Perindopril tosilate 5mg / Indapamide 1.25mg tablets

OBJECTIVE: The aim of this study was to assess the reduction in all-cause death and cardiovascular outcomes associated with the administration of the thiazide-like diuretic indapamide monotherapy or in combination with perindopril as a blood pressure lowering drug in randomized controlled trials (RCTs). METHOD: Aggregate data from four published RCTs conducted versus matching placebo were pooled: PATS, a 2-year study (indapamide), and PROGRESS, a 4-year study (indapamide and perindopril), both in patients with a history of stroke or transient ischemic attack; ADVANCE, a 4-year study in patients with type 2 diabetes and cardiovascular risk factor (single-pill combination perindopril/indapamide) and HYVET, a 2-year study in very elderly hypertensive individuals (indapamide and an option of perindopril). The pooled effect (fixed and random) estimate (hazard ratio) was reported with corresponding 95% confidence intervals and P values. Treatment discontinuations were also analysed to assess the net benefit of the treatment. RESULTS: The population involved 24 194 patients (active: 12 113, placebo: 12 081). The fixed-effects meta-analysis of the three mortality endpoints found low statistical heterogeneity ( I2 = 0). Statistically significant risk reductions in the indapamide with or without perindopril-treated patients as compared to placebo were observed for all-cause death (-15%), cardiovascular death (-21%), fatal stroke (-36%) and all strokes (-27%). Other cardiovascular outcomes were improved (risk reduction, 22 to 36%). As expected, discontinuation rates for safety (two studies) were higher in the active group (6.4 vs. 3.9%), while they were similar when discontinuation for any reason is concerned (18.4 vs. 18.0%). CONCLUSION: Across medium to high cardiovascular risk population, long-term indapamide, mostly combined with perindopril-based treatment, provided evidence of benefit on mortality and morbidity.

Abstract licence: CC BY-NC-ND

The single-pill combination (SPC) of perindopril (PER)/indapamide (IND)/amlodipine (AML) is a valuable and convenient treatment option for patients with hypertension controlled with two-drug SPC of PER/IND + AML given as two separate pills at the same dose level. PER [an angiotensin-converting enzyme (ACE) inhibitor], IND (a thiazide-like diuretic) and AML (a calcium channel blocker) are well established antihypertensive agents, which have been available for a long time as monotherapies and dual SPCs and have complementary mechanisms of action. Once-daily PER/IND/AML provided effective BP control, with good tolerability, in patients with uncontrolled hypertension in clinical trials and in large observational prospective studies. The efficacy and tolerability of PER/IND/AML was similar to that of PER/IND + AML in a randomized clinical trial. The therapeutic effect of PER/IND/AML was associated with improved health-related quality of life. Thus, switching from the two-pill PER/IND + AML regimen to single-pill PER/IND/AML reduces pill burden and simplifies drug administration, which may improve adherence to treatment, leading to better BP control and clinical outcomes. Approximately one-quarter of patients with hypertension require three antihypertensive agents to achieve BP control. However, complex treatment regimens and high pill burden reduce treatment adherence, which in turn leads to poor BP control. Perindopril (PER), indapamide (IND), amlodipine (AML) belong to the core drug classes for the treatment of hypertension. These drugs have been available for a long time as monotherapies and two-drug single-pill combinations. Once-daily PER/IND/AML provides very good BP control in patients with uncontrolled hypertension and is generally well tolerated. The single-pill PER/IND/AML has similar efficacy and tolerability to PER/IND + AML given as two separate pills. Therefore, switching from PER/IND + AML to PER/IND/AML reduces pill burden and simplifies the treatment regimen, which may improve adherence to treatment, leading to better BP control and clinical outcomes. Thus, PER/IND/AML is a valuable and convenient treatment option for patients with hypertension controlled with PER/IND + AML at the same dose level.

Abstract licence: CC BY-NC

Single-pill combination therapy for hypertension is recognized to improve adherence to treatment. However, less is known about the benefits of triple single-pill combinations. This retrospective observational analysis aimed to assess changes in adherence when treatment was switched from perindopril (PER)/indapamide (IND) + amlodipine (AML) to PER/IND/AML single-pill combination, in Italian clinical practice. This analysis used data extracted from administrative databases of Italian healthcare entities. Adult patients receiving PER/IND/AML were selected, and the prescription date was considered as the index date. Among them, those who had a prescription for PER/IND + AML during the 12 months before the index date and a prescription of PER/IND/AML during 6 months of follow-up were included. Adherence was calculated as the proportion of days covered (PDC: PDC < 40%, non-adherent; PDC = 40–79%, partially adherent; PDC ≥ 80%, adherent). Among the identified patients, 158 were exposed users and were included in the analysis. When patients were compared before and after switch to triple single-pill combination, the proportion of adherent patients was significantly higher with PER/IND/AML single-pill combination (75.3%) than with PER/IND + AML combination (44.3%) (P < 0.05). Conversely, the proportion of non-adherent patients was lower with the PER/IND/AML single-pill combination (14.6%) vs PER/IND + AML (17.7%) (P < 0.001). This real-world analysis showed that switching to a triple single-pill combination could offer an opportunity to improve adherence to antihypertensive treatment in real-life clinical practice. Medication adherence is defined by the World Health Organization as the “extent to which a person’s behavior (in taking medication) corresponds with agreed recommendations from a healthcare provider”. Low levels of medication adherence in hypertension have been linked with increased disease burden and with higher costs for patients. Patients with hypertension whose blood pressure is poorly controlled often need to receive more than one pill. Nevertheless, having to take many pills may result in poor adherence, i.e., patients not taking their treatment as prescribed. Combining multiple drugs into a single pill for the management of hypertension is known to improve adherence; however, limited evidence exists about the benefits of triple single-pill combinations compared with equivalent free combinations in real clinical practice. This analysis evaluated changes in adherence before and after patients switched from a three-drug therapy of perindopril/indapamide single-pill + amlodipine (PER/IND + AML) to perindopril/indapamide/amlodipine (PER/IND/AML) taken as a single pill. In this analysis, real-world data from Italian administrative databases covering around 11% of the Italian population were used. Overall, 158 patients were included. More patients were found to be adherent after switch to PER/IND/AML single pill (75.3% vs 44.3% of PER/IND + AML combination). Partially adherent and poorly adherent patients were fewer with PER/IND/AML single-pill combination (10.1% and 14.6%, respectively) compared to PER/IND + AML combination (38.0% and 17.7%, respectively). These findings indicate that switching to a simplified therapy in which all three drugs are taken in one pill may offer an opportunity for increasing the number of patients that are adherent to their medication.

Abstract licence: CC BY-NC

OBJECTIVES: This analysis compared adherence, cardiovascular (CV) events and all-cause mortality incidence, and healthcare costs among hypertensive patients treated with perindopril (PER)/indapamide (IND)/amlodipine (AML) in single-pill combination (SPC) vs. multiple-pill combination, in a real-world setting in Italy. METHODS: In this observational retrospective analysis of Italian administrative databases, adult patients treated with PER/IND/AML between 2010 and 2020 were divided into two cohorts: single-pill vs. multiple-pill. Patient data were available for at least one year before and after index date. Propensity score matching (PSM) was applied to reduce selection bias. Adherence was defined as proportion of days covered: non-adherence, <40%; partial adherence, 40-79%, and adherence ≥80%. Mortality incidence and CV events as single, or composite, endpoints were evaluated after first year of follow-up. Healthcare cost analyses were performed from the perspective of the Italian National Health Service. RESULTS: Following PSM, the single-pill cohort included 12 150 patients, and the multiple-pill cohort, 6105. The SPC cohort had a significantly higher percentage of adherent patients vs. the multiple-pill cohort (59.9% vs. 26.9%, P < 0.001). Following the first year of follow-up, incidence of all-cause mortality, and combined endpoint of all-cause mortality and CV events were lower in the SPC cohort compared with multiple-pill cohort. Average annual direct healthcare costs were lower in the single-pill cohort (€2970) vs. multiple-pill cohort (€3642); cost of all drugs and all-cause hospitalizations were major contributors. CONCLUSION: The SPC of PER/IND/AML, compared with multiple-pill combination, is associated with higher adherence to medication, lower incidence of CV events and mortality, and reduced healthcare costs.

Abstract licence: CC BY-NC-ND

Abstract Simple, diverse univariate spectrophotometric methods were developed and validated for the determination of amlodipine besylate (AM), perindopril arginine (PE), and indapamide (ID). The first method involved direct measurement of AM absorbance at 365 nm within a concentration range of 2.00–40.00 µg/mL, where PE and ID exhibited no spectral interference. To eliminate the contribution of AM from the ternary mixture, its spectrum was divided by a reference spectrum of AM (12 µg/mL), followed by mathematical subtraction of the resulting constant. The spectrum was then multiplied by the AM divisor to yield a corrected spectrum of the PE and ID binary mixture, allowing their quantification. Various approaches were used to quantify both drugs, including measurement of their second (2DD) and first derivative (1DD) spectra at 231.30 nm and 251.00 nm, respectively. Additionally, the ratio difference (RD) technique and dual wavelength (DW) method were employed. The concentration ranges for PE and ID were 5.00–100.00 µg/mL and 1.00–20.00 µg/mL, respectively. Among these methods, the DW technique was the simplest, so it was chosen for dissolution monitoring of PE and ID. These methods were successfully applied to determine AM, PE, and ID in bulk powder, as well as in Triplixam ® tablets, without interference from excipients and in different used dissolution media. The whiteness of the method was evaluated, demonstrating its excellent environmental, analytical and practical efficiency.

Abstract licence: CC BY

Aim. To describe the antihypertensive efficacy of triple fixed­dose combination of amlodipine/indapamide/perindopril and assess the predictors of efficacy in young patients (&lt;50 years). Material and methods. The TRICOLOR study (NCT03722524) is an observational prospective study (n=1247) that demonstrated high antihypertensive effectiveness and good tolerability of the triple single­pill combination (SPC) of amlodipine/ indapamide/perindopril. This subgroup analysis was performed on 199 patients aged &lt;50 years (16% of the total population), and the comparison group consisted of 925 patients (82,3% of the total population) aged 50 years or older. Results. In young patients, during triple therapy with SPC amlodipine/indapa­ mide/perindopril, a positive trend in blood pressure (BP) reduction was observed compared to the baseline: an average decrease in BP after 12 weeks was 32,6 (11,0)/14,8 (8,5) mm Hg (p&lt;0,0001), comparable to patients over 50 years of age in terms of reduction in systolic blood pressure (SBP) and diastolic blood pressure (DBP) after 2, 4 and 12 weeks of follow­up. A greater number of young patients achieved a reduction in blood pressure &lt;140/90 mm Hg after 2 weeks of therapy compared to patients 50 years of age and older (49,7% vs 38,8%, p=0,004), and blood pressure &lt;130/80 mm Hg – after 4 and 12 weeks (51,3% vs 43,5% (p=0,041) and 74,9% vs 67,5% (p=0,038), respectively). Left ventricular hypertrophy was a significant negative predictor of SBP reduction by 12 weeks of therapy, and the presence of grade 2 hypertension (HTN) and statin use, on the contrary, were positive predictors of changes in SBP by the end of observation. More adherent younger patients were significantly more likely to have a decrease in DBP by 12 weeks of follow-up. In addition, in young patients, male sex and the presence of dyslipidemia significantly increased the chances of blood pressure control at the end of observation. Waist circumference, body mass index, and grade 2 HTN were negative predictors of achieving the target blood pressure level. Conclusion. Thus, in young patients, good antihypertensive effectiveness of amlodipine/indapamide/perindopril was observed, comparable in the degree of blood pressure reduction with the older age group of 50 years and older.

Abstract licence: CC BY