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Indian Heart Journal 2014Recent hypertension guidelines recommend initiation of treatment with a fixed dose combination of two drugs for more effective and quicker blood pressure control. Few of... (Observational Study)
Observational Study
OBJECTIVE
Recent hypertension guidelines recommend initiation of treatment with a fixed dose combination of two drugs for more effective and quicker blood pressure control. Few of these have been assessed for efficacy and acceptability. This study examines the short term blood pressure control and acceptability of perindopril, with or without its fixed dose combinations (FDC) with amlodipine and Indapamide in younger patients.
METHODS
In a multicentre prospective observational study, patients with stage 1 hypertension were prescribed perindopril 4 mg per day. Those with stage 2 or 3 hypertension were prescribed a single tablet per day of 4 mg perindopril and 5 mg amlodipine (COVERSYL AM), or 4 mg perindopril and 1.25 mg indapamide (COVERSYL PLUS)for 45 days. The primary outcomes were the frequency of patients achieving blood pressure control and the adverse effect of pedal edema.
RESULTS
Of 426 patients, with a mean age of 45 years, distributed throughout India, and an average (SD) baseline systolic/diastolic blood pressure of 157.2 (13.5)/98.6 (7.4), 303 (71.1%) achieved blood pressure control. Mean (SD) SBP/DBP decreased from baseline by 26.9 (12.6), and DBP by 15.4 (7.2) mm Hg. Few patients discontinued treatment, and the frequency of cough that interfered with sleep and ankle edema was low.
CONCLUSION
In patients requiring combination antihypertensive treatment, the regimen of perindopril alone or its FDC with Indapamide or amlodipine reduces blood pressure effectively, resulting in high rates of blood pressure control over the short term, with a low frequency of side effects including cough and pedal edema.
Topics: Adult; Amlodipine; Antihypertensive Agents; Drug Combinations; Female; Humans; Hypertension; Indapamide; India; Male; Middle Aged; Perindopril; Prospective Studies; Treatment Outcome
PubMed: 25634398
DOI: 10.1016/j.ihj.2014.10.419 -
Revue Medicale de Liege Apr 2018The endothelium plays a vital role as part of the cardiovascular continuum. Risk factors such as hypertension and dyslipidemia unbalance angiotensin II - bradykinin... (Review)
Review
The endothelium plays a vital role as part of the cardiovascular continuum. Risk factors such as hypertension and dyslipidemia unbalance angiotensin II - bradykinin homeostasis, leading to endothelial dysfunction and changes in vascular structure that promote atherosclerosis and thrombosis. When dealing with risk factors, treatment should focus on the prevention and restoration of endothelial function. Not all cardiovascular drugs are able to reverse vascular and structural endothelial dysfunction. Increasing levels of bradykinin is an effect of the use of angiotensin-converting enzyme inhibitors (ACE-Is), and also a fundamental part of their mode of action. The cardiovascular protection observed with ACE-I, and not with sartans, can be explained rationally by the specific effects of bradykinin on the endothelium. In the pharmacological class of ACE-Is, perindopril likely produces the strongest effects on bradykinin, which may explain, at least in part, the documented superiority of this drug in the prevention and treatment of cardiovascular disease.
Topics: Angiotensin-Converting Enzyme Inhibitors; Bradykinin; Cardiovascular Diseases; Endothelium, Vascular; Humans; Perindopril
PubMed: 29676873
DOI: No ID Found -
International Journal of Nephrology and... 2022Lipoprotein glomerulopathy (LPG) is caused by a mutation in the apolipoprotein E gene () gene and is characterized by lipoprotein thrombi in glomerular capillaries....
Lipoprotein glomerulopathy (LPG) is caused by a mutation in the apolipoprotein E gene () gene and is characterized by lipoprotein thrombi in glomerular capillaries. Here, we describe a case of LPG, the first to be reported from Canada and the first case of LPG in North America to be associated with the Tokyo/Maebashi mutation (p.Leu162_Lys164del, traditional nomenclature 142_144del). A 49-year-old man of Chinese descent with a previous diagnosis of dyslipidemia and a new diagnosis of hypertension was found to have proteinuria on routine urinalysis. Renal biopsy showed markedly dilated glomerular capillaries filled with pale staining mesh-like material that stained positive for Oil-Red-O, consistent with lipoprotein thrombi. gene sequencing confirmed the diagnosis of LPG. The patient was treated with fenofibrate and perindopril. His lipid profile normalized and proteinuria dropped to minimal levels. Repeat renal biopsy 2 years after the first showed resolution of lipoprotein thrombi but with rare residual granular densities by electron microscopy consistent with lipoprotein in the subendothelial space, supporting the hypothesis that this subendothelial material contains precursors to lipoprotein thrombi.
PubMed: 35761986
DOI: 10.2147/IJNRD.S364890 -
Advances in Therapy Nov 2023Differences in class or molecule-specific effects between renin-angiotensin-aldosterone system (RAAS) inhibitors have not been conclusively demonstrated. This study used...
Comparing Cardiovascular Outcomes and Costs of Perindopril-, Enalapril- or Losartan-Based Antihypertensive Regimens in South Africa: Real-World Medical Claims Database Analysis.
INTRODUCTION
Differences in class or molecule-specific effects between renin-angiotensin-aldosterone system (RAAS) inhibitors have not been conclusively demonstrated. This study used South African data to assess clinical and cost outcomes of antihypertensive therapy with the three most common RAAS inhibitors: perindopril, losartan and enalapril.
METHODS
Using a large, South African private health insurance claims database, we identified patients with a hypertension diagnosis in January 2015 receiving standard doses of perindopril, enalapril or losartan, alone or in combination with other agents. From claims over the subsequent 5 years, we calculated the risk-adjusted rate of the composite primary outcome of myocardial infarction, ischaemic heart disease, heart failure or stroke; rate of all-cause mortality; and costs per life per month (PLPM), with adjustments based on demographic characteristics, healthcare plan and comorbidity.
RESULTS
Overall, 32,857 individuals received perindopril, 16,693 losartan and 13,939 enalapril. Perindopril-based regimens were associated with a significantly lower primary outcome rate (205 per 1000 patients over 5 years) versus losartan (221; P < 0.0001) or enalapril (223; P < 0.0001). The risk-adjusted all-cause mortality rate was lower with perindopril than enalapril (100 vs. 139 deaths per 1000 patients over 5 years; P = 0.007), but not losartan (100 vs. 94; P = 0.650). Mean (95% confidence interval) overall risk-adjusted cost PLPM was Rands (ZAR) 1342 (87-8973) for perindopril, ZAR 1466 (104-9365) for losartan (P = 0.0044) and ZAR 1540 (77-10,546) for enalapril (P = 0.0003).
CONCLUSION
In South African individuals with private health insurance, a perindopril-based antihypertensive regimen provided better clinical and cost outcomes compared with other regimens.
Topics: Humans; Losartan; Antihypertensive Agents; Enalapril; Perindopril; South Africa; Angiotensin-Converting Enzyme Inhibitors; Hypertension; Blood Pressure
PubMed: 37730949
DOI: 10.1007/s12325-023-02641-8 -
Journal of Medical Case Reports Dec 2018Ace inhibitor-induced angioedema, characterized by sudden-onset swelling of the mucous membrane, skin, or both, is a rare occurrence in the Kingdom of Saudi Arabia....
BACKGROUND
Ace inhibitor-induced angioedema, characterized by sudden-onset swelling of the mucous membrane, skin, or both, is a rare occurrence in the Kingdom of Saudi Arabia. Because of its safety and efficacy, perindopril is a commonly prescribed angiotensin-converting enzyme inhibitor. Here we describe the clinical manifestations, management, and outcome of perindopril-induced angioedema of the lips and tongue in a 65-year-old Saudi man.
CASE PRESENTATION
A 65-year-old Saudi Arab man presented to an emergency department with lip and tongue swelling and dysphagia. There were no systemic symptoms and no past history of a similar event. He had been consuming perindopril 5 mg and amlodipine 5 mg for the last 3 weeks: brand name, Coveram, from the company Servier (Ireland) Industries Ltd.; one tablet of Coveram contains 3.395 mg perindopril corresponding to 5 mg perindopril arginine and 6.935 mg amlodipine besilate corresponding to 5 mg amlodipine. A physical examination revealed considerable swelling of his lips and tongue. Examinations of other systems, including his cardiovascular and respiratory systems, revealed unremarkable findings. All laboratory parameters were also normal. Electrocardiography demonstrated sinus rhythm, a normal P axis, and V-rate of 50-99. A clinical diagnosis of perindopril-induced angioedema was made, and perindopril was discontinued. The angioedema resolved completely after the administration of antihistamines and corticosteroids.
CONCLUSIONS
Angioedema caused by angiotensin-converting enzyme inhibitors is an uncommon occurrence in Saudi Arabia. The findings from this case are expected to raise awareness about this condition among clinicians in this country.
Topics: Adrenal Cortex Hormones; Aged; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Histamine Antagonists; Humans; Lip Diseases; Male; Perindopril; Saudi Arabia; Tongue Diseases
PubMed: 30514395
DOI: 10.1186/s13256-018-1910-x -
American Journal of Cardiovascular... Jun 2019Angiotensin-converting enzyme inhibitors and calcium channel blockers in combination are widely recommended in hypertension guidelines. The advantages of single-pill... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Angiotensin-converting enzyme inhibitors and calcium channel blockers in combination are widely recommended in hypertension guidelines. The advantages of single-pill combinations (SPCs) are increasingly recognized, so a dosage-adapted combination of perindopril and amlodipine was developed for the initial management of hypertension.
OBJECTIVE
This randomized trial evaluated the blood pressure (BP)-lowering efficacy of four incremental doses of perindopril/amlodipine SPC in adults with mild-to-severe hypertension.
METHODS
Eligible patients (N = 1617) were randomized to SPC perindopril 3.5 mg/amlodipine 2.5 mg (i.e., 3.5/2.5 mg) daily, uptitrating as required on a monthly basis up to 14/10 mg until BP < 140/90 mmHg (< 130/80 mmHg in patients with diabetes). The primary endpoint (proportion with controlled BP at each uptitrated dose) was evaluated at 6 months, and safety was evaluated at 9 months; 24-h ambulatory BP measurement and BP variability were also investigated. Control-arm participants (n = 1653) were randomized to irbesartan 150 mg daily, uptitrating over 3 months to irbesartan/hydrochlorothiazide 300/25 mg.
RESULTS
Significant increases in BP control were observed with each dosage increment of perindopril/amlodipine, which was well tolerated, rising from 21% (3.5/2.5 mg) to 30% (7/5 mg), 37% (14/5 mg), and 42% (14/10 mg) after 1, 2, 3, and 6 months, respectively. Reductions in mean systolic and diastolic BP occurred with each incremental dose of perindopril/amlodipine. After 6 months, mean BP had fallen by 24.8/10.8 mmHg. Irbesartan-based therapy reduced clinic and 24-h BP similarly to perindopril/amlodipine, but perindopril/amlodipine reduced BP variability more in comparison.
CONCLUSIONS
Incremental uptitration with dosage-adapted perindopril/amlodipine SPC is a safe and effective strategy for managing hypertension.
TRIAL REGISTRATION
EudraCT (No. 2006-005799-42).
Topics: Aged; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Dose-Response Relationship, Drug; Double-Blind Method; Drug Combinations; Female; Humans; Hypertension; Male; Middle Aged; Perindopril; Severity of Illness Index
PubMed: 30919249
DOI: 10.1007/s40256-018-00314-4 -
Diabetes Therapy : Research, Treatment... Jul 2022Cardiovascular disease (CVD) is a leading cause of death globally, driven by the high rates of risk factors, such as diabetes and hypertension. As the prevalence of... (Review)
Review
Cardiovascular disease (CVD) is a leading cause of death globally, driven by the high rates of risk factors, such as diabetes and hypertension. As the prevalence of these risk factors is particularly high in the Gulf region, better diagnosis and management of type 2 diabetes (T2D) and hypertension has the potential to dramatically reduce adverse cardiovascular outcomes for individuals in that part of the world. This article provides a summary of presentations made during the EVIDENT summit, a virtual symposium on Evidence in Diabetes and Hypertension, held in September 2021, including a review of the various guidelines for both T2D and hypertension, as well as recent findings relevant to the safety and efficacy for therapies relating to these conditions. Of relevance to the Gulf region, the risk of hypoglycaemia with sulfonylureas during Ramadan was reviewed. For the management of T2D, sulfonylureas have been a long-standing medication used to achieve glycaemic control; however, differences have emerged between early and later generations, with recent studies suggesting improvements in the safety profiles of late-generation sulfonylureas. For patients with hypertension, incremental therapy changes are recommended to reduce the risk of cardiovascular complications that are associated with increasing blood pressure. For first-line therapy, angiotensin-converting enzyme inhibitors (ACEi), such as perindopril, have been demonstrated to reduce the risk of cardiovascular and all-cause mortality. The addition of calcium channel blockers and diuretics to ACEi has been shown to be effective in patients with poorly controlled hypertension. The different renin-angiotensin-aldosterone system inhibitors are reviewed, and the benefit of combination therapies, including amlodipine and indapamide in patients with difficult-to-control hypertension, is investigated. The benefits of lifestyle modifications for these patients are also discussed, with important clinical considerations that are expected to inform patient management in daily clinical practice.
PubMed: 35679010
DOI: 10.1007/s13300-022-01282-4 -
Frontiers in Pharmacology 2021Wear particles may induce osteoclast formation and osteoblast inhibition that lead to periprosthetic osteolysis (PPOL) and subsequent aseptic loosening, which is the...
Wear particles may induce osteoclast formation and osteoblast inhibition that lead to periprosthetic osteolysis (PPOL) and subsequent aseptic loosening, which is the primary reason for total joint arthroplasty failure. Local bone renin-angiotensin system (RAS) has been found to participate in the pathogenic process of various bone-related diseases via promoting bone resorption and inhibiting bone formation. However, it remains unclear whether and how local bone RAS participates in wear-particle-induced PPOL. In this study, we investigated the potential role of RAS in titanium (Ti) particle-induced osteolysis and osteoclast and osteoblast differentiation . We found that the expressions of AT1R, AT2R and ACE in the interface membrane from patients with PPOL and in calvarial tissues from a murine model of Ti-particle-induced osteolysis were up-regulated, but the increase of ACE in the calvarial tissues was abrogated by perindopril. Moreover, perindopril mitigated the Ti-particle-induced osteolysis in the murine model by suppressing bone resorption and increasing bone formation. We also observed in RAW264.7 macrophages that Ang II promoted but perindopril suppressed Ti-particle-induced osteoclastogenesis, osteoclast-mediated bone resorption and expression of osteoclast-related genes. Meanwhile, Ang II enhanced but perindopril repressed Ti-particle-induced suppression of osteogenic differentiation and expression of osteoblast-specific genes in mouse bone marrow mesenchymal stem cells (BMSCs). In addition, local bone RAS promoted Ti-particle-induced osteolysis by increasing bone resorption and decreasing bone formation through modulating the RANKL/RANK and Wnt/β-catenin pathways. Taken together, we suggest that inhibition of RAS may be a potential approach to the treatment of wear-particle-induced PPOL.
PubMed: 34248634
DOI: 10.3389/fphar.2021.684375 -
Journal of Hypertension Sep 2023To compare adherence to antihypertensive treatment between patients prescribed a three-drug single-pill combination (SPC) of perindopril/amlodipine/indapamide (P/A/I)...
OBJECTIVE
To compare adherence to antihypertensive treatment between patients prescribed a three-drug single-pill combination (SPC) of perindopril/amlodipine/indapamide (P/A/I) vs. the combination of an angiotensin-converting enzyme inhibitor (ACEI), a calcium-channel blocker (CCB), and a diuretic (D) as a two-drug SPC plus a third drug given separately.
METHODS
Using the healthcare utilization database of the Lombardy Region (Italy), the 28 210 patients, aged at least 40 years, who were prescribed P/A/I SPC during 2015-2018 were identified and the date of the first prescription was defined as the index date. For each patient prescribed the SPC, a comparator who started ACEI/CCB/D treatment as a two-pill combination was considered. Adherence to the triple combination was assessed over the year after the index date as the proportion of the follow-up days covered by prescription (PDC). Patients who had a PDC >75% were defined as highly adherent to drug therapy. Log-binomial regression models were fitted to estimate the risk ratio of treatment adherence in relation to the drug treatment strategy.
RESULTS
About 59 and 25% of SPC and two-pill combination users showed high adherence, respectively. Compared with patients under a three-drug two-pill combination, those who were treated with the three-drug SPC had a higher propensity to be highly adherent to the triple combination (2.38, 95% confidence interval: 2.32-2.44). This was the case regardless of the sex, age, comorbidities, and number of co-treatments.
CONCLUSIONS
In a real-life setting, patients under three-drug SPC exhibited more frequently a high adherence to antihypertensive treatment than those prescribed a three-drug two-pill combination.
Topics: Humans; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Calcium Channel Blockers; Drug Combinations; Drug Therapy, Combination; Hypertension; Medication Adherence; Adult
PubMed: 37432906
DOI: 10.1097/HJH.0000000000003497 -
Frontiers in Physiology 2023Angiogenesis is an important exercise-induced response to improve blood flow and decrease vascular resistance in spontaneously hypertensive rats (SHR), but some...
Angiogenesis is an important exercise-induced response to improve blood flow and decrease vascular resistance in spontaneously hypertensive rats (SHR), but some antihypertensive drugs attenuate this effect. This study compared the effects of captopril and perindopril on exercise-induced cardiac and skeletal muscle angiogenesis. Forty-eight Wistar rats and 48 SHR underwent 60 days of aerobic training or were kept sedentary. During the last 45 days, rats were treated with captopril, perindopril or water (Control). Blood pressure (BP) measurements were taken and histological samples from the tibialis anterior (TA) and left ventricle (LV) muscles were analyzed for capillary density (CD) and vascular endothelial growth factor (VEGF), VEGF receptor-2 (VEGFR-2) and endothelial nitric oxide synthase (eNOS) protein level. Exercise increased vessel density in Wistar rats due to higher VEGFR-2 (+17%) and eNOS (+31%) protein level. Captopril and perindopril attenuated exercise-induced angiogenesis in Wistar rats, but the attenuation was small in the perindopril group, and this response was mediated by higher eNOS levels in the Per group compared to the Cap group. Exercise increased myocardial CD in Wistar rats in all groups and treatment did not attenuate it. Both exercise and pharmacological treatment reduced BP of SHR similarly. Rarefaction was found in TA of SHR compared to Wistar, due to lower levels of VEGF (-26%) and eNOS (-27%) and treatment did not avoid this response. Exercise prevented these reductions in control SHR. While rats treated with perindopril showed angiogenesis in the TA muscle after training, those rats treated with captopril showed attenuated angiogenesis (-18%). This response was also mediated by lower eNOS levels in Cap group compared with Per and control group. Myocardial CD was reduced in all sedentary hypertensive compared with Wistar and training restored the number of vessels compared with sedentary SHR. In conclusion, taken into account only the aspect of vessel growth, since both pharmacological treatments reduced BP in SHR, the result of the present study suggests that perindopril could be a drug of choice over captopril for hypertensive practitioners of aerobic physical exercises, especially considering that it does not attenuate angiogenesis induced by aerobic physical training in skeletal and cardiac muscles.
PubMed: 37284543
DOI: 10.3389/fphys.2023.1147525