The association between ACE inhibitors and psoriasis based on the drug-targeted Mendelian randomization and real-world pharmacovigilance analyses.

BACKGROUND: Although a growing number of observational studies suggest that angiotensin-converting enzyme inhibitors (ACEIs) intake may be a risk factor for psoriasis, evidence is still insufficient to draw definitive conclusions. RESEARCH DESIGN AND METHODS: Drug-targeted Mendelian randomization (DTMR) was used to analyze the causality between genetic proxied ACEIs and psoriasis. Furthermore, we performed a disproportionality analysis based on the FDA adverse event reporting system (FAERS) database to identify more suspicious subclasses of ACEIs. RESULTS: Using two kinds of genetic proxy instruments, the present DTMR research identified genetic proxied ACEIs as risk factors for psoriasis. Furthermore, our disproportionality analysis revealed that ramipril, trandolapril, perindopril, lisinopril, and enalapril were associated with the risk of psoriasis, which validates and refines the findings of the DTMR. CONCLUSIONS: Our integrative study verified that ACEIs, especially ramipril, trandolapril, perindopril, lisinopril, and enalapril, tended to increase the risk of psoriasis statistically.

ARNI Versus Perindopril for Remodeling in HFrEF. A Cohort Study.

Introduction: Ventricular remodeling is a mal-adaptive process. Both angiotensin-converting enzyme inhibitors and sacubitril/valsartan have been shown to reverse remodeling in mostly uncontrolled observational studies. There is a lack of head-to-head studies. Methods: This cohort study compares the remodeling effects of angiotensin receptor blockers combined with a neprilysin inhibitor (ARNI) and perindopril in heart failure with reduced ejection fraction (HFrEF) patients between January 2017 and December 2020. Inclusion criteria: (i) age > 18 years, (ii) recent diagnosis of de-novo HFrEF (EF < 40%), (iii) baseline echocardiography performed not more than 2 months prior to treatment onset, and (iv) follow-up echocardiography performed not earlier than 6 months and not later than 18 months posttreatment onset. No prior treatment with renin-angiotensin-aldosterone system inhibitors was permitted in the ARNI group. Left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV), and left ventricular end-systolic volume (LVESV) were analyzed. A two-way repeated measure ANOVA (for normally distributed) and generalized estimating equation test for nonnormally distributed interval dependent variables. Mean comparison between and within groups was performed using the Bonferroni test. Results: Following an average treatment period of 9 months, LVEF improved from 24.9% to 36.4% for ARNI and from 28.7% to 40.5% for perindopril, increments of 11.5% and 11.8% resp. (Bonferroni test [P ≤ .05]). LVEDV was reduced by 8.4 mL and 3.2 mL, and LVESV by 17.9 mL and 10.8 mL for ARNI and perindopril resp. Only the reduction of LVESV for ARNI was statistically significant (P = .007). Conclusion: Both ARNI and perindopril yielded a significant improvement in the LVEF within 9 months. The remodeling effect of ARNI seems stronger because of the greater improvements in left ventricular volumes.

A randomized trial of genotype-guided perindopril use.

OBJECTIVE: Cough caused by angiotensin-converting enzyme inhibitors (ACEIs) limits their clinical application and cardiovascular benefits. This randomized trial investigated whether genotype-guided perindopril use could reduce drug-related cough in 20 to 79-year-old individuals with hypertension. METHODS: After screening 120 patients and randomization, 68 were assigned to genotyping ( n  = 41) and control ( n  = 27) groups. NELL1 p.Arg382Trp (rs8176786) and intron (rs10766756) genotype information was used to subdivide the genotyping group into high-risk and low-risk subgroups with at least one or no risk alleles for ACEI-related cough, respectively. The high-risk subgroup received candesartan (8 mg/day) for 6 weeks, whereas the low-risk subgroup received perindopril (4 mg/day). The control group, which was not genotyped, received perindopril (4 mg/day). The primary outcome variables were cough and moderate/severe cough; the secondary outcome variable was any adverse event. RESULTS: During the 6-week period, the risk of cough was lower in the genotyping group than in the control group [five (12.2%) and nine (33.3%) participants, respectively; hazard ratio: 0.25; log-rank P  = 0.017]. The moderate/severe cough risk was also lower in the genotyping group [one (2.4%) and five (18.5%) participants, respectively; hazard ratio: 0.12; log-rank P  = 0.025]. Differences in cough (hazard ratio: 0.56; log-rank P  = 0.32) and moderate/severe cough risk (hazard ratio: 0.26; log-rank P  = 0.19) between the low-risk and control groups were not significant. The risk of total adverse events was similar between any two groups. CONCLUSION: Cough risk was lower during genotype-guided treatment than during conventional treatment. These results support the utility of NELL1 variant data in clinical decision making to personalize renin-angiotensin system blocker therapy use. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT05535595 (retrospectively registered at September 7, 2022).

Effectiveness and Tolerability of Bisoprolol/Perindopril Single-Pill Combination in Patients with Arterial Hypertension and a History of Myocardial Infarction: The PRIDE Observational Study.

INTRODUCTION: This study assessed the real-life effectiveness of a single-pill combination (SPC) of bisoprolol/perindopril for controlling blood pressure (BP) and symptoms of angina in patients with hypertension and a history of myocardial infarction (MI). METHODS: Eligible patients with arterial hypertension and a history of MI were aged 18-79 years and had initiated bisoprolol/perindopril SPC within 3 months of study enrollment as part of routine Russian clinical practice. The primary endpoint was mean change in systolic and diastolic BP (SBP/DBP) at week 12 compared with baseline (data collected retrospectively). Secondary endpoints were assessed at weeks 4 and 12 and included mean change in resting heart rate (HR), proportion of patients reaching target level of resting HR, antianginal effectiveness of the SPC, and proportion of patients reaching target BP levels. RESULTS: A total of 504 patients were enrolled, of whom 481 comprised the full analysis set (mean age 61.4 ± 8.9 years, 68% men). Mean baseline SBP/DBP and HR values were 148.9 ± 16.8/87.7 ± 11.0 mmHg and 77.4 ± 10.5 bpm, respectively. Mean durations of hypertension and CAD were 12.8 ± 8.4 and 6.1 ± 6.3 years, respectively, and time since MI was 3.8 ± 5.3 years. At week 12, SBP/DBP had decreased by 24.9/12.2 mmHg (P < 0.001 vs baseline). Target BP (< 140/90 mmHg) was achieved by 69.8% and 95.9% of patients at weeks 4 and 12, respectively, and target HR (55-60 bpm) by 17.3% and 34.5% at weeks 4 and 12 versus 3.1% at baseline (P < 0.001). Reductions in angina attacks, nitrate consumption, and improvements in HR were statistically significant. Treatment was well tolerated. CONCLUSION: Treatment of symptomatic patients with CAD, hypertension, and a history of MI with a bisoprolol/perindopril SPC was associated with significant decreases in SBP/DBP and a high proportion of patients achieving BP treatment goals. This was accompanied by improvements in angina symptoms and reductions in HR in a broad patient population representative of those seen in everyday clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT04656847.

Antihypertensive effect of telmisartan versus perindopril in hypertensive patients.

OBJECTIVE: We performed this meta-analysis determining the antihypertensive effect of telmisartan versus perindopril in patients with essential hypertension. BACKGROUND: The comparison of antihypertensive effects between telmisartan and perindopril were controversial. METHODS: Pubmed, Web of Science, and Cochrane Central were searched for all published studies. RESULTS: The antihypertensive effects were assessed in 753 patients included in 7 trials with a mean follow-up of 20 ± 16 weeks. There was no significant difference between telmisartan and perindopril in reduction of systolic blood pressure (SBP, weighted mean differences (WMD) 0.02 (95% confidence interval (CI), ‒2.78, 2.81) mm Hg, p > 0.05). The reduction of diastolic BP (DBP) treated with telmisartan was greater than perindopril in these patients (WMD ‒2.05 (95% CI, ‒2.60, ‒1.49) mm Hg, p < 0.001). Considering the effects of different doses on BP reduction, a sub-analysis was performed. The reduction of DBP treated with 40 mg/day telmisartan was greater than 4‒5 mg/day perindopril (WMD ‒2.18 (95% CI, ‒2.83, ‒1.53) mm Hg, p 0.05). CONCLUSION: The reduction of DBP is greater treated with telmisartan than perindopril in patients with essential hypertension (Tab. 2, Fig. 4, Ref. 34). Text in PDF www.elis.sk Keywords: essential hypertension, blood pressure, telmisartan, perindopril, meta-analysis.

Evaluation of the Safety and Efficacy of Dual Therapy Perindopril/Amlodipine in the Management of Hypertension. A Systematic Review and Meta-Analysis.

INTRODUCTION: Hypertension represent the commonest cause of death in 2017. Hypertension is classified into two types which are primary or essential hypertension and secondary hypertension. The perindopril-amlodipine combination showed a significant effect in reduction of the elevated BP and the cardiovascular complications. AIM: To evaluate the efficacy and safety of a fixed-dose single-pill combination of perindopril-amlodipine in hypertensive patients. METHODS: We searched PubMed, Medline, SCOPUS, and Web of Science for relevant clinical trials. Quality appraisal was evaluated according to GRADE and we assessed the risk of bias using Cochrane's risk of bias tool. We included the following outcomes: systolic blood pressure, diastolic blood pressure, pulse pressure, mean blood pressure, heart rate, cough, dizziness, headache, and peripheral edema. We performed the analysis of homogeneous data under the fixed-effects model, while analysis of heterogeneous data was analyzed under the random-effects model. We conducted a meta-regression according to the dose. RESULTS: We included ten clinical trials. The pooled analysis showed that there was a significant reduction of the systolic blood pressure, diastolic blood pressure, pulse plessure, mean blood pressure, and heart rate after the the perindopril-amlodipine combination (MD = 18.96 [14.32, 23.60], P < 0.0001), (MD = 11.90 [8.45, 15.35], P < 0.0001), (MD = 8.44 [6.91, 9.97], P = 0.0001), (MD = 13.07 [5.86, 20.29], P = 0.0004), and (MD = 2.93 [0.89, 4.96], P = 0.005), respectively. The results of the meta-regression revealed that the efficacy is increased by increasing the dose (P < 0.001) CONCLUSION: The use of the perindopril-amlodipine combination had a significant effect on the reduction of SBP, DBP, mean blood pressure, pulse pressure, and HR.

Use of Perindopril Arginine/Indapamide/Amlodipine in the Management of Hypertension in Two Sub-Saharan African Island Countries of Madagascar and Mauritius.

INTRODUCTION: Most patients with hypertension in sub-Saharan Africa require two or more drugs to control their blood pressure. Triple fixed-dose combination therapy of perindopril arginine/indapamide/amlodipine is more effective in lowering blood pressure, offers better target organ protection and has increased adherence compared to monotherapy and free combination therapy, and is safe to use. This observational study evaluates the effectiveness of perindopril arginine/indapamide/amlodipine in controlling blood pressure at least 1 month after treatment initiation and assesses patient- and physician- reported drug tolerance over a 3-month period in Madagascar and Mauritius. METHODS: A total of 198 patients with hypertension in ambulatory care who had been on fixed-dose combination of perindopril arginine, indapamide, and amlodipine for at least 4 weeks were included. The main outcome measures were changes in systolic and diastolic blood pressure, attainment of blood pressure control under 140/90 mmHg and 130/80 mmHg, self-reported drug tolerance by the patient, and perceived drug tolerance by the treating physician. Data was collected at 1 month and 3 months. RESULTS: Mean systolic blood pressure was significantly lower at the 1-month (- 3.4 mmHg, p = 0.002) and 3-month (- 8.5 mmHg, p < 0.0001) visits. Diastolic blood pressure also decreased significantly (- 2.4 mmHg at 1-month, p = 0.017 and - 5.4 mmHg at the 3-month visits, p < 0.0001). At 3 months, 80.4% of the patients attained blood pressure targets less than 140/90 mmHg and 42.7% attained targets less than 130/80 mmHg on the basis of their baseline blood pressure. Excellent drug tolerance was reported by more than 90% of patients and physicians at the 1-month visit and by more than 95% at the 3-month visit. CONCLUSION: Triple fixed-dose therapy of perindopril arginine/indapamide/amlodipine continues to show additional blood pressure-lowering capacity even months after initiating the treatment in patients with hypertension in Madagascar and Mauritius. It is also well tolerated by patients with hypertension and assessed as safe to use by physicians.

Perindopril/Indapamide/Amlodipine in Hypertension: A Profile of Its Use.

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.

Efficacy of Single-Pill, Triple Antihypertensive Therapy in Patients with Uncontrolled Hypertension: A Systematic Review and Meta-analysis.

INTRODUCTION: Systemic arterial hypertension is the most common preventable risk factor for all causes of morbidity and mortality worldwide with a prevalence of 35-40% of the adults. Despite the wide variety of effective antihypertensive medications, most hypertensive patients remain uncontrolled. However, the combination of ACE inhibitor, diuretics, and calcium antagonist for the triple therapy in a single Pill Combination (SPC) is an efficient regimen in hypertension management. It is recommended by the ESH 2018 guideline, which offers better efficacy and compliance to treatment. AIM: To evaluate the efficacy of perindopril/indapamide/amlodipine single-pill combination in patients with uncontrolled hypertension. METHODS: We searched PubMed, Scopus, Web of Science, and Cochrane CENTRAL for relevant clinical trials. We conducted the risk of bias assessment using Cochrane's risk of bias tool. We performed the analysis of continuous data using mean difference (MD) and relative 95% confidence interval (CI), while dichotomous data were analyzed using risk ratio (RR) and relative 95% CI. We included the analysis of the following outcomes: systolic blood pressure (SBP), Diastolic blood pressure (DBP), Heart rate (HR), 24 h Ambulatory blood pressure monitoring (ABPM) for SBP, and 24 h ABPM for DBP. RESULTS: We included six clinical trials. We found that the triple therapy significantly reduces SBP by 24 mmHg (MD = - 24.65 [22.41, 26.89], (P < 0.01)), DBP by 12 mmHg (MD = 12.41 [11.53, 13.29], (P < 0.01)), 24-h ABPM for SBP by 14 mmHg (MD = 14.08 [9.10, 19.05], (P < 0.01)), and ABPM 24 h DBP by 7 mmHg (MD = 7.01 [5.37, 8.65], (P < 0.01)). We noted no significant difference of the single pill on heart rate (MD = 0.81 [- 0.04, 1.67], (P = 0.06). CONCLUSION: perindopril/indapamide/amlodipine is effective in reducing systolic and diastolic blood pressures by 24 and 12 mmHg respectively. Over 24 h, the combination reduced systolic and diastolic blood pressures by 14 and 7 mmHg respectively.

DiffErenCes in AntihypertenSive Drug Blood Levels in Patients with HypertensiON (DECISION): Protocol for a Prospective Observational Study Comparing Pharmacokinetics and Pharmacodynamics Between Young and Elderly Patients.

Adequate controlled blood pressure decreases the risk of cardiovascular events. However, the elderly are more vulnerable and thereby more prone to side effects of antihypertensive drugs. A lack of pharmacokinetic and pharmacodynamic (PK/PD) studies in older patients makes specific and tailored advices towards antihypertensive drug therapy difficult. The aim of our study, DiffErenCes In antihypertenSive drug levels In patients with hypertensiON (DECISION), is to fill in this PK/PD knowledge gap and move towards precision dosing. DECISION is a prospective observational PK/PD study set up to determine the difference in exposure to the antihypertensive drugs, losartan and perindopril, measured by drug levels in blood. The area under the curve (AUC; PK) and furthermore the association between the AUC and the effect on blood pressure (PD) will be compared between elderly and younger patients.

The Efficacy and Tolerability of a Fixed Combination of Perindopril and Indapamide in the Treatment of Unregulated Essential Hypertension - a Postmarketing Study.

OBJECTIVE: The objective of this non-interventional post-marketing clinical trial was to analyze the antihypertensive effect and safety of a fixed combination of perindopril and indapamide in the treatment of unregulated essential hypertension. PATIENTS AND METHODS: The prospective clinical trial included patients aged 20 to 75 years with essential hypertension and blood pressure values ≥ 140/90 mmHg at baseline. On the basis of the investigator's decision, patients received 2 mg perindopril + 0.625 mg indapamide (group 2+0.625) or 4 mg perindopril + 1.25 mg indapamide (group 4+1.25). RESULTS: The study included 1173 patients (426 patients in group 2+0.625 and 747 patients in group 4+1.25) at 27 investigational centers in Bosnia and Herzegovina. Mean blood pressure values at baseline and visits after nine months were significantly higher in the 4+1.25 group compared to the 2+0.625 group. There was a significant drop in systolic and diastolic blood pressure in both groups. The target values of systolic and diastolic blood pressure, according to the European Society of Cardiology (2018), were reached after nine months of therapy by more than 80% of patients in the 2+0.625 group, and this number was significantly higher compared to the 4+1.25 group where more than 60% of patients reached target values. Newly diagnosed patients had a better response to therapy. The percentage of patients receiving additional antihypertensive therapy decreased by the end of the study. Age, gender and the existence of diabetes mellitus were identified as negative predictors of target blood pressure achievement. The therapy showed a good safety profile. CONCLUSION: A fixed combination of perindopril and indapamide was effective and safe in the treatment of unregulated essential hypertension.

Concomitant Treatment of Hypertensive Patients with Bisoprolol and Perindopril in Routine Clinical Practice: A Post Hoc Analysis of the CONFIDENCE II, PROTECT I, and PROTECT III Observational Studies.

INTRODUCTION: The combination of angiotensin-converting enzyme inhibitors and beta-blockers is recommended in a wide range of patients with hypertension, including those with stable coronary artery disease and/or elevated heart rate. This post hoc analysis of three observational studies provides effectiveness and safety data on treatment with perindopril on top of bisoprolol-based therapy, in routine clinical practice. METHODS: Data were analyzed from three open-label, prospective, multicenter, observational studies of Canadian patients with mild-to-moderate hypertension, which shared the same inclusion and exclusion criteria, treatment duration, and primary outcome. This post hoc analysis focused on the subpopulation of patients treated with perindopril on top of bisoprolol-based therapy. All patients were followed for 16 weeks and underwent baseline, week 4, and week 16 visits. Primary outcomes were mean changes in blood pressure (BP) and proportion of patients achieving BP control (< 140/90 mmHg) in the full analysis set (FAS). RESULTS: A total of 845 patients (mean age 68.3 ± 11.3 years, mean baseline BP 151.5/86.0 mmHg) were analyzed in the FAS. After 16 weeks, mean SBP/DBP decreased by - 20.4/- 9.8 mmHg with statistically significant reductions observed at all visits in all three studies allowing 78% of patients to achieve the BP treatment goal. No statistically significant changes in heart rate were observed and no serious adverse events reported. The most frequent doses of bisoprolol and perindopril were 5 + 4 mg (34.9%), followed by 5 + 8 mg (16.9%), and 2.5 + 4 mg (12.5%). CONCLUSION: The addition of perindopril on top of bisoprolol-based therapy in patients with mild-to-moderate hypertension was associated with significant reductions in BP compared with baseline and with achievement of BP targets in the majority of patients. The results suggest this strategy is safe and effective for use in routine clinical practice.

A Randomized, Double-blind, Active-controlled, Two Parallel-Group, Optional Titration, Multicenter, Phase IIIb Study to Evaluate the Efficacy and Safety of Fimasartan Versus Perindopril Monotherapy With and Without a Diuretic Combination in Elderly Patients With Essential Hypertension.

PURPOSE: The efficacy and tolerability of fimasartan in elderly patients have not been fully evaluated. This study was therefore conducted to determine the efficacy and tolerability of fimasartan compared with perindopril in elderly Korean patients aged >70 years with essential hypertension (defined by a mean sitting systolic blood pressure [SBP] ≥140 mm Hg). METHODS: This randomized, double-blind, active-controlled, 2 parallel-group, optional titration, multicenter, Phase IIIb trial (FITNESS [Fimasartan in the Senior Subjects]) enrolled 241 patients from 23 cardiac centers in the Republic of Korea between August 2017 and December 2019. After the placebo run-in period, treatment started with fimasartan 30 mg or perindopril arginine 2.5 mg once daily at a 1:1 ratio; if BP was not controlled at week 4, the dose was doubled. If BP was not controlled at week 8, a diuretic combination (fimasartan 60 mg/hydrochlorothiazide 12.5 mg or perindopril arginine 5 mg/indapamide 1.25 mg) was administered. After 16 weeks of the double-blind treatment, the patients with controlled BP participated in an 8-week open-label extension study, with the 2 groups unified by fimasartan 60 mg with or without hydrochlorothiazide 12.5 mg for 8 weeks. The primary outcome was a change in SBP for 8 weeks. The secondary outcomes included a change in sitting diastolic BP (DBP) for 8 weeks and changes in SBP and DBP for 4, 16, and 24 weeks. FINDINGS: At week 8, mean SBP significantly decreased from baseline in both groups: -14.2 (14.4) mm Hg in the fimasartan group and -9.0 (16.1) mm Hg in the perindopril group. The difference between the 2 groups was 5.4 (2.1) mm Hg, indicating the noninferiority of fimasartan to perindopril. Moreover, fimasartan exhibited a higher BP-lowering effect than perindopril (P = 0.0108). In addition, reductions in SBP and DBP from baseline to weeks 4, 8, and 16 were significantly greater in the fimasartan group than in the perindopril group, although the SBP reduction was comparable at week 16. Both groups reported an excellent mean compliance rate of 97.4% (4.7%) through week 16. During the study period, 82 adverse events were reported in 52 patients, 40 in the fimasartan group and 42 in the perindopril group (P = 0.4647). Dizziness was the most commonly reported adverse event (7 cases). Remarkably, only 1 case of orthostatic hypotension was reported during the study period. IMPLICATIONS: In elderly patients with essential hypertension, fimasartan 30 to 60 mg with a possible hydrochlorothiazide 12.5-mg combination was noninferior to perindopril 2.5 to 5 mg with a possible indapamide 1.25-mg combination. Furthermore, fimasartan exhibited higher BP-lowering efficacy than perindopril. There was no difference in tolerability between the 2 groups. Clinicaltrials.gov Identifier: NCT03246555.

Bioequivalence study of two perindopril tert-butylamine tablet formulations in healthy Chinese subjects under fasting and fed conditions: A randomized, open-label, single-dose, crossover trial.

BACKGROUND: To evaluate the bioequivalence between test and reference formulations of perindopril tert-butylamine under fasting and fed conditions and to assess their pharmacokinetic (PK) and safety profiles. METHOD: A randomized, open-label, single-dose, crossover trial was conducted in healthy Chinese subjects. Test or reference perindopril tert-butylamine tablets (4 mg) were randomly given to subjects under fasting (2-period crossover, with an administration sequence of test tablet (T), reference tablet (R) or RT) and fed (4-period crossover, with an administration sequence of TRTR or RTRT) conditions, while each single administration was followed by a 14-day washout period. The plasma concentrations and corresponding non-compartmental PK parameters of perindopril and perindoprilat were determined. The two formulations were considered to be bioequivalent if the 90 % confidence intervals (CIs) of the geometric mean (GM) ratio (test/reference) for Cmax, AUC0-t, and AUC0-∞ (perindopril) was both within the range of 80-125 %. Safety assessments including vital signs, physical examination, laboratory examination, 12-lead ECG and reports of treatment emergent adverse events (TEAEs) were carefully documented. RESULTS: A total of 64 subjects (32 in each trial) were randomized and all completed the trials. Regardless of fasting or fed trials, the PK characteristics of perindopril and perindoprilat for the test formulation were similar to those of the reference formulation (all P > 0.05). The 90 % CIs of the geometric mean (GM) ratio for Cmax, AUC0-t, and AUC0-∞, respectively, were 92.86-106.81 %, 98.44-102.88 % and 98.48-103.02 % under the fasting condition and 90.64-110.04 %, 96.95-101.90 % and 96.83-101.78 % under the fed condition, which were both within the pre-specified range of 80-125 %. A total of 10 (31.3 %) fasted subjects and 11 (34.4 %) fed subjects experienced 11 and 24 TEAEs, respectively, all of which were within the severity of grade 1. The incidence of TEAEs and drug-related TEAEs were similar between test and reference formulations (all P > 0.05) and no serious TEAEs or deaths occurred during the trials. CONCLUSIONS: The test and reference formulations of perindopril tert-butylamine tablets (4 mg) were bioequivalent and well tolerated in healthy Chinese subjects under fasting and fed conditions.

Blood-pressure Lowering Efficacy and Safety of Perindopril / Indapamide / Amlodipine Single-pill Combination in Hypertensive Patients: Phase III Trial in India.

BACKGROUND: Hypertension is the biggest contributor to global burden of disease and mortality. Increasing compliance with antihypertensive treatment and achieving a wide BP control in the population represents a major challenge for clinical practice. The benefits of single pill combination versus free-equivalent combination has been demonstrated in several meta-analyses and is now strongly supported by the latest 2018 ESC/ESH guidelines. The RAAS blocker with CCB and thiazide like diuretic is proposed as the optimal combination in patients inadequately controlled by two drugs. OBJECTIVE: To assess the blood pressure control rate, safety, tolerability and quality of life with triple-drug SPC in patients with grade II/ III hypertension. METHODS: Hypertensive patients uncontrolled (BP ≥ 140/90 mmHg) on two-drug therapy were recruited in an open-label, phase III clinical trial conducted in outpatient setting in India with 6 months treatment period. No other antihypertensive medication except the study medication was received by the patients. RESULTS: Out of 218 evaluable patients the observed average blood pressure reduction achieved from baseline to end of study at 6 months was Systolic Blood Pressure (SBP) 28.5 mm Hg / Diastolic Blood Pressure (DBP) 13.8 mm Hg. The quality of life (QoL) questionnaire demonstrated improvement in QoL for all patients. CONCLUSION: This study showed the clinical efficacy, safety and acceptability of the perindopril/indapamide/amlodipine SPC in patients with grade 2/3 hypertension inadequately controlled with two-drug therapy. The clinical effectiveness was observed in more than 96 % patients. The benefit of single-pill combination (SPC) therapy in hypertension control was reconfirmed in this study.

Fimasartan versus perindopril with and without diuretics in the treatment of elderly patients with essential hypertension (Fimasartan in the Senior Subjects (FITNESS)): study protocol for a randomized controlled trial.

BACKGROUND: Hypertension is an important risk factor for cardiovascular disease, even in the elderly. Fimasartan is a new non-peptide angiotensin II receptor blocker with a selective type I receptor blocking effect. The objective of this study is to confirm the safety and the non-inferiority of the blood pressure-lowering effect of fimasartan compared with those of perindopril, which has been proven safe and effective in elderly patients with hypertension. METHODS: This is a randomized, double-blind, active-controlled, two-parallel group, optional-titration, multicenter, phase 3 study comparing the efficacy and safety of fimasartan and perindopril arginine. The study population consists of individuals 70 years old or older with essential hypertension. The primary outcome will be a change in sitting systolic blood pressure from baseline after the administration of the investigational product for 8 weeks. The secondary outcomes will be a change in sitting diastolic blood pressure from baseline and changes in sitting systolic blood pressure and diastolic blood pressure from baseline after the administration of the investigational product for 4, 16, and 24 weeks. The sample size will be 119 subjects for each group to confer enough power to test for the primary outcome. DISCUSSION: Research to confirm the efficacy and safety of a new medicine compared with those of previously proven anti-hypertensive drugs is beneficial to guide physicians in the selection of therapeutic agents. If it is confirmed that the new drug is not inferior to the existing drug, the drug will be considered as an option in the treatment of hypertension in elderly patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03246555 , registered on July 25, 2017.

Short-term effects of perindopril-amlodipine vs perindopril-indapamide on blood pressure control in sub-Saharan type 2 diabetic individuals newly diagnosed for hypertension: A double-blinded randomized controlled trial.

Poor blood pressure (BP) control contributes to complications in sub-Saharan African (SSA) type 2 diabetic individuals. Experts have advocated the use of combination therapies for effective BP control in these patients. The suggested combinations should include a RAAS antagonist and either a CCB or a thiazide diuretic; however, their efficacy is yet to be established in SSA. We investigated the short-term effects of two combination therapies on BP control in SSA type 2 diabetic individuals. This was a double-blinded randomized controlled trial conducted at the Yaoundé Central Hospital (Cameroon) from October 2016 to May 2017. We included type 2 diabetic patients, newly diagnosed for hypertension. After baseline assessment and 24-hour ABPM, participants were allocated to receive either a fixed combination of perindopril + amlodipine or perindopril + indapamide for 42 days. Data analyses followed the intention-to-treat principle. We included fifteen participants (8 being females) in each group. Both combinations provided good circadian BP control after 6 weeks with similar efficacy. Twenty-four-hour SBP dropped from 144 to 145 mm Hg vs 128 to 126 mm Hg with perindopril-amlodipine and perindopril-indapamide, respectively (P = 0.003 for both groups). Twenty-four-hour DBP dropped from 85 to 78 mm Hg (P = 0.013) vs 89 to 79 mm Hg (P = 0.006) in the same respective groups. No significant adverse effect was reported. A fixed initial combination of perindopril-amlodipine or perindopril-indapamide achieved similar effective BP control after 6 weeks in SSA type 2 diabetic individuals with newly diagnosed hypertension. Therefore, these combinations can be used interchangeably in this indication.

The effect of perindopril on echocardiographic parameters, NYHA functional class and serum NT-proBNP values in patients with diastolic heart failure.

INTRODUCTION: Growing evidence has demonstrated that diastolic heart failure occurs in about half of heart failure (HF) patients. We investigated the effects of perindopril on echocardiographic parameters, New York Heart Association (NYHA) functional class and serum N-terminal pro B-type natriuretic peptide (NT-proBNP) levels in patients with diastolic heart failure. METHODS: In total, 108 diastolic heart failure patients aged ≥ 50 years, who had diastolic dysfunction with an ejection fraction ≥ 50%, were enrolled and randomised to one of the two study groups. Perindopril was initiated in the study group and the control group was given standard therapy. Echocardiographic parameters, NT-proBNP levels and NYHA classes were recorded. The patients were followed for 11 (three to 16) months. Eighty-eight patients completed the study. RESULTS: Although diastolic parameters were not changed, A' (septal) velocity (10.8 vs 9.9 cm/s) and Sm (septal) velocity (8.5 vs 7.6 cm/s) were significantly increased in the perindopril compared to the control group. A significant increase in A' (septal) velocity (+0.61 vs -0.28 cm/s, p = 0.04) and a slight increase in Sm (septal) velocity (+0.99 vs 0.36 cm/s, p = 0.054) were noted in the perindopril group. CONCLUSIONS: Tissue Doppler septal late diastolic velocities and septal systolic myocardial velocities increased in the perindopril group but NT-proBNP levels, and NYHA class was not changed in this study population.