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Hypertension in Patients with Advanced Chronic Kidney Disease
Published in Giuseppe Mancia, Guido Grassi, Konstantinos P. Tsioufis, Anna F. Dominiczak, Enrico Agabiti Rosei, Manual of Hypertension of the European Society of Hypertension, 2019
Charalampos Loutradis, Pantelis Sarafidis
The RAS blockers class is used as in hemodialysis patients, mostly due to continuation of hypertension treatment before dialysis, or for other comorbidities. However, their effect on cardiovascular outcomes is examined in relatively few studies, as in the case of other antihypertensive classes (86,134). One randomized study (Fosinopril in Dialysis [FOSIDIAL]) has prospectively evaluated the effects of fosinopril (up to 20 mg/day t.i.d) and placebo therapy on cardiovascular events (152). Almost 400 hemodialysis patients with or without hypertension but with LVH were included and followed-up for 4 years. Hypertensive patients on fosinopril had a higher drop in pre-dialysis SBP (fosinopril 11.7; placebo 5.4 mmHg; p = 0.002), but hazard ratios for the primary endpoint of fatal and nonfatal CV events was similar between the fosinopril and placebo groups (RR: 0.93; 95% CI: 0.68–1.26) (152). In a meta-analysis of smaller studies comparing RAAS blockers versus other classes, placebo or no treatment in hemodialysis found similar hazard ratios for the two patient groups (153). From the three studies included in this meta-analysis, the first randomized 80 patients to candesartan (4–8 mg/day) or nothing, and after 19 months patients on candesartan had significantly lower cardiovascular events and mortality (16.3% vs. 45.9%, p > 0.01 and 0% vs. 18.9%, p > 0.001, respectively) (154). Another open-label study randomized 360 hemodialysis patients with hypertension to ARB or nothing. No difference was noted in pre-hemodialysis BP changes between the start and the end of the study in the two study arms, but ARB use was associated with lower cardiovascular event occurrence (HR 0.51; 95% CI: 0.33–0.79) (155). Finally, in a more recent study, 469 hypertensive hemodialysis patients were randomly assigned to olmesartan (10–40 mg/day) or other treatment, but olmesartan was not associated with significant reductions in cardiovascular risk (HR 1.00; 95% CI: 0.71–1.40) or mortality (HR 0.97; 95% CI: 0.62–1.52) (156). Overall, a superiority of ACEIs and ARBs over other antihypertensive drugs has not been demonstrated until now in dialysis patients, and antihypertensive treatment per se rather than the use of a RAS-blocker could be the factor reducing cardiovascular risk (86). Importantly, almost all ARBs are not dialyzed and do not require dosage modification in dialysis, whereas ACEIs have differences regarding their dialyzability.
Ingestion-time differences in the pharmacodynamics of dual-combination hypertension therapies: Systematic review and meta-analysis of published human trials
Published in Chronobiology International, 2022
Ramón G. Hermida-Ayala, Artemio Mojón, José R. Fernández, Michael H. Smolensky, Ramón C. Hermida
Meng et al. (2010) researched the ingestion-time differences in effects of the fosinopril/amlodipine (ACEI/CCB) dual-combination in a trial of 40 hypertensive patients (22 men/18 women, 52.7 ± 11.1 years of age) whose BP remained uncontrolled when either one of the medications was ingested as a monotherapy in the morning. Patients were randomized into two groups for 4 weeks of therapy; those of Group-A routinely ingested 5 mg amlodipine in the morning (07:00–08:00 h) and 10 mg fosinopril at bedtime, and those of Group-B consistently ingested the two medications together in the morning. The nighttime SBP/DBP means of the Group-A patients were reduced by a substantially, almost 3-fold, greater amount than those of the Group-B patients (−22.4/-17.4 vs. −7.6/-6.3 mmHg; P < .001). Additionally, normalization of the 24 h BP dipper patterning was highly successful in Group-A, but not in Group-B, patients, i.e., the sleep-time relative SBP decline was increased by 5.7% (P < .001) in Group-A towards the more normal dipper 24 h SBP profile, but actually decreased by a similar 5.7% amount (P < .001) in Group-B participants towards the more abnormal non-dipper 24 h SBP profile.
COVID-19: a novel menace for the practice of nephrology and how to manage it with minor devastation?
Published in Renal Failure, 2020
Sena Ulu, Ozkan Gungor, Ebru Gok Oguz, Nuri Baris Hasbal, Didem Turgut, Mustafa Arici
Answer: There is limited data about the pharmacokinetics of antivirals (atazanavir, lopinavir/ritonavir, remdesivir, favipiravir, chloroquine, hydroxychloroquine, nitazoxanide, ribavarin, tocilizumab) used in the COVID-19. Concerns may be the followings [32]:ACEIs: Benazepril increases the level of atazanavir, and antiviral drug level monitoring is recommended. Fosinopril may increase the level of lopinavir/ritonavir, but blood level monitoring is not necessary.ARBs: Valsartan increases the level of atazanavir and lopinavir/ritonavir and should be used carefully. Irbesartan and losartan reduce the level of lopinavir/ritonavir slightly.Diuretics: Indapamide increases the blood level of atazanavir and lopinavir/ritonavir; close drug level monitoring is required for concomitant use.Calcium channel blockers: Concomitant use of lercanidipine with atazanavir or lopinavir/ritonavir is contraindicated. Other calcium channel blockers also interact with atazanavir, lopinavir/ritonavir, level monitoring is recommended.
Pharmacotherapy and treatment options for HIV-associated nephropathy
Published in Expert Opinion on Pharmacotherapy, 2018
Steven Menez, Mohamad Hanouneh, Blaithin A. McMahon, Derek M. Fine, Mohamed G. Atta
From a clinical standpoint, a number of case reports and small studies have investigated the role of angiotensin-converting enzyme (ACE) inhibition in HIVAN [53,54]. Kimmel et al. published a matched cohort study of 18 patients with biopsy proven HIVAN, 9 of whom received captopril and 9 without ACE inhibitor (ACEi) therapy [55]. Renal survival, defined as time from biopsy with or without initiation ACEi therapy to time on dialysis, was significantly longer for patients receiving captopril (156 days vs. 37 days; P < 0.002). Following a case report of successful ACEi use in a patient with HIVAN, Burns and colleagues published a retrospective study of ACEi therapy in 20 patients with HIVAN in 1997 [56,57]. Out of 11 patients with non-nephrotic proteinuria, 7 received fosinopril 10 mg daily, while 4 did not. At 24-week follow up, those who received ACEi had a lower sCr and 24-h protein excretion compared to those without treatment (P = 0.06 and 0.02, respectively). Out of the other 9 patients who did have nephrotic range proteinuria, 5 patients received fosinopril therapy. In this population, those who received ACEi therapy had a lower 24-h protein excretion at 12-week follow up (P = 0.02). More recently, Wei and colleagues conducted a prospective cohort study of 44 patients with biopsy-proven HIVAN, enrolled prior to severe kidney injury with an enrollment criterion being a sCr level <2.0 mg/dL [58]. Over the course of more than 5 years, 28 patients were treated with fosinopril 10 mg daily while 16 were given placebo. Again, renal survival, or time to ESRD, was significantly longer in those patients treated with ACEi (479.5 days vs. 146.5 days; P < 0.0001).