Reno protective role of amlodipine in patients with hypertensive chronic kidney disease.

Chronic kidney disease (CKD) and hypertension (HTN) are closely associated with an overlapping and intermingled cause and effect relationship. Decline in renal functions are usually associated with a rise in blood pressure (BP), and prolonged elevations in BP hasten the progression of kidney function decline. Regulation of HTN by normalizing the BP in an individual, thereby slowing the progression of kidney disease and reducing the risk of cardiovascular disease, can be effectively achieved by the anti-hypertensive use of calcium channel blockers (CCBs). Use of dihydropyridine CCBs such as amlodipine (ALM) in patients with CKD is an attractive option not only for controlling BP but also for safely improving patient outcomes. Vast clinical experiences with its use as monotherapy and/or in combination with other anti-hypertensives in varied conditions have demonstrated its superior qualities in effectively managing HTN in patients with CKD with minimal adverse effects. In comparison to other counterparts, ALM displays robust reduction in risk of cardiovascular endpoints, particularly stroke, and in patients with renal impairment. ALM with its longer half-life displays effective BP control over 24-h, thereby reducing the progression of end-stage-renal disease. In conclusion, compared to other classes of CCBs, ALM is an attractive choice for effectively managing HTN in CKD patients and improving the overall quality of life.

A Retrospective, Observational, EMR-Based Real-World Evidence Study to Assess the Incidence of Pedal Edema in Essential Hypertensive Patients on Amlodipine or Cilnidipine.

INTRODUCTION: Calcium channel blockers have pedal edema as one of the confining factors of treatment. A real-world study may help evident reality of the situation in regular Indian clinical practice. The aim of the study is to assess effectiveness and incidence of pedal edema in essential hypertensive patients treated with amlodipine or cilnidipine monotherapy. METHODS: Retrospective EMR data of adult essential hypertensive patients, prescribed amlodipine (n = 800) or cilnidipine (n = 800) as monotherapy, were analyzed. Incidence of pedal edema from baseline visit was analyzed in terms of dose and duration of treatment. The changes in systolic (SBP) and diastolic blood pressure (DBP) from baseline and proportion of patients achieving target BP goals were assessed. RESULTS: In amlodipine and cilnidipine groups, mean changes in SBP and DBP from baseline to end of the study period were 28.4 and 15.1 mmHg and 24.3 and 13.5 mmHg, respectively (p value <0.05). More than 50% of patients in both groups achieved BP goal at the end of the study (p value 0.266). In amlodipine group, total 23.9% reported pedal edema, while in cilnidipine, 27.6% (p value 0.0863). At the end of the study, 3.5% and 8.2% of patients remain with pedal edema, respectively, in both groups (pvalue <0.005). CONCLUSION: Amlodipine demonstrated greater BP reduction at a lower average dose, better efficacy, and tolerability in terms of pedal edema count as a lesser number of patients reported edema at the end of the study and a higher percentage of patients continued the prescribed baseline dosage regimen as compared to cilnidipine. Thus, the study established amlodipine as an effective and well-tolerated antihypertensive for Indians.

Fondaparinux: A cornerstone drug in acute coronary syndromes.

In acute coronary syndrome (ACS), the use of anticoagulants in conjunction with antiplatelet agents in the acute phase has resulted in reduced ischemic events and is more effective than either class of drug used alone. Though parenteral anticoagulation is essential at the time of diagnosis, a balance must be made between ischemic benefit and the increased risk of bleeding when prescribing anticoagulants. Adverse events associated with anticoagulants, such as heparin-induced thrombocytopenia, bleeding problems, and the need for close monitoring of anticoagulant activity, have contributed to finding agents that reduce these limitations. Studies like the Organization to Assess Strategies in Ischemic Syndromes 5 and 6 and their meta-analysis have proven the efficacy of Fondaparinux over the entire ACS spectrum. The convenience of administration (once daily), lack of monitoring, reduction in mortality, and better safety profile make Fondaparinux a simple and effective anti-coagulant for the management of ACS.

Evaluation of Effectiveness and Tolerability of Fondaparinux in the Management of Symptomatic Acute Coronary Syndrome: A Real-World Evidence-Based Study on an Indian Population.

INTRODUCTION: Fondaparinux is a low molecular weight heparin anticoagulant used to manage the full spectrum of acute coronary syndrome (ACS) patients and has proved its efficacy and safety in multiple clinical trials. However, there are limited data available showing whether the same results could be reproduced in real-world practice on an Indian population. Our objective was to determine the effectiveness and tolerability of fondaparinux in the management of symptomatic ACS in real-world clinical practice. METHODS: The EMR data of hospitalized ACS patients (n = 611), from January 2015 to January 2020, representing UA or NSTEMI or STEMI and were prescribed fondaparinux (2.5 mg once daily) to manage ACS were analyzed. The effectiveness was analyzed as recurrence of ACS and tolerability as total incidence of major bleeding during hospitalization, at 30 days and 180 days. Appropriate statistical analysis was used with a statistically significance of p value < 0.05. RESULTS: The incidence of recurrent ACS was not seen during hospitalization and in the first 30 days, while in only 0.65% (n = 4) patients, ACS reoccurred within 180 days. In a mean duration of 172.75 ± 3.20 days, UA was reported in 0.49% (n = 3) patients, NSTEMI in 0.16% (n = 1) of patients, and STEMI was not documented. None of the major bleeding events occurred during the entire study period, whereas minor bleeding events were reported during hospitalization 0.98% (n = 6) and at 30 days 0.16% (n = 1). The bleeding events were statistically insignificant (p value > 0.05). No incidences of stent thrombosis were reported during the entire study period. CONCLUSIONS: In the real world, fondaparinux was found to be effective and tolerable when used to manage symptomatic ACS patients regardless of revascularization procedure with no incidence of stent thrombosis, and minimal recurrent ACS and insignificant increase in bleeding events.

Effectiveness and Tolerability of Fondaparinux vs Enoxaparin in a Population of Indian Patients with Symptomatic Deep Vein Thrombosis: A Retrospective Real-World Study.

BACKGROUND: Fondaparinux is the first approved anticoagulant drug among factor Xa inhibitors, with proven effectiveness and safety in preventing deep vein thrombosis. However, limited data are available supporting the benefit-risk profile of fondaparinux vs enoxaparin in a real-world group of Indian patients with deep vein thrombosis. OBJECTIVE: To compare the effectiveness and tolerability of fondaparinux vs enoxaparin in patients with symptomatic deep vein thrombosis in a long-term real-world setting. METHODS: Data from the electronic medical records of adult patients diagnosed with deep vein thrombosis prescribed fondaparinux (n = 503) or enoxaparin (n = 508) as monotherapy were analyzed. Effectiveness was analyzed in terms of recurrence, duration, and type of deep vein thrombosis event, and tolerability as bleeding events at initial hospitalization and follow-up visits up to 3 months duration. Appropriate statistical methods were used to determine the significance (p < 0.05) between the two groups. RESULTS: The deep vein thrombosis recurrence in the fondaparinux group was non-inferior (2.78%) when compared with enoxaparin (3.76%), with a mean duration of 47 and 48 days, respectively. The number of events and mean duration of events (in days) were not significant (p > 0.05). Major bleeding events were higher in the enoxaparin group at 3.17% than the fondaparinux group at 2.19%, and the difference was not statistically significant (p > 0.05). CONCLUSIONS: The weight-based, once-daily subcutaneous fondaparinux dose showed non-inferior effectiveness and a comparable tolerability profile when compared with the twice-daily enoxaparin dose for the management of symptomatic deep vein thrombosis.

Retrospective, Observational Study to Determine the Choice of Antihypertensive agent According to Stage of Hypertension, Risk factors and Co-morbidities in Real World Setting in India: A Report of Baseline Data.

BACKGROUND: The present study intended to estimate the comorbidities and risk factors among patients with hypertension in India. Further, the current practice of hypertension management was evaluated and the choice of therapy was assessed based on hypertension grade, risk factors, and comorbidities. METHODS: Electronic medical record data (June 2017-June 2019) of Indian adult hypertensive patients (≥140/90 mmHg) who had two blood pressure (BP) readings were retrospectively analyzed. Demographic characteristics, BP readings, comorbidities, medications and co-medications, and laboratory data were collected at baseline. Grids based on hypertension grade (I, II, and III), demographic factors, risk factors, and comorbidities were created and prescribed antihypertensive drugs (AHDs) in each grid were evaluated. RESULTS: Among 100,075 patients, the proportion of patients in 18-40 year, 40-65 year, and >65 year age groups were 11.4%, 65.1%, and 23.4%, respectively. Proportion of men and women was similar (52.0% vs 47.9%). Proportion of patients with BMI <25 Kg/m2 was 8.1%, 25-29.9 Kg/m2 was 11.9%, and >30 Kg/m2 was 8.8%. Mean BP of patients with hypertension was: grade I (145.05/90.73 mmHg), grade II (160.07/95.64 mmHg), and grade III (180.82/102.76 mmHg). Mean low density lipoprotein (113.26 mg/dL), serum creatinine (2.28 mg/dL), mean HbA1c (8.7%) levels were highest among patients with grade III hypertension. Commonly observed comorbidities were type 2 diabetes mellitus (T2DM: 51.5%), dyslipidemia (36.4%), and chronic kidney disease (CKD: 4.4%). Top concomitant medications included anti-diabetic therapies (34.6%), drugs for dyslipidemia (30.0%), and anti-platelet therapies (6.9%). CONCLUSION: Most prescribed AHD monotherapies were angiotensin receptor II blockers (ARBs) and calcium channel blockers (CCBs) and most prescribed combination therapies were ARBs + diuretics and ARBs + CCBs. Telmisartan and amlodipine+telmisartan for patients with comorbid T2DM or dyslipidemia and metoprolol for those with coronary artery disease were the commonly prescribed AHDs.

Effect of Amlodipine in Stroke and Myocardial infarction: A Systematic Review and Meta-analysis.

INTRODUCTION: Hypertension is a progressive cardiovascular condition arising from complex aetiologies. Progression is strongly associated with functional and structural abnormalities that lead to multi-organ dysfunction. Stroke and myocardial infarction are two of the major complications of hypertension in India. Various anti-hypertensive drugs, such as calcium channel blockers (CCBs), beta-blockers, diuretics, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, have been the medications of choice for disease management and are known to be effective in reducing the complications of hypertension. CCBs, such as amlodipine, are also currently being used and proven to be effective, although their beneficial effects in the management of complications of hypertension like stroke and myocardial infarction (MI) have yet to be proven. Therefore, the aim of this systematic review was to evaluate the effect of amlodipine on stroke and MI in hypertensive patients. METHODS: A systematic search of English electronic databases was performed for studies with sufficient statistical power that were published between 2000 andl 30 August 2020, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. A total of 676 papers were screened, and 13 were found eligible to be included in the meta-analysis. Studies that included patients who suffered from MI or stroke and were under amlodipine treatment were included in the analysis. The odds ratio and the risk ratio of amlodipine compared to active control/placebo were noted from the studies and statistically analyzed. RESULTS: Amlodipine had a significant effect in reducing stroke and MI in hypertensive patients. Similar to results published in reports, this systematic review proved that the hazard ratio for amlodipine was < 1 for stroke (0.69-1.04) and MI (0.77-0.98), showing that amlodipine accounted for better prevention of stroke and MI. CONCLUSION: In the pooled analysis of data from 12 randomised controlled trials and one double-blinded cohort study measuring the effect of CCBs, we found that the CCB amlodipine reduced the risk of stroke and MI in hypertensive patients. Superior results for amlodipine were found in ten of the 13 studies included in this meta-analysis.

Demographic profile, clinical characteristics and medical management patterns of Indian coronary artery disease patients: a nationwide urban-based, real-world, retrospective, observational electronic medical record study- report of baseline data.

Background: This is the first detailed Indian electronic medical record (EMR)-based real-world observational study to understand the clinical characteristics, associated comorbidities/risk factors and treatment(s) of CAD patients across India.Methods: EMR data of adult Indians (aged ≥ 18 years) diagnosed with CAD was retrospectively analyzed.Results: The majority of the participants had stable IHD (93%), were men (68.5% in ACS, 59.8% in stable IHD), most common age group was 40-64 years in ACS (56.6%) and stable IHD (51.4%). Both are common in metros (ACS 52%, 62% stable IHD). There is a high frequency of hypertension (38.2% in ACS, 59% in stable IHD) and diabetes mellitus (32.3% in ACS, 57.6% in stable IHD). Most common treatments are antiplatelet drugs and lipid-lowering drugs (96%).Conclusions: In India, stable IHD is the most prevalent form in vast majority of patients. The patients with CAD are mostly males, are mainly located in metros and majority fall between the age group of 40-64. The major comorbidities are hypertension and diabetes mellitus. Sociodemographic and clinical characteristics for CAD in India may not be similar to what is reported from the west. There is a significant difference in drug usage and adherence to guidelines in India for CAD.

Effectiveness and Effect on Renal Parameters of Amlodipine vs. Other Dihydropyridine Calcium Channel Blockers in Patients with Essential Hypertension: Retrospective Observational Study Based on Real-World Evidence from Electronic Medical Records.

INTRODUCTION: The renoprotective effects of dihydropyridine calcium channel blockers (CCBs) have been established as non-inferior to other classes of antihypertensive drugs. Studying their effect on renal outcome parameters, specifically for amlodipine as monotherapy, in real-world settings can further help in expanding its usage among Indian patients. This study was performed to assess the effects of amlodipine and other dihydropyridine CCBs (cilnidipine, benidipine and azelnidipine) on renal parameters and effectiveness in blood pressure reduction in Indian patients. METHODS: The retrospective data of adult patients (> 18 years) with essential hypertensive who were prescribed amlodipine (n = 92), cilnidipine (n = 91), benidipine (n = 70) or azelnidipine (n = 71) as monotherapy were analyzed. The renal outcomes, serum creatinine, estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN), microalbumin, urine albumin-to-creatinine ratio (UACR), sodium and potassium levels, and mean changes in BP were analyzed from baseline to 12 months. Appropriate statistical methods were used to determine the significance (p value < 0.05). RESULTS: From baseline to the end of the study, mean serum creatinine changed from 0.98 ± 0.17 to 1.07 ± 0.28 mg/dL with amlodipine, 0.97 ± 0.18 to 1.13 ± 0.50 mg/dL with cilnidipine, 0.98 ± 0.30 to 0.97 ± 0.27 mg/dL wi th benidipine, and 0.99 ± 0.23 to 0.98 ± 0.25 mg/dL with azelnidipine (p = 0.01). The mean microalbumin and UACR were reduced from baseline to the end of the study (p = 0.06 and p > 0.05). No significant changes were observed in BUN, sodium or potassium levels. Overall, for all CCBs, the mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) values were reduced from baseline to the end of the study (p = 0.002). At the end of the study, the average dose of amlodipine was 7.25 mg, and the average reduction in SBP and DBP per mg dose was 1.54 and 0.57 mmHg. The corresponding numbers for the other CCBs were as follows: cilnidipine, 14.28 mg, 0.26 and 0.01; benidipine, 5.71 mg, 0.41 and 0.11; azelnidipine, 15.88 mg, 0.13 and 0.06. CONCLUSION: Amlodipine and other CCBs demonstrated good efficacy and similar effects on renal parameters from baseline to end of study. Amlodipine also showed higher potency by demonstrating greater BP reduction at a lower dose. Thus, amlodipine can remain a preferred choice among CCBs, even with the advent of the newer CCBs.

Effectiveness of Telmisartan on Blood Pressure Control in Hypertensive Patients in India: A Real-World Retrospective Study from Electronic Medical Records.

INTRODUCTION: The effectiveness of telmisartan has been reported in Indian clinical trials; however, real-world data are limited. We aimed to provide real-world evidence regarding the effectiveness of telmisartan as monotherapy or in combination with other antihypertensive drugs (AHDs) in Indian patients with essential hypertension. METHODS: Electronic medical record data of adult patients diagnosed with essential hypertension (≥ 140/90 mmHg) and who were prescribed telmisartan as mono- or add-on therapy were retrospectively analyzed. Patients were classified according to the number of AHD classes prescribed on initiating telmisartan. Change in systolic and diastolic blood pressure (SBP and DBP) after a month of treatment and the proportion of patients who achieved treatment goals according to the 2018 European Society of Cardiology/European Society of Hypertension guidelines were evaluated. RESULTS: A majority (90.6%) of the 1304 patients included in the study were on telmisartan monotherapy or telmisartan + 1 AHD. The mean (95% confidence interval [CI]) change in the telmisartan monotherapy group was SBP (-13.3 [-14.6, -12.0] mmHg) and DBP (-7.2 [-7.9, -6.5] mmHg), and the mean (95% CI) change in the telmisartan + 1 AHD group was SBP (-10.8 [-13.1, -8.5] mmHg) and DBP (-6.5 [-7.7, -5.3] mmHg) (P < 0.001 for all). SBP and DBP goals were achieved by 35.9% and 47.3% of patients on telmisartan monotherapy and by 35.9% and 46.8% of patients on telmisartan + 1 AHD. Among patients with comorbid diabetes, the mean (95% CI) change in the telmisartan monotherapy group was SBP (-13.3 [-15.0, -11.6] mmHg) and DBP (-7.3 [-8.2, -6.5] mmHg), and the mean (95% CI) change in the telmisartan + 1 AHD group was SBP (-13.0 [-16.5, -9.5] mmHg) and DBP (-6.9 [-8.7, -5.1] mmHg) (P < 0.001 for all). SBP and DBP goals were achieved by 31.7% and 39.7% of patients on telmisartan monotherapy and by 31.9% and 41.8% of patients on telmisartan + 1 AHD. CONCLUSION: Telmisartan may be a good candidate for blood pressure control in Indian patients with essential hypertension and comorbidities.

Effectiveness of Amlodipine on Blood Pressure Control in Hypertensive Patients in India: A Real-World, Retrospective Study from Electronic Medical Records.

BACKGROUND: The effectiveness of amlodipine has been reported in clinical trials in India. However, real-world data on the effectiveness of amlodipine in India is limited. OBJECTIVE: To provide real-world evidence regarding the effectiveness of amlodipine as monotherapy or in combination with other antihypertensive drugs (AHDs) in Indian patients with essential hypertension. METHODS: Electronic medical record data of adult patients who were diagnosed with essential hypertension (≥ 140/90 mmHg) and were prescribed amlodipine as monotherapy or add-on therapy were retrospectively analyzed. Patients were classified based on the number of AHD classes prescribed on initiation of amlodipine. Change in systolic (SBP) and diastolic (DBP) blood pressure from baseline was the primary endpoint. Evaluation of proportion of patients who achieved treatment goals as per 2018 European Society of Cardiology/European Society of Hypertension guidelines was the secondary endpoint. Readings were obtained before initiating amlodipine and after at least a month of therapy with amlodipine. RESULTS: Among the 462 included patients, the majority (90.7%) were on amlodipine monotherapy or amlodipine + 1AHD. Mean (95% confidence interval [CI]) change in the amlodipine monotherapy group was: SBP (- 12.1 [- 14.9, - 9.3] mmHg) and DBP (- 7.5 [- 8.9, - 6.1] mmHg) and mean (95% CI) change in the amlodipine + 1AHD group was: SBP (- 17.8 [- 21.0, - 14.6] mmHg) and DBP (- 9.5 [- 11.0, - 8.0] mmHg) (P < 0.001 for all). SBP and DBP goals were achieved by 31.4% and 42.9% of patients on amlodipine monotherapy and by 38.9% and 51.8% of patients on amlodipine + 1AHD, respectively. Among patients aged ≤ 45 years, mean (95% CI) change in the amlodipine monotherapy group was: SBP (- 11.7 [- 16.0, - 7.4] mmHg; P < 0.001) and DBP (- 7.2 [- 9.7, - 4.7] mmHg; P < 0.001) and mean (95% CI) change in the amlodipine + 1AHD group was: SBP (- 14.6 [- 21.9, - 7.3] mmHg; P < 0.05) and DBP (- 10.6 [- 14.8, - 6.4] mmHg; P < 0.01). SBP and DBP goals were achieved by 35.4% and 33.8% of patients on amlodipine monotherapy and by 48.0% and 56.0% of patients on amlodipine + 1AHD, respectively. Among patients aged ≥ 65 years, mean (95% CI) change in the amlodipine monotherapy group was: SBP (- 13.9 [- 20.2, - 7.6] mmHg; P < 0.01) and DBP (- 8.5 [- 11.4, - 5.7] mmHg; P < 0.001) and mean (95% CI) change in the amlodipine + 1AHD group was: SBP (- 22.4 [- - 28.8, - 16.0] mmHg; P < 0.001) and DBP (- 10.8 [- 14.0, - 7.6] mmHg; P < 0.001). SBP and DBP goals were achieved by 25.5% and 13.7% of patients on amlodipine monotherapy and by 29.8% and 14.0% of patients on amlodipine + 1AHD. CONCLUSION: Amlodipine prescribed as monotherapy or add-on therapy during routine clinical practice significantly reduced BP in ≤ 45- and ≥ 65-year-old Indian patients with mild to moderate hypertension, emphasizing that amlodipine may be a good candidate for BP control in Indian patients with essential hypertension in these age groups.

Effectiveness of Olmesartan on Blood Pressure Control in Hypertensive Patients in India: A Real World, Retrospective, Observational Study from Electronic Medical Records.

BACKGROUND: Real-world data on the effectiveness of antihypertensive drugs (AHDs) in India is limited. The present study aims to provide updated evidence regarding the effectiveness of olmesartan as monotherapy or in combination with other AHDs in Indian patients with essential hypertension. METHODS: Electronic medical record data of adult patients who were diagnosed with essential hypertension (≥140/90 mmHg) and were prescribed olmesartan as mono- or add-on therapy were retrospectively analyzed. Patients were classified based on the number of AHD classes prescribed on initiation of olmesartan. Change in systolic and diastolic blood pressure (SBP and DBP) from baseline was the primary endpoint. Secondary endpoint was evaluation of proportion of patients who achieved treatment goals as per 2018 European Society of Cardiology/European Society of Hypertension guidelines. Readings were obtained before initiating olmesartan and after at least a month of therapy with olmesartan. RESULTS: Among the 459 included patients, majority were on olmesartan monotherapy or olmesartan+1AHD (91.7%). Mean (95% confidence interval [CI]) change in olmesartan monotherapy group was: SBP (-13.4 [-15.7, -11.1] mmHg) and DBP (-8.3 [-9.5, -7.1] mmHg) and mean (95% CI) change in olmesartan+1AHD group was: SBP (-11.7 [-15.1, -8.3] mmHg) and DBP (-6.6 [-8.3, -4.9] mmHg) (P<0.001 for all). SBP and DBP goals were achieved by 40.4% and 50.3% of patients on olmesartan monotherapy and by 36.1% and 46.2% of patients on olmesartan+1AHD. Among patients with comorbid diabetes, mean (95% CI) change in olmesartan monotherapy group was: SBP (-15.5 [-18.6, -12.4] mmHg) and DBP (-8.7 [-10.2, -7.2] mmHg) and mean (95% CI) change in olmesartan+1AHD group was: SBP (-13.5 [-18.3, -8.7] mmHg) and DBP (-7.6 [-9.8, -5.4] mmHg) (P<0.001 for all). SBP and DBP goals were achieved by 38.5% and 49.4% of patients on olmesartan monotherapy and by 31.7% and 42.9% of patients on olmesartan+1AHD. CONCLUSION: Olmesartan prescribed as mono- or add-on therapy during routine clinical practice significantly reduced blood pressure in Indian patients with essential hypertension as well as in patients with comorbid diabetes.