P4561Patients adherence with fixed dose combinations of renin-angiotensin-aldosterone system inhibitors in hypertension

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
G A Simonyi ◽  
T Ferenci ◽  
E Finta ◽  
S Balogh ◽  
M Medvegy

Abstract Introduction The latest ESC/ESH guidelines recommended fixed dose combinations (FDC) for first therapy in hypertension. Preferred two-drug combinations are a RAS (renin–angiotensin system) blocker with a CCBs (calcium channel blockers) or a diuretic. There are no available data about these FDCs adherence in hypertension. Aim To assess one year persistence of recommended FDCs (RAS-inhibitors/CCBs or diuretics) in hypertensive patients. Method Prescriptions database of National Health Insurance Found in Hungary on pharmacy-claims were analysed between October 1, 2012 and September 30, 2013. We identified patients who filled prescriptions for FDCs of RAS-inhibitors/CCBs or diuretics prescribed for the first time in hypertensive patients who have not received similar drugs during one year before. To model the persistence, the apparatus of survival analysis was used, where “survival” was the time to abandon the medication. Results 443,149 patients met the inclusion criteria. One-year persistence rate and hazard ratio (HR) of discontinuation (reference was ACEi/indapamide FDC) in patients with ACEi/CCB FDCs (n=124,154) was 44,95% (HR=0.69, [CI: 0.68–0.69], p<0.0001), ARB/HCT FDCs (n=109,707) was 42,52% (HR=0.80, [CI: 0.81–0.83], p<0.0001), ACEi/indapamide FDC (n=127,757) was 37,27% (HR=1.00, reference), ARB/CCB FDCs (n=13,542) was 29.04% (HR=1.19, [CI: 1.17–1.22], p<0.0001) and ACEi/HCT FDCs (n=67,989) was 27.47% (HR=1.17, [CI: 1.15–1.18], p<0.0001). One year peristence of FDCs Conclusions We have found significant difference between FDC s of RAS-inhibitors in hypertensive in relation of patients adherence. Our result demonstrated that ACEi/CCBs FDC therapy has the best one year persistence rate.

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Keiichi Ikeda ◽  
Tsuyoshi Isaka ◽  
Kouki Fujioka ◽  
Yoshinobu Manome ◽  
Katsuyoshi Tojo

Aldosterone, a specific mineralocorticoid receptor (MR) agonist and a key player in the development of hypertension, is synthesized as a final product of renin-angiotensin-aldosterone system. Hypertension can be generally treated by negating the effects of angiotensin II through the use of angiotensin-converting enzyme inhibitors (ACE-Is) or angiotensin II type 1 receptor antagonists (ARBs). However, the efficacy of angiotensin II blockade by such drugs is sometimes diminished by the so-called “aldosterone breakthrough” effect, by which ACE-Is or ARBs (renin-angiotensin system (RAS) inhibitors) gradually lose their effectiveness against hypertension due to the overproduction of aldosterone, known as primary aldosteronism. Although MR antagonists are used to antagonize the effects of aldosterone, these drugs may, however, give rise to life-threatening adverse actions, such as hyperkalemia, particularly when used in conjunction with RAS inhibitors. Recently, several groups have reported that some dihydropyridine Ca2+channel blockers (CCBs) have inhibitory actions on aldosterone production inin vitroand in the clinical setting. Therefore, the use of such dihydropyridine CCBs to treat aldosterone-related hypertension may prove beneficial to circumvent such therapeutic problems. In this paper, we discuss the mechanism of action of CCBs on aldosterone production and clinical perspectives for CCB use to inhibit MR activity in hypertensive patients.


Heart ◽  
2018 ◽  
Vol 105 (3) ◽  
pp. 204-209 ◽  
Author(s):  
Frank Moriarty ◽  
Kathleen Bennett ◽  
Tom Fahey

ObjectiveWhile fixed-dose combinations (FDC) can improve adherence, they may add complexity to the prescribing/dispensing process, potentially increasing risk of medication errors. This study aimed to determine if prescriptions for antihypertensive FDCs increase the risk of therapeutic duplication and drug–drug interactions (DDI).MethodsThis retrospective observational study used administrative pharmacy claims data from the Irish Primary Care Reimbursement Service. Prescriptions dispensed to adults in 2015 were included if they contained an antihypertensive FDC, or the same drugs prescribed separately. The outcomes were therapeutic duplication and potentially serious DDI involving FDC drugs. Relative risk (RR) of these outcomes, adjusted for prescription and patient factors, was determined using generalised linear models with Poisson distributions and propensity score matching.ResultsThis study included 307 833 FDC prescriptions (67.0%) and 151 632 separate component prescriptions. Half of patients prescribed FDCs were female with a mean age of 67.1 (SD 12.5) years and, compared with separate component prescriptions, FDCs were less often coprescribed with other cardiovascular medications. Therapeutic duplication occurred in 0.8% of prescriptions, most often involving calcium channel blockers, and 10.6% contained a DDI (most often amlodipine and simvastatin). The RR of therapeutic duplication on FDC prescriptions compared with separate component prescriptions was 1.46 (95% CI 1.17 to 1.83) and the adjusted RR was 2.06 (95% CI 1.64 to 2.60). For DDIs, there was no significant difference between FDC and separate component prescriptions after confounder adjustment.ConclusionsThis study found FDCs were associated with increased risk of duplication. When considering prescribing FDCs, this safety consideration should be weighed against potential benefits.


2017 ◽  
Vol 158 (42) ◽  
pp. 1669-1673 ◽  
Author(s):  
Gábor Simonyi ◽  
Tamás Ferenci

Abstract: Introduction: In the treatment of hypertension avoiding adverse cardiovascular complications to achieve target blood pressure is essential. The appropriate drug selection, and if necessary to change to combination therapy, patients adherence is important which may help fixed dose combination. Aim: The aim of the authors was to investigate the one year adherence of the ramipril and ramipril/amlodipine fixed dose combination in hypertensive patients. Method: Prescriptions database of the National Health Insurance Fund in Hungary on pharmacy-claims was analysed between October 1, 2012 and September 30, 2013. The authors identified patients who filled prescriptions for ramipril monotherapy and fixed dose combinations of ramipril/amlodipine prescribed for the first time in hypertensive patients who have not received similar drugs in the previous year. To model the adherence, the apparatus of survival analysis was used, where “survival” was the time to abandon the medication. As it was available to month precision, discrete time survival analysis was applied: a generalized linear model was estimated with complementary log-log link function with the kind of drug being the only explanatory variable. Results: 92,546 patients met the inclusion criteria. During the trial period, ramipril therapy or ramipril/amlodipine fixed dose combination was started in 82,251 and 10,295 patients, respectively. One year persistence rate in patients with ramipril was 30% and 54% in patients with ramipril/amlodipine fixed dose combination therapy. Considering only the 360-day study period, the mean duration of persistence was 189.9 days in patients on ramipril and 270.6 days on ramipril/amlodipine fixed dose combination therapy. The hazard of discontinuation was more than twofold higher during treatment with ramipril compared with the use of the ramipril/amlodipine fixed dose combination therapy (HR = 2.11 [95% CI: 2.05–2.17], p<0,001). Conclusions: There is a significant difference between the one year persistence of ramipril and ramipril/amlodipine fixed dose combination therapy in hypertension. The result demonstrated that ramipril/amlodipine fixed dose combination therapy has a better one year persistence rate. When the next step is necessary to achieve target blood pressure, ramipril/amlodipine fixed dose combination therapy is preferable. Orv Hetil. 2017; 158(42): 1668–1673.


2020 ◽  
Author(s):  
Yi Zhang ◽  
Shikai Yu ◽  
Yawei Xu ◽  
Bryan Williams

ABSTRACTBackgroundEarly observational studies suggested that the use of the renin angiotensin system (RAS) inhibitors, specifically angiotensin converting enzyme inhibitors or angiotensin receptor blockers, may increase the risk of infection with SARS-CoV-2 and adversely affect the prognosis or survival of infected patients. To explore the impact of RAS inhibitor use on the risk of SARS-CoV-2 infection and the prognosis of SARS-CoV-2 infected patients, from all published studies.Methods and FindingsA systematic review and meta-analysis of the use of RAS inhibitors in relation to infection with SARS-CoV-2 and/or the severity and mortality associated with COVID-19 was conducted. English language bibliographic databases PubMed, Web of Science, OVID Embase, Scopus, MedRxiv, BioRxiv, searched from Jan 1st, 2020 to July 20th, 2020. 58 observational studies (69,200 COVID-19 patients and 3,103,335 controls) were included. There was no difference in the susceptibility to SARS-CoV-2 infection between RAS inhibitor users and non-users (unadjusted OR 1.05, 95% CI 0.90 to 1.21), (adjusted OR 0.93, 95% CI 0.85 to 1.02), (adjusted HR 1.07, 95% CI 0.87 to 1.31). There was no significant difference in the severe Covid-19 case rate between RAS inhibitor users and non-users (unadjusted OR 1.05, 95% CI 0.81 to 1.36), (adjusted OR 0.76, 95% CI 0.52 to 1.12), or in mortality due to COVID-19 between RAS inhibitor users and non-users (unadjusted OR 1.12, 95% CI 0.88 to 1.44), (adjusted OR 0.97, 95% CI 0.77 to 1.23), (adjusted HR 0.62, 95% CI 0.34 to 1.14).ConclusionsIn the most comprehensive analysis of all available data to date, treatment with RAS inhibitors was not associated with increased risk of infection, severity of disease, or mortality due to COVID-19. The best available evidence suggests that these treatments should not be discontinued on the basis of concern about risk associated with COVID-19.


2016 ◽  
Vol 157 (11) ◽  
pp. 425-429 ◽  
Author(s):  
Gábor Simonyi ◽  
Tamás Ferenci

Introduction: Hypertension and dyslipidemia are modifiable cardiovascular risk factors. In Hungary hypertension and dyslipidemia are quite frequent conditions. The patients’ adherence is very important factor to reach the targets. Aim: The aim of the authors was to investigate the one-year persistence of the atorvastatin therapy and atorvastatin and amlodipine fixed dose combination. Method: National Health Insurance Found prescriptions database of Hungary on pharmacy claims between October 1, 2012 and September 30, 2013 was analyzed. The authors identified patients who filled prescriptions for atorvastatin and amlodipine fixed dose combination and atorvastatin prescribed for the first time. Patients did not receive similar drugs for one year before the study. To model the persistence, the apparatus of survival analysis was used, where “survival” was the time to abandon the medication. As it was available to month precision, discrete time survival analysis was applied: a generalized linear model was estimated with complementary log-log link function with the kind of drug being the only explanatory variable. Results: During the trial period, atorvastatin and atorvastatin plus amlodipine fixed dose combination was started in 192,579 and 24,433 patients, respectively. One year persistence rate in patients with atorvastatin and amlodipine fixed dose combination was 43%, and 21% in patients with atorvastatin therapy. The 360-days-restricted study period, the mean duration of persistence was 221.4 (SE: 0.894) days in patients on atorvastatin and amlodipine fixed dose combination and 153.0 days (SE: 0.297) in those on atorvastatin regimen. The hazard of discontinuation was almost twofold higher during treatment with atorvastatin therapy compared with the use of the atorvastatin and amlodipine fixed dose combination (hazard ratio = 1.85, p<0.0001). Conclusions: There is a significant difference between the one-year persistence of atorvastatin therapy and atorvastatin plus amlodipine fixed dose combination. The result demonstrate that atorvastatin and amlodipine fixed dose combination is favourable to reach double goals on blood pressure and LDL-cholesterol. Orv. Hetil., 2016, 157(11), 425–429.


2019 ◽  
Vol 160 (9) ◽  
pp. 343-348
Author(s):  
Gábor Simonyi ◽  
Tamás Ferenci ◽  
Ervin Finta ◽  
Iván Igaz ◽  
Sándor Balogh ◽  
...  

Abstract: Introduction: The most recent European guidelines for the treatment of hypertension suggest the use of renin-angiotensin-aldosterone system antagonists (RAAS inhibitors) and calcium channel blockers (CCBs) or diuretics fixed-dose combinations (FDCs) as the first therapeutic option. In antihypertensive therapy, the patient’s adherence is one of the most important factors in reducing unwanted cardiovascular events. Aim: Our aim was to assess the one-year persistence of angiotensin-converting enzyme inhibitor (ACEI) and CCB FDCs in hypertensive patients. Method: Authors have analysed the prescription database of the National Health Insurance Fund in Hungary on pharmacy claims between October 1, 2012 and September 30, 2013. Those patients were identified who filled prescriptions for FDCs of ACEI and CCBs prescribed for the first time for hypertensive patients and who had not received similar drugs during the year before. Apparatus of survival analysis was used, where ‘survival’ was the time to abandon the medication. Results: 124 388 patients met the inclusion criteria. One-year persistence rate and hazard ratio (HR) of discontinuation in patients with ramipril/amlodipine FDC was 54% (HR = 1.00, reference), perindopril/amlodipine 47% (HR = 1.30, p<0.0001), lisinopril/amlodipine 36% (HR = 1.79, p<0.0001), ramipril/felodipine 26% (HR = 2.28, p<0.0001) and trandolapril/verapamil 12% (HR = 4.13, p<0.0001). The average survival time of drug limited to 360 days was 270.2 days for ramipril/amlodipine FDC, 242.7 days for perindopril/amlodipine FDC, 211.2 days for lisinopril/amlodipine FDC, 186.3 days for ramipril/felodipine FDC and 125.7 days for trandolapril/verapamil FDC. Conclusions: The authors demonstrated that the one-year persistence of ACEI/CCB FDCs was significantly different in hypertensive patients. Ramipril/amlodipine FDC was more advantageous for patient adherence. Orv Hetil. 2019; 160(9): 343–348.


Author(s):  
Chen Chen ◽  
Feng Wang ◽  
Peng Chen ◽  
Jiangang Jiang ◽  
Guanglin Cui ◽  
...  

Abstract Background There has been significant controversy regarding the effects of pre‐hospitalization use of renin‐angiotensin system (RAS) inhibitors on the prognosis of hypertensive COVID‐19 patients. Methods and Results We retrospectively assessed 2,297 hospitalized COVID‐19 patients at Tongji Hospital in Wuhan, China, from January 10 th to March 30 th , 2020; and identified 1,182 patients with known hypertension on pre‐hospitalization therapy. We compared the baseline characteristics and in‐hospital mortality between hypertensive patients taking RAS inhibitors (N=355) versus non‐RAS inhibitors (N=827). Of the 1,182 hypertensive patients (median age 68 years, 49.1% male), 12/355 (3.4%) patients died in the RAS inhibitors group vs. 95/827 (11.5%) patients in the non‐RAS inhibitors group (p<0.0001). Adjusted hazard ratio for mortality was 0.28 (95% CI 0.15‐0.52, p<0.0001) at 45 days in the RAS inhibitors group compared with non‐RAS inhibitors group. Similar findings were observed when patients taking angiotensin receptor blockers (N=289) or angiotensin converting enzyme inhibitors (N=66) were separately compared with non‐RAS inhibitors group. The RAS inhibitors group compared with non‐RAS inhibitors group had lower levels of C‐reactive protein (median 13.5 vs. 24.4 pg/mL; p=0.007) and interleukin‐6 (median 6.0 vs. 8.5 pg/mL; p=0.026) on admission. The protective effect of RAS inhibitors on mortality was confirmed in a meta‐analysis of published data when our data were added to previous studies (odd ratio 0.44, 95% CI 0.29–0.65, p<0.0001). Conclusions In a large single center retrospective analysis we observed a protective effect of pre‐hospitalization use of RAS inhibitors on mortality in hypertensive COVID‐19 patients; which might be associated with reduced inflammatory response.


2020 ◽  
Vol 2 (1) ◽  
pp. 4-8
Author(s):  
Bando H

Currently, major categories of antihypertensive agents include diuretics, beta-blockers, calcium channel blockers (CCBs), renin-angiotensin system (RAS) inhibitors [angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB)]. Among them, RAS (ACE inhibitors and ARB) would be recommended to be a first-line treatment when providing antihypertensive agents for hypertensive patients with diabetes, cardiovascular disease, and impaired renal function. Randomized controlled trials (RCT) of RAS inhibitors compared with other antihypertensive showed a rather lower relative risk (RR). They are all-cause death (RR – 0.95), cardiovascular death (RR – 0.84), incidence of cardiovascular disease (RR – 0.93), and incidence of renal dysfunction (RR – 0.91).


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