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Concept: Perindopril


Patients with hypertension often require a combination of three antihypertensive agents to achieve blood pressure control, but very few single-pill triple combinations are available. The aim of this study was to determine whether a single-pill triple combination of perindopril, indapamide, and amlodipine was as effective as a dual-pill combination of perindopril/indapamide plus separate amlodipine at reducing blood pressure in patients with uncontrolled, essential hypertension.

Concepts: Hypertension, Randomized controlled trial, Blood pressure, Amlodipine, Control, Prehypertension, Perindopril


BackgroundWe examined whether the level of highsensitivity C-reactive protein (hsCRP), a marker of low-grade inflammation, predicted the response of clinic and ambulatory blood pressure (BP) to antihypertensive treatment.MethodsA randomized, open-label, multicenter trial was performed in 88 hypertensive patients (mean age = 63.4 years) allocated to receive losartan 50 mg or amlodipine 5 mg for 4 weeks, and each treatment was changed to losartan 50 mg/hydrochlorothiazide (HCTZ) 12.5 mg in combination or amlodipine 10 mg for a further 4 weeks. Clinic and ambulatory BP were measured before and after 8 weeks of treatment, and hsCRP was measured at baseline.ResultsThe patients were divided into groups with hsCRP levels above and below the median (0.47 mg/L) for the study population. In the total population, 24-hour systolic BP (SBP) (P = 0.03) and daytime SBP (P = 0.01) were significantly higher in the above-median hsCRP group after 8 weeks of treatment. In multivariable regression analysis, baseline hsCRP was a significant determinant of the percentage change in daytime SBP (β = 0.29; P = 0.02) in the total population. In the losartan/HCTZ treatment group, changes in 24-hour SBP, daytime SBP, and diastolic BP were significantly smaller in the above-median hsCRP group than the below-median hsCRP group, whereas the amlodipine group did not show these differences.ConclusionsBaseline low-grade inflammation in patients with hypertension was associated with a poor ambulatory BP response, especially with losartan/HCTZ treatment. Initial measurement of hsCRP could be useful for selection of an appropriate antihypertensive drug.Clinical Trials REGISTRATIONTrial Number UMIN000002438.

Concepts: Regression analysis, Hypertension, Measurement, Blood pressure, C-reactive protein, Amlodipine, Ambulatory blood pressure, Perindopril


To examine the antihypertensive efficacy and safety of indapamide sustained-release (SR)/amlodipine compared with enalapril/amlodipine in patients 65 years and older with uncontrolled blood pressure (BP) on monotherapy, a post hoc analysis of the NESTOR trial (Natrilix SR vs Enalapril in Hypertensive Type 2 Diabetics With Microalbuminuria) was conducted. NESTOR randomized 570 patients (n=197, aged ≥65 years) with hypertension (systolic BP 140-180/diastolic BP <110 mm Hg) to indapamide SR 1.5 mg or enalapril 10 mg. If target BP (<140/85 mm Hg) was not achieved at 6 weeks, amlodipine 5 mg was added with uptitration to 10 mg if required. A total of 107 patients aged 65 years and older received dual therapy (53 indapamide SR/amlodipine and 54 enalapril/amlodipine). Amlodipine uptitration occurred in 22 and 24 patients, respectively. At 52 weeks, mean systolic BP (±SE) reduction was significantly greater with indapamide SR/amlodipine vs enalapril/amlodipine 6.2±2.7 mm Hg (P=.02). Indapamide SR/amlodipine was also associated with a greater BP response rate (88% vs 75%, respectively). Both regimens were well tolerated. Indapamide SR/amlodipine may be more effective than enalapril/amlodipine for lowering systolic BP in patients with hypertension aged 65 years and older.

Concepts: Myocardial infarction, Hypertension, Diabetes mellitus type 2, Diabetes mellitus, Stroke, Blood pressure, Microalbuminuria, Perindopril


OBJECTIVES:: High blood pressure (BP) has been associated with increased risk of dementia. Concerns have been raised about lowering BP too far in the very elderly and thereby increasing risk. There is some evidence to suggest a potential ‘J’-shaped relationship between DBP and risk of cognitive impairment. This was investigated using data from the HYpertension in the Very Elderly Trial (HYVET). METHODS:: HYVET was a double-blind, placebo-controlled trial of antihypertensives in patients aged at least 80 years with an untreated SBP of 160-199 mmHg. Active medication was indapamide sustained release 1.5 mg+/- perindopril 2-4 mg to reach goal pressure of less than 150/80 mmHg. Incident dementia was a secondary endpoint and was not significantly different between the two treatment groups. The relationship between pressure and incident dementia was assessed using Cox proportional hazards regression with BP entered as either a discrete (quartile analysis) or continuous predictor variable. Achieved BP was calculated as the mean of all pressures from the 9 month visit onwards. RESULTS:: During a mean follow-up of 2.2 years 263 incident cases of dementia were diagnosed. After adjustment for various covariates, baseline DBP was inversely related to incident dementia (P = 0.0064). Achieved DBP did not predict later dementia in the placebo group (P = 0.43), but showed a U-shaped relationship in the active treatment group (P = 0.0195). The relationship between incident dementia and DBP did however not differ significantly between the placebo and active treatment groups (P = 0.38). SBP was not associated with incident dementia, at baseline (P = 0.62) or during follow-up (placebo group P = 0.13, active group P = 0.36). Wider achieved pulse pressure (PP) was associated with increased risk of dementia in both treatment groups (placebo P = 0.032, active P = 0.0046). The same tendency was observed for baseline PP (P = 0.095). CONCLUSION:: Wider PP may possibly indicate an increased risk for dementia. Active treatment may act to change the shape of the relationship between DBP and dementia. Future studies need to focus on exploring the ideal goal pressure for this age group.

Concepts: Myocardial infarction, Hypertension, Stroke, Blood pressure, Placebo, Prehypertension, Mean arterial pressure, Perindopril


We conducted a prospective, non-interventional, multicenter study to examine the effect of a fixed-dose combination of perindopril/amlodipine in patients with arterial hypertension.

Concepts: Myocardial infarction, Atherosclerosis, Hypertension, Coronary artery disease, Blood pressure, Amlodipine, ACE inhibitor, Perindopril


We present two cases of paraplegic patients who developed secondary Raynaud’s phenomenon. A 43-year-old man with paraplegia presented with dark purple discoloration and skin defects on his left second and third toes and complained of a cold sensation in both feet for a period of 1 year. He had been taking diuretics for 4 years. The capillary refilling time for both affected toes was delayed. His antihypertensive drug was changed to a calcium channel blocker under suspicion of Raynaud’s phenomenon aggravated by hydrochlorothiazide, and the capillary refilling time normalized within 3 days. The toe skin defect was covered with a skin graft. A 51-year-old man with paraplegia presented with cyanotic color change and recurrent unstable wounds on his toes. He was also taking diuretics for hypertension. Suspecting secondary Raynaud’s phenomenon aggravated by diuretics, we changed the diuretics to olmesartan medoxmil 20 mg and amlodipine besylate 2.5 mg per day. Subsequently, he has had no unstable wounds for 30 months. If hypertensive patients with paraplegia complain of skin discoloration in their extremities, Raynaud’s phenomenon should be considered and the antihypertensive drug may need to be stopped in order to improve the wound-healing process.

Concepts: Hypertension, Blood pressure, Diuretic, Calcium channel blocker, Amlodipine, Hydrochlorothiazide, Biofeedback, Perindopril


Controlling blood pressure is a global health priority; single-pill antihypertensive combinations may improve adherence, persistence, and outcomes. Areas Covered: A novel combination of perindopril arginine and amlodipine besylate was recently approved. A systematic review of the literature revealed its most common adverse effects as: peripheral edema (depending on the dose of amlodipine, but attenuated by perindopril), cough, dizziness and hypotension. Dose-dependent hyperkalemia, impairment of renal function (especially in renovascular hypertension), angioedema, and teratogenicity were derived from experience with other ACE-inhibitors. Expert Opinion. Substantial clinical trial experience with amlodipine or perindopril suggests that these two agents effectively lower blood pressure, and can reduce the risk of major adverse cardiovascular events, as in the Anglo-Scandinavian Cardiac Outcomes Trial. The incidence of adverse effects reported in clinical trials is lower than expected, likely due to exclusion of subjects previously exposed to its components; the nature of open-label, uncontrolled observational studies; and difficulty in recognizing and measuring cough and pedal edema. This new formulation of perindopril arginine protects its ethyl ester, without requiring physical separation from amlodipine in a single pill, and is less hygroscopic than perindopril erbumine. These and other attributes may make this combination an attractive addition to the antihypertensive armamentarium.

Concepts: Nephrology, Clinical trial, Hypertension, Blood pressure, Amlodipine, ACE inhibitor, Peripheral edema, Perindopril


The fixed association of atorvastatin, perindopril and amlodipine was recently launched by the firm SERVIER under the name of Lipertance®. It is the first fixed association of a statin, an ACE inhibitor and a calcium blocker present on the Belgian market to handle the risk factors that are hypertension and dyslipidemia which can be used both in primary and secondary cardiovascular prevention. The interests of such a triple combined therapy are many in terms of morbimortality reduction, as observed in ASCOT trial. Besides these results, the association of these three agents gives probably a synergic effect, which would be more effective to protect both heart and vessels. Moreover, a fixed association will improve treatment compliance and adherence, which are generally quite poor in the management of cardiovascular risk factors. Lipertance® is available with three different doses : 20/5/5 mg, 20/10/5 mg and 40/10/10 mg, respectively for atorvastatin, perindopril and amlodipine. Contraindications and side effects are the same as each component of this association and are well known.

Concepts: Myocardial infarction, Hypertension, Effect, Blood vessel, Effectiveness, Amlodipine, ACE inhibitor, Perindopril


To study treatment persistence and mortality using a single-pill, fixed-dose combination tablet compared with a two-pill combination for hypertension.

Concepts: Hypertension, Amlodipine, Perindopril


The etiology of essential hypertension is multifactorial. Therefore, treatment with combinations of antihypertensive agents acting on multiple targets is necessary for successful therapy in the majority of patients. According to the experience and clinical data accumulated so far, combination therapy with three agents from different pharmacological classes is required in approx. 30% of patients in order to achieve long-term blood pressure control. The primary objective of the PETRA study was to evaluate the efficacy of blood pressure (BP) control with once daily administration of the different dosage strengths of the once-daily, triple fixed combination of perindopril, indapamide, and amlodipine. The evaluation was based on office BP readings and ambulatory blood pressure monitoring (ABPM) data gathered in routine clinical practice.

Concepts: Medicine, Hypertension, The Canon of Medicine, Blood pressure, Amlodipine, Ambulatory blood pressure, Prehypertension, Perindopril