Free Combination Therapy Research Articles

Abstract P361: Single Pill Combination Therapy is Not Superior to Free Combination Therapy for Controlling Hypertension

Introduction: The 2017 AHA guidelines advocate the use of ambulatory blood pressure monitoring (ABPM) for assessing the response to anti-hypertensive therapy and favor the use of single pill combination therapy for patients on multiple drugs. We aimed to investigate whether single pill combination therapy was superior to free pill combination therapy for attainment of goal blood pressure. Methods: We used data from 1074 consecutive ABPM studies performed between February 2017 and March 2018 to identify patients who received the following drug combinations as either single pill or free pills: ACEI/HCTZ, ARB/HCTZ, ACEI/CCB, ARB/CCB. Goal blood pressure was defined as an average awake blood pressure below 130/80 mmHg. Results: There were 193 patients in the single pill combination group and 136 patients in the free pill combination group. There was no difference between the groups regarding age, gender, number of antihypertensive drugs, and previous cardiovascular disease except for previous stroke which was more common in the free pill combination group. Compared to single pill combination, free pill combination showed a trend to superiority in the rate of blood pressure control in all drug combinations, with statistical significance reached only when comparing pooled groups (see table). Conclusions: Single pill combination therapy was not superior to free pill combination therapy for attainment of goal blood pressure.

The Effect of Exforge-HCT on Blood Pressure Control in Omani Hypertensive Patients Attending Sultan Qaboos University Hospital

Background: Hypertension is worldwide health burden. The major concern about hypertension is that it is usually asymptomatic until it causes end organ damages. The management of hypertension usually starts with monotherapy which fails in achieving targeted BP control in many patients. Therefore, they are switched to combination therapy. Fixed combination therapy is proven to be more effective in controlling hypertension than free combination therapy. Exforge-HCT is a fixed combination drug consisting of Amlodipine, Valsartan and Hydrochlorothiazide. Its effectiveness is not known in Omani hypertensive patients. Aim: To evaluate the role of exforge-HCT in control of blood pressure in Omani hypertensive patients attending SQUH and its effectiveness based on gender. Method: This is a retrospective study. Data was gathered using HIS from January 2013 to June 2016. Patients taking Exforge-HCT were screened for eligibility for the study. Blood pressure measurements before and after using Exforge-HCT were recorded. Patients were grouped according to gender, number of co-morbidities and number of medications used before EXFORGE-HCT into two groups; group one: those who were on triple free drug combination therapy and group two: those who were on dual free drugs. P value of less than 0.05 was considered significant. Results: Total number of patients was 115 with female being 57% and male being 42%. The Level of control of hypertension increased from 22% to 33%. Over all Significant reduction in blood pressure was observed, but there was no gender difference in response to Exforge-HCT. There was significant difference in the response to Exforge-HCT between the medication groups but the response according to gender in each group remains the same. Response to Exforge-HCT was the same regardless the number of co-morbidities in both gender. Conclusion: Exforge-HCT showed significant reduction in BP but no gender difference in response. There was significant difference in the response between the two medication groups. However, the response between genders remains the same in each co-morbidity and medication group. Further prospective study is needed to confirm these findings.

Comparison of Adherence to Glimepiride/Metformin Sustained Release Once-daily Versus Glimepiride/Metformin Immediate Release BID Fixed-combination Therapy Using the Medication Event Monitoring System in Patients With Type 2 Diabetes

PurposeThe purpose of this study was to compare the adherence of the glimepiride/metformin sustained release (GM-SR) once-daily fixed-dose combination and glimepiride/metformin immediate release (GM-IR) BID fixed-dose combination in type 2 diabetes therapies. MethodsAn open-label, randomized, multicenter, parallel-group study was conducted at 11 hospitals in the Republic of Korea. A total of 168 patients with type 2 diabetes treated with >4 mg of glimepiride and 1000 mg of metformin by using free or fixed-dose combination therapy for at least 2 weeks were enrolled. Patients were randomized to receive GM-SR 4/1000 mg once-daily or GM-IR 2/500 mg BID for 24 weeks. Adherence was compared by using the Medication Event Monitoring System (MEMS). FindingsA significant difference in adherence was observed between the 2 groups. Overall adherence, defined by the number of container openings divided by the number of prescribed doses, was 91.7% in the GM-SR group and 88.6% in the GM-IR group (P < 0.001). The percentage of treatment days with the correct number of doses taken was 85.3% in the GM-SR group and 75.1% in the GM-IR group (P < 0.001). The percentage of missed doses was 11.7% in the GM-SR group and 15.3% in the GM-IR group (P < 0.001). The percentage of doses taken in the correct time window and therapeutic coverage were higher in the GM-SR group (P < 0.001). There was no significant difference in glycosylated hemoglobin changes or number of adverse events between the 2 groups. A total of 168 patients randomized to receive GM-SR once daily (86 patients) or GM-IR twice daily (82 patients). Mean Age were 57.8 ± 9.6 years old. Male : female ratio was 47.6 : 52.4 %. Body mass index were 66.3 ± 12.0 kg/m2, Diabetes duration were 10.5 ± 6.6 years. ImplicationsThis study showed that patient adherence with GM-SR once daily was significantly better than with GM-IR BID. ClinicalTrials.gov identifier: NCT01620489.

Use and effectiveness of a fixed-ratio combination of insulin degludec/liraglutide (IDegLira) in a real-world population with type 2 diabetes: Results from a European, multicentre, retrospective chart review study.

AimsTo describe the real‐world use and effectiveness of IDegLira, a fixed‐ratio combination of the basal insulin degludec, and the glucagon‐like peptide‐1 receptor agonist (GLP‐1RA) liraglutide.Materials and MethodsThis European, multicentre, retrospective chart review comprised adults (n = 611) with type 2 diabetes, who started IDegLira ≥6 months before data collection. Clinical characteristics were assessed at baseline (defined as the most recent recording during the 6 months before the first IDegLira prescription) and 3, 6, 9 and 12 months (± 45 days for each time point) after commencing IDegLira, where data were available.ResultsBaseline regimens included non‐injectable medications (19%), basal insulin (19%), GLP‐1RA (10%), free combination therapy (insulin/GLP‐1RA, 24%) and multiple daily‐dose insulin injections (MDI, 28%), all ± oral antidiabetic drugs. After 6 months, significant glycated haemoglobin (HbA1c) reductions were observed in patients overall and in all subgroups (−10 mmol/mol [−0.9%] overall; P < .0001), and a significant reduction in mean body weight (−0.7 kg; P < .05) was observed in patients overall and in patients receiving MDI (−2.4 kg; P < .0001). The mean IDegLira dose was 22, 30 and 32 dose steps at initiation, and at 6 and 12 months follow‐up, respectively. In total, only 67 patients reached the maximum 50 dose steps, with most coming from the free combination therapy (n = 31) or MDI (n = 15) baseline regimen groups. Hypoglycaemia rates were reduced by 82% (rate ratio 0.18; P < .0001) in the 6‐month period after vs before IDegLira initiation. Overall, a total of 12 patients experienced 15 events in the 6 months after IDegLira initiation.ConclusionIn real‐world practice, after 6 months and at a moderate dose, IDegLira resulted in substantial reductions in HbA1c and body weight, with a reduced risk of hypoglycaemia.

Sample Extraction and Simultaneous Chromatographic Quantitation of Doxorubicin and Mitomycin C Following Drug Combination Delivery in Nanoparticles to Tumor-bearing Mice.

Combination chemotherapy is frequently used in the clinic for cancer treatment; however, associated adverse effects to normal tissue may limit its therapeutic benefit. Nanoparticle-based drug combination has been shown to mitigate the problems encountered by free drug combination therapy. Our previous studies have shown that the combination of two anticancer drugs, doxorubicin (DOX) and mitomycin C (MMC), produced a synergistic effect against both murine and human breast cancer cells in vitro. DOX and MMC co-loaded polymer-lipid hybrid nanoparticles (DMPLN) bypassed various efflux transporter pumps that confer multidrug resistance and demonstrated enhanced efficacy in breast tumor models. Compared to conventional solution forms, such superior efficacy of DMPLN was attributed to the synchronized pharmacokinetics of DOX and MMC and increased intracellular drug bioavailability within tumor cells enabled by the nanocarrier PLN. To evaluate the pharmacokinetics and bio-distribution of co-administered DOX and MMC in both free solution and nanoparticle forms, a simple and efficient multi-drug analysis method using reverse-phase high performance liquid chromatography (HPLC) was developed. In contrast to previously reported methods that analyzed DOX or MMC individually in the plasma, this new HPLC method is able to simultaneously quantitate DOX, MMC and a major cardio-toxic DOX metabolite, doxorubicinol (DOXol), in various biological matrices (e.g., whole blood, breast tumor, and heart). A dual fluorescent and ultraviolet absorbent probe 4-methylumbelliferone (4-MU) was used as an internal standard (I.S.) for one-step detection of multiple drug analysis with different detection wavelengths. This method was successfully applied to determine the concentrations of DOX and MMC delivered by both nanoparticle and solution approaches in whole blood and various tissues in an orthotopic breast tumor murine model. The analytical method presented is a useful tool for pre-clinical analysis of nanoparticle-based delivery of drug combinations.

OP.4C.08] ROLE OF THE FIXED-DOSE TRIPLE COMBINATION THERAPY IN THE MANAGEMENT OF UNCONTROLLED HYPERTENSION

Objective: Blood pressure (BP) control is difficult to achieve with current BP-lowering drugs. Therefore, uncontrolled hypertension (HT) despite drug treatment with free recommended combinations remains the main goal in clinical practice. In this study the efficacy of a triple fixed-combination (TFC) of anti-hypertensive drugs in hypertensive subjects with uncontrolled HT was evaluated.Design and method: Forty-one hypertensives (mean age 59.2 ± 12.7 years, 63.4% males) with uncontrolled essential HT (clinic systolic BP > = 140 or diastolic BP > = 90 mmHg) previously treated with anti-hypertensive therapy with a renin-angiotensin-aldosterone system (RAAS) inhibitor (ramipril 5 to 10 mg or olmesartan 10 to 40 mg daily) plus hydrochlorothiazide (12.5 to 25 mg daily) were switched to once daily TFC therapy with perindopril (5 to 10 mg), indapamide (1.25 to 2.5 mg) and amlodipine (5 to 10 mg). These subjects were age-sex- matched with hypertensive patients taking a free-combination therapy including a RAAS inhibitor, a diuretic and a calcium channel blocker (CCB). Clinic BP and ambulatory BP (ABPM) were evaluated at baseline and after 1-month follow-up. Analysis of variance for repeated measures was provided. Results: In both treatment groups, a significant reduction of all the components of clinic and ABPM values was found (data not shown) at the end of follow-up. When ABPM values were considered, at the follow-up a significant reduction of the 24 h, daytime and night-time systolic and pulse pressure was found in the TFC group than in the free combination therapy group (Figure). Diastolic BP and heart rate remained unchanged. No patients were lost at the follow-up and no side effects were observed. Conclusions: A TFC of perindopril, amlodipine and indapamide appears to be safe, well tolerated and effective in reducing systolic and pulse pressure in hypertensive patients uncontrolled by a free antihypertensive therapy including a RAAS inhibitor, a diuretic and a CCB.

A Comparison of Health Care Resource Utilization and Costs for Patients with Allergic Rhinitis on Single-Product or Free-Combination Therapy of Intranasal Steroids and Intranasal Antihistamines

A Comparison of Health Care Resource Utilization and Costs for Patients with Allergic Rhinitis on Single-Product or Free-Combination Therapy of Intranasal Steroids and Intranasal Antihistamines

Free versus Fixed Combination Antihypertensive Therapy for Essential Arterial Hypertension: A Systematic Review and Meta-Analysis.

BackgroundIn a free drug combination, each Blood pressure (BP)-lowering drug is administered as a separate pill, while in a fixed drug combination several BP-lowering agents are combined in a single pill. Using a single pill may enhance compliance and simplify treatment, which would translate into better clinical outcomes. The objective of this meta-analysis is to compare the effects of using a fixed combination versus free combination of BP-lowering agents in the management of patients with essential hypertension.MethodsWe searched Cochrane CENTRAL, MEDLINE, and EMBASE for randomized clinical trials (RCTs) addressing the objective of the review and assessing at least one of the following outcomes: BP-lowering efficacy, rapidity in achieving BP target, compliance, incidence of side effects, mortality, and morbidity. Two review authors independently selected eligible studies, abstracted data, and assessed risk of bias of included trials. The primary meta-analyses used a random-effects model.ResultsWe identified seven RCTs with a total of 397 participants. Meta-analysis of efficacy in controlling BP showed a non-significant reduction of mean systolic BP of 0.81 mmHg (95% CI -3.25, 1.64) favoring the fixed combination group. As for adverse events, results showed a non-significant 13% risk reduction favoring the free combination (risk ratio 1.13, 95% CI 0.85, 1.5). Low quality of evidence was noted for both outcomes. Rapidity in achieving BP target was assessed in only one trial, and the results favored the fixed combination. Adherence to treatment was assessed in three trials, no pooled analysis was possible for this outcome. None of the included trials assessed mortality and morbidity.ConclusionThe available low quality evidence does not confirm or rule out a substantive difference between fixed combination and free combination therapy in the management of HTN. Well designed RCTs with a long duration of follow-up and assessment of morbidity and mortality outcomes are needed.

Economic evaluation of single-pill combination of indapamide and amlodipine in the treatment of arterial hypertension in the Polish setting.

Arterial hypertension is a common disorder that affects around 9 million adults in Poland. Single-pill combinations (SPCs) for the treatment of arterial hypertension have significant advantages over the free combinations, resulting in lower risk of cardiovascular events and lower consumption of medical resources. The current ESC/ESH 2013 guidelines for the first time recommend treatment with a combination of thiazide-like diuretic with calcium channel blocker. Currently, no such combination is reimbursed from public funds in Poland. To assess the economic value of treatment with SPC of indapamide and amlodipine (Tertens-AM®) for hypertensive patients compared with free combination therapy (FC), in the Polish setting. As there are currently no published data directly estimating the additional effect of using indapamide + amlo-dipine SPC vs. FC, two extreme approaches are presented: with difference in effectiveness due to improved adherence to the treatment estimated from published studies on other molecules used in hypertension such as SPCs and FCs - the base-case approach (1); and assuming no difference of effectiveness or adherence between SPC and FC of indapamide and amlodipine - the conservative approach (2). Modelling was carried out based on the Markov process in lifetime horizon. In the base-case approach, with the difference in effectiveness between SPC and FC, it was assumed that the differences in compliance translate into the differences in systolic blood pressure. Patients' characteristics were correlated with the risk of events associated with cardiovascular disease, based on the prediction algorithms from the Framingham Heart Study. Costs were considered from a National Health Fund (NHF) perspective and NHF and patient's perspective, and therefore direct medical costs were only included. The treatment with SPC of indapamide and amlodipine in place of FC resulted in 7.6 additional days of life in full health and longer overall patient survival by 2.9 days. The replacement of FC with SPC would result in national savings from both NHF perspective and NHF and patient's perspective, irrespective of the assumption of the difference in adherence between SPC and FC. The savings would amount to 1.602-3.954 million PLN and 16.498-19.186 million PLN from NHF perspective and NHF and patient's perspective, respectively. The treatment with SPC of indapamide and amlodipine for hypertensive patients was found to be dominant over FC or at least less expensive than treatment with FC when the difference in effectiveness was neglected. The replacement of FC with SPC would result in savings from both NHF perspective and NHF and patient's perspective.

Safety and efficacy of initial combination of linagliptin and metformin in patients with type 2 diabetes: A subgroup analysis of Indian patients from a randomized, double-blind, placebo-controlled study.

Context and Objectives:The number of people with diabetes is increasing exponentially in India. Owing to a unique “Asian Indian Phenotype,” Indians develop diabetes a decade earlier and have an earlier onset of complications than Western populations. Therefore, it is essential to evaluate more effective treatment strategies at an earlier stage of disease progression, such as initial combination therapy, in Indian patients. In this study, we evaluated the efficacy and safety of initial combination therapy with linagliptin plus metformin in comparison to linagliptin or metformin monotherapy in Indian patients with type 2 diabetes mellitus.Methods:This is a subgroup analysis of Indian patients who participated in a Phase III, 24-week, double-blind, placebo-controlled, trial. Overall, 249 Indian patients were randomized to one of six treatment arms (Two free combination therapy arms: Linagliptin 2.5 mg twice daily [bid] + either low [500 mg, n = 36] or high [1000 mg, n = 44] dose metformin bid and four monotherapy arms: Linagliptin 5 mg once daily [qd, n = 40], metformin 500 mg [n = 49] or 1000 mg bid [n = 45], or placebo [n = 23]).Results:The placebo-corrected mean change in glycated hemoglobin from baseline (8.9%) to week 24 was −1.83% for linagliptin + metformin 1000 mg bid; −1.46% for linagliptin + metformin 500 mg bid; −1.30% for metformin 1000 mg bid; −1.00% for metformin 500 mg bid; and −0.77% for linagliptin 5 mg qd. None of the patients in the combination therapy arms had hypoglycemia, whereas there was one event in the metformin 1000 mg bid arm. Rates of adverse event were similar across various treatments.Conclusions:In this subgroup analysis of Indian patients, initial combination therapy with linagliptin + metformin was more efficacious in improving glycemic control than the monotherapy arms, with a comparable tolerability profile. The results were comparable to the overall population.

Examining equity in access to long-lasting insecticide nets and artemisinin-based combination therapy in Anambra state, Nigeria

BackgroundIn order to achieve universal health coverage, the government of Anambra State, southeast Nigeria has distributed free Long-lasting Insecticide treated Nets (LLINs) to the general population and delivered free Artemisinin-based Combination Therapy (ACT) to pregnant women and children less than 5 years. However, the levels of coverage with LLINS and ACTs is not clear, especially coverage of different socio-economic status (SES) population groups. This study was carried out to determine the level of coverage and access to LLINs and ACTs amongst different SES groups.MethodsA questionnaire was used to collect data from randomly selected households in 19 local government areas of the State. Selected households had a pregnant woman and/or a child less than 5 years. The lot quality assurance sampling (LQAS) methodology was used in sampling. The questionnaire explored the availability and utilization of LLINs and ACTs from 2394 households. An asset-based SES index was used to examine the level of access of LLINS and ACTs to different SES quintiles.ResultsIt was found that 80.5 % of the households had an LLIN and 64.4 % of the households stated that they actually used the nets the previous night. The findings showed that 42.3 % of pregnant women who had fever within the past month received ACTs, while 37.5 % of children ≪5 years old who had malaria in the past month had received ACTs. There was equity in ownership of nets for the range 1–5 nets per household. No significant SES difference was found in use of ACTs for treatment of malaria in children under five years old and in pregnant women.ConclusionsThe free distribution of LLINs and ACTs increased household coverage of both malaria control interventions and bridged the equity gap in access to them among the most vulnerable groups.

Initial combination of linagliptin and metformin improves glycaemic control in type 2 diabetes: a randomized, double‐blind, placebo‐controlled study

To evaluate the efficacy and safety of initial combination therapy with linagliptin plus metformin versus linagliptin or metformin monotherapy in patients with type 2 diabetes. In this 24-week, double-blind, placebo-controlled, Phase III trial, 791 patients were randomized to one of six treatment arms. Two free combination therapy arms received linagliptin 2.5 mg twice daily (bid) + either low (500 mg) or high (1000 mg) dose metformin bid. Four monotherapy arms received linagliptin 5 mg once daily, metformin 500 mg or 1000 mg bid or placebo. Patients with haemoglobin A1c (HbA1c) ≥11.0% were not eligible for randomization and received open-label linagliptin + high-dose metformin. The placebo-corrected mean (95% confidence interval) change in HbA1c from baseline (8.7%) to week 24 was -1.7% (-2.0, -1.4) for linagliptin + high-dose metformin, -1.3% (-1.6, -1.1) for linagliptin + low-dose metformin, -1.2% (-1.5, -0.9) for high-dose metformin, -0.8% (-1.0, -0.5) for low-dose metformin and -0.6 (-0.9, -0.3) for linagliptin (all p < 0.0001). In the open-label arm, the mean change in HbA1c from baseline (11.8%) was -3.7%. Hypoglycaemia occurred at a similar low rate with linagliptin + metformin (1.7%) as with metformin alone (2.4%). Adverse event rates were comparable across treatment arms. No clinically significant changes in body weight were noted. Initial combination therapy with linagliptin plus metformin was superior to metformin monotherapy in improving glycaemic control, with a similar safety and tolerability profile, no weight gain and a low risk of hypoglycaemia.

Abstract P55: Comparison of Real World Adherence, Healthcare Resource Utilization, and Cost for Valsartan/Amlodipine Single Pill Combination versus Angiotensin-Receptor Blocker/Calcium-Channel Blocker Free Combination Therapy

Objective: To evaluate adherence, healthcare resource utilization and cost outcomes of valsartan/amlodipine single pill combination (SPC) versus angiotensin-receptor blocker (ARB)/calcium-channel blocker (CCB) free combination (FC) therapy in hypertensive patients. Methods: A retrospective database study was conducted using a large US commercial insurance claims database for the period 01/01/2007-04/30/2008. Two cohorts of patients receiving valsartan/amlodipine SPC or ARB/CCB FC were identified. All patients were ≥18 years old with at least 1 medical claim for hypertension (ICD 9 401.x-404.x) with ≥6 months pre- and ≥12 months post-index follow up and ≥2 filled prescriptions with days supply ≥90 days for the index therapy over follow up. Primary outcomes were proportion of days covered, days to discontinuation (defined as a gap in therapy of 30 days), and all-cause healthcare cost and utilization. Multivariate regression analysis was conducted to control for baseline characteristics, including age, gender, region, comorbidities, pill burden, and resource utilization and cost. Results: A total of 3259 (13.1%) of patients were included in the valsartan/amlodipine SPC cohort and 21,597 (86.9%) in the ARB/CCB FC cohort. At baseline, patients taking SPC were more likely to be male, older, and reside in the Southern US. After adjusting for baseline differences through risk-adjusted logistic regression, adherence rates for patients taking SPC therapy were significantly higher compared to patients taking FC therapy (OR 1.38, 95% CI 1.27-1.51). Patients taking SPC therapy were also significantly less likely to discontinue their index therapy (HR 0.87, p&lt;0.001). Total all-cause health care costs were 11% greater for patients in the FC cohort compared to patients taking SPC therapy (p&lt;0.001). In addition, patients in the SPC cohort were less likely to have ER visits and hospitalizations during the follow up period. Conclusion: Use of valsartan/amlodipine single pill combination therapy in hypertensive patients was associated with significantly better adherence and lower cost and healthcare resource utilization compared to ARB/CCB free combination therapy.

V-006 DIFFERENTIAL EFFECTS ON COMPLIANCE AND ITS ASSOCIATED FACTORS AMONG PATIENTS SWITCHED FROM FREE-COMBINATION TO FIXED-DOSE COMBINATION OF ANTIHYPERTENSIVE AGENTS

Subtitle Compliance and fixed-dose combination Background Real life evidences showing that fixed-dose combinations (FDC) of antihypertensive agents are associated with improved compliance than the corresponding free-combination therapies are invariably from parallel group comparisons. However, direct comparison of FDC with free-combination therapies with regard to compliance in the same hypertensive patients switched from free-combination to FDC is still lacking. Methods This study was a retrospective cohort analysis using the Taiwan National Health Insurance database from January 2001 to December 2007. The date of switching from free-combinations to FDC was set as the index date. Patients included should fulfill 2 criteria: (1) use of an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) and a diuretic within the preceding 12 months of the index date, and (2) use of an FDC consisting of an ACE inhibitor or ARB plus a diuretic 12 months after the index date. Compliance was measured by medication possession ratio (MPR). Results A total of 896 patients were included. As a whole, MPR increased significantly from 42% in the pre-index free-combination period to 69% in the post-index FDC period (difference, 27%; 95%CI, 24% to 30%). The improvement in MPR was most evident in patients with a MPR of <50% in the pre-index period (difference, 44%; 95%CI, 41% to 47%), whereas for those with a pre-index MPR of ≥80%, MPR decreased in the post-index period (difference, −13%; 95%CI, −9% to −17%). Factors independently associated with improvement in MPR included only the number of concomitant medications after adjustment for MPR in the pre-index period. Conclusions In patients switched from free-combination to FDC of antihypertensive agents, MPR increased significantly if the compliance with free-combination was not optimal. However, for patients with good compliance with free-combination therapies, switching to FDC resulted in a decrease in MPR, which might be due to the lack of flexibility in dosing with FDC.

Abstract P60: The Effect of Angiotensin Receptor Blocker/Calcium Channel Blocker Single Pill Combination Therapy on Adherence to Antihypertensive Treatment

Objective: To evaluate the impact of ARB/CCB single pill combination therapy on adherence to antihypertensive (AHY) treatment. Methods: A retrospective data analysis was performed using pharmacy claims data from a national pharmacy benefit management company. The study included patients who were newly initiated on ARB/CCB treatment between 01/01/2007 and 08/31/2008, age ≥18 years, and continuously enrolled in the same health plan for 6 months prior to and 13 months after starting ARB/CCB treatment. Patients who started either valsartan and amlodipine or amlodipine and olmesartan medoxomil ARB/CCB single pill combinations were assigned to the single pill combination (SPC) group. The ARB/CCB free combination (FC) group included patients who used a combination of single-agent ARB and CCB treatment. Outcome variables were persistence, defined as time to discontinuation of therapy, and adherence, defined as proportion of days covered (PDC) ≥0.80. Propensity score weighted multivariable regression models were used to estimate the impact of combination pill therapy. Covariates included age, gender, baseline comorbidities, insurance type, geographic region, copayment, and history of other AHY use. Results: The final sample contained 2,312 patients in the ARB/CCB FC group and 2,213 patients in the ARB/CCB SPC group. After adjustment for differences in baseline characteristics, a Cox proportional hazards model showed that patients in the SPC group were 24% less likely to discontinue ARB/CCB therapy as compared to patients in the FC group (HR 0.76, 95% CI 0.73-0.79, p&lt;0.0001). A logistic model showed that patients in the SPC pill group had a 90% greater odds of being adherent compared to patients in the FC group (OR 1.90, 95% CI 1.75-2.08, p&lt;0.0001). In both models, higher copayment (copayment $50 and above) was associated with poorer persistence and adherence in comparison to patients who faced copayment $0-$5: HR=1.15, p&lt;0.001 and OR=0.67, p&lt;0.0001. Conclusion: Patients using single pill combination ARB/CCB therapy were more likely to be persistent and adherent to treatment as compared to patients taking free combination therapy.

Modern Clinical Management of Arterial Hypertension

Blood pressure control is a key element in any cardiovascular prevention strategy. However, it is also one of the least frequently achieved goals in modern strategies for the clinical management of cardiovascular diseases, resulting in high impact in terms of cardiovascular morbidity and mortality. Among different factors that can be identified as the causes of poor blood pressure (BP) control in the general population of patients with hypertension, the excessive use of monotherapy, as opposed to combination therapy, is arguably one of the most significant. In this perspective, the use of combination therapies having synergic and complementary actions has been shown to reduce BP levels to increase the percentage of patients who respond to antihypertensive treatment and achieve the recommended BP targets. Moreover, recent studies have demonstrated that these strategies provide effective protection against hypertension-related organ damage, as well as a significant reduction of major cardiovascular events. While currently available evidence supports an increasingly important role of combination therapies compared with monotherapies, several other issues remain to be clarified. Among these, it has not yet been clearly established which classes of drugs should be considered for combination strategies, at what doses each component should be used, and whether combination strategies may be definitively considered as a first choice for the treatment of hypertensive patients at cardiovascular risk. Another relevant aspect concerns the choice between fixed and free combination therapies. This article discusses and analyses the different factors that may contribute to achieve effective BP control. In particular, the potential benefits and drawbacks associated with the use of fixed versus free combination therapies for hypertension treatment will be examined and discussed. The benefits of using combination strategies based on drugs that antagonize the renin-angiotensin system and dihydropyridine calcium antagonists will also be discussed, with a particular focus on amlodipine besylate combination therapies.

Comparison of real-world adherence, healthcare resource utilization and costs for newly initiated valsartan/amlodipine single-pill combination versus angiotensin receptor blocker/calcium channel blocker free-combination therapy

Objective:To compare adherence, healthcare costs and utilization of valsartan/amlodipine single-pill combination (SPC) and angiotensin-receptor blocker/calcium-channel blocker multiple-pill free-combination (ARB + CCB FC) therapy using real-world data.Methods:A retrospective study (January 1, 2007 to April 30, 2009) was conducted using US commercial healthcare insurance claims. Patients were assigned to two cohorts: ‘valsartan/amlodipine SPC cohort’ and ‘ARB + CCB FC therapy cohort’. The primary endpoints were adherence and persistence. The secondary endpoints were 1-year healthcare costs and utilization.Results:Out of 12,628 eligible patients 3259 (26%) were included in the valsartan/amlodipine SPC cohort and 9369 (%74) in the ARB + CCB FC cohort. Risk-adjusted adherence rates were higher for valsartan/amlodipine SPC patients [OR: 1.38, 95% CI: (1.24, 1.53)]. The Cox proportional hazard model showed that valsartan/amlodipine SPC cohort patients were less likely to discontinue medication (HR: 0.87, p < 0.001). Comparison between the groups also yielded that total healthcare costs of valsartan/amlodipine SPC patients were 16–20% lower than ARB + CCB FC therapy patients (p < 0.0001).Limitations:Since claims data are collected for payment purposes rather than research purposes, the study is bound by limitations for the retrospective analysis. For example, the presence of a claim for a filled prescription does not indicate that the medication was consumed or taken as prescribed. Data on health behaviors and patient lifestyle were not available. Over-the-counter medications and clinical disease severity were not available in the dataset. Incorrect coding is also a possibility. However, we have used previously validated datasets where these effects are minimal. Heterogeneity of the sample may create bias in our estimates, however, we have used advanced statistical methods to control for observed and unobserved bias.Conclusion:The real-world use of valsartan/amlodipine SPC was associated with better adherence and persistence relative to ARB + CCB FC therapy among patients with hypertension. Moreover, patients taking single-pill combination therapy had lower healthcare costs and utilization.

Adherence and persistence of single-pill ARB/CCB combination therapy compared to multiple-pill ARB/CCB regimens

Objective:To evaluate the impact of angiotensin receptor blocker (ARBs)/dihydropyridine calcium channel blockers (CCBs) single-pill combination (SPC) on adherence to antihypertensive treatment in comparison to free combination of ARBs and CCBs.Research design and methods:A retrospective data analysis was performed using pharmacy claims data from a national pharmacy benefit management company. The study included patients who were newly initiated on ARB/CCB treatment between 01/01/2007 and 08/31/2008, aged ≥18 years, and continuously enrolled in the same health plan for 12 months prior to and 13 months after starting ARB/CCB treatment. Outcome variables were persistence, defined as time to discontinuation of therapy, and adherence, defined as proportion of days covered (PDC) ≥ 0.80. Propensity score weighting was used to balance the characteristics of the two groups.Results:The final sample contained 2312 patients in the free-combination group and 2213 patients in the SPC group. Patients in the SPC group and the free-combination group were different in age, gender, type of insurance, history of antihypertensive therapy and co-morbidities. These differences were largely normalized after propensity score adjustment. Multivariate logistic model regression showed that patients in the SPC group had a 90% greater odds of being adherent to index therapy compared to patients in the free-combination group (odds ratio [OR] 1.90, 95% confidence interval [CI] 1.75–2.08, p < 0.001). A Cox proportional hazards model showed that patients in the SPC group were less likely to discontinue ARB/CCB SPC therapy compared to patients in the free-combination group (hazard ratio [HR] 0.66, 95% CI 0.63–0.70, p < 0.001). In both models, higher copayment (copayment $50 and above) was associated with worse persistence and adherence in comparison to patients who had a lower copayment ($0-$5): HR = 1.23, p < 0.001 and OR = 0.67, p < 0.001.Conclusion:Patients using SPC ARB/CCB therapy were more likely to be persistent and adherent to treatment compared to patients taking free-combination therapy.

Controlling malaria in Niger with bednets: how to take the Big Picture

Results and discussion During the first year of follow-up, vector dynamics showed an overall decrease in malaria transmission, but this was highly variable from village to village. Indeed, the second year of survey showed a return to transmission levels close to the pre-intervention period. A study of microsatellite markers showed no modification of the genetic structure in the two malaria vectors An. gambiae and An. arabiensis. However, a clear increase of the resistant allele of the kdr gene resistence to the pyrethroid insecticide used in the bed nets was observed. This clearly demonstrated that the main target vectors were reached. As measured by ovarian tracheoles observation, the parity rate of vectors was not significantly decreased. However, the index sporozoite decreased in the first year and remained low in the second year. Indeed, the parasite prevalence and the gametocyte carriage were shown decreasing in the children under five. This continued in 2007 as the National Malaria Control Program provided free artemisinin-based combination therapies as first line treatment for malaria in children under five. The national survey network showed a decrease in malaria cases, as confirmed in our sentinelle sites. However the biological confirmation of cases by HRP2 plasmodial antigen research has increased during the two years of follow-up. This could be explained by the more accurate diagnosis by peripheral health personal with the help of rapid diagnostic tests.

Evaluation of compliance and health care utilization in patients treated with single pill vs. free combination antihypertensives

Objectives:To compare compliance/persistence, health care resource utilization, and costs associated with single-pill combination (SPC) vs. free-combination (FC) therapies among adult hypertension patients at the national and state level. Combination therapies with angiotensin receptor blocker (ARB) + calcium channel blocker, ARB + hydrochlorothiazide, and angiotensin-converting enzyme inhibitor + hydrochlorothiazide were evaluated.Methods:Patients initiated on SPC or FC were identified in the MarketScan Database (2006–2008). Multivariate regression models were used to compare the health care outcomes of SPC vs. FC use during the 6-month study period. National- and state-level outcomes were analyzed and reported. Compliance was measured by medication possession ratio (MPR), and persistence was assessed based on treatment discontinuation (i.e., a lapse in therapy exceeding 30 days). Utilization and cost outcomes included frequencies of inpatient and emergency room (ER) visits and changes in health care costs from baseline.Results:Adjusting for baseline characteristics, SPC patients (N = 382,476) demonstrated significantly higher MPR than FC patients (N = 197,375) (difference = 11.6%; 95% confidence interval [CI]: 11.4%, 11.7%). SPC patients had fewer all-cause hospitalizations (adjusted incidence rate ratio [IRR] = 0.77; 95% CI: 0.75, 0.79) and ER visits (adjusted IRR = 0.87; 95% CI: 0.86, 0.89) than FC patients. Results for cardiovascular-related utilization were similar to all-cause results. Compared to FC, SPC patients showed significantly greater reductions post-therapy initiation in all-cause medical costs by −$208 (95% CI: −$302, −$114), but larger increases in hypertension-related prescription costs by $53 (95% CI: $51, $55). State-level results were generally consistent in magnitude and direction for comparisons of compliance and utilization, with greater regional variation in costs. Limitations include the possibility of residual confounding from factors not observable in claims.Conclusion:SPC use was associated with significantly better compliance/persistence and fewer hospitalizations and ER visits than FC in hypertensive patients at the national level and in almost all states. Larger reductions in medical costs with SPC use more than offset higher drug costs within most states.