Unfixed Combination Research Articles

ВЛИЯНИЕ ГИПОТЕНЗИВНОЙ ТЕРАПИИ НА ПОКАЗАТЕЛИ ГЕМОДИНАМИКИ У БОЛЬНЫХ ГИПЕРТОНИЧЕСКОЙ БОЛЕЗНЬЮ В СОЧЕТАНИИ С РЕВМАТОИДНЫМ АРТРИТОМ

Introduction. The appointment of antihypertensive therapy in patients with comorbidity of primary hypertension and rheumatoid arthritis, considering the activity of rheumatoid arthritis is not always specified, and therefore is an urgent issue that may cause a discrepancy between the hemodynamic influence of the prescribed therapy and the nature of existing hemodynamic shifts in this category of patients. Aim. Impact evaluation of the 6-month antihypertensive therapy with drugs of various classes on the hemodynamic parameters of the circulatory system in patients with hypertension stage II combined with rheumatoid arthritis, including its activity. Material and methods. Patients complying the inclusion criteria by age (58.6±6.4 years), hypertension duration (11.2±1.6 years), debut (aged 45-64 years) and rheumatoid arthritis experience (7.2±2.1 years) were formed into three groups: Group I included 277 patients with hypertension stage II (136 men, 141 women); Group II consists of 142 patients (28 men, 114 women) with hypertension stage II and rheumatoid arthritis (in the stage of clinical and laboratory remission); and in Group III there were 112 patients (20 men, 92 women) with hypertension stage II and rheumatoid arthritis (in the stage of clinical and laboratory exacerbation). Antihypertensive therapy was administered by polyclinic physicians. Lisinopril, nebivolol, losartan, amlodipine, indapamide and an unfixed combination of lisinopril and indapamide were prescribed as monotherapy drugs. The follow up period has lasted for 6 months. Results and discussion. Effectiveness control of the prescribed therapy in 6 months was presented in patients in Groups I and II with positive dynamics of morphometric and velocity parameters, in patients in Group III, the indicators were less significant and more delayed. Conclusion. Rheumatoid arthritis presence adds additional changes in the dynamics of the hemodynamic influence of the prescribed antihypertensive therapy, and is determined by the activity degree of the disease and the adequacy of basic anti- inflammatory therapy.

Fixed versus Unfixed Combination of Topical Latanoprost/Timolol for Glaucoma: An Observational Study Investigating the Level of Adherence and Ocular Surface Health.

To investigate the effect of fixed combination versus concomitant unfixed topical glaucoma treatment on patients' adherence and ocular surface health. This is a 6-month, prospective, parallel-group, observational study in patients with ocular hypertension (OHT), primary open-angle glaucoma (POAG), or exfoliation glaucoma (XFG). A total of 142 patients with similar baseline characteristics were enrolled in this study. Seventy-one patients received a Latanoprost 0.005%/Timolol 0.5% fixed combination in the evening, whereas seventy-one patients received the unfixed treatment with Latanoprost 0.005% in the evening and Timolol 0.5% twice daily. The primary outcome was the adherence rate at baseline, and at the 3- and 6-month follow-up visits. The secondary outcomes included the signs of ocular surface disease (OSD) and intraocular pressure (IOP). The adherence of patients treated with the fixed combination was higher than the unfixed treatment at the 3-month (78.0% vs. 63.0%, p < 0.001) and at the 6-month visits (73.0% vs. 58.5%, p < 0.01). The Break-up Time, Schirmer test, and Van Bijsterveld score were worse in the unfixed group at baseline and all subsequent examinations (p < 0.05 for all comparisons). There were no differences in the mean IOP between groups at baseline, 1-, and 3-month visits. IOP appears higher in the unfixed group at 6 months (16.7 vs. 15.0 mmHg, p < 0.01). The patients with ocular hypertension and primary open-angle glaucoma treated with a fixed combination are significantly more adherent and show a healthier ocular surface than those treated with an unfixed combination. The study provides significant evidence of the benefits of fixed combination treatment.

IMPACT ASSESSMENT MONO- AND COMBINATION ANTIHYPERTENSIVE THERAPY LERCANIDIN AND DILTIAZEM ON CENTRAL BLOOD PRESSURE AND ARTERIAL STIFFNESS IN PATIENTS WITH MILD TO MODERATE ARTERIAL HYPERTENSION

Nowadays widely debated search of new methods to reduce cardiovascular risk in thepopulation. Many randomized studies have proven the value of the arterial wall stiffnessin the forecast deterioration of cardiac patients. Therefore, based on these considerationstherapy that improves the elasticity of the arteries may have greater efficacy in preventingmajor cardiovascular events.Purpose – to compare the effectiveness of combination lerсanidipin and diltiazem indifferent dose in patients with mild and moderate arterial hypertension on effects oncentral blood pressure and arterial stiffness.Materials and methods. The study included 123 patients with mild to moderate arterialhypertension, the average office systolic (SBP) / diastolic (DBP) blood pressure – 149,12/ 91,92 ± 1,42 / 0,93 mm Hg. Average age of patients was 51,83 ± 0,86 years. All patientswere divided into group therapy. The first group (n = 20) – diltiazem administered topatients at a dose of 240 mg per day in two divided doses. The second group (n = 20) –patients lerkanidipin 20 mg administered once daily. The third group (n = 22) – patientsintended unfixed combination lerkanidipin 20 mg and 240 mg diltiazem day. The fourthgroup (n = 20) – patients intended unfixed combination lerkanidipin 10 mg and 240 mgdiltiazem day. The fifth group (n = 21) –patients intended unfixed combination lerkanidipin10 mg and 120 mg diltiazem day. The sixth group (n = 20) – patients intended unfixedcombination lerkanidipin 20 mg and 120 mg diltiazem day.All patients at the beginning and end of treatment conducted the following studies:measurement of body weight and height, calculation of body mass index. Measurementoffice SBP, DBP and HR, ambulatory blood pressure monitoring (DMAT), determinationof pulse wave velocity in elastic arteries (PWVe) and muscle (PWVm) types, the definitionof central BP, biochemical blood which included determination of total cholesterol(cholesterol), triglycerides (TG), high density lipoprotein cholesterol (HDL cholesterol),low density lipoprotein cholesterol (LDL-C). Duration of treatment was 1 month.Results. After analyzing all the data, it was found that the сentral blood pressure in alltreatment groups decreased effectively and equally. In the group of 240 mg diltiazemcentral BP significantly decreased by 10.95 mmHg; in group lercanidipin 20 mg 12.18mmHg; in the combination group lercanidipin 20 mg / diltiazem 240 mg 14.13 mm Hg. Inthe combination group lercanidipin 10 mg / diltiazem 240 mg central BP decreased on11.93 mmHg; in the combination group lercanidipin 10 mg / diltiazem 120 mg centralblood pressure decreased on 13.11 mmHg; in the combination group lercanidipin 20 mg /diltiazem 120 mg central blood pressure decreased on 14.82 mmHg. That is, all selectedtreatment regimens were equally effective in reducing central blood pressure. There wasno negative impact on the treatment of all levels of blood lipid spectrum. All treatmentregimen did not significantly affect the average values of indicators characterizing theelastic properties of the arteries (due to short-term observation).Conclusion. Therapy based on both mono and combination lercanidipin and diltiazemwas effective in reducing central blood pressure and did not significantly affect theaverage values of indicators characterizing the elastic properties of the arteries.

Chronic use of the unfixed combination of ACE-inhibitors and beta-blockers in Italy from 2013 to 2019 through the healthcare administrative data.

The association between an ACE-inhibitor and a beta-blocker is recommended in case of complicated arterial hypertension and heart failure with reduced ejection fraction. This retrospective drug-utilization study has described its chronic use from the Italian National Healthcare Service perspective. From the ReS (Ricerca e Salute) database, collecting Italian healthcare administrative data, patients receiving an ACE-inhibitor or a beta-blocker from 2013 to 2019 were selected. The prevalence of use (patients treated/1000 inhabitants) and of continuous treatment (patients treated for ≥80% period from the supply to the end of the same year - by means of dosage units - per 1000 inhabitants) of each single active substance were assessed. Among patients continuously treated, those supplied with an ACE-inhibitor and a beta-blocker (unfixed and fixed combinations) were analyzed in terms of prevalence of continuous treatment. Subjects treated with the unfixed combination ramipril-bisoprolol in 2019 were characterized by gender and age. The prevalence of ACE-inhibitors' use increased from 49.7/1000 inhab. in 2013 to 50.2 in 2019: ramipril was the most supplied each year (28.9 to 31.6/1000 inhab.). The prevalence of continuous treatment increased from 27.4 to 28.3/1000 inhab.: ramipril the most continuously dispensed (16 to 18/1000 inhab.). The prevalence of beta-blockers' use increased from 61.0 to 90.4/1000 inhab.: bisoprolol the most supplied and with the highest increase (27.1 to 52.2/1000 inhab.). The prevalence of continuous treatment increased from 33.1 to 55.8/1000 inhab.: bisoprolol the most continuously dispensed (18 to 37/1000 inhab.). Among patients with continuous supplies, from 49,843 a 51,496 were treated with associations between an ACE-inhibitor and a beta-blocker on an ongoing basis. Half of them were continuously treated with the unfixed combination ramipril-bisoprolol (4.3 to 4.8/1000 inhab.). In 2019, subjects with continuous supplies of ramipril-bisoprolol were mainly males (63.4%) and elderly (mean age 71±12), and the prevalence of use increased with age. These findings, together with recommendations from the main international guidelines encourage to make available also ramipril and bisoprolol as fixed dose combination, in order to simplify the therapy administration and improve the adherence, especially among elderly and patients with multimorbidity.

Therapeutic strategy in patients with long-lasting essential hypertension with comorbid type 2 diabetes mellitus and obesity

Background: Presently the level of blood pressure (BP) control is extremely unsatisfactory in hypertensive patients throughout the world. The aim of our study was to find the optimal drug therapy for patients with hard-to-treat essential hypertension (EH) associated with type 2 diabetes mellitus (T2DM) and obesity, namely the comparison of strategies of fixed and non-fixed combination. Material and methods: Eighty-seven patients with EH, T2DM and obesity were enrolled into the study. Two groups were formed: the 1st group — 41 patients received antihypertensive therapy in the form of unfixed combination of drugs (“multi-pill”) perindopril, indapamide and amlodipine; the 2nd — 46 patients, who received the same drugs, but in a fixed-dose combination (“single pill”). Results: A favorable treatment result was found for fixed-dose combination of antihypertensive drugs, with significant reduction in the frequency of visits to the doctor: relative risk (RR) — 1.27 (95% CI: 1.01‒1.61), p = 0.045, and odds ratio (OR) — 3.10 (95% CI: 1.05‒9.13), p = 0.04. That indicates that patients on fixed-dose combination were less likely to visit a doctor with complaints. Patients on single-pill therapy were less likely to get to progression (worsening) group in contrast to multi-pill non-fixed combination: RR — 1.37 (95% CI: 1.02‒1.84), p = 0.03; OR — 2.91 (95% CI: 1.12‒7.59), p = 0.03. Conclusion: The single-pill triple combination has significant advantage compared to multi-pill regimen in hard-totreat hypertensive patients with comorbid T2DM and obesity. Fixed-dose triple combination leads to significantly faster achievement of blood pressure control.

Comparison of adherence between fixed and unfixed topical combination glaucoma therapies using Japanese healthcare/pharmacy claims database: a retrospective non-interventional cohort study

BackgroundAdherence to chronic therapies is crucial to prevent the progression of disease, such as glaucoma. However, only a limited number of studies have investigated them using real-world data in Japan. This study aimed to evaluate Japanese patients’ adherence to fixed- and unfixed-combination eye drops as a second-line therapy for glaucoma in real-world practice.MethodsThis retrospective, non-interventional cohort study utilized a commercially available Japanese healthcare database (MinaCare database). Medical/pharmacy claims data were collected from 2011 to 2016. The primary endpoint was adherence to medications, assessed by proportion of days covered (PDC) with medication during a 12-month post-index period. Meanwhile, the secondary endpoints included the persistence rate.ResultsA total of 738 patients were included in this study: 309 and 329 in the fixed- and unfixed-combination cohorts, respectively. Prostaglandin analog (PG)/β-blocker (BB) was most commonly claimed in 241/309 (78.0%) patients in the fixed-combination cohort. In the unfixed-combination cohort, PG and BB were claimed in 130/329 (39.5%) patients, whereas PG and α2-agonist were claimed in 87/329 (26.4%) patients. Patients were more adherent to the fixed-combination than the unfixed-combinations (mean PDCs [SD], 79.1% [32.1] vs. 62.2% [38.0]; P < 0.0001). The proportion of patients with good adherence (PDC ≥ 80%) was also higher in the fixed-combination cohort (69.6%) than in the unfixed-combination cohort (48.6%) (P < 0.0001). During the 12-month post-index period, the persistence rate was higher in the fixed-combination cohort than in the unfixed-combination cohort (47.6% [95% confidence intervals (CI): 41.9–53.0] vs. 24.9% [95% CI: 20.4–29.7], P < 0.0001).ConclusionsJapanese patients with glaucoma preferred the fixed-combination therapies over the unfixed-combination therapies. Hence, fixed-combination therapies would contribute to the improvement of adherence.

Persistence and treatment patterns of fixed combination drugs for glaucoma: a retrospective claims database study in Japan

BackgroundPoor persistence with glaucoma therapy can lead to disease progression and subsequent blindness. Persistence with second-line glaucoma combination treatment in a Japanese real-world setting and whether it differed from fixed and unfixed combination drugs was investigated.MethodsThis was a retrospective, non-interventional, cohort study using data from a Japanese medical claims database. Patients with glaucoma aged ≥20 years with a first drug claim for glaucoma treatment between 01 July 2005 and 30 October 2014 and with data for > 6 months before and after this first prescription were included. The primary endpoint was duration of drug persistence among glaucoma patients with and without the use of fixed combination drugs in the year following initiation of second-line combination treatment.ResultsOf 1403 patients included in the analysis, 364 (25.94%) received fixed combination drugs and 1039 (74.06%) received unfixed combination drugs as second-line treatment. Baseline characteristics were generally comparable between the groups. A total of 39.01% of patients on fixed combination drugs, compared with 41.67% of patients on unfixed combination drugs, persisted on their glaucoma drugs 12 months post second-index date. Median persistence durations for the fixed combination drugs and unfixed combination drugs groups were 6 (95% confidence interval [CI]: 5–8) and 7 months (95% CI 6–9), respectively. Patients who received prostaglandin analogs (PGAs) were the most persistent with their treatment (n = 99, 12.84%). Patients diagnosed with primary open-angle glaucoma were less likely to experience treatment modification (hazard ratio [HR]: 0.800, 95% CI 0.649–0.986, P = 0.036), while those diagnosed with secondary glaucoma were more likely to experience treatment modification (HR: 1.678, 95% CI 1.231–2.288, P = 0.001) compared with glaucoma suspects.ConclusionsIn this retrospective claims database study, the persistence rate of second-line glaucoma combination treatment was low, with no difference in persistence between glaucoma patients receiving unfixed combination drugs compared with fixed combination drugs. Patients on PGA showed greater persistence rates compared with other treatments.

Рекомендации по артериальной гипертензии 2018 и 2019 годов: остается ли место свободным комбинациям?

Рекомендации по артериальной гипертензии 2018 и 2019 годов: остается ли место свободным комбинациям?

Meibomian Gland Features and Conjunctival Goblet Cell Density in Glaucomatous Patients Controlled With Prostaglandin/Timolol Fixed Combinations: A Case Control, Cross-sectional Study.

To investigate, using in vivo confocal microscopy (IVCM), the Meibomian gland (MG) features and conjunctival goblet cell density (GCD) in glaucomatous patients controlled with prostaglandin/timolol fixed combinations (PTFCs). In this cross-sectional study, 60 white patients were treated with PTFCs, 15 with latanoprost+timolol (L+T) unfixed combination, and 15 controls were enrolled. Patients underwent the Ocular Surface Disease Index questionnaire, tear film breakup time, corneal staining, Schirmer test I, and IVCM of MGs and goblet cells. The main outcome measures were: mean Meibomian acinar density (MMAD) and area (MMAA), inhomogeneity of glandular interstice (InI) and acinar wall (InAW), and GCD. PTFCs were: latanoprost/timolol (LTFC, 15 eyes), travoprost/timolol (TTFC, 15), bimatoprost/timolol (BTFC, 15), and preservative-free bimatoprost/timolol (PF-BTFC, 15) fixed combinations. Mean time on therapy did not differ among treatments. IVCM documented lower GCD, MMAD, and MMAA (P<0.001), and greater InI and InAW (P<0.05) in glaucoma patients compared with controls. L+T showed worse values compared with PTFCs and PF-BTFC (P<0.05). Preserved PTFCs showed lower MMAD, MMAA, GCD, and greater InI and InAW compared with PF-BTFC (P<0.05) and controls (P<0.001). Differences were not found among PTFCs. InI and InAW significantly correlated with Ocular Surface Disease Index and breakup time (P<0.001), corneal staining (P<0.05), and GCD (P<0.001); GCD correlated with MMAD (P<0.05). PTFCs were less toxic towards MGs and goblet cells compared with the L+T unfixed combination, with PF-BTFC presenting the most tolerated profile. These findings should be carefully considered given the role of these structures in the induction of the glaucoma-related ocular surface disease.

Evaluation of efficacy of the fixed vs unfixed combination of latanoprost and timolol in patients of open-angle glaucoma and ocular hypertension insufficiently controlled on timolol and latanoprost monotherapy

Background: Glaucoma is a term describing a group of ocular disorders with multifactorial etiology united by a clinically characteristic intraocular pressure (IOP) associated optic neuropathy. Elevated IOP is identified as the only known risk factor which can be modified by anti-glaucomatous treatments. Patients who do not achieve target IOP levels with a single ocular hypotensive agent often are prescribed concomitant therapy with a medication that has a different mechanism of action. Aims and Objectives: The aim was to evaluate the efficacy of the fixed and unfixed combinations of latanoprost and timolol in patients of open-angle glaucoma and ocular hypertension (OH). Materials and Methods: A comparative randomized open-label trial was conducted on newly diagnosed patients of open-angle glaucoma and OH who were receiving either latanoprost 0.005% once daily or either timolol SR 0.5% once or twice daily in the preceding 4 weeks and whose IOP was not controlled with the prior monotherapy of latanoprost or timolol and remained ≥21 mmHg were included in the study. Patients were randomized to two groups to receive the following medication - Group I: Fixed combination eye drops of latanoprost (0.005%) and timolol SR (0.5%), once a day, in the dose of 1 drop at 9 LTFC and Group II: Unfixed combination of latanoprost (0.005%), once a day in the dose of 1 drop at 9 pm and timolol SR (0.5%), once a day in the dose of 1 drop at 9 am (LTuFC). Patients were evaluated at 0, 2, 4, 6, and 12 weeks for the assessment of IOP and Visual acuity. Results: Both LTFC (Group I) and LTuFC (Group II) caused a reduction in IOP which was statistically highly significant (P 0.05). Conclusion: Both the regimens on comparison revealed similar efficacy thereby failing to prove superiority over each other. Thus, the clinicians have a wider choice of fixed or unfixed combinations of latanoprost and timolol, when monotherapy of either drug fails.

Comparative Effect of Latanoprost/Timolol Fixed Combination and Unfixed Combination in Patients with Ocular Hypertension Attending Irrua Specialist Teaching Hospital, Irrua, Nigeria

Studies comparing the effect of fixed and unfixed combination of latanoprost and timolol are limited globally and nearly absent among the Nigerian population. This study therefore compares the effect of fixed and unfixed combination of latanoprost and timolol on intraocular hypertension among Nigerian population. The study was a randomized control trial consisting of 102 patients with ocular hypertension who received latanoprost/timolol fixed combination (n=48) and latanoprost/timolol unfixed combination (n=54) for medical reasons. Follow-up visits over 30 weeks was scheduled for 2 weeks from entry date and thereafter every 4 weeks for the remaining 28 weeks making a total of 9 clinic visitations. During the period of the study, the ophthalmologists followed usual care routines and intraocular pressures were recorded while also observing adverse events and evaluating efficacy, safety, tolerability and compliance. Overall, there was 47.73% reduction of intraocular pressure with fixed combination of latanoprost/timolol as against 43.26% reduction with unfixed combination. The greatest reduction impacts were observed two weeks after commencing treatment (-8.27mmHg and -5.74mmHg for fixed and unfixed combinations respectively) and then efficacy reduces progressively for both drugs. This study showed that latanoprost and timolol combinations are effective for intraocular hypertension. However, fixed combination was observed to be more effective compared to unfixed combination at least among Nigerian population.

The Association of Chronic Topical Prostaglandin Analog Use With Meibomian Gland Dysfunction.

To evaluate the association of long-term prostaglandin analog (PGA) use with meibomian gland dysfunction (MGD) in medically treated glaucoma patients. This was a prospective cross-sectional study conducted at a single academic setting. In total, 70 eyes of 70 patients with a medical diagnosis of glaucoma who were on long-term (>12 mo) topical hypotensive medication(s) were included. Patients were classified based on whether they were on PGA or non-PGA class of medication(s). MGD was defined based on meibomian gland terminal duct obstruction and graded between 1 and 5 based on severity. For all subjects, ocular surface disease index questionnaire, break-up time, lissamine green staining, and Schirmer test (under topical anesthesia) was administered. Student t test, Mann-Whitney U test, and χ test was used in statistical evaluations. Forty-five age-matched healthy control subjects who were not on any topical medications were also included. In total, 25 patients (35.7%) were on PGA monotherapy, 21 (30.0%) were treated with fixed or unfixed PGA combination regimens, and 24 (34.3%) were on non-PGA medications. MGD prevalence was higher in patients treated with PGA monotherapy (92.0%) compared with those receiving non-PGA therapy (58.3%) (P=0.02). Obstructive type of MGD was detected in the majority of patients treated with PGAs (95.7%). Grade 2 and 3 MGD was noted in 80.5% of patients on PGA. Patients on PGA had worse ocular surface disease index and ocular surface test results (P<0.001) compared with those of control subjects. Long-term administration of PGA is associated with obstructive type of MGD.

The Efficacy of a Latanoprost/Timolol Fixed Combination Versus Latanoprost and Timolol Gel-forming Solution Unfixed Combination on Daytime Intraocular Pressure.

To evaluate the effect of a latanoprost/timolol fixed combination (LTFC) versus a latanoprost and timolol gel-forming solution unfixed combination (LTuFC) on daytime intraocular pressure (IOP) levels and fluctuations. This was an 8-week, randomized, parallel-group study. Ninety eyes of 90 patients diagnosed with primary open-angle glaucoma or ocular hypertension that were insufficiently controlled with latanoprost monotherapy were enrolled. Randomized patients received either a single evening dose of LTFC or unfixed combination of latanoprost administered once daily in the evening and timolol gel-forming solution administered once daily in the morning without a washout period. IOP measurements were taken at 8 AM, 11 AM, 2 PM, and 5 PM. The mean IOP, daytime IOP measurements, and fluctuation in IOP were assessed at weeks 4 and 8. The mean IOP reduction from baseline to each visit was significant in both groups (P<0.01). There was a significant difference in the mean IOP between groups at week 4 (P=0.0021). At week 8, the mean IOP reduction was 3.2 ± 2.1 and 5.7 ± 3.2 mm Hg in LTFC and LTuFC groups, respectively, and the difference was significant (P=0.001). A decrease in the daytime IOP fluctuation was observed in both groups over time, but the decrease in each group was not significant. At week 8, the mean IOP measurements at 8 AM, 11 AM, 2 PM, and 5 PM in LTuFC group were significantly lower than in the LTFC group (P=0.024, 0.0001, 0.0008, and 0.0011, respectively). The concomitant use of latanoprost and timolol gel-forming solution leads to a larger additional IOP reduction and lower daytime IOP levels as compared with the fixed combination.

Comparison of the effects of bimatoprost and a fixed combination of latanoprost and timolol on 24-hour blood and ocular perfusion pressures: the results of a randomized trial.

BackgroundTo compare the effect of bimatoprost and the fixed combination latanoprost-timolol (LTFC) on 24-hour systolic (SBP) and diastolic (DBP) blood pressure and on 24-hour ocular perfusion pressure (OPP).Methods200 patients with glaucoma or ocular hypertension, controlled on the unfixed combination of latanoprost and timolol or eligible for dual therapy being not being fully controlled on monotherapy were enrolled in a randomized, double-masked, placebo-controlled, multicentre clinical trial. They were randomized to LTFC (8 a.m.) or bimatoprost (8 p.m.) and received 24-hour IOP curve at baseline, 6 and 12 weeks (supine and sitting position IOPs were recorded at 8 p.m., midnight, 5 a.m., 8a.m., noon and 4 p.m.). Holter 24-hour blood pressure curve was obtained between weeks 2 and 12. SBP, DBP, OPP were calculated and compared with ANOVA. Rates of diastolic OPP (DPP) ≤50, ≤40, ≤30 mmHg in the 2 groups were calculated and compared using Fisher’s test.ResultsMean baseline SBP and DBP were 136.5 ± 18.3 vs 134.2 ± 20.1 mmHg (p = 0.1) and 79.1 ± 10.2 vs 78.2 ± 10.1 mmHg (p = 0.4) in the bimatoprost and LTFC groups respectively. Holter SBP was significantly higher for bimatoprost (135.1 mmHg vs 128.1 mmHg, p = 0.04), while no statistically significant difference in DBP was found. DPP was similar in the 2 groups, and proportions of patients with at least one value of the 24-hour curve ≤50, ≤40, ≤30 mmHg were 94%, 86%, 41% respectively.ConclusionsBimatoprost and LTFC had similar DBPs and OPPs; SBP was significantly lower with LTFC. In this study, the percentage of “dippers” was considerably higher than the one described in previous studies on the role of perfusion pressure in glaucoma.Trial registrationNCT02154217, May 21, 2014.

Fixed combination of latanoprost and timolol vs the individual components for primary open angle glaucoma and ocular hypertension: a systematic review and meta-analysis.

To assess the effects of the fixed combination of 0.005% latanoprost and 0.5% timolol (FCLT) vs their individual components for primary open angle glaucoma (POAG) and ocular hypertension (OHT). After searched PubMed, EMBASE, the Cochrane Library and SCI, all randomized controlled clinical trials (RCTs) and cross-over studies were included. The control groups were the mono therapy or the concomitant therapy of latanoprost and timolol. The outcomes were visual field defect, optic atrophy, mean intraocular pressure (IOP) and IOP fluctuation. The analysis was carried out in RevMan version 5.1 software. The post-intervention mean IOP of FCLT was significantly lower compared to timolol [mean difference (MD) -2.92, 95%CI -3.28 to -2.55, P<0.00001] and latanoprost (MD -1.11, 95%CI -1.51 to -0.72, P<0.00001). The post-intervention IOP fluctuation was also significantly lower compared to timolol (MD -0.88, 95%CI -1.23 to -0.53, P<0.00001) and latanoprost (MD -0.63, 95%CI -1.04 to -0.22, P=0.002). The mean IOP was higher in FCLT morning dose group than the one in unfixed combination of 0.005% latanoprost and 0.5% timolol (UFCLT) (MD 1.10, 95%CI 0.81 to 1.39, P<0.00001). Otherwise, there was no difference between FCLT evening dose group and UFCLT (MD 0.34, 95% CI -0.01 to 0.69, P=0.06). There was no statistical difference for the incidence of visual field defect and optic atrophy between FCLT and the monotherapy of components. A better IOP lowering effect has been demonstrated for FCLT compared to the mono therapy of components. The IOP lowering effect was worse for FCLT morning dose and almost same for FCLT evening dose compared to the UFCLT. We need more long-term high quality RCTs to demonstrate the outcomes of visual field defect and optic atrophy.

Efficacy and safety of switching to latanoprost 0.005%-timolol maleate 0.5% fixed-combination eyedrops from an unfixed combination for 36 months.

PurposeWe prospectively investigated the intraocular pressure (IOP)-reducing effect, the visual field-maintenance effect, and the adverse reactions caused by administration of latanoprost/timolol maleate fixed-combination eyedrops for 3 years.Subjects and methodsThe subjects were 162 patients (162 eyes) with glaucoma or ocular hypotension who were using latanoprost and timolol maleate eyedrops concomitantly. The latanoprost and timolol maleate eyedrop regimen was discontinued without any washout period and subsequently changed to a latanoprost–timolol maleate fixed-combination eyedrop regimen. IOP values before the change and at 6, 12, 18, 24, 30, and 36 months after the change were measured and compared. The Humphrey visual field test was conducted before the change and at 12, 24, and 36 months after the change, and mean-deviation values were compared. Adverse reactions were assessed at every checkup.ResultsThe IOPs before the change and at 6–36 months after the change were 15.2±3.3 mmHg and 14.3–15.2 mmHg, respectively, and a significant decrease was observed at 36 months after the change (P<0.01). Mean-deviation values before the change and at 12–36 months after the change were −9.11±6.94 dB and −10.08 to −9.22 dB, respectively, and these values were not significantly different (P=0.2148). Within the 36-month period, the eyedrops were discontinued because of insufficient IOP decrease in 33 cases (20.4%) and adverse reactions in eleven cases (6.8%).ConclusionIOP and the visual field were maintained for 3 years when a latanoprost and timolol maleate eyedrop regimen was changed to a latanoprost–timolol maleate fixed-combination eyedrop regimen. However, administration of the latanoprost–timolol maleate fixed-combination eyedrops was discontinued in approximately 27% of cases because of insufficient IOP decrease and adverse reactions.

PSS29 - The Cost-Effectiveness of Bimatoprost 0.03%/Timolol 0.05% Preservative-Free Fixed Combination Compared with Dorzolamide/Timolol Preservative-Free Fixed Combination and 2-Bottle Unfixed Combinations for the Treatment of Primary Open-Angle Glaucoma in the United Kingdom

PSS29 - The Cost-Effectiveness of Bimatoprost 0.03%/Timolol 0.05% Preservative-Free Fixed Combination Compared with Dorzolamide/Timolol Preservative-Free Fixed Combination and 2-Bottle Unfixed Combinations for the Treatment of Primary Open-Angle Glaucoma in the United Kingdom

Efficacy of Timolol 0.1% Gel and a Prostaglandin Analog in an Unfixed Combination Compared to the Corresponding Fixed Combinations

To investigate the intraocular pressure (IOP) reduction with prostaglandin analogs (PGAs)-timolol fixed combinations versus the unfixed combination of the same PGAs and timolol 0.1% in gel-forming carbomer. Patients with primary open-angle glaucoma (POAG) receiving for at least 4 weeks the fixed combinations of PGA-timolol, administered once a day in the evening (0.005% latanoprost with 0.5% timolol, 0.004% travoprost with 0.5% timolol, 0.03% bimatoprost with 0.5% timolol) were switched to an unfixed combination of the same PGA (once a day in the evening) with timolol 0.1% in gel-forming carbomer (once a day in the morning) for at least 4 weeks. The primary endpoint was to compare efficacy of fixed vs unfixed combinations in lowering IOP. The effects of both regimens on short-term IOP fluctuations were also assessed. A total of 32 patients (64 eyes) fulfilled inclusion criteria: 17 patients received latanoprost-timolol fixed combination, 9 travoprost-timolol fixed combination, 6 bimatoprost-timolol fixed combination. For all considered time periods each unfixed combination induced an IOP reduction significantly higher than the corresponding fixed combination (paired t test: p<0.05 in all measurements). The diurnal IOP reduction was significantly higher during the unfixed combinations (p<0.001). Unfixed combinations significantly decreased IOP diurnal fluctuations and increased the percentage of patients with daily IOP fluctuation ≤2 mm Hg. In this pilot study, PGA and timolol seems to be more effective in POAG treatment when administered as unfixed combinations, reducing both IOP and daily fluctuations. The once a day timolol 0.1% gel-forming carbomer may be a valuable option in PGA-timolol unfixed combination regimen.

Subclinical Increased Anterior Stromal Reflectivity With Topical Taprenepag Isopropyl

To assess the effect of topical taprenepag isopropyl on each layer of the cornea by confocal microscopy. Thirty-two ocular hypertensive or glaucoma patients were randomized into a 2-period, crossover study of 14 days of 0.1% taprenepag alone and in unfixed combination with 0.005% latanoprost (combination therapy). Baseline and sequential slit-lamp biomicroscopy, fluorescein staining, central ultrasonic pachymetry, and confocal microscopy were performed. Confocal images were analyzed for the density of the central superficial and basal epithelium, midstromal keratocytes, and endothelium, as well as endothelial coefficient of variation and percentage of hexagonal cells, and reflectivity of anterior stromal and midstromal layers. Corneal staining increased from baseline, reaching a peak at day 13 (69% and 63% of subjects treated with monotherapy and combination therapy, respectively), which resolved by day 35. A statistically significant increase in mean corneal thickness for both eyes and both treatments occurred on days 7 and 13 (range, 20-27 μm; P < 0.001) but recovered (≤ 6 μm) by day 35. No statistically significant changes were observed in the basal epithelial, midstromal, or endothelial cells. Mean ratio of average reflectivity of anterior stroma to midstroma increased on days 13 and 35 in period 1 for each treatment (range, 1.2-1.9; P < 0.001), and this increase persisted during period 2. Anterior stromal reflectivity may remain increased even when biomicroscopic and confocal images of corneal layers remain normal or have recovered after topical taprenepag. This subclinical measure may be useful to detect a persistent adverse effect of a topical agent on the cornea.

Prostaglandin Analogs and Timolol-Fixed Versus Unfixed Combinations or Monotherapy for Open-Angle Glaucoma: A Systematic Review and Meta-Analysis

To estimate the intraocular pressure (IOP)-lowering effect of prostaglandin analogs (PGAs) administered in combination with β-blockers. We searched the Medline and Embase databases for randomized trials comparing topical therapies with PGAs and timolol administered as monotherapy (Mt), or in fixed (FC) or unfixed combinations (UC) to patients with glaucoma or ocular hypertension. The efficacy endpoint was the mean difference (MeD) in the reduction in IOP from baseline; the tolerability endpoint was the incidence of hyperemia. The 18 eligible trials involved 23 comparisons of FC versus Mt, and 5 of FC versus UC. The FCs were less efficacious than UCs (MeD: 0.69, 95% CI: 0.29 to 1.08). In comparison with timolol Mt, the latanoprost/timolol FC led to a greater IOP reduction (MeD: -2.74, 95% CI: -3.24 to -2.23) than the bimatoprost/timolol FC (MeD: -1.49, 95% CI: -1.86 to -1.12) or the travoprost/timolol FC (MeD: -1.93, 95%CI: -2.98 to -0.88). The FCs led to a lower hyperemia risk than UCs [relative risk (RR): 0.70, 95% CI: 0.43 to 1.14] and PGA Mt (RR: 0.61, 95% CI: 0.53 to 0.70). FCs are more efficacious than their individual components, but less efficacious than their respective UCs. FCs lead to a lower hyperemia risk than UCs and their respective PGA Mts.