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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., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: To assess real-life effectiveness of a perindopril/indapamide (Per/Ind) single-pill combination (SPC) in patients with hypertension (HT) and type 2 diabetes mellitus (T2DM), obesity and/or metabolic syndrome (MetS)., Methods: This post hoc analysis pooled raw data from four large observational studies (FORTISSIMO, FORSAGE, ACES, PICASSO). Patients, most with uncontrolled blood pressure (BP) on previous treatments were switched to Per/Ind (10 mg/2.5 mg) SPC at study entry. Office systolic and diastolic blood pressures (SBP and DBP) were measured at baseline, 1 month and 3 months., Results: In the overall pooled population (N = 16,763), mean age was 61 ± 12 years, HT duration 11 ± 8 years, and baseline SBP/DBP 162/94 mmHg. T2DM, obesity and MetS were present in 21%, 49% and 27% of patients, respectively. Subgroups had similar mean age and HT duration to the overall population; patients with T2DM were slightly older (64 ± 10 years) with a longer HT duration (13 ± 8 years). Mean BP was approximately 160/95 mmHg in each subgroup. At 1 month, mean SBP decreased by approximately 20 mmHg in the overall population, and by a further 10 mmHg at 3 months. Similar results were observed in the three subgroups, with mean changes from baseline at 3 months of - 28 ± 15/- 13 ± 10 in T2DM; - 30 ± 15/- 14 ± 10 in obesity; and - 31 ± 15/- 15 ± 9 mmHg in MetS. BP decreases were greatest in patients with grade II or grade III HT. BP control rates (< 140/90 mmHg or 140/85 mmHg for T2DM) at 3 months were 59% in T2DM, 67% in obese, and 66% in MetS. No specific safety concerns were raised, particularly concerning ionic (Na, K) or metabolic profiles., Conclusions: Switching to Per/Ind SPC led to rapid and effective BP decreases in patients with T2DM, obesity, or MetS. BP control was achieved in 6-7 out of 10 previously treated but uncontrolled patients. Treatment was well tolerated. The results confirm the beneficial effects of a Per/Ind SPC for difficult-to-control patient populations.

Purpose: To compare the effectiveness on blood pressure (BP) of initial two-drug therapy versus monotherapy in hypertensive patients., Methods: Using the Clinical Practice Research Datalink, linked with Hospital Episode Statistics and Office for National Statistics, we identified a cohort of adults with uncontrolled hypertension, initiating one or two antihypertensive drug classes between 2006 and 2014. New users of two drugs and monotherapy were matched 1:2 by propensity score. Main exposure was "as-treated," ie, until first regimen change. Primary and secondary endpoints were systolic and diastolic BP control and major adverse cardiovascular event (MACE), respectively. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazard models., Results: Of 54 523 eligible patients, 3256 (6.0%) were initiated to a two-drug combination. Of these, 2807 were matched to 5614 monotherapy users. Mean exposure duration was 12.7 months, with 76.5% patients changing their initial regimen. Two-drug therapy was associated with a clinically significant BP control increase in all hypertensive patients (HR = 1.17 [95%CI: 1.09-1.26]), more so in patients with grade 2-3 hypertension (HR = 1.28 [1.17-1.41]). An increase of 27% in BP control (HR = 1.27 [1.08-1.49]) was observed in patients initiating an ACEi+CCB combination compared with initiators of either single class. No significant association was found between two-drug therapy and MACE. Several sensitivity analyses confirmed the main findings., Conclusions: Few patients initiated therapy with two drugs, reflecting UK guidelines' recommendation to start with monotherapy. This study supports the greater effectiveness of two-drug therapy as the initial regimen for BP control., (© 2019 The Authors. Pharmacoepidemiology & Drug Safety Published by John Wiley & Sons Ltd.)

The aim of the study was to evaluate the antihypertensive efficacy and tolerability of the low-dose combination of the angiotensin-converting enzyme inhibitor perindopril 2 mg plus the diuretic indapamide 0.625 mg (P/I) compared with the angiotensin II antagonist losartan 50 mg (L50) in the treatment of essential hypertension. Patients (n = 277) were randomised, double-blind and allocated to receive either P/I or L50 once daily for a period of 12 weeks. Responder and normalisation rates in the two groups were compared by a chi 2 test. Ambulatory blood pressure monitoring results were compared using the one-tailed Student's t-test. Normalisation rates were significantly greater in the P/I group (76.0%) than in the L50 group (60.0%) (p = 0.009). Responder rates were significantly higher in the P/I group (91.7%) than in the L50 group (81.8%) (p = 0.025). The average blood pressure reductions were: in sSBP (P/I-L50 = -2.4 mmHg; CI: 6.2; 1.3) and sDBP (P/I-L50 = -2.0 mmHg; CI: -4.2; 0.2). The average night-time SBP decrease (ABPM) was significantly greater in the P/I group (p = 0.041). The tolerability was comparable between the two groups in terms of emergent adverse events related to treatment (12.4% for P/I patients and 8.4% for L50 patients). Laboratory evaluations did not show any significant variations. It was concluded the low-dose P/I combination had significantly higher responder and normalisation rates than L50. This study also confirmed the good tolerability of both treatments.

This epidemiological study was carried out as a 3-year follow-up project to assess the incidence of transient ischemic attacks (TIAs) and strokes; 8,846 treated hypertensive patients (mean BP, 149/84 mm Hg) aged 65 years or over (mean age, 73.7 +/- 6.3 years), devoid of symptoms of dementia and with documented vascular risk factors were recruited from January 1994 to August 1995, by 1,598 general practitioners in connection with 36 referral university neurology units throughout metropolitan France. Among these patients, 506 (5.7%) had at least one cerebrovascular event during the follow-up period: 309 (3.5%) experienced one or more isolated TIAs, and 197 (2.2%) had a stroke with or without a preceding TIA. A total of 510 TIAs were reported. The stroke subtypes were ischemia, hemorrhage, and unclassified in 70, 16, and 15% of the cases, respectively. The estimated annual stroke incidence was 7.42 per thousand. Of the 197 patients who developed strokes, 51 (26%) died. This case-fatality rate should be compared with the 4.5% mortality rate observed in the whole population during the study period. The 3 subgroups (with isolated TIAs, strokes, or no events during the study) were found to differ regarding age, sedentary lifestyle, past history of cardiovascular events, duration of hypertension, and evidence of complicated hypertension (univariate analysis). The factors identified as predictive of a stroke (multivariate analysis) were: the patient's age; sedentary lifestyle; pulse pressure (SBP-DBP); identification of TIA at baseline, and presence of arrhythmias., (Copyright 2001 S. Karger AG, Basel)