Combination Of Calcium Channel Blocker Research Articles

DISTRESS ASSOCIATED WITH SIDE EFFECTS OF CALCIUM CHANNEL BLOCKERS AMONG A COHORT OF NEWLY DIAGNOSED WITH HYPERTENSION

Antihypertensive therapy with calcium channel blockers (CCBs) is reported to be frequently associated with varying levels of distress due to their side effects. The severity of distress may result in patients intentionally interrupting or withdrawing from therapy. In clinical settings, distress from side effects of drug(s) are sometimes left unreported, overlooked or poorly resolved by clinicians. The aim of this study was to assess distress due to side effects of commonly prescribed CCB-based antihypertensive therapies.This was a prospective observational study among patients newly diagnosed with primary hypertension being treated with either CCB monotherapies or combination regimens as initial therapy. A total of 180 patients enrolled completed the eight week study and their data used in final analysis. The subjects were allocated into six treatment groups of 30 each and given either amlodipine 10mg, nifedipine 20mg, bendrofluthiazide (monotherapies) or their combinations with bendrofluthiazide 5mg or Lisinopril 5mg (dual therapies). The level of distress before and after initiation of therapy was compared using Students t test and P values ≤ 0.05 was considered statistically significant. Patients on dual therapies reported more side effects compared to monotherapies. The most commonly reported side effects included loss of libido (38% - 47%), pitting edema (28% - 35%), headache (26% - 36%), muscle cramps (9% - 18%) and fatigue (17% - 30%). Distress score of monotherapies (14.9) and dual therapies (15.3) was considered mild (< 25 threshold). There was significant reduction in distress with bowel upset (P = 0.001), insomnia (P = < 0.001), pain (P = 0.001), breathing difficulties (P = 0.009) and concentration for BDF containing regimen (P = 0.001). Distress among Lisinopril containing regimens involved appetite (P = 0.003), pain (P = 0.002) and fatigue (P = 0.003). Overall, distress due to side effects was mild for all the antihypertensive drug(s). Keywords: Antihypertensives, Calcium channel blockers, Distress, Hypertension, Nifedipine, Side effects

Combined use of beta-blockers and non-dihydropyridine calcium channel blockers: possible or contraindicated?

One of the most effective medications used for various cardiac diseases and syndromes to improve symptoms and, in some cases, prognosis, are betablockers (BBs) and calcium channel blockers (CCBs). The combination of BBs and dihydropyridine CCBs has a synergistic clinical effect and is well tolerated. The clinical effects of a combination of beta blockers and non-dihydropyridine CCBs (verapamil, diltiazem) are also synergistic. However, this combination increases the incidence of side effects and complications of drug therapy.The article discusses the controversial issues of such a combination and substantiates the main conclusion that the discussed combination is not applicable in routine practice. This position should be clearly reflected in all Russian cardiology guidelines. However, the article discusses the possible combined use of BBs with nondihydropyridine CCBs in isolated cases, excluding contraindications, taking into account almost daily monitoring of tolerability, individual characteristics of the patient and by decision of a medical team.

Angiotensin receptor blockers reduced the risk of post stroke cognitive impairment among first‐ever ischemic stroke patients

AbstractBackgroundThe effect of antihypertensive drug classes in reducing the risk of post‐stroke cognitive impairment (PSCI) remains elusive. We aimed to investigate the association between antihypertensive drug classes and the risk of PSCI among ischemic stroke patients using data collected from a tertiary hospital in Indonesia.MethodsWe carried out a retrospective analysis of data from a medical database in Sardjito General Hospital Yogyakarta, Indonesia. We identified the first‐ever ischemic stroke patients hospitalized between June 2018 to May 2019 and whose serial measurements of cognitive function were available up to 90 days after stroke. The effect of antihypertensive drug classes on PSCI was measured by using multivariate logistic regression analysis.ResultsWe found 71.11% patients developed PSCI at 90 days after stroke. Forty‐one patients (44.09%) received no antihypertensive drugs, 14 (15.05%) with angiotensin receptor blockers (ARB), 20 (21.50%) with calcium channel blockers (CCB), and 18 (19.35%) with combination of ARB and CCB. After controlling covariates, we found that ARB reduced the risk of PSCI by 64% (aOR 0.364, 95% CI = 0.14‐0.91, p<0.05), with improvement of total MoCA‐INA score by 3.113 points (p<0.05).ConclusionsAmong first‐ever ischemic stroke patients, ARB showed more favorable outcome on reducing the risk of PSCI and improving cognitive performance at 90 days after stroke. These findings may contribute to assist clinicians for selecting antihypertensive drug classes in PSCI prevention.

THU529 Challenges In The Management Of Biochemically Silent Paraganglioma

Abstract Disclosure: S. Dewan: None. A. Farooqi: None. J. Jun: None. Biochemically silent Pheochromocytoma and Paraganglioma (PPGL) are rare neuro-endocrine tumors because of which there is low quality evidence and insufficient guidelines for their management. 74-year-old Female was referred to our Endocrine clinic for incidentally discovered Retroperitoneal mass on MRI. On evaluation patient reported having concerns of escalating anxiety, difficult to control HTN and episodic flushing after physical activity in the last one year. A CT abdomen and pelvis with contrast was ordered which showed 1.7 x 1.8 cm mass anterior to the L5 vertebral body just caudal to the aortic bifurcation. The biochemical work up including 24-hour urine Metanephrines (104 ug/24 hr; n 52-341), Normetanephrines (479 ug/24 hr; n 88-444), Total Metanephrines (583 ug/24 hr; n 88-444), 3 Methoxytyramine (166 mcg/24 hr; n <242) was inconclusive. For further evaluation PET CT DOTATATE scan was ordered which showed the lesion to be DOTATAE somatostatin analogue avid, consistent with somatostatin receptor positive neuroendocrine tumor. Patient was scheduled for surgery in 2 weeks and was started on Terazosin in addition to her anti HTN medications Amlodipine, Losartan and HCTZ. The surgery had to be rescheduled due to inadequate blood pressure control. Her amlodipine and Terazosin dosage were gradually increased while the procedure was rescheduled. Eventually she underwent Laparotomy exploration and resection of the lesion. Patient tolerated the procedure well and had no major intra or post operative fluctuations in her blood pressure, heart rate or blood glucose. According to the Endocrine Surgery team, the tumor could not be sufficiently removed since it was immovable during surgery and could not be delineated from the spine. The post-operative CT scan showed nodular lesion at aortic bifurcation slightly increased in soft tissue component from prior CT scan. After discussions with surgery and oncology team, patient opted for imaging surveillance for now and will consider genetic counseling and/or radiation therapy if the tumor increases in size. Untreated PPGL carries a high risk of cardiovascular morbidity and mortality, and some may also be malignant with a propensity to cause mass effects and metastasis. Currently, there are scarce evidence-based studies comparing treatment options in biochemically silent PPGL, and there is no consensus for the most appropriate peri-operative management of biochemically silent PPGL. This case adds to the literature on how a combination of calcium channel blocker and alpha blocker can be used to achieve peri-operative blood pressure and heart rate control with no major side effects. It also demonstrates the importance of functional imaging, especially in clinically or radiologically suspected PPGL, even with a normal biochemical work up. We suggest multi-disciplinary evaluation and individualized management to ensure positive outcomes. Presentation: Thursday, June 15, 2023

PS-BPC06-4: RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM INHIBITORS VERSUS CALCIUM CHANNEL BLOCKERS IN ASSOCIATION WITH MORTALITY RATE IN COVID-19 HYPERTENSIVE PATIENTS: THE EFFECT OF AGE

Objective: To study the association of calcium channel blockers (CCBs), the renin-angiotensin-aldosterone system (RAAS) inhibitors or their combination as antihypertensive medications and the clinical outcome of COVID-19 infection. Design and method: This is a retrospective cohort study using de-identified data retrieved from clinical records of COVID-19 patients in two isolation centers. Medical history, demographic data, symptoms, complications and laboratory investigations were extracted from clinical records of 406 confirmed COVID-19 hospitalized patients between Feb 2020 and July 2021. Hypertension and antihypertensive treatments were confirmed by medical history and clinical records. Continuous variables were presented as means ± standard deviation (SD) while categorical variables were presented as percent proportions. Logistic regression was used to assess the impact of antihypertensive drugs (RAAS inhibitors, CCBs, combination of RAAS inhibitors and CCBs and those not receiving medication) on the prognosis of COVID-19 patients and to explore the risk factors associated with mortality. Result: Out of 406 hospitalized COVID-19 patients, 242 (59.6%) had a history of hypertension. Hypertensive patients under the age of 65 years and receiving RAAS inhibitors or the combination of both RAAS inhibitors and CCBs were at higher risk of mortality than those on CCBs only (odds ratio [OR]: 4.45, 95% confidence interval [CI]: 1.56–12.56, P = 0.005 and OR:3.57, CI: 1.03–12.36, P = 0.045 respectively). Antihypertensive medications did not seem to influence mortality rates among hypertensive patients above 65 years. Routine laboratory investigations were not significantly different between the subgroups receiving different antihypertensive medications regardless of age. Cough was the only symptom associated with mortality among patients under 65 years (OR:2.34, CI:1.24–4.41, P = 0.009). Type II respiratory failure was significantly associated with death among hypertensives under 65 years (OR:5.43, CI:1.08–28.07, P = 0.044) whereas acute kidney injury and septic shocks are the common complications related to death among hypertensives above 65 years (OR:3.59, CI:1.54–8.36, P = 0.003 and OR:7.87, CI: 1.68–36.78, P = 0.009 respectively). Conclusion: Administration of CCBs may improve the outcome of COVID-19 hypertensive patients under 65 years of age. Antihypertensive treatment does not seem to influence the prognosis of COVID-19 patients above 65 years. Such results may affect management strategy of COVID-19 hypertensive patients. Type-II respiratory failure among patients under 65 years of age, acute kidney injury and septic shock among those above 65 years are the most serious complications that can lead to death regardless of blood pressure.

Current practice toward the use of antihypertensive agents in the management of hypertension – A cross-sectional study among Indian physicians

Objective: The objective of this study was to assess current practices and usage patterns of antihypertensive medications in managing hypertension (HTN) in India. Materials and Methods: A cross-sectional, observational digital study was conducted among health-care practitioners (HCPs) across India (November 2022–March 2023). Results: A total of 792 HCPs (cardiologists, consulting, and general physicians) participated in this study. According to 63.38% of HCPs, 20–50 essential HTN patients seek consultation weekly. The majority of patients were in the age range of 40–60 years (84.09%). A total of 67.55% of HCPs mentioned that systolic blood pressure (BP) ranged between 140 and 160 mmHg. Type 2 diabetes mellitus was the most common comorbidity among hypertensive patients (84.09%). In total, 53.79% and 37.37% of HCPs preferred angiotensin receptor blockers (ARBs)/angiotensin-converting enzyme and calcium channel blockers (CCBs) as the first choice of antihypertensive agents. The majority of HCPs (>69%) preferred prescribing a triple-drug fixed-dose combination (FDC) of CCBs + ARB + diuretics in hypertensive patients with coronary artery disease (CAD) and resistant HTN. The majority (89.90%) of HCPs preferred prescribing FDC of CCBs over monotherapy. Amlodipine (>55%) followed by cilnidipine (>32%) were preferred CCBs for young and older hypertensive patients. In patients with essential HTN without any CVD, amlodipine (72.85%) was the preferred CCB. Vascular selectivity (59.09%) and longer half-life (54.55%) were important factors for prescribing CCBs. Resistant HTN, inadequate BP control with monotherapy, and the presence of CAD were all (62.63%) important considerations for FDC with CCBs. The underutilization of CCBs in managing HTN (63.88%) was highlighted. Conclusion: Overall responses provide a comprehensive overview of the prevailing perception and the usage patterns of antihypertensive agents employed by HCPs in India.

PS-C26-11: THERAPEUTIC EFFECTS OF ADDING THIAZIDE DIURETIC OR MINERAL CORTICOID RECEPTOR BLOCKER IN HYPERTENSIVE PATIENTS GIVEN ARB AND CALCIUM CHANNEL BLOCKER

We compared the addition of a thiazide diuretic (TZD) and a mineral corticoid receptor blocker (MRB) to in 13 hypertensive patients who did not achieve the target blood pressure level with the combination of an angiotensin II receptor blocker (ARB) and a calcium channel blocker (CCB). A randomized crossover study was performed giving 1–2 mg trichlormethiazide (TCM) or 1.25–2.5 mg esaxerenone (ESX) in addition to ARB and CCB combination for 12–16 weeks each. The office blood pressure was comparable between the high-dose TCM period (131/73 mmHg) and the ESX period (129/72 mmHg). The morning and the evening home blood pressures were also comparable in the TCM and the ESX periods. As for the laboratory data, serum Na (-1.2 mEq/L, p = 0.013) was significantly decreased and uric acid (+1.1 mg/dL, p < 0.001) was increased by TCM, while serum K was slightly increased by ESX (+0.2 mEq/L, p = 0.042). The estimated GFR was significantly reduced both by TCM and ESX (66 and 67 vs 72 mL/min/1.73m2, p = 0.023 and 0.047), however, ESX but not TCM significantly reduced the urinary excretions of albumin (81 vs 148 mg/gCreatinine, p = 0.035) and liver-type fatty acid binding protein. Reductions in plasma brain natriuretic peptide (BNP) and high-sensitivity C-reactive protein (CRP) were significant in the TCM and the ESX periods, respectively. Circulating markers of oxidative stress such as oxidized LDL and reactive oxygen metabolites were not affected by either TCM or ESX. In the combination drug therapy of hypertension, ESX, as a MRB, has a hypotensive effects comparable to TZD and may have advantage over in protecting kidney without raising uric acid although care should be taken for the increase in serum K.

ROSuvastatin and Amlodipine as free or fixed combination on theRApeutic taRgets and treatment Adherence in hypertensive, hypercholesterolemic individuals. ROSA RARA: a spontaneous, observational study conducted by italian outpatient cardiologists

Background: Hypertension and LDL hypercholesterolemia often coexist, and their effective treatment has favorable implications for cardiovascular health. We aimed at defining the impact of amlodipine and rosuvastatin as free or fixed combinations on blood pressure (BP) and LDL-cholesterol, and the satisfaction with treatment, in hypertensive individuals with LDL hypercholesterolemia. Methods: A spontaneous longitudinal observational study was conducted at Italian cardiology outpatients clinics. Eligible individuals (age ≥ 18y, informed consent, stable 5 or 10 mg amlodipine therapy in addition to a RAAS inhibitor, stable 10 or 20 mg rosuvastatin therapy) underwent home and office BP and LDL-cholesterol assessment at 12 and 24 weeks. BP and LDL-cholesterol control rates and satisfaction with the fixed combination were assessed. Results: 285 participants were enrolled (51%M; 67 ± 10y; 94 on the free combination). At 12 weeks, mean BP and LDL-cholesterol were reduced in both groups, with higher hypertension control rates in the fixed combination group; at 24 weeks they were further reduced compared with baseline, and home systolic BP was lower in the fixed than the free combination group (121.9 ± 17.6 vs 129.4 ± 8.5 mmHg; p = 0.03). Patients in the fixed combination reported higher satisfaction with this regimen than with the free combination. Conclusions: The fixed combination of calcium channel blocker and statin appears to have advantages in terms of clinical efficacy and patients’ satisfaction.

Population aspects of arterial hypertension therapy. Focus on fixed combinations

High blood pressure (BP) remains the leading risk factor for coronary heart disease, stroke, other cardiovascular diseases, chronic kidney disease, and dementia. Objective. To estimate the frequency of prescribing antihypertensive drugs (AHD) with the allocation of the proportion of fixed combinations (FC) among people aged 25–64 years examined in 16 regions of the Russian Federation as part of the ESSE-RF and ESSE-RF2 studies.Design and methods. The analysis included the results of a survey of representative samples of the population of the Russian Federation in the ESSE-RF studies (2012–2014, men: N = 8376 and women N = 13546 people) and ESSE-RF2 (2017, men: N = 3000 and women N = 3714 people). Each participant signed an informed consent. Arterial hypertension (AH) was defined as systolic BP ≥ 140 mm Hg and/or diastolic BP ≥ 90 mm Hg and/or if the examined reported taking AHD. Under the lack of control of AH, we understood the proportion of patients (%) with BP levels ≥ 140/90 mm Hg of the total number of patients with AH. Information about the AHD taken was recorded from the words of the patient (trade name of the drug) followed by coding according to the International Nonproprietary Names of Drugs.Results. In the Russian population, there was a decrease in the proportion of uncontrolled BP from 78,5 % (95 % confidence interval (CI) 77,7–79,3) in ESSE-RF to 73,0% (95 % CI 71,3–74,6) in ESSE-RF2. FC intake was detected in 15,6 % (95 % CI 13,8–18,0) of patients treated in the ESSE-RF study, while the proportion of such patients in the ESSE-RF2 decreased to 10,9% (95% CI 9,2–12,8), p < 0,001. The most common FC was the combination of an angiotensin-converting enzyme inhibitors (ACEI) and a diuretic (ESSE-RF: 49,1 % and ESSE-RF2: 45,9 %). In second place in ESSE-RF is a diuretic + angiotensin receptor blockers (25,8 %), in ESSE-RF2 — calcium channel blockers (CCB) + ACEI (22,4%). A more modern combination, namely: the combination of ACEI and CCB, was noted only in 8,7% in ESSE-RF, while in ESSE-RF2 the proportion of this FC increased by 2,5 times.Conclusions. In the population of the Russian Federation, only 10 %-15 % of patients with AH receive FC AHD. An increase in FC intake may contribute to an increase in adherence to therapy, which is extremely important for the Russian population with poor BP control.

Ефективність і безпечність фіксованих комбінацій блокаторів повільних кальцієвих каналів, блокаторів рецепторів ангіотензину та тіазидних діуретиків у лікуванні артеріальної гіпертензії

Наведено аналіз результатів дослідження ефективності й безпечності фіксованих комбінацій блокатора повільних кальцієвих каналів (БКК) амлодипіну й блокатора рецепторів ангіотензину (БРА) валсартану (Комбісарт) та амлодипіну, валсартану й тіазидного діуретика гідрохлортіазиду (Комбісарт Н) компанії ПАТ «Київський вітамінний завод» порівняно з препаратами Ексфорж й Ексфорж Н (Novartis Pharma, Швейцарія) у лікуванні хворих на артеріальну гіпертензію ІІ–ІІІ стадії. Установлена терапевтична еквівалентність Комбісарту і Комбісарту Н референтним — Ексфоржу й Ексфоржу Н. Продемонстрована ефективність досліджуваних препаратів щодо зниження артеріального тиску, покращення його контролю протягом доби при комбінації БРА і БКК із тіазидним діуретиком, добра переносимість Комбісарту і Комбісарту Н, що підвищує комплайєнтність пацієнтів до лікування артеріальної гіпертензії.

The Effect of Captopril on the Decrease of Systolic and Diastolic Blood Pressure in Hypertension Rat with Kidney Dysfunction Complications

The most commonly used antihypertensives in Indonesia vary according to the age of the patient. At the age of 40-60 years, angiotensin-converting enzyme inhibitor (ACEi) and calcium channel blockers (CCBs) are usually given to older patients. All age groups were treated with a combination of CCB and angiotensin receptor blocker (ARB). Captopril is one of the ACE inhibitor classes, and captopril can lower blood pressure, improve renal impairment, and suppress kidney inflammation through the inactivation of NF-κB in hypertensive mice. Hypertension is closely related to renal dysfunction, requiring blood pressure to be lowered to the normotensive range to prevent progressive kidney damage. In the acute reperfusion stage, captopril prevents excessive angiotensin II synthesis, improves renal dysfunction, inhibited intrarenal inflammation, and better histopathologic findings. Most of the renoprotective effects of captopril occur in the acute reperfusion stage. At the same time, captopril significantly reduces NO availability, exacerbates intrarenal hypoxia, and exacerbates oxidative stress. This study aims to determine the effect of captopril on systolic blood pressure and diastolic blood pressure. In this study, all experimental animals were made hypertensive first by inducing 8% NaCl for 21 days given orally. Then the group with renal complications was induced by administering gentamicin for seven days provided intraperitoneally. Blood creatinine levels were measured using a Photometer5010V5 +. Measurement of systolic blood pressure and diastolic blood pressure using the Non-Invasive Blood Pressure (NIBP) instrument. The data from this study were analyzed using two-way ANOVA. The results showed that complications of renal dysfunction in hypertensive rats had a significant effect on reducing systolic blood pressure and diastolic blood pressure (p ˂ 0.05). The administration of captopril at doses of 1.25 mg, 2.5 mg, and 5 mg significantly affected decreased systolic blood pressure and diastolic blood pressure (p ˂ 0.05). Captopril 5 mg dose was the most effective in lowering systolic blood pressure and diastolic blood pressure.

Central and peripheral hemodynamic responses to orthostasis in hypertensive males with chronic venous disorders taking combined therapy with a calcium channel blocker and an angiotensin-converting enzyme inhibitor

Aim . To study the characteristics of central and peripheral hemodynamic responses to orthostasis in hypertensive (HTN) males with chronic venous disorders (CVD) taking combined therapy with a calcium channel blocker (CCB) and an angiotensinconverting enzyme (ACE) inhibitor. Material and methods . In 46 men 30-50 years old with uncontrolled HTN taking antihypertensive therapy, a comparative assessment of the dynamics of systolic blood pressure (SBP), diastolic blood pressure (DBP), peripheral venous pressure (PVP), lumen diameter and area, blood flow velocity of superficial and deep veins of the left leg in response to orthostasis. Venous hemodynamics was studied by duplex ultrasound. PVP was assessed by oscillometry on the thigh and ultrasound of the great superficial vein. A comparative dynamic analysis of these parameters was carried out in patients of two groups: 23 hypertensive patients without CVD and 23 patients with HTN and CVD. CVD was assessed using Comprehensive Energy Assistance Program (CEAP). Orthostasis was performed before and after 14 days of antihypertensive therapy with a combination of CCB and ACE inhibitors. Results . Central and peripheral hemodynamic responses to orthostasis before treatment in patients of both groups was the same — a decrease in SBP, DBP and PVP, expansion of superficial and deep veins, and a decrease in venous blood flow velocity. As a result of treatment, 43 patients achieved the first target office SBP (<140 mm Hg). Of these, there were 21 HTN patients without CVD and 22 patients with CVD. After treatment, most responses to orthostasis in both groups was similar to pre-treatment ones. However, differences were also noted — in both groups, the DBP increased; SBP decreased only in men with CVD. In patients with CVD, the posterior tibial vein (PTV) dilated and blood flow velocity decreased after treatment in response to orthostasis, while in patients without CVD, there was a narrowing of PTV and blood flow acceleration. After treatment, patients with CVD were characterized by a larger diameter and area of the lumen of superficial and deep veins than those without CVD in response to orthostasis. Conclusion . Orthostasis before antihypertensive therapy in patients both with and without CVD is characterized by an identical hemodynamic response — a decrease in SBP, DBP, PVP expansion of superficial and deep veins, and a decrease in venous blood flow velocity. After 14-day antihypertensive therapy, there were differences in hemodynamic response between the study groups. In patients with HTN and CVD, CCB and ACE inhibitors therapy leads to a redistribution of central and peripheral circulation and increases the dilatation of the veins in response to orthostasis.

Renin–angiotensin system blockers and susceptibility to COVID-19: an international, open science, cohort analysis

SummaryBackgroundAngiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have been postulated to affect susceptibility to COVID-19. Observational studies so far have lacked rigorous ascertainment adjustment and international generalisability. We aimed to determine whether use of ACEIs or ARBs is associated with an increased susceptibility to COVID-19 in patients with hypertension.MethodsIn this international, open science, cohort analysis, we used electronic health records from Spain (Information Systems for Research in Primary Care [SIDIAP]) and the USA (Columbia University Irving Medical Center data warehouse [CUIMC] and Department of Veterans Affairs Observational Medical Outcomes Partnership [VA-OMOP]) to identify patients aged 18 years or older with at least one prescription for ACEIs and ARBs (target cohort) or calcium channel blockers (CCBs) and thiazide or thiazide-like diuretics (THZs; comparator cohort) between Nov 1, 2019, and Jan 31, 2020. Users were defined separately as receiving either monotherapy with these four drug classes, or monotherapy or combination therapy (combination use) with other antihypertensive medications. We assessed four outcomes: COVID-19 diagnosis; hospital admission with COVID-19; hospital admission with pneumonia; and hospital admission with pneumonia, acute respiratory distress syndrome, acute kidney injury, or sepsis. We built large-scale propensity score methods derived through a data-driven approach and negative control experiments across ten pairwise comparisons, with results meta-analysed to generate 1280 study effects. For each study effect, we did negative control outcome experiments using a possible 123 controls identified through a data-rich algorithm. This process used a set of predefined baseline patient characteristics to provide the most accurate prediction of treatment and balance among patient cohorts across characteristics. The study is registered with the EU Post-Authorisation Studies register, EUPAS35296.FindingsAmong 1 355 349 antihypertensive users (363 785 ACEI or ARB monotherapy users, 248 915 CCB or THZ monotherapy users, 711 799 ACEI or ARB combination users, and 473 076 CCB or THZ combination users) included in analyses, no association was observed between COVID-19 diagnosis and exposure to ACEI or ARB monotherapy versus CCB or THZ monotherapy (calibrated hazard ratio [HR] 0·98, 95% CI 0·84–1·14) or combination use exposure (1·01, 0·90–1·15). ACEIs alone similarly showed no relative risk difference when compared with CCB or THZ monotherapy (HR 0·91, 95% CI 0·68–1·21; with heterogeneity of >40%) or combination use (0·95, 0·83–1·07). Directly comparing ACEIs with ARBs demonstrated a moderately lower risk with ACEIs, which was significant with combination use (HR 0·88, 95% CI 0·79–0·99) and non-significant for monotherapy (0·85, 0·69–1·05). We observed no significant difference between drug classes for risk of hospital admission with COVID-19, hospital admission with pneumonia, or hospital admission with pneumonia, acute respiratory distress syndrome, acute kidney injury, or sepsis across all comparisons.InterpretationNo clinically significant increased risk of COVID-19 diagnosis or hospital admission-related outcomes associated with ACEI or ARB use was observed, suggesting users should not discontinue or change their treatment to decrease their risk of COVID-19.FundingWellcome Trust, UK National Institute for Health Research, US National Institutes of Health, US Department of Veterans Affairs, Janssen Research & Development, IQVIA, South Korean Ministry of Health and Welfare Republic, Australian National Health and Medical Research Council, and European Health Data and Evidence Network.

Single pill regimen improves persistence and leads lo better clinical outcome compared to identical multi pill combination. Results of START, a German claims data analysis

Abstract Background/Introduction The current ESC/ESH-Guidelines for the treatment of arterial hypertension (AH) recommend initiation and escalation of medical treatment using renin–angiotensin–aldosterone system (RAAS) blocker, diuretics (D) and/or calcium channel blockers (CCB). They also recommend a single pill (SP) regimen to improve persistence, to increase blood pressure control and to reduce cardiovascular events. Purpose Data showing an advantage for a SP regimen compared to the identical loose combination (LC) regarding all these parameters in a single study are missing. We report now the results comparing SP with identical LC regarding persistence and cardiovascular outcomes in daily practice. Methods This was a retrospective, non-interventional analysis of an anonymized claims dataset covering patients suffering from cardiovascular diseases insured by the German AOK PLUS public health insurance in the years 2012–2017. Patients at age ≥18 years with an indication for the use of a combination of RAAS-blockers, D and/or CCB as SP or identical LC were followed up for 1 year. After 1:1-Propensity Score Matching (PSM) persistence (defined as redemption of prescription with a lack >60 days) and clinical outcomes were compared using non-parametric tests. Results After PSM, baseline characteristics were comparable between SP and LC groups. Each group included 10,801 patients with valsartan/amlodipine, 1,026 with candesartan/amlodipine, 1,823 with amlodipine/valsartan/hydrochlorothiazide (HCT), and 15,349 with ramipril/amlodipine as SP or identical LC. 8 clinical outcomes were compared for each combination. Persistence to treatment was significant higher in the SP group. In 27 of 32 comparisons a significantly lower Incidence Rate Ratio (IRR) was identified for SP. This was confirmed by time-to-event-analysis. The largest patient group (ramipril/amlodipine) showed a significant lower risk for SP observed for stroke (IRR=0.746; 95% CI 0.627–0.886; p<0.001), transitory ischemic attack (IRR=0.693; 95% CI 0.496–0.963; p=0.023), myocardial infarction (IRR=0.623; 95% CI 0.493–0.784; p<0.001), coronary artery disease (IRR=0.579; 95% CI 0.462–0.723; p<0.001), heart failure (IRR=0.468; 95% CI 0.409–0.534; p<0.001), all cause hospitalization (IRR=0.670; 95% CI 0.652–0.687; p<0.001), cardiovascular hospitalization (IRR=0.596; 95% CI 0.519–0.685; p<0.001), and all cause mortality (IRR=0.526; 95% CI 0.463–0.596; p<0.001) compared to LC. Conclusion A SP regimen improves persistence to medication, reduces cardiovascular events and total mortality compared to identical LC. The results of the START study strongly support the use of a SP concept in the AH medication treatment as recommended by the current ESH/ESC-Guidelines for the treatment of AH. Funding Acknowledgement Type of funding source: None

Assessment of suitable antihypertensive therapies: Combination with high-dose amlodipine/irbesartan vs triple combination with amlodipine/irbesartan/indapamide (ASAHI-AI study).

Angiotensin receptor blockers (ARBs) plus calcium channel blockers (CCBs) are a widely used combination therapy for hypertensive patients. In order to determine which combination was better as the next-step therapy for standard-dose combination of ARBs and CCBs, a combination with high-dose CCBs or a triple combination with diuretics, the authors conducted a prospective, randomized, open-label trial to determine which of the following combination is better as the next-step treatment: a combination with high-dose CCBs or a triple combination with diuretics. Hypertensive outpatients who did not achieve their target blood pressure (BP) with usual dosages of ARBs and amlodipine 5mg were randomly assigned to treatment with irbesartan 100mg/amlodipine 10mg (Group 1: n=48) or indapamide 1mg in addition to ARBs plus amlodipine 5mg (Group 2: n=46). The primary end point was changes in the systolic BP (SBP) and diastolic BP (DBP) after the 12-week treatment period, while secondary end points were changes in BP after the 24-week treatment period and laboratory values. At 12weeks, the SBP/DBP significantly decreased from 152.1/83.4mmHg to 131.5/76.1mmHg in Group 1 and 153.9/82.1mmHg to 132.7/75.9mmHg in Group 2. Although both groups produced a similar efficacy in reducing the SBP/DBP (-19.2/-9.2mmHg in Group 1 and -21.6/-8.8mmHg in Group 2; SBP P=.378, DBP P=.825), high-dose CCBs combined with ARBs controlled hypertension without elevation of serum uric acid. These results will provide new evidence for selecting optimal combination therapies for uncontrolled hypertensive patients.

Drug utilization study in patients of hypertension in tertiary care hospital

Background: Hypertension is the most common modifiable risk factor for cardiovascular diseases, stroke and renal failure. Drug utilization research facilitates the rational use of drugs and provides an insight into the pattern of drug use. As such, the present study was conducted to assess the prescribing patterns of antihypertensive agents and to observe the disparity between the recommended and actual practices for pharmacological management of hypertension at a tertiary care hospital.Methods: A prospective, observational and cross-sectional study was conducted in Department of Pharmacology in collaboration with Department of Medicine in a tertiary healthcare hospital. As per inclusion criteria, patients with hypertension visiting Medicine OPD from 1st October 2018 to 31st December 2018 were enrolled in the study.Results: A total of 390 prescriptions were collected. It was observed that majority of the study patients were female (53.84%) and were >60 years of age. Average number of drugs prescribed per prescription was 4.18. Multiple drug regimen (67.69%) was the mainstay therapy in our study. Prevalence of two drug combination was the highest (46.92%) followed by monotherapy (32.3%). Calcium channel blockers (CCBs) (amlodipine) was the most frequently prescribed class in monotherapy (19.23%). In two drug regimens, the combination of CCB with angiotensin-converting enzyme inhibitors (ACEIs) (combination of amlodipine and enalapril) was prescribed the most (28.46%) whereas prescription of combination of ACEI, beta-blocker (BB) and CCB (enalapril, atenolol and amlodipine combination) was the highest (13.84%) in three drug regimens.Conclusions: The prescription pattern of antihypertensive drugs was found to be rational and mainly in accordance with Joint National Committee VIII guidelines. All the drugs were prescribed by their generic names which suggests awareness among prescribers regarding WHO policies for generic prescribing.

Differences in the effects of various classes of antihypertensive drugs in combination therapy on indicators of arterial hemodynamics, vascular wall stiffness and structural-functional state of heart in patients with arterial hypertension of 1 — 2 degrees

The aim — to compare the effect of 6‑month treatment of patients with arterial hypertension (AH) of 1 — 2 degrees with angiotensin converting enzyme (ACE) or angiotensin II receptor blockers (ARB) in combination with a thiazide diuretic (indapamide) and dihydropyridine calcium channel blockers (CCB) in combination with a diuretic on indicators of brachial and central arterial pressure (AP), elastic properties of the arteries and the structural and functional state of the heart, depending on age.Materials and methods. The study included 320 patients (156 men and 164 women) aged from 35 to 80 years (mean age 62.8 ± 0.61 years) with uncomplicated AH of stage I — II, degree 1 — 2 (62.0 % and 38, 1 %, correspondingly). Depending on age, the patients were divided into two groups: 0.05). In both subgroups of patients aged 0.05). In the group treated with Arifam, the baseline HR values correlated with AP (r = –0.357, p 0.05). In patients aged ≥ 65 years, the antihypertensive effect of therapy with the combination of ACE inhibitor/ARB and indapamide was not accompanied by changes in MMI LV and indicators of LV systolic and diastolic function (all p > 0.05). In the group treated with Arifam there was a decrease in end‑diastolic and end‑systolic volumes (by 9.7 % (p 0.05).Conclusions. In spite of the same positive effect of 6‑month therapy with combinations of ACE inhibitors/ARB with indapamide and BPC with indapamide on brachial and central AP in older patients with hypertension of 1 — 2 degrees, the fixed combination of BPC amlodipine with indapamide (Arifam) had an advantage over the combination based on an ACE inhibitor (ARB) regarding the reduction of brachial, central, mean brachial and mean central AP, augmentation, pulse wave velocity, MMI of LV, left atrium volume index, E/e’ of LV, which was associated with an increase in heart rate (an average of 4.6 per 1 min).

Study of Prescribing Pattern, Identification of Drug Related Problems and Therapeutic Intervention in Cardio Vascular Diseases (CVD) Patients

Cardiovascular disease (CVD) is a disorder of heart and blood vessels. CVD is one of the major causes of deaths in India, which contributed around 30 to 40%. The aim of the study was to study the prescribing pattern of drugs, identification of drug related problems and therapeutic intervention in CVD patients. A hospital based prospective and observational study was carried out for a period of nine months in a south Indian tertiary care hospital. Among 120 selected patients, 79 were male (65.83%) and 41 were female (34.16%), more number of patients (35) were between the age group of 55-64 (29.16%) of which 27 were males & 8 were females, and very less number of patients (6) were between the age group 85-94 (5%) of which all the 6 were male. Hypertension is the most commonest and dominant disorder, which affected 47(39.16%) patients, in which 30 were male (25%) and 17 were female (14.16%). Most common risk factor is HTN followed with smoking and diabetes of 45 patients (37.5%). The most often prescribed pattern adopted in CVD is Dual therapy, it is most frequently used therapy 50 (41.66%) and quadruple therapy is less frequently 6(6.5%) used. The diuretics and calcium channel blocker combination were maximally prescribed class of drugs as a dual therapy. A total of 47 drug-drug interactions were found, among 12 were major, 15 were moderate and 20 were minor interactions. Clinical pharmacist has intervened with the help of other health care professionals in order to reduce the risk factor and minimise the drug-drug interactions. The study provides the benefits of presence of clinical pharmacist in a hospital setting, in order to prevent the medication related errors and provide the expertise pharmacotherapy opinion in CVD patients, which improves the patient compliance. Hence study justifies a need of active collaboration between clinical pharmacist, physician and other health care professionals for the better management of CVD patients.
 Keywords: Prescribing Pattern; Cardio Vascular Diseases; Drug Related Problems; Therapeutic Intervention.

EVALUATION OF RESPONSE TO ANTIHYPERTENSIVE’S IN PREECLAMPSIA AND GESTATIONAL HYPERTENSION CASES WITH DIFFERENT ACE GENE INSERTION/DELETION GENOTYPES

Objective: The objective of this research study was to investigate if there exists a relationship between angiotensin converting enzyme (ACE) genes insertion/deletion (I/D) genotypes and the antihypertensive treatment being received by preeclampsia (PE) and gestational hypertension (GH) patients.Methods: A total of 50 PE and 35 GH cases were included. ACE gene I/D genotyping was carried out on the blood samples of cases and correlated with the antihypertensive treatment being received by these patients. Details of antihypertensives being received by them were nifedipine (a calcium channel blocker 10 mg) and methyldopa (an alpha 2 receptor agonist 250 mg) which is considered as the first-line of treatment. 30 normotensive pregnant women of comparable gestational period served as controls.Results: It was observed that a combination of calcium channel blocker (nifedipine 10 mg), as well as alpha 2 agonist (methyldopa 250 mg), was required in patients with D’ allele containing genotypes. However, PE and GH patients with II genotype as well as those of GH patients responded well to either nifedipine or methyldopa. If confirmed these results appear to be of clinical significance as prior knowledge of ACE I/D genotypes will be useful in the management of PE cases in general and severe PE cases in particular.Conclusion: Prior knowledge of ACE I/D genotypes appears to be helpful in the management of PE and GH cases.

Comparison of effects between calcium channel blocker and diuretics in combination with angiotensin II receptor blocker on 24-h central blood pressure and vascular hemodynamic parameters in hypertensive patients: study design for a multicenter, double-blinded, active-controlled, phase 4, randomized trial

BackgroundHypertension is a risk factor for coronary heart disease and stroke, and is one of the leading causes of death. Although over a billion people are affected worldwide, only half of them receive adequate treatment. Current guidelines on antihypertensive treatment recommend combination therapy for patients not responding to monotherapy, but as the number of pills increase, patient compliance tends to decrease. As a result, fixed-dose combination drugs with different antihypertensive agents have been developed and widely used in recent years. CCBs have been shown to be better at reducing central blood pressure and arterial stiffness than diuretics. Recent studies have reported that central blood pressure and arterial stiffness are associated with cardiovascular outcomes. This trial aims to compare the efficacy of combination of calcium channel blocker (CCB) or thiazide diuretic with an angiotensin receptor blocker (ARB).MethodsThis is a multicenter, double-blinded, active-controlled, phase 4, randomized trial, comparing the antihypertensive effects of losartan/amlodipine and losartan/hydrochlorothiazide in patients unresponsive to treatment with losartan. The primary endpoint is changes in mean sitting systolic blood pressure (msSBP) after 4 weeks of treatment. Secondary endpoints are changes in msSBP, mean 24-h ambulatory mobile blood pressure, mean 24-h ambulatory mobile central SBP, mean 24-h ambulatory carotid-femoral pulse wave velocity, ambulatory augmentation index, and microalbuminuria/proteinuria after 20 weeks of treatment. The sample size will be 119 patients for each group in order to confer enough power to test for non-inferiority regarding the primary outcome.ConclusionThe investigators aim to prove that combination of a CCB with ARB shows non-inferiority in lowering blood pressure compared with a combination of thiazide diuretic and ARB. We also hope to distinguish the subset of patients that are more responsive to certain types of combination drugs. The results of this study should aid physicians in selecting appropriate combination regimens to treat hypertension in certain populations.Trial registrationClinicalTrials.gov NCT02294539. Registered 12 November 2014.