with baseline values (128 ± 14 mm Hg/82 ± 8 mm Hg vs 143 ± 12 mm Hg/91 ± 7 mm Hg, P < 0.05 for both). The mean final dose of irbesartan was 243.8 ± 63.5 mg daily after a 7-week titration period. Mean daytime (6 am to 6 pm) BP decreased from 146 ± 11 mm Hg/94 ± 7 mm Hg to 130 ± 14 mm Hg/84 ± 8 mm Hg (P < 0.05), and nighttime (6 pm to 6 am) BP decreased from 139 ± 14 mm Hg/88 ± 7 mm Hg to 127 ± 15 mm Hg/81 ± 9 mm Hg (P < 0.05). The BP decrease was more pronounced during the day. Before treatment, the circadian variation showed a peak BP at 11 am and a nadir at 4 am. After treatment, significant BP reductions versus baseline (P < 0.05 for both diastolic and systolic BP) were observed for 23 of the 24 hourly mean points. The circadian rhythm of BP cycles was preserved. Mean heart rate did not change after treatment. Two patients reported dizziness and 1 reported heartburn.Conclusions: Irbesartan administered as once-daily monotherapy provided effective BP control during 23 of the 24 hourly mean points while preserving the circadian rhythm of BP cycles, and was well tolerated.     

Effectiveness of hydrochlorothiazide in combination with telmisartan and olmesartan in adults with moderate hypertension not controlled with monotherapy: a prospective, randomized, open-label, blinded end point (PROBE), parallel-arm study

Background:The potential combinations of antihypertensive agents are many, and making rational choices depends on the characteristics of each drug and on their complementary mechanisms of action.Objective: The aim of this study was to evaluate the effectiveness of adding hydrochlorothiazide (HCTZ) 12.5 mg to olmesartan 20 mg or telmisartan 80 mg on blood pressure (BP) in patients with moderate hypertension.Methods: Consecutive outpatients at the Centro per l'Ipertensione e la Fisiopatologia Cardiovascolare, University of Pavia, Pavia, Italy, of both sexes aged 39 to 75 years were considered eligible for enrollment if they had a sitting diastolic BP (DBP) ->99 mm Hg and <110 mm Hg at the end of an initial 2-week washout period. Patients were random- ized to olmesartan 20 mg QD or telmisartan 80 mg QD according to a prospective, open-label, blinded end point, parallel-arm design. After 8 weeks of monotherapy, patients whose BP was not controlled (DBP ->90 mm Hg) received HCTZ 12.5 mg QD for 8 additional weeks. Clinical and ambulatory BPs were measured at the end of the washout period and at the end of both treatment periods. Adverse events (AEs) were recorded from spontaneous reports and direct inquiry from investigators.Results: One hundred forty-five patients, all of whom were white, were recruited for the study. After the initial washout period, 13 patients did not meet the inclusion criteria and 6 refused to continue. A total of 126 white patients (69 men, 57 women; mean [SD] age, 60.2 [11.6] years) were randomized to receive monotherapy. Of these, 35 patients (56%) in the olmesartan group and 33 (52%) in the telmisartan group had previously received antihypertensive therapy. At the end of monotherapy, the 52 patients in the olmesartan group and the 49 patients in the telmisartan treatment group who were still in the study and had their BP inadequately controlled by treatment had HCTZ 12.5 mg QD added to their treatment regimen. Both combinations induced a greater ambulatory mean (SD) systolic BP (SBP) and DBP reduction than monothera- py (SBP: 145.3 [6.1] in the olmesartan group and 140.1 [6.4] in the telmisartan group, P < 0.05; DBP: 88.1 [5.1] in the olmesartan group and 84.9 [4.9] in the telmisartan group, P < 0.05). The mean (SD) reduction from baseline in the telmisartan/HCTZ-treated patients (21.5 [10.1]/14.6 [5.2] mm Hg for 24 hours, 21.8 [10.2]/14.9 [5.2] mm Hg for daytime, and 20.4 [10.3]/13.7 [5.9] mm Hg for nighttime; all, P < 0.001 vs baseline) was significantly greater than that observed in the olmesartan/HCTZ-treated patients (18.8 [9.8]/12.3 [4.9] mm Hg for 24 hours, 19.3 [9.8]/12.8 [4.9] mm Hg for daytime, and 17.4 [10.2]/10.6 [5.5] mm Hg for nighttime; all, P < 0.001 vs baseline), with a significant difference between the 2 treatment groups (P < 0.01). Compared with mono- therapy, the add-on effect of HCTZ 12.5 mg QD administration was significantly greater in the telmisartan group than in the olmesartan group (P < 0.05); the differ- ence being more evident for nighttime BP values (SBP, P 0.031; DBP, P 0.025). Reported AEs were similar in the olmesartan/HCTZ and the telmisartan/HCTZ groups (4 patients [7%] vs 3 patients [6%]).Conclusion: The addition of HCTZ 12.5 mg to telmisartan 80 mg monothera- py was associated with greater BP reduction than the addition of the same dose of HCTZ to olmesartan 20 nag monotherapy in these patients previously uncontrolled on monotherapy.     

Association of Hypertension with Knee Pain Severity Among People with Knee Osteoarthritis

PurposeTo examine the association of hypertension with knee pain severity in individuals with knee osteoarthritis (OA).DesignCross-sectional study of baseline data collected by the Osteoarthritis Initiative.MethodsParticipants with knee OA (N=1,363) were categorized into four groups based on blood pressure (BP): 1) systolic < 120 mm HG and diastolic < 80 mm Hg; 2) 120 ≤ systolic < 130 mm Hg and diastolic < 80 mm Hg; 3) 130 ≤ systolic < 140 mm Hg or 80 ≤ diastolic < 90 mm Hg; 4) systolic ≥ 140 mm Hg or diastolic ≥ 90 mm Hg. OA knee pain severity was measured by Pain subscale of Western Ontario and McMaster Universities Osteoarthritis Index in the past 48 hours, Pain subscale of Knee Injury and Osteoarthritis Outcome Score (KOOS) in the past 7 days, and numeric rating scale (NRS) in the past 30 days. Linear regression was used to examine the relationship between hypertension and knee pain severity.ResultsCompared with the normal BP group, individuals with stage 2 hypertension reported significantly higher OA knee pain severity by KOOS in the past 7 days (β=-2.05 [95% CI -4.09, -0.01], p=0.049) and by NRS in the past 30 days (β=0.31 [95% CI 0.01, 0.62], p=0.045) after adjustments for demographic and medical factors.ConclusionsHypertension was associated with higher OA knee pain severity in individuals with knee OA.Clinical ImplicationsNurses can recommend adjunctive non-pharmacological treatments and adherence strategies to help control hypertension, which may help decrease OA knee pain.     

Efficacy and Safety of 30-Mg Fimasartan for the Treatment of Patients With Mild to Moderate Hypertension: An 8-Week,Multicenter, Randomized,Double-Blind,Phase III Clinical Study

Purpose

The standard 60-mg dose of fimasartan, a newly developed selective angiotensin II receptor blocker, is effective and safe for use in patients with mild to moderate hypertension. This study aimed to compare the efficacy and safety of low-dose (30 mg) fimasartan and placebo or valsartan (80 mg) for 8 weeks in patients with mild to moderate hypertension.

Methods

In this randomized trial, 293 patients (219 men; mean age, 54.24 [9.77] years) with mild to moderate hypertension were enrolled. After randomization to receive 30-mg fimasartan (n = 115), placebo (n = 117), or 80-mg valsartan (n = 61), the treatment dose was kept constant without dose escalation for 8 weeks. The primary end point was improvement in sitting diastolic blood pressure (SiDBP) from baseline to 8 weeks that was compared between treatments with low-dose fimasartan and placebo. The secondary end point was the overall efficacy and safety of low-dose fimasartan compared with that of placebo or valsartan.

Findings

At week 8, SiDBP changed by –9.93 (8.86) mm Hg in the fimasartan group and by –2.08 (9.47) mm Hg in the placebo group, which indicated significant antihypertensive efficacy (P < 0.0001). Efficacy was shown at week 4 as measured by SiDBP (–9.96 [7.73] vs –2.27 [7.85] mm Hg; P < 0.0001) or sitting systolic blood pressure (SiSBP) (–16.18 [14.44] vs –1.95 [13.48] mmHg; P < 0.0001) and at week 8 as determined by SiSBP (–15.35 [16.63] vs –2.30 [14.91] mm Hg; P < 0.0001). The fimasartan group exhibited more potent antihypertensive efficacy than the valsartan group both at week 4 (SiDBP, –9.96 [7.73] vs –6.53 [9.58] mm Hg [P = 0.0123]; SiSBP, –16.18 [14.4] vs –7.65 [12.89] mm Hg [P = 0.0002]) and at week 8 (SiDBP, –9.93 [8.86] vs –5.47 [8.96] mm Hg [P = 0.0021]; SiSBP, –15.35 [16.63] vs –7.49 [13.68] mm Hg [P = 0.0021]). Most treatment-emergent adverse events (TEAEs) were mild (89 of 95), and there were no serious TEAEs. The incidence of TEAEs was 19.1% in the fimasartan group, 22.6% in the placebo group, and 13.6% in the valsartan group, with no significant differences.

Implications

Low-dose fimasartan (30 mg) was well tolerated during the study period with no significant TEAEs. Low-dose fimasartan had an effective blood pressure–lowering effect that was greater than that of 80-mg valsartan in patients with mild to moderate hypertension. ClinicalTrials.gov identifier: NCT01672476.     

Antihypertensive effect of zofenopril plus hydrochlorothiazide versus zofenopril monotherapy in patients with essential hypertension according to their cardiovascular risk level: A post hoc analysis

Background: International guidelines recommend the use of angiotensin-converting enzyme inhibitors, possibly in combination with other antihypertensive drugs, to treat hypertension with associated risk factors.Objective: The aim of this study was to compare the antihypertensive effect of the combination of zofenopril plus hydrochlorothiazide versus zofenopril monotherapy in patients with essential hypertension, according to their cardiovascular risk level.Methods: This was a post hoc analysis of a previously published efficacy and tolerability study. After a 4-week placebo washout, patients with mild to moderate essential hypertension (diastolic blood pressure [DBP] 95-115 mm Hg), aged 18 to 75 years, were randomized at a ratio of 2:1:1 to treatment with zofenopril 30 mg plus hydrochlorothiazide 12.5 mg or monotherapy with zofenopril 30 mg or hydrochlorothiazide 12.5 mg for 12 weeks in an international, multicenter, double-blind study. This period was followed by 24 weeks of open-label treatment. Systolic BP [SBP] and DBP were measured by mercury sphygmomanometry, and changes associated with treatment were calculated. Patients' cardiovascular risk was computed using the Heart Score algorithm. Patients were classified in quartiles according to distribution of cardiovascular risk level, and comparisons were limited to the zofenopril plus hydrochlorothiazide and zofenopril monotherapy treatment groups. The primary end point was change in office DBP.Results: Two hundred forty-six patients (139 men, 107 women; mean [SD] age, 54 [11] years) were included in the analysis. Mean baseline cardiovascular risk was similar in the zofenopril plus hydrochlorothiazide group and the zofenopril monotherapy group (7% vs 9%). DBP and SBP reductions with treatment were significantly greater (both, P < 0.01) with combination treatment than with monotherapy for each quartile of cardiovascular risk. Cardiovascular risk reduction at the end of the 12 weeks of double-blind treatment was greater in the zofenopril plus hydrochlorothiazide group than in the zofenopril monotherapy group (1.9% vs 0.2%; P < 0.01), particularly in the group of patients with the highest cardiovascular risk at baseline (5.2% vs 2.0%). At the end of the 24-week open-label treatment period, the mean reduction in cardiovascular risk was also significantly greater in the combination treatment group than in the monotherapy group (1.4% vs 0.5%; P < 0.01).Conclusions: In these hypertensive patients, combination treatment with zofenopril plus hydrochlorothiazide was associated with a significantly greater decrease in BP compared with zofenopril monotherapy, regardless of the patient's cardiovascular risk. The difference between combination treatment and monotherapy was particularly evident for the group of patients at highest risk.     

Comparison of amlodipine and enalapril in the treatment of isolated systolic hypertension in the elderly: an open-label, randomized, parallel-group study

Background: The benefits of treating isolated systolic hypertension (ISH) are well established, but the most appropriate drug choice is still uncertain.Objective: The purpose of this study was to compare amlodipine, a calcium channel blocker, with enalapril, an angiotensin-converting enzyme inhibitor, in the treatment of ISH in a cohort of elderly patients (≥60 years of age).Methods: Ambulatory patients with ISH (seated systolic blood pressure [SBP] >160 mm Hg and <220 mm Hg; diastolic blood pressure [DBP] <95 mm Hg) who had not been treated previously or who had stopped their medication at least 4 weeks before the study were enrolled. Patients were randomized to receive amlodipine 5 mg/d or enalapril 10 mg/d. After 4 weeks of treatment, the dose was doubled for those patients whose sitting SBP had not decreased to <150 mm Hg or by >20 mm Hg, and treatment was continued for an additional 4 weeks.Results: A total of 89 patients were randomized to treatment, 46 to amlodipine and 43 to enalapril; 1 patient in the enalapril group died due to ischemic stroke despite adequate blood pressure control. The absolute reductions in seated and standing SBP/DBP were similar with both drugs after 8 weeks: 27 mm Hg/4.6 mm Hg with amlodipine and 23.9 mm Hg/3.9 mm Hg with enalapril (sitting) and 25.1 mm Hg/4.1 mm Hg and 21.3 mm Hg/4.2 mm Hg (standing) with amlodipine and enalapril, respectively (P = NS). At 4 weeks, 24 patients (52.2%) in the amlodipine group and 33 patients (76.7%) in the enalapril group had their medication dose doubled because their SBP was not adequately controlled with the initial dose (P < 0.01). At the end of the study, 24 patients were taking 10 mg amlodipine and 22 patients were taking 5 mg (mean dose 7.6 ± 2.5 mg); 33 patients were taking 20 mg enalapril and 10 patients were taking 10 mg (mean dose 17.8 ± 4.1 mg). Side effects occurred significantly more frequently in the amlodipine group (P = 0.01).Conclusion: The results of this study suggest that amlodipine and enalapril are similarly effective in treating ISH in elderly patients, with few side effects.     

Postmarketing surveillance study of benazepril in chinese patients with hypertension: An open-label, experimental, epidemiologic study

Background

Benazepril hydrochloride is an angiotensin-converting enzyme inhibitor. Previous clinical trials show that antihypertensive treatment with benazepril provides effective blood pressure (BP) control and is generally well tolerated by patients with hypertension. However, the long-term antihypertensive effects and tolerability of benazepril remain to be established in Chinese patients with hypertension.

Objective

The aim of this study was to investigate the long-term efficacy and tolerability of benazepril in Chinese patients with essential hypertension.

Methods

This 36-month, community-based, open-label, postmarketing surveillance study was conducted in the Nanshi District (Shanghai, China). Chinese patients with essential hypertension were to receive 1 or more benazepril tablets PO QD in the morning for 36 months. Data for BP and pulse pressure (PP) were collected at baseline (month 0) and throughout the surveillance period. The rate of patients achieving BP targets (systolic BP [SBP]/diastolic BP [DBP], <140/<90 mm Hg) was determined, as was the rate of decrease in BP. Subanalyses by sex and age group also were conducted.

Results

A total of 1831 patients (1090 men, 741 women; mean [SD] age, 55.8 [10.1] years [range, 35-88 years]) entered the study. After the 36-month treatment period, 75.7% of patients receiving benazepril as prescribed (1289 patients) had achieved the SBP target, 87.4% achieved the DBP target, and 71.5% achieved both targets. After 36 months of treatment, the mean (SD) decreases in SBP, DBP, and PP were 15.1 (0.4) mm Hg, 11.0 (0.3) mm Hg, and 4.2 (0.4) mm Hg, respectively, among compliers. In general, the rate of BP decrease slowed over time. No serious adverse drug reactions (ADRs) were detected during the 36-month follow-up period. All ADRs except cough (19.9%) occurred at a relatively low incidence rate (<3.0%). The cumulative incidence of benazepril related cough was statistically significantly higher in women than in men (23.6% vs 18.8%, respectively; P = 0.007). Of the 1831 patients studied, 1360 patients (74.3%) persisted in taking benazepril and were considered optimally compliant at 36-month follow-up.

Conclusion

In this study of Chinese patients with hypertension, benazepril was associated with prolonged, stable efficacy in lowering BP and relatively low incidence of ADRs.     

Effects of low-dose treatment with felodipine versus fosinopril in Chinese patients with nonischemic heart failure and normal blood pressure: A double-blind, randomized, crossover study

Background: Two second-generation calcium channel blockers, felodipine and amlodipine besylate, have been associated with similar high mortality rates in patients with ischemic heart failure (HF) but not in patients with nonischemic causes of HF. In patients with nonischemic HF, amlodipine might have a beneficial effect on survival. However, no difference in mortality rates was found between felodipine and placebo in a nonischemic HF group. Felodipine 10 mg/d was used in 1 large study, a dose considered high for nonischemic HF usually associated with normal blood pressure (BP).Objective: The aim of this study was to compare the effects of 12-week, low-dose treatment with felodipine versus those of an angiotensin-converting enzyme inhibitor, fosinopril sodium, in patients with nonischemic HF and normal BP.Methods: This double-blind, randomized, crossover trial was conducted at Taipei Medical University Hospital (Taipei, Taiwan). Patients aged ≥ 18 years with angiographically proved, nonischemic HF and normal BP who were being treated with an optimal regimen of digitalis and diuretics were enrolled. After a 2-week run-in period, patients were randomized to first receive 12 weeks of treatment with felodipine tablets (2.5 mg/d) or fosinopril tablets (7.5 mg/d) and, after a 2-week washout period, were crossed over to the opposite treatment. Efficacy analysis was performed before (baseline) and after treatment and included symptomatic assessment using a 7-grade clinical scale; 2-dimensional echocardiography (2-D echo); exercise tests; and neurohumoral data, including plasma renin activity, plasma aldosterone, and 24-hour urinary epinephrine (E) and norepinephrine (NE) measurements. The primary end point was death due to HF, and the secondary end point was hospital admission due to worsening HF. Compliance was measured using a pill count at the end of each treatment period.Results: We enrolled 33 patients. One developed worsening HF during the run-in period and was admitted. A total of 32 patients entered the study (18 men, 14 women; mean [SD] age, 48.2 [6.3] years [range, 34-56 years]; mean [SD] systolic BP, 117.2 [9.8] mm Hg [range, 100-138 mm Hg]; mean [SD] diastolic BP, 59.4 [5.7] mm Hg [range, 50-72 mm Hg]). No hospital admission or cardiac death due to HF occurred during 12 weeks of treatment. Twenty-seven patients were included in the felodipine assessment, and 30 patients were included in the fosinopril assessment. Significant improvement in clinical score was noted in both treatment groups (both P < 0.01). The clinical scores did not differ significantly between the 2 treatments. No significant differences were found in 2-D echo parameters between treatments or within groups after treatment versus baseline. Significant improvement in exercise duration was noted with both study drugs after treatment versus baseline (both P < 0.01). No significant difference in exercise duration was found between the 2 treatments. Urinary E and NE were not significantly different between treatments or after treatment with either study drug compared with baseline.Conclusion: The present findings suggest that, in Chinese patients with moderate to severe HF who have normal BP and insignificant coronary artery disease and were being treated with diuretics and digitalis, a 12-week, low-dose course of felodipine (2.5 mg/d) as a vasodilator was associated with as satisfactory an outcome as standard treatment with fosinopril (7.5 mg/d).     

Treatment of hypertension in an elderly outpatient population in the Netherlands

Background: The treatment of older patients with hypertension has been controversial—in addition to uncertainty regarding appropriate blood pressure (BP) targets in the very old, there are concerns that excessive BP lowering could result in adverse events such as falls, stroke, and cognitive problems. The Hypertension in the Very Elderly Trial (HYVET), however, found that lowering BP in patients aged ≥80 years was associated with decreased morbidity and mortality.Objective: This study compared the findings of HYVET with data from a population of elderly outpatients with hypertension in a clinical practice setting.Methods: This was a retrospective study of prospectively collected data from patients aged ≥80 years with a history of hypertension who visited a geriatric diagnostic day clinic in the Netherlands in 2004. The data were analyzed to determine how many patients were being prescribed antihypertensive medication, how many would have been eligible for HYVET, how many achieved adequate BP control, and whether reaching BP goals was associated with the number and type of antihypertensive medications received or with eligibility for HYVET.Results: During 2004, 518 patients aged ≥80 years visited the geriatric diagnostic day clinic, of whom 147 met the criteria for inclusion in this study. One hundred forty-one patients (95.9%) were receiving antihypertensive medication, although only 52 (35.4%) would have been eligible for HYVET. Dementia, which was an exclusion criterion in HYVET, was the major reason for ineligibility (70 [47.6%]). Greater proportions of patients in this study had comorbidities compared with the HYVET population (stroke: 22.4% vs 6.7%, respectively; myocardial infarction: 7.5% vs 3.1%; heart failure: 11.6% vs 2.9%; diabetes mellitus: 21.1% vs 6.8%). At the time of the clinic visit, 50.3% of patients had adequate BP control, as defined in HYVET (systolic BP <150 mm Hg and diastolic BP <80 mm Hg). Levels of BP control were similar in patients who would and would not have been ineligible for HYVET. Only the mean (SD) number of antihypertensive medications received was significantly associated with the achievement of BP control compared with failure to achieve adequate BP control (2.2 [1.0] vs 1.8 [1.1], respectively; P < 0.05).Conclusions: Based on the findings of this study, the benefits of treating elderly patients with hypertension in clinical practice may be lower than those reported by HYVET. The study results support the current recommendation that all patients with hypertension should be treated with >1 antihypertensive medication if adequate control is not achieved at low doses of a single medication.     

Primary Care–based,Pharmacist–physician Collaborative Medication-therapy Management of Hypertension: A Randomized,Pragmatic Trial

Purpose

A collaborative pharmacist–primary care provider (PharmD-PCP) team approach to medication-therapy management (MTM), with pharmacists initiating and changing medications at separate office visits, holds promise for the cost-effective management of hypertension, but has not been evaluated in many systematic trials. The primary objective of this study was to examine blood pressure (BP) control in hypertensive patients managed by a newly formed PharmD-PCP MTM team versus usual care in a university-based primary care clinic.

Methods

This randomized, pragmatic clinical trial was conducted in hypertensive patients randomly selected for PharmD-PCP MTM or usual care. In the PharmD-PCP MTM group, pharmacists managed drug-therapy initiation and monitoring, medication adjustments, biometric assessments, laboratory tests, and patient education. In the usual-care group, patients continued to see their PCPs. Participants were aged ≥18 years, were diagnosed with hypertension, had a most recent BP measurement of ≥140/≥90 mm Hg (≥130/≥80 mm Hg if codiagnosed with diabetes mellitus), were on at least 1 antihypertensive medication, and were English speaking. The primary outcome was the difference in the mean change from baseline in systolic BP at 6 months. Secondary outcomes included the percentage achieving therapeutic BP goal and the mean changes from baseline in diastolic BP and low- and high-density lipoprotein cholesterol.

Findings

A total of 166 patients were enrolled (69 men; mean age, 67.7 years; PharmD-PCP MTM group, n = 75; usual-care group, n = 91). Mean reduction in SBP was significantly greater in the PharmD-PCP MTM group at 6 months (–7.1 [19.4] vs +1.6 [21.0] mm Hg; P = 0.008), but the difference was no longer statistically significant at 9 months (–5.2 [16.9] vs –1.7 [17.7] mm Hg; P = 0.22), based on an intent-to-treat analysis. In the intervention group, greater percentages of patients who continued to see the MTM pharmacist versus those who returned to their PCP were at goal at 6 months (81% vs 44%) and at 9 months (70% vs 52%). No significant between-group differences in changes in cholesterol were detected at 6 and 9 months; however, the mean baseline values were near recommended levels. The PharmD-PCP MTM group had significantly fewer PCP visits compared with the usual-care group (1.8 [1.5] vs 4.2 [1.0]; P < 0.001).

Implications

A PharmD-PCP collaborative MTM service was more effective in lowering BP than was usual care at 6 months in all patients and at 9 months in patients who continued to see the pharmacist. Incorporating pharmacists into the primary care team may be a successful strategy for managing medication therapy, improving patient outcomes and possibly extending the capacity of primary care. ClinicalTrials.gov identifier: NCT01973556.     

Effect of Catheter-Based Renal Denervation on Uncontrolled Hypertension: A Systematic Review and Meta-analysis

ObjectiveTo assess the efficacy and safety of catheter-based renal denervation (RDN) for the treatment of uncontrolled hypertension by conducting a systematic review and a meta-analysis.MethodsThe Medline, Cochrane Library, and Embase databases were searched for clinical studies between January 1, 2009, and July 16, 2018. Studies that evaluated the effect of RDN on uncontrolled hypertension were identified. The primary endpoints were changes in 24-hour ambulatory systolic blood pressure (BP) and office systolic BP. The secondary endpoints included changes in 24-hour ambulatory diastolic BP, office diastolic BP, and major adverse events.ResultsAfter a literature search and detailed evaluation, 12 randomized controlled trials with a total of 1539 individuals were included in the quantitative analysis. Pooled analyses indicated that RDN was associated with a significantly greater reduction of 24-hour systolic BP (mean difference [MD], ?4.02 mm Hg; 95% CI, ?5.49 to ?2.56; P<.001) and office systolic BP (MD, ?8.93 mm Hg; 95% CI, ?14.03 to ?3.83; P<.001) than controls. Similarly, RDN significantly reduced 24-hour diastolic BP (MD, ?2.05 mm Hg; 95% CI, ?3.05 to ?1.05; P<.001) and office diastolic BP (MD, ?4.49 mm Hg; 95% CI, ?6.46 to ?2.52; P<.001). RDN was not associated with an increased risk of major adverse events (relative risk, 1.06; 95% CI, 0.72 to 1.57; P=.76).ConclusionsCatheter-based RDN was associated with a significant BP-lowering benefit without increasing major adverse events.