Clinical outcomes and healthcare costs in hypertensive patients treated with a fixed-dose combination of amlodipine/valsartan.
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ABSTRACT:
SUBMITTER: Tung YC
PROVIDER: S-EPMC8031572 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:To compare the fixed-dose combination (FDC) of amlodipine/valsartan 5/80?mg with valsartan 160?mg monotherapy for efficacy and safety in hypertensive patients. METHODS:We designed this double-blind, randomized, and noninferiority trial in which patients with elevated systolic blood pressure (SBP) and/or diastolic blood pressure (DBP) were randomly assigned to receive amlodipine/valsartan 5/80?mg FDC or valsartan 160?mg monotherapy for 8 weeks. The primary endpoint was changes in office SBP and DBP from baseline to 8 weeks. Twenty-four-hour blood pressure (BP) and the incidence of adverse events were recorded. RESULTS:A total of 42 patients underwent randomization. At 8 weeks, office SBP changes were -16.5 ± 15.5 mmHg (p < 0.001) with amlodipine/valsartan 5/80?mg FDC and -6.9 ± 11.4 mmHg (p = 0.012) with valsartan 160?mg monotherapy while corresponding changes in office DBP were -9.8 ± 7.7 mmHg (p < 0.001) and -2.5 ± 6.6 mmHg (p = 0.095), respectively. The between-group differences were -9.6 mmHg (95% CI, -18.1 to -1.1; p = 0.028) for SBP and -7.3 mmHg (95% CI, -11.8 to -2.8; p = 0.002) for DBP. Furthermore, reductions in both 24-hour SBP (-9.2 mmHg; 95% CI, -16.4 to -2.1; p = 0.013) and DBP (-4.6 mmHg; 95% CI, -9.2 to -0.1; p = 0.048) were consistently greater with amlodipine/valsartan 5/80?mg FDC than with valsartan 160?mg. Overall, 27 and 23 adverse events occurred in the amlodipine/valsartan 5/80?mg FDC group and in the valsartan 160?mg monotherapy group, respectively. The majority were mild and were not related to study medications. There were no significant differences in safety between two treatments. CONCLUSION:Efficacy of amlodipine/valsartan 5/80?mg FDC was superior to that of valsartan 160?mg monotherapy while both treatments were well-tolerated.
| S-EPMC7526577 | biostudies-literature
Project description:The objective of study was to compare the pharmacokinetic and safety profiles of a fixed-dose combination (FDC) formulation of 5/160/20 mg amlodipine/valsartan/atorvastatin with those of separate formulations of a 5/160-mg amlodipine/valsartan tablet and a 20-mg atorvastatin tablet. This was a randomized, open-label, single-dose, 3-sequence, 3-period replicate crossover study with 42 subjects. Serial blood samples for pharmacokinetic assessment were collected up to 72 hours postdose. For establishing bioequivalence (BE) for amlodipine, valsartan, and atorvastatin, a reference-scaled average BE approach was used if applicable, as well as the conventional limit of 0.80-1.25. The 90% confidence intervals (CIs) for the geometric mean ratios (GMRs) for the maximum plasma concentration (Cmax ) and the area under the curve to the last measurable concentration (AUCt ) between the FDC and separate formulations were within the 0.80-1.25 limit for all analytes but atorvastatin. The estimated within-subject standard deviation of the log-transformed values of the separate formulations, the reference intervention, was 0.3804 for the Cmax of atorvastatin, being set at 0.7489-1.3352 for the BE acceptance limit. For both the Cmax and AUCt for atorvastatin, the GMRs lay within 0.80-1.25, and the 90%CIs for the GMRs were within the BE acceptance limit. This 3-period replicate crossover study demonstrated the BE of the FDC formulation of amlodipine, valsartan, and atorvastatin and the separate formulations of an amlodipine/valsartan tablet and an atorvastatin tablet. A similar incidence of treatment-emergent adverse events (TEAEs) was observed in both interventions, and headache was the most common TEAE.
| S-EPMC7187173 | biostudies-literature
Project description:Two or more antihypertensive agents are required to achieve blood pressure control for the most hypertensive patients. However, comparison of clinical outcomes between fixed-dose combinations (FDC) and free-equivalent combinations of renin-angiotensin system (RAS) inhibitor and thiazide diuretic is lacking nowadays. Patients who were newly diagnosed with hypertension between July 1st, 2008 and December 31st, 2011 and prescribed with FDC (n = 13 176) or free combinations of RAS inhibitors and thiazide diuretic (n = 4392) were identified from the National Health Insurance Research Database of Taiwan and matched in 3:1 ratio using the propensity score method. The primary end point was major adverse cardiovascular events (MACE). The secondary end points were hospitalization of heart failure, new diagnosis of chronic kidney disease, and the initiation of dialysis. Compared with he FDC group was associated with better medication adherence compared with the free combination group. FDC of RAS inhibitor and thiazide diuretic reduced MACE (hazard ratio [HR]: 0.85; 95% confidence interval [CI]: 0.74-0.97; P = 0.017), hospitalization for heart failure and initiation of dialysis compared with the free combination regimens. The outcome benefits of FDC was mainly driven by reduced cardiovascular and renal events in the patients with proportion of days covered <80%. In this retrospective claims database analysis, compared with the free combination regimens, the use of FDC of RAS inhibitor and thiazide diuretic was associated with improved medication compliance and clinical outcomes in the management of hypertension, particularly in the patients with poor medication adherence.
| S-EPMC8031089 | biostudies-literature
Project description:AimsTo demonstrate the benefit of the combination amlodipine/valsartan 5/160 mg over amlodipine 10 mg, in producing a lower incidence of peripheral oedema for a comparable mean sitting systolic blood pressure (MSSBP) reduction.MethodsAfter a 4-week amlodipine 5 mg run-in phase, inadequately controlled hypertension patients (aged > or = 55 years, MSSBP > or = 130 and < or = 160 mmHg) were randomised to receive amlodipine/valsartan 5/160 mg or amlodipine 10 mg for 8 weeks, followed by amlodipine/valsartan 5/160 mg for 4 weeks for all patients. Primary variables were MSSBP change from baseline to week 8 and incidence of peripheral oedema reported as an AE. Resolution of peripheral oedema was assessed 4 weeks after switching patients from amlodipine 10 mg to amlodipine/ valsartan 5/160 mg.ResultsAt week 8, MSSBP showed greater reduction with amlodipine/valsartan 5/160 mg than amlodipine 10 mg (least square mean: -8.01 vs.-5.95 mmHg, p < 0.001 for non-inferiority and p = 0.002 for superiority). Systolic control, overall BP control and systolic response rate at week 8 were significantly higher with combination than amlodipine 10 mg (34 vs. 26%; 57 vs. 50%; 36.57 vs. 27.77%, respectively). Incidence of peripheral oedema was significantly lower with the combination than amlodipine 10 mg (6.6 vs. 31.1%, p < 0.001). Peripheral oedema resolved in 56% patients who switched from amlodipine 10 mg to the combination, without the loss of effect on BP reduction.ConclusionIn non-responders to amlodipine 5 mg, treatment with amlodipine/valsartan 5/160 mg induced significantly less peripheral oedema than amlodipine 10 mg for similar BP reduction. Peripheral oedema resolved in > 50% patients switching from amlodipine 10 mg to the combination.
| S-EPMC2705817 | biostudies-literature
Project description:This post hoc analysis from the Sevikar Compared to the Combination of Perindopril Plus Amlodipine on Central Arterial Blood Pressure in Patients With Moderate-to-Severe Hypertension (SEVITENSION) study assessed the efficacy and tolerability of olmesartan (OLM) and amlodipine (AML) in reducing central systolic blood pressure (CSBP) compared with perindopril (PER) plus AML in hypertensive patients with type 2 diabetes. Patients were randomized to OLM/AML 40/10 mg or PER/AML 8/10 mg for 24 weeks. The primary efficacy endpoint was the absolute change in CSBP from baseline to week 24, which was greater with OLM/AML (-13.72±1.14 mm Hg) compared with PER/AML (-10.21±1.11 mm Hg). The between-group difference was -3.51±1.60 mm Hg (95% confidence interval, -6.66 to -0.36 mm Hg) and was within the noninferiority margin (2 mm Hg) as well as the superiority margin (0 mm Hg). In addition, OLM/AML was associated with a higher proportion of patients achieving blood pressure normalization. In hypertensive patients with diabetes, the fixed-dose combination of OLM/AML was superior to PER/AML in reducing CSBP, as well as other secondary endpoints.
| S-EPMC8032048 | biostudies-literature
Project description:IntroductionMany patients need more than one antihypertensive agent for effective blood pressure (BP) control. Prescription of a fixed-dose combination (FDC) of bisoprolol and amlodipine in one tablet has been shown to significantly improve patient adherence. This non-interventional study investigated the effects on adherence and BP control of switching from a free-dose combination of the two antihypertensive substances to a FDC in a larger patient population.MethodsPatients aged ?18 years with essential hypertension were switched at least 4 weeks prior to study initiation from a free-dose combination of bisoprolol and amlodipine to the FDC. Dosage adjustment was implemented only if medically indicated. Adherence was assessed on the basis of the ratio of pills used to pills dispensed (%) at each visit (pill count). BP and key laboratory values were determined at baseline, 3 and 6 months.Results10,532 patients (average age 59 years; 48% female) were recruited between 2013 and 2014; 22% of patients had type 2 diabetes and 38% had cardiovascular disease. The mean doses of the freely combined drugs prior to switching were 5.5 mg bisoprolol and 6.1 mg amlodipine once daily. The mean daily doses prescribed in the FDC were 5.8 and 6.4 mg, respectively. Pill counts at 6 months revealed a good to excellent adherence in >95% of the patients. Comparison of BP at baseline and at 6 months showed substantial changes (mean systolic BP: 147.3 vs. 130.9 mmHg; mean diastolic BP: 87.9 vs. 79.1 mmHg). Clinically relevant improvement in systolic BP was established for 82% of patients. In patients with comorbidities, switching to FDC produced a substantial improvement in BP. A total of 89 (0.7%) adverse events (AEs) were reported, including edema, headache, dizziness, bradycardia, nausea, and skin reactions. Only three AEs were classified as serious.ConclusionThese data from a non-interventional study in a large patient population demonstrate the benefits of prescribing a FDC of bisoprolol-amlodipine in terms of an excellent adherence and an associated improvement in control of previously elevated BP, which may be relevant in real-life practice.FundingMerck KGaA.
| S-EPMC4675749 | biostudies-literature
Project description:Heart failure is a global problem with elevated prevalence, and it is associated with substantial cardiovascular morbidity and mortality. Treating heart-failure patients has been a very challenging task. This review highlights the main pharmacological developments in the field of heart failure with reduced ejection fraction, giving emphasis to a drug that has a dual-acting inhibition of the neprilysin and renin-angiotensin-aldosterone system. Neprilysin is an enzyme that participates in the breakdown of biologically active natriuretic peptides and several other vasoactive compounds. The inhibition of neprilysin has been a therapeutic target for several drugs tested in cardiovascular disease, mainly for heart failure and/or hypertension. However, side effects and a lack of efficacy led to discontinuation of their development. LCZ696 is a first-in-class neprilysin- and angiotensin-receptor inhibitor that has been developed for use in heart failure. This drug is composed of two molecular moieties in a single crystalline complex: a neprilysin-inhibitor prodrug (sacubitril) and the angiotensin-receptor blocker (valsartan). The PARADIGM-HF trial demonstrated that this drug was superior to an angiotensin-converting enzyme inhibitor (enalapril) in reducing mortality in patients with heart failure with reduced ejection fraction. The ability to block the angiotensin receptor and augment the endogenous natriuretic peptide system provides a distinctive mechanism of action in cardiovascular disease.
| S-EPMC4869613 | biostudies-other
Project description:Background: Uncontrolled blood pressure is a major risk factor for cardiovascular diseases. Fixed-dose combination (FDC) therapy offers a promising approach to addressing this challenge by providing a convenient single-tablet solution that enhances the effectiveness of blood pressure control. In our systematic review, we assess the effectiveness of perindopril/amlodipine FDC in managing blood pressure. Methods: We conducted a comprehensive search across four primary electronic databases, namely, PubMed, Virtual Health Library (VHL), Global Health Library (GHL), and Google Scholar, as of 8 February 2022. Additionally, we performed a manual search to find relevant articles. The quality of the selected articles was evaluated using the Study Quality Assessment Tools (SQAT) checklist from the National Institute of Health and the ROB2 tool from Cochrane. Results: Our systematic review included 17 eligible articles. The findings show that the use of perindopril/amlodipine FDC significantly lowers blood pressure and enhances the quality of blood pressure control. Compared to the comparison group, the perindopril/amlodipine combination tablet resulted in a higher rate of blood pressure response and normalization. Importantly, perindopril/amlodipine FDC contributes to improved patient adherence with minimal side effects. However, studies conducted to date have not provided assessments of the cost-effectiveness of perindopril/amlodipine FDC. Conclusion: In summary, our analysis confirms the effectiveness of perindopril/amlodipine FDC in lowering blood pressure, with combination therapy outperforming monotherapy and placebo. Although mild adverse reactions were observed in a small subset of participants, cost-effectiveness assessments for this treatment remain lacking in the literature.
| S-EPMC10895423 | biostudies-literature
Project description:Hypertension remains a significant health burden in the United States, with almost one in three adults affected, and is an independent risk factor for cardiovascular and renal disease. The goal of antihypertensive treatment is to reduce cardiovascular and renal morbidity and mortality by reducing blood pressure (BP). Guidelines recommend a target BP of <140/90 mmHg, with a more stringent goal of <130/80 mmHg for patients with diabetes and chronic renal disease. However, BP goal attainment rates remain low and most patients require therapy with two or more antihypertensive agents. Combination antihypertensive therapy usually employs agents from different classes, thus benefitting from complementary mechanisms of action to achieve greater BP control with fewer side effects. Patient adherence to therapy is enhanced by formulating treatments as fixed-dose (single-pill) combinations. One example is the combination of amlodipine, a dihydropyridine calcium channel blocker (CCB), with olmesartan medoxomil, an angiotensin receptor blocker (ARB). Here, the rationale for the use of CCB/ARB combination therapy is discussed, as well as the pharmacology and tolerability of the amlodipine/olmesartan medoxomil combination and its efficacy in terms of achieving BP goal in patients with hypertension. Advantages of its use from the patient's perspective are also discussed.
| S-EPMC3172072 | biostudies-other
Project description:The objective of this trial was to compare the blood-pressure lowering efficacy of amlodipine/losartan combination with amlodipine monotherapy after 6 weeks of treatment in Korean patients with stage 2 hypertension.In this multi-center, double-blind, randomized study, adult patients (n = 148) with stage 2 hypertension were randomized to amlodipine 5 mg/losartan 50 mg or amlodipine 5 mg. After 2 weeks, patients with systolic blood pressure (SBP) > 140 mmHg were titrated to amlodipine 10 mg/losartan 50 mg or amlodipine 10 mg. After 4 weeks of titration, hydrochlorothiazide 12.5 mg could be optionally added to both groups. The change from baseline in SBP was assessed after 6 weeks. The responder rate (defined as achieving SBP < 140 mmHg or DBP < 90 mmHg) was also assessed at 2, 6 and 8 weeks as secondary endpoints. Safety and tolerability were assessed through adverse event monitoring and laboratory testing. Baseline demographics and clinical characteristics were generally similar between treatment groups. Least-square mean reduction in SBP at 6 weeks (primary endpoint) was significantly greater in the combination group (36.5 mmHg vs. 31.6 mmHg; p = 0.0117). The responder rate in SBP (secondary endpoints) was significantly higher in the combination group at 2 weeks (52.1% vs. 33.3%; p = 0.0213) but not at 6 weeks (p = 0.0550) or 8 weeks (p = 0.0592). There was no significant difference between groups in the incidence of adverse events.These results demonstrate that combination amlodipine/losartan therapy provides an effective and generally well-tolerated first line therapy for reducing blood pressure in stage 2 hypertensive patients.ClinicalTrials.gov: NCT01127217.
| S-EPMC3219858 | biostudies-literature