Browsing by Subject "Antihypertensive Agents"

Now showing 1 - 6 of 6
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    Clinical Pharmacology of Antihypertensive Therapy for the Treatment of Hypertension in CKD
    (American Society of Nephrology, 2019-05-07) Sinha, Arjun D.; Agarwal, Rajiv; Medicine, School of Medicine
    CKD is common and frequently complicated with hypertension both predialysis and in ESKD. As a major modifiable risk factor for cardiovascular disease in this high-risk population, treatment of hypertension in CKD is important. We review the mechanisms and indications for the major classes of antihypertensive drugs, including angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, β-adrenergic blocking agents, dihydropyridine calcium channel blockers, thiazide diuretics, loop diuretics, mineralocorticoid receptor blockers, direct vasodilators, and centrally acting α-agonists. Recent evidence suggests that β-adrenergic blocking agents may have a greater role in patients on dialysis and that thiazide diuretics may have a greater role in patients with advanced CKD. We conclude with sharing our general prescribing algorithm for both patients with predialysis CKD and patients with ESKD on dialysis.
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    Effect of lisinopril and atenolol on aortic stiffness in patients on hemodialysis
    (American Society of Nephrology (ASN), 2015-04-07) Georgianos, Panagiotis I.; Agarwal, Rajiv; Department of Medicine, IU School of Medicine
    BACKGROUND AND OBJECTIVES: Whether improvements in arterial compliance with BP lowering are because of BP reduction alone or if pleiotropic effects of antihypertensive agents contribute remains unclear. It was hypothesized that, among patients on hemodialysis, compared with a β-blocker (atenolol), a lisinopril-based therapy will better reduce arterial stiffness. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Among 200 participants of the Hypertension in Hemodialysis Patients Treated with Atenolol or Lisinopril Trial, 179 patients with valid assessment of aortic pulse wave velocity at baseline (89 patients randomly assigned to open-label lisinopril and 90 patients randomly assigned to atenolol three times a week after dialysis) were included in the secondary analysis. Among them, 109 patients had a valid pulse wave velocity measurement at 6 months. Monthly measured home BP was targeted to <140/90 mmHg by addition of antihypertensive drugs and dry weight adjustment. The difference between drugs in percentage change of aortic pulse wave velocity from baseline to 6 months was analyzed. RESULTS: Contrary to the hypothesis, atenolol-based treatment induced greater reduction in aortic pulse wave velocity relative to lisinopril (between drug difference, 14.8%; 95% confidence interval, 1.5% to 28.5%; P=0.03). Reduction in 44-hour ambulatory systolic and diastolic BP was no different between groups (median [25th, 75th percentile]; atenolol: -21.5 [-37.7, -7.6] versus lisinopril: -15.8 [-28.8, -1.5] mmHg; P=0.27 for systolic BP; -14.1 [-22.6, -5.3] versus -10.9 [-18.4, -0.9] mmHg, respectively; P=0.30 for diastolic BP). Between-drug difference in change of aortic pulse wave velocity persisted after adjustments for age, sex, race, other cardiovascular risk factors, and baseline ambulatory systolic BP but disappeared after adjustment for change in ambulatory systolic BP (11.8%; 95% confidence interval, -2.3% to 25.9%; P=0.10). CONCLUSIONS: Among patients on dialysis, atenolol was superior in improving arterial stiffness. However, differences between atenolol and lisinopril in improving aortic stiffness among patients on hemodialysis may be explained by BP-lowering effects of drugs.
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    Hypertension in hemodialysis patients treated with atenolol or lisinopril: a randomized controlled trial
    (Oxford University Press, 2014-03-01) Agarwal, Rajiv; Sinha, Arjun D.; Pappas, Maria K.; Abraham, Terri N.; Tegegne, Getachew G.; Department of Medicine, IU School of Medicine
    Background The purpose of this study was to determine among maintenance hemodialysis patients with echocardiographic left ventricular hypertrophy and hypertension whether in comparison with a β-blocker-based antihypertensive therapy, an angiotensin converting enzyme-inhibitor-based antihypertensive therapy causes a greater regression of left ventricular hypertrophy. Methods Subjects were randomly assigned to either open-label lisinopril (n = 100) or atenolol (n = 100) each administered three times per week after dialysis. Monthly monitored home blood pressure (BP) was controlled to <140/90 mmHg with medications, dry weight adjustment and sodium restriction. The primary outcome was the change in left ventricular mass index (LVMI) from baseline to 12 months. Results At baseline, 44-h ambulatory BP was similar in the atenolol (151.5/87.1 mmHg) and lisinopril groups, and improved similarly over time in both groups. However, monthly measured home BP was consistently higher in the lisinopril group despite the need for both a greater number of antihypertensive agents and a greater reduction in dry weight. An independent data safety monitoring board recommended termination because of cardiovascular safety. Serious cardiovascular events in the atenolol group occurred in 16 subjects, who had 20 events, and in the lisinopril group in 28 subjects, who had 43 events {incidence rate ratio (IRR) 2.36 [95% confidence interval (95% CI) 1.36–4.23, P = 0.001]}. Combined serious adverse events of myocardial infarction, stroke and hospitalization for heart failure or cardiovascular death in the atenolol group occurred in 10 subjects, who had 11 events and in the lisinopril group in 17 subjects, who had 23 events (IRR 2.29, P = 0.021). Hospitalizations for heart failure were worse in the lisinopril group (IRR 3.13, P = 0.021). All-cause hospitalizations were higher in the lisinopril group [IRR 1.61 (95% CI 1.18–2.19, P = 0.002)]. LVMI improved with time; no difference between drugs was noted. Conclusions Among maintenance dialysis patients with hypertension and left ventricular hypertrophy, atenolol-based antihypertensive therapy may be superior to lisinopril-based therapy in preventing cardiovascular morbidity and all-cause hospitalizations. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases; ClinicalTrials.gov number: NCT00582114)
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    Pharmacotherapy of Hypertension in Chronic Dialysis Patients
    (American Society of Nephrology, 2016-11-07) Georgianos, Panagiotis I.; Agarwal, Rajiv; Medicine, School of Medicine
    Among patients on dialysis, hypertension is highly prevalent and contributes to the high burden of cardiovascular morbidity and mortality. Strict volume control via sodium restriction and probing of dry weight are first-line approaches for the treatment of hypertension in this population; however, antihypertensive drug therapy is often needed to control BP. Few trials compare head-to-head the superiority of one antihypertensive drug class over another with respect to improving BP control or altering cardiovascular outcomes; accordingly, selection of the appropriate antihypertensive regimen should be individualized. To individualize therapy, consideration should be given to intra- and interdialytic pharmacokinetics, effect on cardiovascular reflexes, ability to treat comorbid illnesses, and adverse effect profile. β-Blockers followed by dihydropyridine calcium-channel blockers are our first- and second-line choices for antihypertensive drug use. Angiotensin–converting enzyme inhibitors and angiotensin receptor blockers seem to be reasonable third–line choices, because the evidence base to support their use in patients on dialysis is sparse. Add-on therapy with mineralocorticoid receptor antagonists in specific subgroups of patients on dialysis (i.e., those with severe congestive heart failure) seems to be another promising option in anticipation of the ongoing trials evaluating their efficacy and safety. Adequately powered, multicenter, randomized trials evaluating hard cardiovascular end points are urgently warranted to elucidate the comparative effectiveness of antihypertensive drug classes in patients on dialysis. In this review, we provide an overview of the randomized evidence on pharmacotherapy of hypertension in patients on dialysis, and we conclude with suggestions for future research to address critical gaps in this important area.
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    Race and sex differences in response to endothelin receptor antagonists for pulmonary arterial hypertension
    (Elsevier, 2012-01) Gabler, Nicole B.; French, Benjamin; Strom, Brian L.; Liu, Ziyue; Palevsky, Harold I.; Taichman, Darren B.; Kawut, Steven M.; Halpern, Scott D.; Biostatistics, School of Public Health
    Background Recently studied therapies for pulmonary arterial hypertension (PAH) have improved outcomes among populations of patients, but little is known about which patients are most likely to respond to specific treatments. Differences in endothelin-1 biology between sexes and between whites and blacks may lead to differences in patients' responses to treatment with endothelin receptor antagonists (ERAs). Methods We conducted pooled analyses of deidentified, patient-level data from six randomized placebo-controlled trials of ERAs submitted to the US Food and Drug Administration to elucidate heterogeneity in treatment response. We estimated the interaction between treatment assignment (ERA vs placebo) and sex and between treatment and white or black race in terms of the change in 6-min walk distance from baseline to 12 weeks. Results Trials included 1,130 participants with a mean age of 49 years; 21% were men, 74% were white, and 6% were black. The placebo-adjusted response to ERAs was 29.7 m (95% CI, 3.7-55.7 m) greater in women than in men (P = .03). The placebo-adjusted response was 42.2 m for whites and −1.4 m for blacks, a difference of 43.6 m (95% CI, −3.5-90.7 m) (P = .07). Similar results were found in sensitivity analyses and in secondary analyses using the outcome of absolute distance walked. Conclusions Women with PAH obtain greater responses to ERAs than do men, and whites may experience a greater treatment benefit than do blacks. This heterogeneity in treatment-response may reflect pathophysiologic differences between sexes and races or distinct disease phenotypes.