Efficacy and safety of stabilised hydrogen peroxide cream (Crystacide) in mild-to-moderate acne vulgaris: a randomised,controlled trial versus benzoyl peroxide gel

BACKGROUND: Benzoyl peroxide (BP) is a first-line topical treatment in acne vulgaris (AV). However, its use can cause mild skin irritation and dryness. A new formulation of hydrogen peroxide stabilised (HPS) in monoglycerides cream (Crystacide 1%), indicated in the topical treatment of superficial skin infections, is now available as an alternative treatment. STUDY AIM: To evaluate efficacy and local tolerability of HPS in mild-to-moderate AV in comparison with BP gel. METHODS AND PATIENTS: In a randomised, prospective, investigator-masked parallel-group, 8-week trial, 60 patients (24 men, 36 women, mean age 25 +/- 6 years) with mild-to-moderate AV, affecting mainly the face, were enrolled in the study, after their informed consent. HPS or BP (PanOxyl gel 4%) was applied topically twice daily for 8 weeks. STUDY OUTCOMES: The study endpoints were: (1) Reduction in mean inflammatory (IL), noninflammatory (NIL) and total (TL) acneic lesions in comparison with baseline; (2) Local tolerability assessed evaluating erythema, dryness and burning sensation, using a 0-3 qualitative score (score 0 = poor tolerability; score 3 = very good tolerability). RESULTS: TL, NIL, and IL were assessed by an investigator unaware of treatment allocation at baseline, and week 8. The tolerability score (TS) was assessed at week 4 and 8. At baseline, the two groups were well matched for the main clinical and demographic characteristics. All patients concluded the trial. At week 0, in the HPS group TL, NIL and IL (mean +/- SD) were: 35 +/- 8, 20 +/- 6 and 16 +/- 7. At week 8, HPS reduced TL to 16 +/- 7; NIL to 9 +/- 3 and IL to 7 +/- 3 (p < 0.001). At baseline, TL, NIL and IL, in the BP group, were 32 +/- 9, 24 +/- 8 and 18 +/- 7, respectively. At week 8, BP reduced TL, NIL and IL to 14 +/- 9; 7 +/- 5 and 7 +/- 3 (p < 0.001). In comparison with baseline values, the percentage reductions of IL were 58% and 61% for HPS and BP,respectively (p = n.s.). At the end of the study the TS was 2.9 +/- 0.2 in HPS group and 2.4 +/- 0.8 in BP group (p < 0.025). Two patients in HPS group (6%) and seven patients (23%) in BP group suffered from mild-to-moderate local erythema. CONCLUSIONS: HPS has shown to be as effective as BP in reducing both inflammatory and noninflammatory AV lesions in patients with mild-to-moderate disease. In comparison with BP 4% gel, HPS cream shows a better local tolerability profile.     

Efficacy and safety of the single pill combination of amlodipine 10 mg plus valsartan 160 mg in hypertensive patients not controlled by amlodipine 10 mg plus olmesartan 20 mg in free combination

ABSTRACT

Background and objective: For patients with moderate hypertension (grade 2, defined as systolic blood pressure [SBP] 160–179?mmHg and/or diastolic blood pressure [DBP] 100–109?mmHg), current guidelines recommend initial combination therapy and rapid dose-adjustment to achieve blood pressure goal. In this study we investigated the efficacy and tolerability of the single pill combination of amlodipine 10?mg plus valsartan 160?mg (A?10?+?Val 160) in patients not controlled by the free combination of amlodipine 10?mg plus olmesartan 20?mg (A?10?+?O 20).

Methods: In this prospective, open-label, non-randomized trial, 257 patients with mean sitting DBP of 100–109?mmHg at trough entered a 4 week treatment phase with A?10?+?O 20 in free combination once daily. Patients in whom DBP remained uncontrolled were switched in a second 4 week treatment phase to A?10?+?Val 160. The primary efficacy variable was the reduction in DBP at week 8 compared to week 4 in the intent-to-treat population.

Results: In the total cohort, baseline SBP/DBP of 164.2?±?9.8/103.6?±?2.1?mmHg decreased by 19.2?±?12.4/14.1?±?7.4?mmHg at week 4. In patients who did not achieve BP control (n?=?175), subsequent treatment with A?10?+?Val 160 for 4 weeks reduced SBP from 149.6?±?11.1 at week 4 by 7.9?mmHg at week 8 (95% CI: 6.1–9.6, p?<?0.0001) and DBP from 93.4?±?3.9?mmHg by 9.1?mmHg (95% confidence interval: 8.1–10.2, p?<?0.0001). The combination of A?10?+?Val 160 was well tolerated, and the observed adverse events (15.3% of patients in phase 2) were consistent with the known drug profiles.

Conclusions: In a study designed to reflect typical clinical practice, in patients not controlled by the free combination of A?10?+?O 20, the single pill combination of A?10?+?Val 160 produced a statistically and clinically significant additional BP reduction and was well tolerated. Potential limitations of the design (open-label, non-controlled design, short term treatment) have to be taken into account.     

Antihypertensive efficacy of indapamide SR in hypertensive patients uncontrolled with a background therapy: the NATIVE study*

ABSTRACT

Objectives: Antihypertensive monotherapy rarely achieves blood pressure (BP) control. NATIVE (NATrilix SR use in combInation antihypertensiVe thErapy) evaluated indapamide sustained release (SR) in hypertensive patients receiving background therapy.

Research design and methods: Patients remaining hypertensive (systolic BP [SBP], 145–180?mmHg; diastolic BP [DBP], 95–105?mmHg) while receiving an angiotensin-converting enzyme (ACE) inhibitor (n = 709), β-blocker (n = 629), calcium-channel blocker (CCB; n = 493), angiotensin II type 1 receptor blocker (ARB; n = 75), α-blocker (n = 29) or other therapy (n = 6) were enrolled, recruited by physicians from 228 centres in Pakistan. Indapamide SR 1.5?mg was administered daily for 3 months with background therapy. BP was assessed every 2 weeks, and blood glucose and total cholesterol were evaluated at baseline and study end in a patient subgroup. Adverse events were also recorded.

Main outcome measures and results: Of 2073 enrolled patients (49% males; mean age 51 years), 1941 received indapamide SR and background therapy. SBP and DBP decreased significantly (SBP, 166 ± 16?mmHg at baseline vs. 132 ± 12?mmHg at 3 months; DBP, 102 ± 8?mmHg vs. 83 ± 6?mmHg; both p < 0.0001 vs. baseline). Patients uncontrolled with an ACE inhibitor, β-blocker, CCB or ARB achieved an SBP/DBP decrease of 34 ± 15/19 ± 9, 33 ± 17/19 ± 10, 33 ± 15/18 ± 8 or 35 ± 16/20 ± 12?mmHg, respectively (all p < 0.0001). In all, 84% of patients achieved target SBP (≤?140?mmHg) and 61% achieved BP normalisation (SBP <?140, DBP <?90?mmHg). The absence of placebo control may lead to an overestimation of the extent of the BP reduction achieved. Glucose and cholesterol levels were unaffected by indapamide SR. Four percent of patients experienced side-effects, which were mild-to-moderate in severity.

Conclusions: In patients with hypertension despite antihypertensive therapy, indapamide SR significantly reduced BP with a good acceptability profile. Indapamide SR may represent an effective additional therapy for patients who do not achieve BP goals with other antihypertensive agents.     

Bisoprolol/amlodipine combination therapy improves blood pressure control in patients with essential hypertension following monotherapy failure

Objective: The efficacy of a bisoprolol/amlodipine fixed-dose combination (FDC) in patients with essential hypertension who had not responded to bisoprolol or amlodipine monotherapy was investigated.

Research design and methods: In an 18 week, multicenter, randomized, comparative phase III study (ClinicalTrials.gov identifier: NCT01977794), patients with blood pressure uncontrolled by bisoprolol or amlodipine monotherapy (5?mg OD) began treatment with bisoprolol/amlodipine FDC 5/5?mg OD. Patients with controlled blood pressure (BP) at week 6/12 continued at current FDC strength, and patients with uncontrolled BP received FDC dose uptitration (maximum dose: 10/10?mg). The primary efficacy endpoint was change in systolic blood pressure (SBP) at week 18 versus baseline (corresponding to SBP under monotherapy), and secondary endpoints included change from baseline in SBP after week 6/12 and percentage of BP-controlled patients at week 6, 12 and 18. Safety was assessed by number/types of adverse events (AEs).

Results: Two hundred patients were randomized to treatment (100 with uncontrolled BP under bisoprolol and 100 under amlodipine monotherapy). Overall, 196 patients were eligible for analysis. The patient groups displayed similar mean SBP reductions from baseline by study end (bisoprolol monotherapy failure: 25.9?±?12.82?mmHg reduction; amlodipine monotherapy failure: 24.7?±?11.67?mmHg reduction; p?<?0.001 for both). Overall mean SBP decreased by 25.3?±?12.25?mmHg (p?<?0.001). Mean heart rate reductions were also observed (bisoprolol monotherapy failure: 6.6?±?9.67 bpm reduction; amlodipine monotherapy failure: 11.5?±?8.65 bpm reduction; p?<?0.001 for both). Most patients (83.2%) displayed BP control with bisoprolol/amlodipine 5/5?mg at 6 weeks. Treatment was well tolerated at all dose levels; treatment-related AEs (mostly of mild/moderate intensity) were reported by 52.5% of patients, with no severe or serious treatment-related AEs reported. As the study focused on hypertension, total cardiovascular risk was not assessed.

Conclusions: Bisoprolol/amlodipine FDC therapy is associated with significant BP improvements in patients with essential hypertension following monotherapy failure.     

Effectiveness of perindopril/amlodipine fixed dose combination in everyday clinical practice: results from the EMERALD study

Objective: The rates of blood pressure (BP) control worldwide are discouraging. This study had the purpose of assessing the effectiveness of perindopril/amlodipine fixed dose combination on BP-lowering efficacy, and recording adherence, safety and tolerability during a 4 month treatment period.

Research design and methods: In this multicenter, observational study 2269 hypertensive patients were prospectively enrolled. The data were recorded at 1 and 4 months of treatment.

Main outcome measures and results: Between the first and third visits mean BP values (systolic/diastolic) decreased from 158.4?±?13.6/89.9?±?8.7?mmHg to 130.0?±?7.9/77.7?±?6.3?mmHg (P?<?0.001). The magnitude of BP reduction depended on baseline blood pressure levels and total cardiovascular (CV) risk (P?<?0.001). Patients with grade 1, 2 and 3 showed a BP reduction of 21.9/10.0?mmHg, 34.4/14.2?mmHg and 51.4/21.2?mmHg, accordingly (P?<?0.001). Patients with very high, high, moderate and low added CV risk showed a BP reduction of 35.7/14.9?mmHg, 27.5/12.1?mmHg, 28.6/12.2?mmHg and 14.5/5.8?mmHg respectively (P?<?0.001). Adherence to treatment was high: 98.3% of the sample was taking the treatment “every day” or “quite often”, while only 15 patients (0.7% of the sample) prematurely discontinued treatment. Study interpretation may be limited by the fact that this is an observational study with no comparator and a short follow-up period.

Conclusions: A perindopril/amlodipine fixed dose combination significantly decreases BP levels. The degree of BP reduction is related to baseline BP levels and total CV risk.     

Attaining United States and European Guideline LDL-C Levels with Simvastatin in Patients with Coronary Heart Disease (the GOALLS Study)

SUMMARY

Objectives: The primary objective was to assess the effects of rilmenidine monotherapy and in combination with perindopril on blood pressure (BP) in patients assessed with grade 1 or 2 essential hypertension. The study also examined the effects of 2-year rilmenidine monotherapy on left ventricular hypertrophy (LVH) and on diastolic function of the left ventricle, along with the effects of rilmenidine on left ventricular mass index in hypertensive patients with no LVH, and the relationship between BP reduction and any change in LVH.

Research design and methods: Mild-to-moderate hypertensive patients (n?=?500) were enrolled in a multicentre 2-year open study and treated with rilmenidine (1-2?mg per day) monotherapy or rilmenidine plus perindopril (2, 4 or 8?mg per day) if control of hypertension was not achieved with rilmenidine monotherapy within 12 weeks. Blood pressure was recorded at regular intervals by the investigators and LVH measured by centralised single-blind echocardiographic reading.

Results: Rilmenidine monotherapy (average dose 1.42?mg) produced a significant decrease in BPfrom the baseline of 163?±?10/100?±?5?mmHg to 134?±?10/86?±?7?mmHg at 1 year and to 136?±?10/84?±?7?mmHg at 2 years (p?2 at 2 years (p?Conclusions: Long-term rilmenidine monotherapy was shown to be efficient in controlling BP and in reducing LVH. The addition of perindopril to rilmenidine monotherapy proved to be effective and well tolerated in those patients who did not respond to rilmenidine alone.     

Initial combination therapy with vildagliptin plus metformin in drug-naïve patients with T2DM: a 24-week real-life study from Asia

Aims: To assess the effectiveness and safety of vildagliptin/metformin initial combination therapy in drug-naïve patients with type 2 diabetes mellitus (T2DM).

Methods: INITIAL was a 24-week prospective, observational study in T2DM patients with glycated hemoglobin (HbA1c)?≥?7.5%, and prescribed vildagliptin/metformin as initial combination therapy. The primary endpoint was change in HbA1c from baseline to week 24. Key secondary endpoints were HbA1c change from baseline to week 12, proportion of patients achieving HbA1c ≤7.0%, change in body weight at 12 and 24 weeks, change in HbA1c by sub-groups (baseline HbA1c, age, body mass index [BMI], dosage strength, co-morbidities) from baseline to week 24, and safety.

Results: A total of 532 patients were enrolled. The mean age, HbA1c, and BMI were 49.6?±?11.27 years, 9.3?±?1.57%, and 26.7?±?4.50?kg/m², respectively. Cardiovascular risk factors present at baseline were dyslipidemia (30.1%), hypertension (29.7%), and obesity (20.9%). The mean reductions in HbA1c from baseline to week 12 (?1.6?±?1.59%) and 24 (?1.9?±?1.70%) were statistically significant (p?Conclusions: Overall, in a relatively young drug-naïve T2DM Asian study population with high baseline HbA1c and often associated with cardiovascular risk factors, vildagliptin/metformin combination therapy was associated with significant and clinically relevant HbA1c reduction from baseline. This effect was seen at week 12, was maintained over 24 weeks, and was accompanied by good tolerability.     

Effectiveness and safety of vildagliptin and vildagliptin add-on to metformin in real-world settings in Egypt – results from the GUARD study

Objective: The GUARD study evaluated the effectiveness, safety, and tolerability of vildagliptin treatment with or without metformin in patients with type 2 diabetes mellitus (T2DM) in real-life settings. Here we present the results of the GUARD study for the patient subset from Egypt.

Research design and methods: This was a 24?±?6 weeks, prospective, non-interventional study that enrolled adult patients with T2DM receiving vildagliptin or vildagliptin?+?metformin combination therapy as per local prescribing information.

Main outcome measures: The primary effectiveness endpoint was change in HbA1c levels from baseline to week 24?±?6 endpoint. Safety was assessed by reporting of adverse events and serious adverse events (SAEs).

Results: Of 2786 patients enrolled from Egypt, 655 received vildagliptin and 2131 received vildagliptin?+?metformin. Overall, at baseline, mean (± standard deviation [SD]) age was 49.5?±?9.49 years, BMI was 31.5?±?4.85?kg/m², HbA1c was 8.4?±?0.86%, and duration of T2DM was 2.3?±?3.78 years. At week 24, significant reductions in mean (±SD) HbA1c were observed in the vildagliptin (?1.47?±?0.79%) and vildagliptin?+?metformin (?1.62?±?0.82%) groups (both p?Conclusion: In a real-world setting, vildagliptin, with or without metformin, resulted in significant reductions in HbA1c and was well tolerated in patients with T2DM from Egypt. Limitations of the study include non-randomization and the open-label, observational nature of the study.     

Effectiveness of a trandolapril-based treatment regimen in subjects with isolated systolic hypertension in Canada

ABSTRACT

Objective: This report evaluates the effectiveness of a titration-based, escalating dose regimen based on trandolapril in subjects with isolated systolic hypertension (ISH) treated in Canadian clinical practice.

Methods: Substudy of the TRAIL (Trandolapril Regimen Applied In real Life) study; a prospective, open-label, single cohort, multicentre study in 192 Canadian primary care practices. Subjects with ISH received trandolapril therapy, initiated at 1?mg/day (0.5?mg/day in subjects on diuretics) and increased to 2 or 4?mg at 4 and 9 weeks, respectively, in those not achieving blood-pressure (BP) targets, subject to tolerability. If BP was not controlled after 14 weeks of treatment subjects could be put on trandolapril 4?mg/verapamil 240?mg while continuing the diuretic, or verapamil could be added to the existing regimen. The observation period was 26 weeks. The primary outcome measure was the achievement of target BP levels after 14 weeks.

Results: Systolic BP (SBP) was significantly (p?<?0.01) reduced from 167.3?±?8.7?mmHg at baseline to 136.8?±?14.0?mmHg (means?±?SD) at Week 14. The reductions were maintained at Week 26: mean SBP at this time point was 137.4?±?12.5?mmHg. The target BP levels of ≤140/90?mmHg at Week 14 was reached by 67% of subjects with ISH. Among study limitations were the observational design; the lack of randomisation and control group, and the fact that subjects with ISH represented a comparatively small number of subjects.

Conclusions: A titration-based, escalating-dose regimen based on trandolapril is effective in subjects with ISH under treatment conditions seen in general clinical practice in Canada.     

Exenatide effects on diabetes,obesity, cardiovascular risk factors and hepatic biomarkers in patients with type 2 diabetes treated for at least 3 years

ABSTRACT

Background: Exenatide, an incretin mimetic for adjunctive treatment of type 2 diabetes (T2DM), reduced hemoglobin A_1c (A1C) and weight in clinical trials. The objective of this study was to evaluate the effects of?≥?3 years exenatide therapy on glycemic control, body weight, cardiometabolic markers, and safety.

Methods: Patients from three placebo-controlled trials and their open-label extensions were enrolled into one open-ended, open-label clinical trial. Patients were randomized to twice daily (BID) placebo, 5?µg exenatide, or 10?µg exenatide for 30 weeks, followed by 5?µg exenatide BID for 4 weeks, then 10?µg exenatide BID for ≥3 years of exenatide exposure. Patients continued metformin and/or sulfonylureas.

Results: 217 patients (64% male, age 58?±?10 years, weight 99?±?18?kg, BMI 34?±?5?kg/m², A1C 8.2?±?1.0% [mean?±?SD]) completed 3 years of exenatide exposure. Reductions in A1C from baseline to week 12 (?1.1?±?0.1% [mean?±?SEM]) were sustained to 3 years (?1.0?±?0.1%; p?<?0.0001), with 46% achieving A1C?≤?7%. Exenatide progressively reduced body weight from baseline (?5.3?±?0.4?kg at 3 years; p?<?0.0001). Patients with elevated serum alanine aminotransferase (ALT) at baseline (n?=?116) had reduced ALT (?10.4?±?1.5?IU/L; p?<?0.0001) and 41% achieved normal ALT. Patients with elevated ALT at baseline tended to lose more weight than patients with normal ALT at baseline (?6.1?±?0.6?kg vs. ?4.4?±?0.5?kg; p?=?0.03), however weight change was minimally correlated with baseline ALT (r?=??0.01) or ALT change (r?=?0.31). Homeostasis Model Assessment B (HOMA-B), blood pressure, and aspartate aminotransferase (AST) all improved. A subset achieved 3.5 years of exenatide exposure and had serum lipids available for analysis (n?=?151). Triglycerides decreased 12% (p?=?0.0003), total cholesterol decreased 5% (p?=?0.0007), LDL-C decreased 6% (p?<?0.0001), and HDL-C increased 24% (p <?0.0001). Exenatide was generally well tolerated. The most frequent adverse event was mild-to-moderate nausea. The main limitation of this study is the open-label, uncontrolled nature of the study design which does not provide a placebo group for comparison.

Conclusion: Adjunctive exenatide treatment for ≥3 years in T2DM patients resulted in sustained improvements in glycemic control, cardiovascular risk factors, and hepatic biomarkers, coupled with progressive weight reduction.     

Effects of vildagliptin versus saxagliptin on daily acute glucose fluctuations in Chinese patients with T2DM inadequately controlled with a combination of metformin and sulfonylurea

Objective The present study aimed to compare the effects of the dipeptidyl peptidase-4 (DPP-4) inhibitors vildagliptin and saxagliptin on 24?hour acute glucose fluctuations in Chinese patients with type 2 diabetes mellitus (T2DM) inadequately controlled with a combination of metformin and sulfonylurea.

Research design and methods This was a 24 week, prospective, randomized, open-label, active-controlled study. Patients (N?=?73) with T2DM who had inadequate glycemic control (HbA1c 7.0%–10.0%) with a stable dosage of metformin plus gliclazide for more than 3 months were randomized to receive either vildagliptin 50?mg twice daily (BID, n?=?37) or saxagliptin 5?mg once daily (QD, n?=?36). Change in mean amplitude of glycemic excursions (MAGE) was assessed at the end of 24 weeks.

Results At baseline, the mean (±SD) age was 62.9?±?6.55 years, disease duration was 7.0?±?2.33 years, and HbA1c was 8.4?±?0.68%. After 24 weeks of treatment, the MAGE decreased from 5.81?±?1.16?mmol/L to 4.06?±?0.86?mmol/L (p<0.001) in the vildagliptin group and from 5.66?±?1.14?mmol/L to 4.79?±?1.25?mmol/L (p?=?0.003) in the saxagliptin group. The mean change in MAGE in the vildagliptin group was significantly greater than that in the saxagliptin group (1.74?±?0.48?mmol/L vs. 0.87?±?0.40?mmol/L, p<0.001). The mean change in HbA1c, from baseline to the study endpoint, in the vildagliptin and saxagliptin groups, was 1.22?±?0.40% and 1.07?±?0.36%, respectively, with no significant difference between the groups (p?=?0.091). The overall safety and tolerability of vildagliptin and saxagliptin were similar. The limitations of the study were a small number of patients and open-label administration of the study drug.

Conclusion Vildagliptin produced a significantly greater reduction in acute glucose fluctuations compared with saxagliptin when added to a dual combination of metformin and sulfonylurea in Chinese patients with T2DM.

Chinese clinical trial registration number ChiCTR-TRC-13003858.     

Efficacy,tolerability and safety of the fixed combination of bimatoprost 0.03% and timolol 0.5% in a broad patient population: multicenter,open-label observational study*

ABSTRACT

Objective: To evaluate intraocular pressure (IOP)-lowering efficacy, tolerability, and safety of the fixed combination of bimatoprost 0.03% and timolol 0.5% (Ganfort^?) among German patients.

Methods: Multicenter, observational, open-label study of patients with primary open angle glaucoma or ocular hypertension (n?=?606). As determined by participating physicians, patients had insufficient IOP control and required a medication change. They were switched to once-daily fixed-combination bimatoprost/timolol with no wash-out period. IOP was recorded at treated baseline, 4–6 weeks and 12 weeks after switching. Tolerability was measured using a 4-step scale (excellent, good, moderate, poor) and all adverse events were recorded.

Results: A total of 405 patients switched from monotherapy, 97 switched from other fixed combinations, and 104 switched from non-fixed combinations. Among all patients, 32.5% had used prostaglandin analog (PGA) monotherapy, 8.7% had been using a fixed combination that included a PGA, and 6.9% had been using an adjunctive combination of a PGA and a β-blocker. Mean treated baseline IOP (±SD) for all patients was 20.7?±?3.5?mmHg. Overall, changing medication to fixed-combination bimatoprost/timolol lowered IOP to 16.6?±?2.7?mmHg (p?<?0.001 vs. baseline) after 4–6 weeks and to 16.1?±?2.6?mmHg (p?<?0.001) after 12 weeks; reductions of 19.8% and 22.2%, respectively. Combined bimatoprost/timolol provided an additional IOP reduction versus baseline in most subgroups based on prior treatment. At week 12, patients who had previously used a β-blocker achieved an additional 25.8% decrease from baseline and IOP was reduced by 22.6% in former PGA monotherapy patients. At week 12, 84.6% of all eyes reached a target pressure less than or equal to 18?mmHg. Tolerability of bimatoprost/timolol was rated excellent or good by the physicians for 98.7% of patients and by 96.7% of the patients themselves. Few adverse events occurred during the treatment period.

Conclusions: Although this study was limited by its observational design, our results show that the fixed combination of bimatoprost 0.03%/timolol 0.5% was effective, well tolerated, and safe in a broad patient population.     

Antihypertensive efficacy and tolerability of aliskiren/hydrochlorothiazide (HCT) single-pill combinations in patients who are non-responsive to HCT 25 mg alone*

ABSTRACT

Objective: Thiazide diuretics such as hydrochlorothiazide (HCT) are a widely used first-line treatment for hypertension, but most patients will not achieve blood pressure (BP) control with HCT alone and so will require combination therapy. In this study the efficacy, safety and tolerability of a single-pill combination (SPC) of the direct renin inhibitor aliskiren with HCT were investigated in patients non-responsive to HCT 25?mg therapy.

Methods: In this study, 722 patients with hypertension and an inadequate response to 4?weeks of HCT 25?mg (mean sitting diastolic BP ≥90 and <110?mmHg) were randomized to once-daily, double-blind treatment for 8?weeks with an SPC of aliskiren/HCT 300/25?mg or 150/25?mg, or continued HCT 25?mg monotherapy. Least-squares mean changes in mean sitting systolic/diastolic BP (msSBP/DBP) from double-blind baseline were analyzed for the ITT population at week?8 endpoint.

Results: Aliskiren/HCT 300/25?mg and 150/25?mg SPCs lowered msSBP/DBP from baseline by 16.7/10.7 and 12.9/8.5?mmHg, respectively, both significantly greater reductions than HCT 25?mg alone (7.1/4.8?mmHg; both p?<?0.001). Rates of BP control (<140/90?mmHg) were also significantly higher with aliskiren/HCT 300/25?mg (58%) and 150/25?mg (49%) than with HCT (26%; both p?<?0.001). Aliskiren/HCT 300/25?mg provided significantly greater msSBP/DBP reductions and rates of BP control than the 150/25?mg SPC dose (all p?<?0.05). Aliskiren/HCT SPC treatment showed similar tolerability to HCT alone and a numerically lower incidence of hypokalemia (serum potassium <3.5?mmol/L; aliskiren/HCT, 1.3–2.2%: HCT alone, 3.4%).

Conclusion: Aliskiren/HCT SPCs provide clinically significant BP reductions and improved BP control rates in patients who are non-responsive to HCT 25?mg monotherapy. Limitations of the study were the mainly Caucasian patient population and the non-responder design.     

Effect of pramlintide as an adjunct to basal insulin on markers of cardiovascular risk in patients with type 2 diabetes

ABSTRACT

Objective: Intensification of insulin therapy in patients with type 2 diabetes, while improving glycemic control, often leads to an increase in body weight and other markers of cardiovascular risk. The effects of pramlintide as an adjunct to basal insulin titration (without mealtime insulin) on glycemia and cardiovascular risk markers were examined.

Research design and methods: This was a post hoc analysis of a 16-week, double-blind, placebo-controlled study in patients with type 2 diabetes (N?=?211) using insulin glargine (without mealtime insulin)?±?oral agents. Patients were randomized to treatment with placebo or pramlintide (60 or 120?µg with major meals), and insulin glargine was titrated to target a fasting plasma glucose concentration of ≥70 to <100?mg/dL.

Main outcome measures: Endpoints included the change from baseline to Week 16 in body weight, high sensitivity C-reactive protein (hsCRP), triglycerides, HDL, LDL, and blood pressure.

Results: Pramlintide-treated patients lost weight and placebo-treated patients gained weight during 16 weeks of treatment (?1.6?±?0.3?kg vs. +0.7?±?0.3?kg, p?<?0.001; mean?±?SE). hsCRP was reduced in pramlintide-treated versus placebo-treated patients (?0.8?±?0.2?mg/L vs. 0.1?±?0.2?mg/L, p?<?0.01; mean?±?SE). Patients with baseline hsCRP?>?3?mg/L (high cardiovascular risk) demonstrated greater hsCRP reductions with pramlintide versus placebo treatment at Week 16 (p?<?0.05). Patients with baseline triglycerides ≥150?mg/dL or ≥200?mg/dL (high cardiovascular risk) showed significant reductions from baseline in triglyceride concentrations with pramlintide (?43?±?14?mg/dL or ?59?±?19?mg/dL; p?<?0.05; mean?±?SE) but not with placebo (1?±?29?mg/dLor ?3?±?54?mg/dL; mean?±?SE). No significant differences between pramlintide and placebo were observed for changes in HDL, LDL, or blood pressure. Pramlintide treatment was generally well tolerated. The most frequent adverse event related to pramlintide was mild-to-moderate nausea (31% pramlintide vs. 10% placebo). Pramlintide added to basal insulin did not increase the incidence of hypoglycemia. A limitation of the study was its relatively short duration.

Conclusions: Pramlintide, as an adjunct to basal insulin, was associated with improvements in several cardiovascular risk markers, warranting long-term clinical studies to determine its potential effects on cardiovascular risk.     

A double-blind,randomized study evaluating losartan potassium monotherapy or in combination with hydrochlorothiazide versus placebo in obese patients with hypertension

ABSTRACT

Objectives: The objective of this study was to evaluate the effects of losartan ± hydrochlorothiazide (HCTZ) versus placebo in obese patients with systolic and diastolic hypertension.

Research design and methods: Randomized patients (n = 261) were non-diabetic with systolic blood pressure (SBP) ≥ 140 and ≤ 180?mmHg and diastolic BP (DBP) ≥ 95 and ≤ 115?mmHg, body mass index > 30?kg/m², and waist circumference > 40 (males)/> 35 (females)?inches. Patients were randomized to placebo or a forced titration of losartan 50?mg titrated at 4-week intervals to losartan 100?mg, losartan 100?mg/HCTZ 12.5?mg, and losartan 100?mg/HCTZ 25?mg. Primary efficacy measurements were change from baseline in SBP and DBP at 12 weeks. Secondary measurements were change from baseline in BPs at 8 and 16 weeks, percent responders at 12 and 16 weeks, and safety/tolerability. Post-hoc analyses were BP at 4 weeks and achieve­ment of controlled BP (SBP < 140 and/or DBP < 90?mmHg) at 12 and 16 weeks.

Results: Losartan 50?mg reduced BP from 151.6/99.2?mmHg at baseline to 140.1/89.8?mmHg at week 4 (post hoc), 139.5/89.6?mmHg with losartan 100?mg at week 8 (secondary), 134.3/85.9?mmHg with losartan 100?mg/HCTZ 12.5?mg at week 12 (primary), and 132.1/84.9?mmHg with losartan 100?mg/HCTZ50?mg at week 16 (secondary) (all p < 0.05). Rates of clinical adverse experi­ences were similar between treatment groups. A limitation of these analyses is the relatively rapid rate of study drug titration, which may not have allowed for the evaluation of the full treatment effect at each titration step.

Conclusions: We conclude that losartan alone or in combination with HCTZ was generally well tolerated and effective in the treatment of elevated systolic and diastolic BP in obese patients with hypertension.     

China STudy of valsartan/amlodipine fixed-dose combination-bAsed long-Term blood pressUre management in HypertenSive patients: a one-year registry (China STATUS III)

Objective: The present observational study evaluated long-term management of hypertension in patients who received treatment with valsartan and amlodipine in a single-pill combination (Val/Aml SPC) in a real-world setting in China (Chinese Clinical Trial Registry number ChiCTR1900021324).

Methods: This was a prospective, observational, multicenter, real-world registry study wherein patients with hypertension who had already received Val/Aml SPC (80/5?mg) for at least 4?weeks before study enrollment were observed for 1?year. Investigators recorded patient data every 3?months and essentially five times during the 1?year follow-up period. Effectiveness was assessed by the blood pressure (BP) control rate and average duration of treatment at the end of the study. Safety was monitored by the incidence of adverse events (AEs) and serious adverse events (SAEs).

Results: Overall, 985 patients were enrolled (mean?±?standard deviation [SD] age: 60.3?±?11.5?years); of these, 894 were included in the full analysis set, 758 of whom completed the study. At baseline, BP was controlled (<140/90?mmHg) in 64.3% of patients on Val/Aml SPC for at least 4?weeks before enrollment. Office BP control rates significantly improved from baseline in 74.1% of patients at 1?year (p?<?.0001). Overall, 575 (87.0%) patients remained on Val/Aml SPC at 1?year (average exposure: 311.5?days). AEs were reported in 23.3% of patients. The majority of AEs were mild to moderate, and 0.6% of patients discontinued Val/Aml SPC because of SAEs.

Conclusion: This study provides evidence that Val/Aml SPC effectively reduced BP over the long term among Chinese hypertensive patients, with a good adherence and tolerability profile, and that most hypertensive patients may benefit from this combination.     

Inhaled loxapine for agitation in patients with personality disorder: an initial approach

Inhaled Loxapine (IL) has demonstrated efficacy in the treatment of agitation in schizophrenic and bipolar patients, although data in patients with Personality Disorder (PD) are scarce. To evaluate the effectiveness and safety of IL in the treatment of agitation in PD, data from 41 patients who presented at our unit with acute agitation and were treated with 9.1?mg of IL were collected retrospectively. The results showed that IL significantly decreased agitation within 10 minutes and its effect was greater at 20 minutes (Positive and Negative Syndrome Scale-excited component: from 22.78?±?4.39 at baseline to 11.14?±?4.17 at 20 minutes; p?<?0.001; Agitation and Calmness Evaluation Scale: from 1.80?±?0.49 at baseline to 4.53?±?1.05 at 20 minutes; p?<?0.01) without any severe adverse reactions registered. IL led to fast, safe and well-tolerated control of agitation in patients with PD.     

Treatment of patients with primary open-angle glaucoma with a fixed combination of brimonidine 0.2%/timolol 0.5%: multicenter,open-label,observational study in Germany*

ABSTRACT

Objective: At the introduction of the fixed-combination of brimonidine/timolol in Germany in 2006, a non-interventional, multicenter, observational, open-label study was initiated to evaluate efficacy, tolerability, and safety of this preparation in a broad patient population.

Methods: The study population comprised patients with bilateral primary open-angle glaucoma or ocular hypertension with insufficient intraocular pressure (IOP) control who participating physicians determined required a change of medication, and who switched to exclusive use of the new fixed-combination brimonidine 0.2%/timolol 0.5%. Patient demographics and information on specific risk factors were collected. IOP readings were recorded for each eye at treated baseline (previous therapy), 4 to 6 weeks, and 12 weeks after changing to twice-daily brimonidine/timolol. Tolerability was measured using a four-step scale ranging from excellent to poor. All adverse events were recorded.

Results: Mean treated baseline IOP (±SD) for all patients (N?=?861) was 20.8?±?3.5?mmHg. Five hundred sixty-five patients switched from monotherapy, 138 patients switched from other fixed combinations, and 158 patients had been using non-fixed combinations of up to four different active agents. The brimonidine/timolol fixed combination provided an additional IOP decrease in most pretreatment subgroups, with an overall reduction to 16.9?±?2.6?mmHg after 4 to 6 weeks and to 16.5?±?2.7?mmHg after 12 weeks. Both of these values were significantly lower than baseline IOP (p?<?0.001). A target pressure of <18?mmHg was achieved in 79.5% of all eyes at week 12. Tolerability of fixed-combination brimonidine/timolol was rated excellent or good by the physicians for 97.1% of patients, and by 93.4% of the patients themselves. Few adverse events occurred during the treatment period.

Conclusions: Although this study was limited by its observational design, our results show that the fixed combination of brimonidine 0.2%/timolol 0.5% was effective, well tolerated, and safe in a broad POAG patient population.     

Enteric-coated budesonide for the induction and maintenance of remission of Crohn’s disease in children

Objective: These studies evaluated the safety and efficacy of enteric-coated budesonide for the induction and maintenance of remission of mild-to-moderate Crohn’s disease (CD) in children.

Methods: The consecutive, multicenter, open-label, non-comparative studies enrolled patients aged 6–17 years. In the induction study, patients with active CD of the ileum and/or ascending colon received budesonide 9?mg or 6?mg once daily for 8 weeks; in the maintenance study, patients in remission received budesonide 6?mg once daily for 12 weeks. The primary objective was assessment of safety, including glucocorticosteroid-related side effects and serum cortisol levels. Efficacy was assessed using the Pediatric Crohn’s Disease Activity Index (PCDAI), and health-related quality of life (HRQoL) using the IMPACT-III questionnaire.

Results: In the induction study (n?=?108), most adverse events were related to CD, commonly abdominal pain; possible glucocorticosteroid-related effects included acne and increased appetite but without significant weight gain. Subnormal morning cortisol levels were observed in 32 of 103 patients after 8 weeks. Budesonide reduced disease activity from baseline (mean?±?standard deviation, 9.1?±?8.5 vs. 19.1?±?10.1, p?p?n?=?50), mean disease activity worsened (p?=?.047) with HRQoL unchanged (p?=?.33).

Conclusions: Budesonide treatment was generally well tolerated, although the potential for adrenal suppression was noted. Budesonide was effective for induction of remission in children with mild-to-moderate CD but not for maintaining remission (ClinicalTrials.gov identifiers: NCT01444092, NCT01453946).     

Additional therapy for cholesterol lowering in ezetimibe-treated,statin-intolerant patients in clinical practice: results from an internal audit of a university lipid clinic

Objective: The aim of our study was to evaluate the tolerability and efficacy of alternative approaches to improve cholesterolemia control in patients with statin-related myalgia treated with ezetimibe.

Research design and methods: We retrospectively evaluated 3534 Clinical Report Forms (CRFs) filled in the period June 2012–June 2015 for first visits to the lipid clinic of the University of Bologna. For this study, we selected 252 CRFs based on the following criteria: statin-related myalgia, previous failed treatment with at least two low-dosed statins, well tolerated treatment with ezetimibe. Then, the following lipid-lowering treatments were added in order to improve the ezetimibe low density lipoprotein cholesterol (LDL-C) lowering efficacy, based on clinical judgment: fenofibrate 145?mg, rosuvastatin 5?mg 1 tablet/week, rosuvastatin 5?mg 2 tablets/week, red yeast rice (standardized in monacolin K 3?mg) + berberine 500?mg, berberine 500?mg b.i.d., phytosterols 900?mg?+?psyllium fiber 3.5?g b.i.d. Patients continuing to claim a tolerable myalgia were then treated with coenzyme Q10 nanoemulsions 200?mg/day.

Results: The treatment with standard lipid-lowering diet plus ezetimibe alone was associated with a mean LDL-C reduction of 17?±?2%. The additive LDL-lowering effect with the various tested treatment was: ?16?±?2% with fenofibrate 145?mg/day, ?13?±?1% with rosuvastatin 5?mg 1 tablet/week, ?17?±?3% with rosuvastatin 5?mg 2 tablets/week, ?19?±?4% with red yeast rice?+?berberine, ?17?±?4% with berberine b.i.d. and ?10?±?3% with phytosterols?+?psyllium b.i.d.; 11% of the patients treated with fenofibrate required treatment modification because of myalgia recurrence, while the percentage was negligible for the other tested treatments. In patients with residual tolerable myalgia, treatment with coenzyme Q10 for 8 weeks was associated with a mean improvement of the graduated myalgia score from 4.8?±?1.9 to 2.9?±?1.3 (p?=?0.013).

Conclusions: Some alternative treatments seems to be effective and well tolerated, thus improving the ezetimibe effect on cholesterolemia.