Efficacy of nebivolol-valsartan single-pill combination in obese and nonobese patients with hypertension.
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ABSTRACT:
SUBMITTER: Mende CW
PROVIDER: S-EPMC5484387 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The single-pill combination (SPC) comprising nebivolol (5 mg), a vasodilatory β1 -selective antagonist/β3 -agonist, and valsartan (80 mg), a renin-angiotensin-aldosterone system inhibitor, is the only Food and Drug Administration-approved β-blocker/renin-angiotensin-aldosterone system inhibitor SPC for hypertension. Additive effects of four nebivolol/valsartan SPC doses (5 mg/80 mg, 5/160 mg, 10/160 mg, 10/320 mg nebivolol/valsartan) were compared with five Food and Drug Administration-approved non-β-blocker/renin-angiotensin-aldosterone system inhibitor SPCs (aliskiren/hydrochlorothiazide, aliskiren/amlodipine, valsartan/amlodipine, aliskiren/valsartan, and telmisartan/amlodipine). Additivity is the ratio of placebo-adjusted SPC blood pressure (BP) reduction to the placebo-adjusted monotherapy component BP reduction sums. A weighted average of comparator scores was calculated and compared vs nebivolol/valsartan. Additivity ratio scores for nebivolol/valsartan SPCs (diastolic BP range: 0.735-0.866; systolic BP range: 0.717-0.822) were similar to the comparator weighted average (diastolic BP: 0.837; systolic BP: 0.825). Among the nebivolol/valsartan SPCs, 5/80 mg had the greatest additivity (diastolic BP: 0.866; systolic BP: 0.822). BP reduction contributions with monotherapy were similar for nebivolol/valsartan 5/80 mg SPC. Additivity scores for nebivolol/valsartan and select non-β-blocker/renin-angiotensin-aldosterone system inhibitor SPCs were comparable.
| S-EPMC5813198 | biostudies-literature
Project description:IntroductionSingle-pill combination (SPC) therapy of two drugs is recommended by international guidelines, including the Chinese guidelines (2010), for the treatment of hypertension in high-risk patients who require marked blood pressure (BP) reductions. Real-world data on the efficacy and safety of valsartan/amlodipine (Val/Aml) SPC are scarce. The present study is the first observational study in China to evaluate the efficacy (primary endpoint) and safety of Val/Aml (80/5 mg) SPC in Chinese patients with hypertension whose BP was not adequately controlled by monotherapy in a real-world setting.MethodsThis prospective, multicenter, open-label, post-marketing observational study included 11,422 Chinese adults (≥18 years) with essential hypertension from 238 sites of 29 provinces who were prescribed once-daily Val/Aml (80/5 mg) SPC. Patients were treated for 8 weeks. The primary efficacy variable of the study included changes in mean sitting systolic BP (MSSBP) and mean diastolic BP (MSDBP) from baseline to week 8 (end point). The secondary efficacy variable of the study included BP control rate and response rate at week 4 and 8. Safety assessments included recording and measurement of all adverse events (AEs) and vital signs in the safety population.ResultsA significant reduction of 27.1 mmHg in MSSBP (159.6 vs. 132.5 mmHg; P < 0.0001) and 15.2 mmHg in MSDBP (95.6 vs. 80.4 mmHg; P < 0.0001) from baseline was observed at week 8. The BP-lowering efficacy of Val/Aml SPC was independent of age and comorbidities. BP control of <140/90 mmHg was achieved in 76.8% (n = 8,692) of the patients. The most frequently reported AEs were dizziness (0.2%), headache (0.2%), upper respiratory tract infection (0.2%), and edema (0.2%). Only three serious AEs were reported and they were not drug-related.ConclusionThis is the first evidence-based real-world data in Chinese hypertensive patients which demonstrate the efficacy and safety of Val/Aml (80/5 mg) SPC.
| S-EPMC4115183 | biostudies-literature
Project description:: To treat hypertension, combining two or more antihypertensive drugs from different classes is often necessary. β-Blockers and renin-angiotensin-aldosterone system inhibitors, when combined, have been deemed 'less effective' based on partially overlapping mechanisms of action and limited evidence. Recently, the single-pill combination (SPC) of nebivolol (Neb) 5 mg - a vasodilatory β1-selective antagonist/β3 agonist - and valsartan 80 mg, an angiotensin II receptor blocker, was US Food and Drug Administration-approved for hypertension. Pharmacological profiles of Neb and valsartan, alone and combined, are well characterized. In addition, a large 8-week randomized trial in stages I-II hypertensive patients (N = 4161) demonstrated greater blood pressure-reducing efficacy for Neb/valsartan SPCs than component monotherapies with comparable tolerability. In a biomarkers substudy (N = 805), Neb/valsartan SPCs prevented valsartan-induced increases in plasma renin, and a greater reduction in plasma aldosterone was observed with the highest SPC dose vs. valsartan 320 mg/day. This review summarizes preclinical and clinical evidence supporting Neb/valsartan as an efficacious and well tolerated combination treatment for hypertension.
| S-EPMC5548499 | biostudies-other
Project description:The use of multiple drug regimens is increasingly recognized as a tacit requirement for the management of hypertension, a necessity fueled in part by rising rates of metabolic syndrome and diabetes. By targeting complementary pathways, combinations of antihypertensive drugs can be applied to provide effective blood pressure control while minimizing side effects and reducing exposure to high doses of individual medications. In addition, combination therapies, including angiotensin converting enzyme (ACE) inhibitors and calcium channel blockers (CCBs), have the added benefit of reducing cardiovascular mortality and morbidity over other dual therapies while providing equivalent blood pressure control. It is possible that angiotensin receptor blockers (ARBs), which unlike ACE inhibitors are minimally affected by upregulation of alternative pathways for angiotensin II accumulation following long-term treatment, would also provide such outcome benefits. At issue, however, is maintaining patient compliance, as adding medications is known to reduce adherence to treatment regimens. The purpose of this review is to summarize existing trial data for the long-term safety and efficacy of a recent addition to the armamentarium of dual-antihypertensive therapeutic options, the telmisartan/amlodipine single pill combination. The areas where long-term data are lacking, notably clinical information regarding minorities and women, will also be discussed.
| S-EPMC3606043 | biostudies-literature
Project description:IntroductionPatients with hypertension often require a combination of three antihypertensive agents to achieve blood pressure control, but very few single-pill triple combinations are available. The aim of this study was to determine whether a single-pill triple combination of perindopril, indapamide, and amlodipine was as effective as a dual-pill combination of perindopril/indapamide plus separate amlodipine at reducing blood pressure in patients with uncontrolled, essential hypertension.MethodsThis international, multicenter, open-label, randomized controlled trial was conducted in men or women aged ≥18 years old with confirmed essential hypertension (SBP ≥140 and <160 mmHg and DBP ≥90 and <100 mmHg), uncontrolled on maximal dose antihypertensive monotherapy or with a single dose of dual therapy. Patients were randomly assigned to: single-pill triple combination of perindopril 5 mg/indapamide 1.25 mg/amlodipine 5 mg (Per/Ind/Aml) or dual-pill combination perindopril 5 mg/indapamide 1.25 mg + amlodipine 5 mg (Per/Ind + Aml) once daily for 12 weeks. The primary endpoint was change in office supine SBP and DBP from baseline to week 12. The proportion of responders defined as those with normalized BP (SBP <140 mmHg and DBP <90 mmHg), and/or decrease of SBP ≥20 mmHg, and/or decrease of DBP ≥10 mmHg at week 12 (W12) compared with baseline was also assessed. Secondary efficacy endpoints included change in office supine SBP and DBP, response, and BP control at weeks 4 and 8. The tolerability of the treatments was also assessed.ResultsA total of 148 patients were randomized: 75 to Per/Ind/Aml and 73 to Per/Ind + Aml. Mean supine SBP and DBP were 149.1 ± 4.7 and 94.1 ± 3.1 mmHg, respectively, with no relevant between-group difference. At week 12, both triple-therapy regimens were associated with clinically significant reductions in SBP compared with baseline (-21.5 ± 11.7 and -20.0 ± 12.9 mmHg, respectively). Reductions in office supine DBP were also clinically significant (-15.3 ± 7.8 and -14.8 ± 9.0 mmHg, respectively). The proportion of treatment responders was high in both groups: 89.2 and 87.1%, respectively. The reduction in office supine SBP/DBP was already evident at week 4 and maintained for the duration of the study in both groups. The majority of patients were treatment responders at week 4 (89.2 and 82.9%, respectively) and had achieved BP control (87.8 vs. 78.6%, respectively), which was maintained until week 12 in both treatment groups. Both treatments were well tolerated with no between-group differences.ConclusionsIn adult patients with uncontrolled essential hypertension on treatment, single-pill triple-combination therapy with Per/Ind/Aml is as effective as the same dose dual-pill combination of Per/Ind + Aml. Both treatments were associated with clinically significant BP reductions compared with baseline and were well tolerated. Clinical trials number: http://www.controlled-trials.com ISRCTN: 16442558.FundingLes Laboratoires Servier.
| S-EPMC5446818 | biostudies-literature
Project description:Despite significant advances in pharmacologic approaches to treat hypertension during the last decades, hypertension- and hypertension-related organ damage are still a high health and economic burden because a large proportion of patients with hypertension do not achieve optimal blood pressure control. There is now general agreement that combination therapy with two or more antihypertensive drugs is required for targeted blood pressure accomplishment and reduction of global cardiovascular risk. The goals of combination therapies are to reduce long-term cardiovascular events by targeting different mechanism underlying hypertension and target organ disease, to block the counterregulatory pathways activated by monotherapies, to improve tolerability and decrease the adverse effects of up-titrated single agents, and to increase persistence and adherence with antihypertensive therapy. Multiple clinical trials provide evidence that fixed-dose combinations in a single pill offer several advantages when compared with loose-dose combinations. This review discusses the advances in hypertension control and associated cardiovascular disease as they relate to the prospect of combination therapy targeting a third-generation beta (?) 1-adrenergic receptor (nebivolol) and an angiotensin II receptor blocker (valsartan) in fixed-dose single-pill formulations.
| S-EPMC4251532 | biostudies-literature
Project description:ObjectiveTo project the 10-year clinical outcomes associated with single pill combination (SPC) therapies compared with multi-pill regimens for the management of hypertension in five countries (Italy, Russia, China, South Korea and Mexico).MethodsA microsimulation model was designed to project health outcomes between 2020 and 2030 for populations with hypertension managed according to four different treatment pathways: current treatment practices (CTP), single drug with dosage titration then sequential addition of other agents (start low and go slow, SLGS), free choice combination with multiple pills (FCC) and combination therapy in the form of a single pill (SPC). Model inputs were derived from the Global Burden of Disease 2017 dataset. Simulated outcomes of mortality, chronic kidney disease (CKD), stroke, ischemic heart disease (IHD), and disability-adjusted life years (DALYs) were estimated for 1,000,000 patients on each treatment pathway.ResultsSPC therapy was projected to improve clinical outcomes over SLGS, FCC and CTP in all countries. SPC reduced mortality by 5.4% in Italy, 4.9% in Russia, 4.5% in China, 2.3% in South Korea and 3.6% in Mexico versus CTP and showed greater reductions in mortality than SLGS and FCC. The projected incidence of clinical events was reduced by 11.5% in Italy, 9.2% in Russia, 8.4% in China, 4.9% in South Korea and 6.7% in Mexico for SPC versus CTP.ConclusionsTen-year projections indicated that combination therapies (FCC and SPC) are likely to reduce the burden of hypertension compared with conventional management approaches, with SPC showing the greatest overall benefits due to improved adherence.
| S-EPMC8790100 | biostudies-literature
Project description:The home blood pressure (BP) control by a single-pill combination of cilnidipine (an L-/N-type calcium channel blocker; CCB) and valsartan (HOPE-Combi) survey is a multicenter, post-marketing, prospective observational study of a single-pill combination of cilnidipine 10 mg and valsartan 80 mg (SPC of Cil/Val) in patients with uncontrolled hypertension. We examined the effects of the SPC of Cil/Val on morning home systolic BP (MHSBP) and morning home pulse pressure (MHPP) of 1036 patients with hypertension over 12 months. MHSBP decreased by 14.0 mm Hg (P < .01), and MHPP decreased by 6.6 mm Hg (P < .01). Moreover, morning home pulse rate (MHPR) decreased by 2.1 bpm (P < .01). A more progressive and greater decrease in MHSBP (-17.2 vs -10.3 mm Hg, P < .01) and MHPP (-7.6 vs -4.9 mm Hg, P < .01) was observed in patients with higher MHPR (≥70 bpm) than in those with lower MHPR (<70 bpm) over the treatment period. In particular, in patients with a wide MHPP (≥70 mm Hg), the difference in the MHPP reduction was greater in patients with higher MHPR than in those with lower MHPR (-17.9 vs -13.6 mm Hg, P < .01). These results suggested that the SPC of Cil/Val, which possesses the unique sympatholytic characteristics of an L-/N-type CCB, was particularly effective in patients with uncontrolled hypertension and sympathetic hyperactivity.
| S-EPMC8029828 | biostudies-literature
Project description:This 8-week, randomized, double-blind, controlled study compared efficacy and tolerability of telmisartan/amlodipine (T/A) single-pill combination (SPC) vs the respective monotherapies in 858 patients with severe hypertension (systolic/diastolic blood pressure [SBP/DBP] ≥180/95 mm Hg). At 8 weeks, T/A provided significantly greater reductions from baseline in seated trough cuff SBP/DBP (-47.5 mm Hg/-18.7 mm Hg) vs T (P<.0001) or A (P=.0002) monotherapy; superior reductions were also evident at 1, 2, 4, and 6 weeks. Blood pressure (BP) goal and response rates were consistently higher with T/A vs T or A. T/A was well tolerated, with less frequent treatment-related adverse events vs A (12.6% vs 16.4%) and a numerically lower incidence of peripheral edema and treatment discontinuation. In conclusion, treatment of patients with substantially elevated BP with T/A SPCs resulted in high and significantly greater BP reductions and higher BP goal and response rates than the respective monotherapies. T/A SPCs were well tolerated.
| S-EPMC8108787 | biostudies-literature
Project description:ObjectiveDespite antihypertensive treatment, most hypertensive patients still have high blood pressure (BP), notably high systolic blood pressure (SBP). The EFFICIENT study examines the efficacy and acceptability of a single-pill combination of sustained-release (SR) indapamide, a thiazide-like diuretic, and amlodipine, a calcium channel blocker (CCB), in the management of hypertension.MethodsPatients who were previously uncontrolled on CCB monotherapy (BP≥140/90 mm Hg) or were previously untreated with grade 2 or 3 essential hypertension (BP≥160/100 mm Hg) received a single-pill combination tablet containing indapamide SR 1.5 mg and amlodipine 5 mg daily for 45 days, in this multicenter prospective phase 4 study. The primary outcome was mean change in BP from baseline; percentage of patients achieving BP control (BP<140/90 mm Hg) was a secondary endpoint. SBP reduction (ΔSBP) versus diastolic BP reduction (ΔDBP) was evaluated (ΔSBP/ΔDBP) from baseline to day 45. Safety and tolerability were also assessed.ResultsMean baseline BP of 196 patients (mean age 52.3 years) was 160.2/97.9 mm Hg. After 45 days, mean SBP decreased by 28.5 mm Hg (95% CI, 26.4 to 30.6), while diastolic BP decreased by 15.6 mm Hg (95% CI, 14.5 to 16.7). BP control (<140/90 mm Hg) was achieved in 85% patients. ΔSBP/ΔDBP was 1.82 in the overall population. Few patients (n = 3 [2%]) reported side effects, and most (n = 194 [99%]) adhered to treatment.ConclusionIn patients who were previously uncontrolled on CCB monotherapy or untreated with grade 2 or 3 hypertension, single-pill combination indapamide SR/amlodipine reduced BP effectively--especially SBP--over 45 days, and was safe and well tolerated.Trial registrationClinical Trial Registry-India CTRI/2010/091/000114.
| S-EPMC3979648 | biostudies-literature