lisinopril and Stroke

Cerebral microvascular dysfunction is commonly seen in Alzheimer's disease (AD) and vascular cognitive impairment (VCI). Cerebrovascular reactivity (CVR) to CO. This study presents findings of candesartan's effects on the secondary outcomes of two double-blind randomized clinical trials of 12-month therapy of candesartan versus lisinopril in VCI (CALIBREX (Candesartan vs Lisinopril Effects on the Brain and Endothelial Function in Executive MCI)) and candesartan versus placebo in prodromal AD (Candesartan's Effects on Alzheimer's Disease and Related Biomarkers (CEDAR)). Primary outcome results of these trials have been reported in previous publications. Participants underwent identical brain blood oxygenation level dependent (BOLD)-CVR in response to a 2-min CO. Data from 102 participants in the CALIBREX study (mean age = 65 years, 45% female, 63% African American) and 59 in the CEDAR study (mean age = 67 years, 32% female, 20% African American) were analyzed. Candesartan was associated with improved whole brain CVR compared to placebo in the CEDAR study (adjusted within-group mean difference for candesartan = 0.27 (95% confidence interval (CI) = 0.006, 0.53) vs placebo = -0.17 (95% CI = 0.42, 0.08), p-value = 0.018), and compared to lisinopril in the CALIBREX study (adjusted within-group mean difference for candesartan = 0.28 (95% CI = 0.10, 0.46) vs lisinopril = -0.08 (95% CI = -0.31, 0.14), p-value = 0.012), independent of blood pressure. In an exploratory meta-analysis of the two trials, improved CVR in the hippocampus was linked to improved attention and working memory (p = 0.044) and a trend for improved executive function (p = 0.087) with candesartan therapy.. This study suggests that candesartan is associated with improved microvascular function in MCI, and these findings are independent of its blood pressure effect in these VCI and prodromal AD populations.

Topics: Aged; Alzheimer Disease; Carbon Dioxide; Cognitive Dysfunction; Female; Humans; Lisinopril; Male; Randomized Controlled Trials as Topic; Stroke

Dysphagia (swallowing problems), which is common after stroke, is associated with increased risk of death or dependency, occurrence of pneumonia, poor quality of life, and longer hospital stay. Treatments provided to improve dysphagia are aimed at accelerating recovery of swallowing function and reducing these risks. This is an update of the review first published in 1999 and updated in 2012.. To assess the effects of swallowing therapy on death or dependency among stroke survivors with dysphagia within six months of stroke onset.. We searched the Cochrane Stroke Group Trials Register (26 June 2018), the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 6) in the Cochrane Library (searched 26 June 2018), MEDLINE (26 June 2018), Embase (26 June 2018), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (26 June 2018), Web of Science Core Collection (26 June 2018), SpeechBITE (28 June 2016), ClinicalTrials.Gov (26 June 2018), and the World Health Organization International Clinical Trials Registry Platform (26 June 2018). We also searched Google Scholar (7 June 2018) and the reference lists of relevant trials and review articles.. We sought to include randomised controlled trials (RCTs) of interventions for people with dysphagia and recent stroke (within six months).. Two review authors independently applied the inclusion criteria, extracted data, assessed risk of bias, used the GRADE approach to assess the quality of evidence, and resolved disagreements through discussion with the third review author (PB). We used random-effects models to calculate odds ratios (ORs), mean differences (MDs), and standardised mean differences (SMDs), and provided 95% confidence intervals (CIs) for each.The primary outcome was functional outcome, defined as death or dependency (or death or disability), at the end of the trial. Secondary outcomes were case fatality at the end of the trial, length of inpatient stay, proportion of participants with dysphagia at the end of the trial, swallowing ability, penetration aspiration score, or pneumonia, pharyngeal transit time, institutionalisation, and nutrition.. We added 27 new studies (1777 participants) to this update to include a total of 41 trials (2660 participants).We assessed the efficacy of swallowing therapy overall and in subgroups by type of intervention: acupuncture (11 studies), behavioural interventions (nine studies), drug therapy (three studies), neuromuscular electrical stimulation (NMES; six studies), pharyngeal electrical stimulation (PES; four studies), physical stimulation (three studies), transcranial direct current stimulation (tDCS; two studies), and transcranial magnetic stimulation (TMS; nine studies).Swallowing therapy had no effect on the primary outcome (death or dependency/disability at the end of the trial) based on data from one trial (two data sets) (OR 1.05, 95% CI 0.63 to 1.75; 306 participants; 2 studies; I² = 0%; P = 0.86; moderate-quality evidence). Swallowing therapy had no effect on case fatality at the end of the trial (OR 1.00, 95% CI 0.66 to 1.52; 766 participants; 14 studies; I² = 6%; P = 0.99; moderate-quality evidence). Swallowing therapy probably reduced length of inpatient stay (MD -2.9, 95% CI -5.65 to -0.15; 577 participants; 8 studies; I² = 11%; P = 0.04; moderate-quality evidence). Researchers found no evidence of a subgroup effect based on testing for subgroup differences (P = 0.54). Swallowing therapy may have reduced the proportion of participants with dysphagia at the end of the trial (OR 0.42, 95% CI 0.32 to 0.55; 1487 participants; 23 studies; I² = 0%; P = 0.00001; low-quality evidence). Trial results show no evidence of a subgroup effect based on testing for subgroup differences (P = 0.91). Swallowing therapy may improve swallowing ability (SMD -0.66, 95% CI -1.01 to -0.32; 1173 participants; 26 studies; I² = 86%; P = 0.0002; very low-quality evidence). We found no evidence of a subgroup effect based on testing for subgroup differences (P = 0.09). We noted moderate to substantial heterogeneity between trials for these interventions. Swallowing therapy did not reduce the penetration aspiration score (i.e. it did not reduce radiological aspiration) (SMD -0.37, 95% CI -0.74 to -0.00; 303 participants; 11 studies; I² = 46%; P = 0.05; low-quality evidence). Swallowing therapy may reduce the incidence of chest infection or pneumonia (OR 0.36, 95% CI 0.16 to 0.78; 618 participants; 9 studies; I² = 59%; P = 0.009; very low-quality evidence).. Moderate- and low-quality evidence suggests that swallowing therapy did not have a significant effect on the outcomes of death or dependency/disability, case fatality at the end of the trial, or penetration aspiration score. However, swallowing therapy may have reduced length of hospital stay, dysphagia, and chest infections, and may have improved swallowing ability. However, these results are based on evidence of variable quality, involving a variety of interventions. Further high-quality trials are needed to test whether specific interventions are effective.

Topics: Acupuncture Therapy; Acute Disease; Deglutition; Deglutition Disorders; Electric Stimulation Therapy; Gastrostomy; Humans; Intubation, Gastrointestinal; Length of Stay; Lisinopril; Metoclopramide; Nifedipine; Physical Stimulation; Pneumonia; Randomized Controlled Trials as Topic; Stroke; Stroke Rehabilitation; Time Factors; Transcranial Direct Current Stimulation

Topics: Adrenergic alpha-Antagonists; Aged; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzothiadiazines; Calcium Channel Blockers; Chlorthalidone; Coronary Disease; Diuretics; Double-Blind Method; Doxazosin; Humans; Hypertension; Lisinopril; Male; Randomized Controlled Trials as Topic; Sodium Chloride Symporter Inhibitors; Stroke

Antihypertensive therapy improves the prognosis of essential hypertension. Therapy reduces mortality and decreases the incidence of myocardial infarction, sudden cardiac death and stroke. Target blood pressure in patients with essential hypertension are levels < or = 140/90 mmHg. In patients with essential hypertension and concomitant diabetes mellitus type 2, blood pressure should be lowered to < or = 130/80 mmHg. Diuretics, beta-blockers, calcium antagonists, angiotensin-converting enyzme (ACE) inhibitors, and angiotensin I (AT(1)) antagonists may nowadays be regarded as drugs of first choice in the treatment of essential hypertension. The Joint National Committee in the USA recommends to start treatment with a thiazide diuretic. A Guidelines Committee of European Society of Hypertension-European Society of Cardiology considers the Endgroups of drugs mentioned above to be equally suitable for the initiation and maintenance of antihypertensive therapy. Both groups of experts agree that in the majority of patients with essential hypertension, a combination of two or more drugs is required to reach target blood pressure. Both groups of experts emphasize that the main benefits of antihypertensive therapy are due to decreasing blood pressure per se.

Topics: Adrenergic beta-Antagonists; Aged; Amlodipine; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzothiadiazines; Calcium Channel Blockers; Cardiovascular Diseases; Chlorthalidone; Clinical Trials as Topic; Death, Sudden, Cardiac; Diuretics; Drug Therapy, Combination; Humans; Hypertension; Lisinopril; Meta-Analysis as Topic; Middle Aged; Myocardial Infarction; Practice Guidelines as Topic; Prognosis; Randomized Controlled Trials as Topic; Risk; Risk Factors; Sodium Chloride Symporter Inhibitors; Stroke; Time Factors

ALLHAT, a randomized, double-blind, active-controlled, multicenter clinical trial of high risk hypertensive participants, compared treatment with an ACE-inhibitor (lisinopril) or calcium channel blocker (amlodipine) with a diuretic (chlorthalidone). Primary outcome was the occurrence of fatal coronary heart disease or nonfatal myocardial infarction. For this report, post-hoc analyses were conducted to determine the contribution of baseline characteristics of participants with or without baseline or incident atrial fibrillation (AF) and atrial flutter (AFL) to stroke, heart failure (HF), coronary heart disease (CHD), and mortality outcomes.. Minnesota Coding of baseline and biennial in-trial ECGs was used to determine the 334 baseline and 537 incident AF/AFL cases, respectively participants with AF/AFL: Cox regression was used to estimate hazard ratios of presence versus absence of either baseline or incident AF/AFL (as time-dependent covariate) for occurrence of stroke, CHD, HF, or mortality, while adjusting for selected baseline characteristics. Adjusted Cox regression was used to obtain hazard ratios (HRs) for presence versus absence of selected baseline characteristics among those with and without either baseline or incident AF/AFL. After adjusting for baseline characteristics, baseline AF/AFL was associated with stroke, HF, and mortality (HRs [95% CIs] 3.18, [2.34-4.33]; 2.65 [2.02-3.49]; and 2.10 [CI, 1.73-2.55], respectively, P < 0.05). Incident AF/AFL was a significant risk factor for HF and mortality (HRs 2.80 and 2.06, respectively, P < 0.05). Risk factor profiles for clinical outcomes for those with and without baseline or incident AF/AFL were largely similar.. AF/AFL is a significant risk factor for stroke, HF, and mortality. Additional risk factors for these outcomes were generally similar for participants with and without baseline or incident AF/AFL.

Topics: Aged; Aged, 80 and over; Amlodipine; Antihypertensive Agents; Atrial Fibrillation; Atrial Flutter; Chlorthalidone; Coronary Disease; Double-Blind Method; Female; Heart Failure; Humans; Hypertension; Lisinopril; Male; Myocardial Infarction; Proportional Hazards Models; Risk Factors; Stroke

High blood pressure (BP) during acute stroke is associated with poorer stroke outcome. Trials of treatments to lower BP have not resulted in improved outcome, but this may be because treatment commenced too late. Emergency medical service staff (paramedics) are uniquely placed to administer early treatment; however, experience of prehospital randomised controlled trials (RCTs) is very limited.. We conducted a pilot RCT to determine the feasibility of a definitive prehospital BP-lowering RCT in acute stroke. Paramedics were trained to identify, consent and deliver a first dose of lisinopril or placebo to adults with suspected stroke and hypertension while responding to the emergency call. Further treatment continued in hospital. Study eligibility, recruitment rate, completeness of receipt of study medication and clinical data (eg, BP) were collected to inform the design of a definitive RCT.. In 14 months, 14 participants (median age=73 years, median National Institute of Health Stroke Scale=4) were recruited and received the prehospital dose of medication. Median time from stroke onset (as assessed by paramedic) to treatment was 70 min. Four participants completed 7 days of study treatment. Of ambulance transported suspected stroke patients, 1% were both study eligible and attended by a PIL-FAST paramedic.. It is possible to conduct a paramedic initiated double-blind RCT of a treatment for acute stroke. However, to perform a definitive RCT in a reasonable timescale, a large number of trained paramedics across several ambulance services would be needed to recruit the number of patients likely to be required.. http://www.clinicaltrials.gov. Unique identifier: NCT01066572.

Topics: Aged; Aged, 80 and over; Antihypertensive Agents; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Early Medical Intervention; Emergency Medical Services; Emergency Medical Technicians; Feasibility Studies; Female; Follow-Up Studies; Humans; Hypertension; Lisinopril; Male; Middle Aged; Pilot Projects; Stroke; Survival Rate; Time Factors; Treatment Outcome

The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was a randomized, double-blind, practice-based, active-control, comparative effectiveness trial in 33,357 high-risk hypertensive participants. ALLHAT compared cardiovascular disease outcomes in participants initially treated with an angiotensin-converting enzyme inhibitor (lisinopril), a calcium channel blocker (amlodipine), or a thiazide-type diuretic (chlorthalidone). We report stroke outcomes in 1517 participants in-trial and 1596 additional participants during post-trial passive surveillance, for a total follow-up of 8-13 years. Stroke rates were higher with lisinopril (6-year rate/100 = 6.4) than with chlorthalidone (5.8) or amlodipine (5.5) in-trial but not including post-trial (10-year rates/100 = 13.2 [chlorthalidone], 13.1[amlodipine], and 13.7 [lisinopril]). In-trial differences were driven by race (race-by-lisinopril/chlorthalidone interaction P = .005, race-by-amlodipine/lisinopril interaction P = .012) and gender (gender-by-lisinopril/amlodipine interaction P = .041), separately. No treatment differences overall, or by race or gender, were detected over the 10-year period. No differences appeared among treatment groups in adjusted risk of all-cause mortality including post-trial for participants with nonfatal in-trial strokes. Among Blacks and women, lisinopril was less effective in preventing stroke in-trial than either chlorthalidone or amlodipine, even after adjusting for differences in systolic blood pressure. These differences abated by the end of the post-trial period.

Topics: Age Factors; Aged; Amlodipine; Cause of Death; Chlorthalidone; Confidence Intervals; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Humans; Hypertension; Kaplan-Meier Estimate; Lisinopril; Male; Middle Aged; Proportional Hazards Models; Risk Assessment; Severity of Illness Index; Sex Factors; Stroke; Survival Rate; Treatment Outcome

To determine whether an angiotensin-converting enzyme inhibitor (lisinopril) or calcium channel blocker (amlodipine) is superior to a diuretic (chlorthalidone) in reducing cardiovascular disease incidence in sex subgroups, we carried out a prespecified subgroup analysis of 15 638 women and 17 719 men in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Total follow-up (active treatment + passive surveillance using national administrative databases to ascertain deaths and hospitalizations) was 8 to 13 years. The primary outcome was fatal coronary heart disease or nonfatal myocardial infarction. Secondary outcomes included all-cause mortality, stroke, combined cardiovascular disease (coronary heart disease death, nonfatal myocardial infarction, stroke, angina, coronary revascularization, heart failure [HF], or peripheral vascular disease), and end-stage renal disease. In-trial rates of HF, stroke, and combined cardiovascular disease were significantly higher for lisinopril compared with chlorthalidone, and rates of HF were significantly higher for amlodipine compared with chlorthalidone in both men and women. There were no significant treatment sex interactions. These findings did not persist through the extension period with the exception of the HF result for amlodipine versus chlorthalidone, which did not differ significantly by sex. For both women and men, rates were not lower in the amlodipine or lisinopril groups than in the chlorthalidone group for either the primary coronary heart disease outcome or any other cardiovascular disease outcome, and chlorthalidone-based treatment resulted in the lowest risk of HF. Neither lisinopril nor amlodipine is superior to chlorthalidone for initial treatment of hypertension in either women or men. Clinical Trial Registration- clinicaltrials.gov; Identifier: NCT00000542.

Topics: Aged; Aged, 80 and over; Amlodipine; Antihypertensive Agents; Calcium Channel Blockers; Chlorthalidone; Coronary Disease; Diuretics; Female; Follow-Up Studies; Heart Failure; Humans; Hypertension; Hypolipidemic Agents; Incidence; Lisinopril; Longitudinal Studies; Male; Middle Aged; Myocardial Infarction; Risk Factors; Sex Factors; Stroke

Nitric oxide synthase 3 (NOS3) catalyzes production of NO in the endothelium and may play a role in cardiovascular disease (CVD). We assessed the pharmacogenetic associations of three NOS3 polymorphisms and three antihypertensive drugs with CVD outcomes. Hypertensive subjects (n = 30,280) from a multi-center, double-blind clinical trial were randomized to chlorthalidone, amlodipine, or lisinopril treatment (mean follow up, 4.9 years). Outcomes included coronary heart disease (CHD: fatal CHD and nonfatal myocardial infarction); stroke; heart failure (fatal, requiring hospitalization, or outpatient treatment); all-cause mortality; and end-stage renal disease (ESRD). Main effects of NOS3 variants on outcome and genotype-treatment interactions were tested. For NOS3 -690 C>T (rs3918226), a higher hazard ratio (HR) was found in minor allele carriers for CHD (CC = 1.00, CT+TT = 1.12 (95% confidence interval (CI) = 1.00-1.26), P = 0.048). For NOS3 -922 A>G (rs1800779), a higher HR was found in minor allele carriers for heart failure (AA = 1.00, AG+GG = 1.10 (CI = 1.00-1.21), P = 0.046). Significant pharmacogenetic findings were observed for stroke and all-cause mortality. For -690 C>T, a lower HR was observed for stroke in minor allele carriers when treated with amlodipine versus lisinopril (CC = 0.85 (CI = 0.73-0.99), CT+TT = 0.49 (CI = 0.31-0.80), P = 0.04). For glu298asp G>T (rs1799983), a lower HR was observed for all-cause mortality in minor allele carriers when treated with amlodipine versus lisinopril (GG = 1.01 (CI = 0.91-1.13), GT+TT = 0.85 (CI = 0.75-0.97), P = 0.04). We observed significant associations with NOS3 variants and CHD and heart failure and significant pharmacogenetic effects for stroke and all cause mortality. This suggests that NOS3 variants may potentially provide useful clinical information with respect to treatment decisions in the future.

Topics: Aged; Alleles; Amlodipine; Antihypertensive Agents; Cardiovascular Diseases; Chlorthalidone; Double-Blind Method; Female; Follow-Up Studies; Genotype; Heart Failure; Humans; Hypertension; Lisinopril; Male; Middle Aged; Nitric Oxide Synthase Type III; Polymorphism, Single Nucleotide; Risk Factors; Stroke

CKD is common among older patients. This article assesses long-term renal and cardiovascular outcomes in older high-risk hypertensive patients, stratified by baseline estimated GFR (eGFR), and long-term outcome efficacy of 5-year first-step treatment with amlodipine or lisinopril, each compared with chlorthalidone.. This was a long-term post-trial follow-up of hypertensive participants (n=31,350), aged ≥55 years, randomized to receive chlorthalidone, amlodipine, or lisinopril for 4-8 years at 593 centers. Participants were stratified by baseline eGFR (ml/min per 1.73 m(2)) as follows: normal/increased (≥90; n=8027), mild reduction (60-89; n=17,778), and moderate/severe reduction (<60; n=5545). Outcomes were cardiovascular mortality (primary outcome), total mortality, coronary heart disease, cardiovascular disease, stroke, heart failure, and ESRD.. After an average 8.8-year follow-up, total mortality was significantly higher in participants with moderate/severe eGFR reduction compared with those with normal and mildly reduced eGFR (P<0.001). In participants with an eGFR <60, there was no significant difference in cardiovascular mortality between chlorthalidone and amlodipine (P=0.64), or chlorthalidone and lisinopril (P=0.56). Likewise, no significant differences were observed for total mortality, coronary heart disease, cardiovascular disease, stroke, or ESRD.. CKD is associated with significantly higher long-term risk of cardiovascular events and mortality in older hypertensive patients. By eGFR stratum, 5-year treatment with amlodipine or lisinopril was not superior to chlorthalidone in preventing cardiovascular events, mortality, or ESRD during 9-year follow-up. Because data on proteinuria were not available, these findings may not be extrapolated to proteinuric CKD.

Topics: Amlodipine; Antihypertensive Agents; Canada; Chlorthalidone; Chronic Disease; Coronary Disease; Double-Blind Method; Female; Glomerular Filtration Rate; Heart Failure; Humans; Hypertension; Hypolipidemic Agents; Incidence; Kaplan-Meier Estimate; Kidney; Kidney Diseases; Kidney Failure, Chronic; Lisinopril; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Proportional Hazards Models; Puerto Rico; Risk Assessment; Risk Factors; Severity of Illness Index; Stroke; Time Factors; Treatment Outcome; United States; United States Virgin Islands

High blood pressure during acute stroke is associated with poorer stroke outcome. Previous trials have failed to show benefit from lowering blood pressure but treatment may have been commenced too late to be effective. The earliest that acute stroke treatments could be initiated is during contact with the emergency medical services (paramedics). However, experience of pre-hospital clinical trials is limited and logistical challenges are likely to be greater than for trials performed in other settings. We report the protocol for a pilot randomised controlled trial of paramedic initiated blood pressure lowering treatment for hypertension in acute stroke.. Double blind parallel group external pilot randomised controlled trial.. Participant recruitment and initial treatment by North East Ambulance Service research trained paramedics responding to the emergency call. Continued treatment in three study hospitals.. Target is recruitment of 60 adults with acute arm weakness due to suspected stroke (within 3 hours of symptom onset) and hypertension (systolic BP>160 mmHg).. Lisinopril 5-10 mg (intervention group), matched placebo (control group), daily for 7 days. Randomisation: Study medication contained within identical pre-randomised "trial packs" carried by research trained paramedics.. Study feasibility (recruitment rate, compliance with data collection) and clinical data to inform the design of a definitive randomised controlled trial (blood pressure monitoring, National Institute of Health Stroke Scale, Barthel ADL Index, Modified Rankin Scale, renal function).. This pilot study is assessing the feasibility of a randomised controlled trial of paramedic initiated lisinopril for hypertension early after the onset of acute stroke. The results will inform the design of a definitive RCT to evaluate the effects of very early blood pressure lowering in acute stroke.. EudraCT: 2010-019180-10ClinicalTrials.gov: NCT01066572ISRCTN: 54540667.

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Double-Blind Method; Drug Administration Schedule; Emergency Medical Services; Emergency Medical Technicians; England; Feasibility Studies; Humans; Lisinopril; Pilot Projects; Research Design; Stroke; Time Factors; Treatment Outcome

Raised blood pressure is common after acute stroke and is associated with an adverse prognosis. We sought to assess the feasibility, safety, and effects of two regimens for lowering blood pressure in patients who have had a stroke.. Patients who had cerebral infarction or cerebral haemorrhage and were hypertensive (systolic blood pressure [SBP] >160 mm Hg) were randomly assigned by secure internet central randomisation to receive oral labetalol, lisinopril, or placebo if they were non-dysphagic, or intravenous labetalol, sublingual lisinopril, or placebo if they had dysphagia, within 36 h of symptom onset in this double-blind pilot trial. The doses were titrated up if target blood pressure was not reached. Analysis was by intention to treat. This trial is registered with the National Research Register, number N0484128008.. 179 patients (mean age 74 [SD 11] years; SBP 181 [SD 16] mm Hg; diastolic blood pressure [DBP] 95 [SD 13] mm Hg; median National Institutes of Health stroke scale [NIHSS] score 9 [IQR 5-16] points) were randomly assigned to receive labetolol (n=58), lisinopril (n=58), or placebo (n=63) between January, 2005, and December, 2007. The primary outcome--death or dependency at 2 weeks--occurred in 61% (69) of the active and 59% (35) of the placebo group (relative risk [RR] 1.03, 95% CI 0.80-1.33; p=0.82). There was no evidence of early neurological deterioration with active treatment (RR 1.22, 0.33-4.54; p=0.76) despite the significantly greater fall in SBP within the first 24 h in this group compared with placebo (21 [17-25] mm Hg vs 11 [5-17] mm Hg; p=0.004). No increase in serious adverse events was reported with active treatment (RR 0.91, 0.69-1.12; p=0.50) but 3-month mortality was halved (9.7%vs 20.3%, hazard ratio [HR] 0.40, 95% CI 0.2-1.0; p=0.05).. Labetalol and lisinopril are effective antihypertensive drugs in acute stroke that do not increase serious adverse events. Early lowering of blood pressure with lisinopril and labetalol after acute stroke seems to be a promising approach to reduce mortality and potential disability. However, in view of the small sample size, care must be taken when these results are interpreted and further evaluation in larger trials is needed.

Topics: Acute Disease; Aged; Antihypertensive Agents; Blood Pressure; Double-Blind Method; Female; Humans; Hypertension; Hypotension; Labetalol; Lisinopril; Male; Pilot Projects; Stroke; Survival Analysis; Treatment Outcome

To assess the effects of acute pressor and depressor blood pressure (BP) manipulation on 2-week death and dependency following acute stroke and investigate the safety and efficacy of such treatments.. A multicentre, prospective, randomised, double-blind, placebo-controlled titrated-dose trial.. Five hospitals in England.. Patients over 18 years admitted to hospital with a clinical diagnosis of suspected stroke and either (1) symptom onset < 36 hours and hypertension, defined as systolic BP (SBP) < 160 mmHg (depressor arm), or (2) symptom onset < 12 hours and hypotension, defined as SBP < or = 140 mmHg (pressor arm).. Patients were allocated to either the pressor or the depressor arm depending on blood pressure at randomisation. The ratio of allocation to active intervention versus matched placebo was 2:1 for the depressor arm and 1:1 for the pressor arm.. The primary end point was death and dependency at 2 weeks, with dependency defined as a modified Rankin score < 3. Secondary end points were the safety of acute pressor (0-12 hours post stroke) and depressor (0-36 hours post stroke) BP manipulation in stroke patients; whether effects of BP reduction are influenced by stroke type (ischaemic versus haemorrhagic); whether alternative routes for administration of antihypertensive therapy (including sublingual and intravenous) are effective in dysphagic stroke patients; whether effects of BP manipulation are influenced by the time to treatment; and the short- and medium-term cost-effectiveness of such therapy in the acute post-stroke period on subsequent disability or death.. 180 patients were recruited over the 36-month trial period, 179 in the depressor arm and one in the pressor arm (who received placebo). No significant difference was found in death or dependency at 2 weeks between those receiving active depressor treatment with lisinopril or labetalol and those receiving placebo, although numbers recruited to the trial were lower than projected. Active treatment was not associated with an increase in early neurological deterioration despite significantly greater reductions in BP at 24 hours and 2 weeks with active therapy compared with placebo. Active treatment was generally well tolerated and treatment discontinuation rates were similar in active and placebo groups. Survival analysis showed that the active treatment group had a lower mortality at 3 months than the placebo group (p = 0.05). The pressor arm was closed early because of problems with recruitment, so no conclusions can be drawn regarding this therapy.. Oral and sublingual lisinopril and oral and intravenous labetalol are effective BP-lowering agents in acute cerebral infarction and haemorrhage and do not increase the likelihood of early neurological deterioration. The study was not sufficiently powered to detect a difference in disability or death at 2 weeks. However, the 3-month difference in mortality in favour of active treatment is of interest, although care must be taken in interpretation of the results. Further work is needed to confirm this and to assess whether there are differences in the effectiveness of labetalol compared with lisinopril in terms of reducing death or dependency after acute stroke, and whether the introduction of treatment post stroke earlier than was achieved here would be of greater benefit.

Topics: Adult; Aged; Antihypertensive Agents; Blood Pressure; Cardiotonic Agents; Cost-Benefit Analysis; Deglutition Disorders; Double-Blind Method; Female; Hospitals; Humans; Hypertension; Hypotension; Infusions, Intravenous; Labetalol; Lisinopril; Male; Middle Aged; Phenylephrine; Placebos; Stroke; Survival Analysis; Time Factors; Treatment Outcome

The FGB gene codes for fibrinogen-beta, a polypeptide of the coagulation factor fibrinogen, which is positively associated with cardiovascular diseases. Studies show that angiotensin-converting enzyme (ACE) inhibitors lower plasma fibrinogen concentrations, whereas diuretics and calcium-channel blockers do not. As carriers of the FGB-455 minor 'A' allele have higher levels of fibrinogen while ACE inhibitors lower it, we hypothesize that 'A' allele carriers benefit more from antihypertensive treatment with ACE inhibitors than calcium-channel blockers or diuretics, relative to 'GG' genotype individuals.. The Genetics of Hypertension Associated Treatment (GenHAT) study [ancillary to Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)] genotyped hypertensive participants for several hypertension-related candidate genes, making this a post-hoc analysis of a randomized trial. In total, 90.1% of the ALLHAT population was successfully genotyped for FGB-455. We included participants (n=30 076) randomized to one of three antihypertensive medications (lisinopril, amlodipine, chlorthalidone), with two treatment comparisons: lisinopril versus chlorthalidone and lisinopril versus amlodipine. The primary outcome of ALLHAT/GenHAT was coronary heart disease, defined as fatal coronary heart disease or non-fatal myocardial infarction, and secondary outcomes included stroke, heart failure, all-cause mortality, and end-stage renal disease (ESRD) with mean follow-up time of 4.9 years. Genotype-by-treatment interactions (pharmacogenetic effects) were tested with the Cox regression.. Stroke: common 'GG' homozygotes had higher risk on lisinopril versus amlodipine [hazard ratio (HR)=1.38, P<0.001], whereas minor 'A' allele carriers had slightly lower risk (HR=0.96, P=0.76; P value for interaction=0.03). Mortality: 'GG' homozygotes had higher risk on lisinopril versus amlodipine (HR=1.12, P=0.02) or chlorthalidone (1.05, P=0.23), whereas 'A' allele carriers had slightly lower risk (HR=0.92, P=0.33 for lisinopril versus amlodipine; HR=0.88, P=0.08 for lisinopril versus chlorthalidone; P value for interactions 0.04 and 0.03, respectively). ESRD: 'GG' homozygotes had higher risk on lisinopril versus chlorthalidone (HR=1.27, P=0.08), whereas 'A' allele carriers had lower risk (HR=0.64, P=0.12; P value for interaction=0.03).. There was evidence of pharmacogenetic effects of FGB-455 on stroke, ESRD, and mortality, suggesting that relative to those homozygous for the common allele, variant allele carriers of the FGB gene at position -455 have a better outcome if randomized to lisinopril than chlorthalidone (for mortality and ESRD) or amlodipine (for mortality and stroke). For the models in which a pharmacogenetic effect was observed, the outcome rates among 'GG' homozygotes were higher in those randomized to lisinopril versus amlodipine or chlorthalidone, whereas minor 'A' allele carriers had lower event rates when randomized to lisinopril versus the other medications.

Topics: Aged; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Calcium Channel Blockers; Chlorthalidone; Coronary Disease; Diuretics; Fibrinogen; Genetic Variation; Genotype; Humans; Hypertension; Kidney Failure, Chronic; Lisinopril; Middle Aged; Stroke; Treatment Outcome

Hypertension immediately after acute ischemic stroke is associated with impaired morbidity and mortality, although there are few data on antihypertensive use immediately after ictus. This randomized, double-blinded, placebo-controlled, parallel-group study explored the hemodynamic effect and safety of oral lisinopril initiated within 24 h after an ictus.. Forty hypertensive (systolic blood pressure [BP] >/=140 or diastolic BP >/=90 mm Hg) acute ischemic stroke patients (14 lacunar, 13 partial anterior, 7 total anterior, 6 posterior circulation infarct) were randomized to 5 mg of oral lisinopril (n = 18) or matching placebo (n = 22). Dose was increased to 10 mg (or 2 x placebo) on day 7 if casual systolic BP was >/=140 mm Hg and continued to day 14. After the initial dose, automated BP levels were monitored for 16 h. The BP levels and stroke outcome measures were assessed at day 14, and all patients were followed to day 90.. At h 4 after the first dose, systolic/diastolic BP change was -20 +/- 21/-6 +/- 10 mm Hg (mean +/- SE) in the lisinopril group and 1 +/- 11/0 +/- 8 mmHg in the placebo group (group differences: systolic BP, P < .05; diastolic BP, P = .07). With a daily dosing regime, systolic BP, mean arterial pressure (MAP), diastolic BP, and pulse pressure (PP) were significantly lower in the lisinopril group compared to the placebo group at day 14 (P < .01). Neurologic and functional measures were similar between groups at follow-up.. Lisinopril, even at small dosages, is well tolerated and an effective hypotensive agent after acute ischemic stroke, gradually reducing BP by 4 h after oral first-dose administration. Oral lisinopril is now being studied in a larger outcome-based trial in acute hypertensive stroke patients.

Topics: Acute Disease; Administration, Oral; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Brain Ischemia; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Heart Rate; Humans; Hypertension; Lisinopril; Male; Stroke; Time Factors; Treatment Outcome

Topics: Aged; Amlodipine; Benzothiadiazines; Blood Chemical Analysis; Chlorthalidone; Diuretics; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Hypertension; Hypertrophy, Left Ventricular; Hypolipidemic Agents; Lisinopril; Male; Middle Aged; Myocardial Infarction; Queensland; Reference Values; Risk Assessment; Severity of Illness Index; Sodium Chloride Symporter Inhibitors; Stroke; Survival Analysis; Treatment Outcome

SBP and DBP have important associations with cardiovascular events, but are seldom considered simultaneously.. This study sought to simultaneously analyze systolic blood pressure (SBP) and diastolic blood pressure (DBP) measurements on the associated risk of a primary composite outcome of all-cause mortality, myocardial infarction (MI), congestive heart failure (CHF), or stroke.. This study analyzed ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) data, which randomized adults to chlorthalidone, amlodipine, or lisinopril. The authors evaluated the simultaneous association of repeated SBP and DBP measurements on the primary composite outcome, and each outcome using proportional hazards regression. The authors report hazard ratios using a "heat map" to represent high and low risk according to SBP and DBP combinations.. During a median follow-up of 4.4 years (interquartile range: 3.6-5.4 years), 33,357 participants experienced 2,636 MIs, 866 CHF events, 936 strokes, and 3,700 deaths; 8,138 patients (24.4%) had at least 1 event. For the composite outcome, all-cause mortality, MI, and CHF, a U-shaped association was observed with SBP and DBP, but the SBP and DBP associated with the lowest hazards differed for each outcome. For example, SBP/DBP of 140-155/70-80 mm Hg was associated with the lowest HR for all-cause mortality, compared with 110-120/85-90 mm Hg for MI and 125-135/70-75 mm Hg for CHF. In contrast, the association of SBP and stroke was linear.. The risk pattern of SBP and DBP differs by clinical outcomes, and the SBP and DBP associated with the lowest risk. Our results suggest individualization of blood pressure targets may depend in part on the cardiovascular event for which the patient is most at risk.

Topics: Aged; Amlodipine; Blood Pressure; Blood Pressure Determination; Cardiovascular Diseases; Chlorthalidone; Diastole; Female; Follow-Up Studies; Heart Failure; Humans; Lisinopril; Male; Middle Aged; Myocardial Infarction; Proportional Hazards Models; Randomized Controlled Trials as Topic; Retrospective Studies; Risk; Risk Assessment; Risk Factors; Stroke; Systole

The aim of this study was to investigate whether there is a genotype-by-treatment interaction in patients experiencing stroke and treated with one of three antihypertensive drugs, that is chlorthalidone, amlodipine, or lisinopril.. A population of 436 African Americans and 539 whites who had experienced stroke in the GenHAT study were genotyped for 768 single nucleotide polymorphisms (SNPs) in 280 candidate genes. To detect a genotype-by-treatment interaction, we used the Pearson's χ-test to assess whether the genotype frequencies differed at the single SNP level for the three drug treatment groups. From these single SNP analyses, we derived a summary statistic for the degree of association at the gene and gene complex levels. This was done by grouping SNPs using information on gene locations and defining gene complexes on the basis of protein-protein interactions. To assess the statistical significance of the observed test statistic, we derived an empirical P-value by simulating data under the null hypothesis.. We found that, in patients who have experienced stroke, there is a significant genetic difference between hypertension drug treatment groups. In African Americans, SNP rs12143842 showed a significant association (P<0.001) with drug treatment. At the gene level, HNRNPA1P4 and NOS1AP in African Americans and PRICKLE1 and NINJ2 in non-Hispanic whites were significantly associated (P<0.01) with drug treatment, whereas none of the gene complexes tested showed significance.. On the basis of the genetic differences between drug treatment groups, we conclude that there may be an interaction between certain genotypes and antihypertensive treatment in stroke patients. This needs to be replicated in other studies.

Topics: Aged; Amlodipine; Chlorthalidone; Female; Genotype; Humans; Lisinopril; Male; Middle Aged; Pharmacogenetics; Polymorphism, Single Nucleotide; Stroke

New imaging techniques have allowed for the rapid and accurate diagnosis of stroke. In this case, we present a 58-year-old woman with multiple large vessel strokes on magnetic resonance imaging. The initial diagnostic workup centered on a rapidly progressive central nervous system vasculitis. Subsequent workup revealed an unusual infectious etiology--cryptococcal meningitis. Although fungal infections can cause vasculitis, this is the first report of a patient with multiple anterior and posterior circulation strokes secondary to Cryptococcus. The diagnosis in cases presenting with encepalopathy and without fever is often delayed.

Topics: Antihypertensive Agents; Diabetes Mellitus, Type 2; Diagnosis, Differential; Diuretics; Female; Furosemide; Humans; Hyperlipidemias; Hypertension; Hypothyroidism; Insulin; Lisinopril; Liver Cirrhosis; Low Back Pain; Magnetic Resonance Imaging; Meningitis, Cryptococcal; Middle Aged; Obesity; Osteoarthritis; Prednisone; Stroke; Thyroxine; Vasculitis, Central Nervous System

To examine the impact of tissue selectivity of angiotensin-converting enzyme (ACE) inhibitors on mortality and morbidity in patients following acute myocardial infarction (AMI).. A retrospective cohort study using a Medicaid claims database was conducted. Patients hospitalized for an AMI and subsequently filling a prescription for an ACE inhibitor were followed longitudinally for the occurrence of cardiovascular-related hospitalizations and all-cause mortality. A subanalysis was also conducted to account for switching/discontinuation of ACE inhibitor therapy. Stepwise (forward conditional) Cox-proportional hazards models were used to analyze the effect of tissue selectivity on study outcomes.. The final study sample consisted of 689 AMI and the results indicated that tissue-selective ACE inhibitors had a protective effect against hospitalization due to stroke/transient ischemic attack (TIA) (hazard ratio [HR] = 0.265; 95% confidence interval [CI] = 0.101-0.698). A similar lower rate in hospitalizations due to heart failure was observed in the group using tissue-selective ACE inhibitors; however, the results were not statistically significant (HR = 0.681; 95% CI = 0.436-1.063). A protective effect was also observed on the combined outcome of hospitalization due to any cardiovascular condition (HR = 0.712; 95% CI = 0.536-0.945). Hospitalizations due to recurrent AMI, need for coronary revascularization procedures, and mortality were not significantly different between patients using tissue-selective and non-tissue-selective ACE inhibitors. The completer subanalysis provided similar findings regarding the impact of tissue selectivity on study outcomes.. Tissue-selective ACE inhibitors may have a protective effect against hospitalization due to stroke/TIA or heart failure when compared to non-tissue-selective ACE inhibitors for patients following AMI.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Cardiovascular Diseases; Comorbidity; Enalapril; Female; Heart Failure; Humans; Lisinopril; Longitudinal Studies; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Organ Specificity; Proportional Hazards Models; Ramipril; Retrospective Studies; Secondary Prevention; Stroke; Survival Analysis

Topics: Antihypertensive Agents; Carbohydrate Metabolism; Clinical Trials as Topic; Diuretics; Drug Therapy, Combination; Drugs, Generic; Heart Diseases; Humans; Hypertension; Hypokalemia; Indapamide; Lipid Metabolism; Lisinopril; Stroke; Thiazides

Topics: Acute Disease; Antihypertensive Agents; Blood Pressure; Clinical Trials as Topic; Humans; Hypertension; Hypotension; Labetalol; Lisinopril; Stroke; Treatment Outcome

Topics: Adrenergic alpha-Antagonists; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Black or African American; Calcium Channel Blockers; Chlorthalidone; Clinical Trials as Topic; Doxazosin; Follow-Up Studies; Heart Failure; Humans; Lisinopril; Middle Aged; Myocardial Infarction; Primary Prevention; Stroke; Time Factors

Previous studies have shown that angiotensin II (Ang II), by mediating rapid recruitment of collateral circulation, has a protective effect in the setting of acute ischaemia. In an experimental model of acute cerebral ischaemia in the gerbil, Fernandez et al. have reported that the mechanism of the protective effect of Ang 11 is blood pressure (BP)-independent, and that the AT1-receptor antagonist, losartan, but not the ACE inhibitor (ACE-I),enalapril, decreases mortality following unilateral carotid artery ligation. The aim of this study was to examine there producibility of the respective effects of losartan and enalapril, and to verify that these differential effects are drug class-related. Acute cerebral ischaemia was induced in anaesthetised gerbils bv unilateral carotid ligation. The effect of pretreatment with two different ACE-I(enalapril and lisinopril), and two different AT1-receptor antagonists (losartan and candesartan), administered orally or intravenously, on mortality were compared. Kaplan-Meier survival curves at day three were analysed bv a log-rank test. Pretreatment with both enalapril and lisinopril significantly decreased survival at day three compared with controls, while the AT1-receptor antagonists losartan and candesartan, despite similarly lowering BP, did not increase mortality. Coadministration of losartan and enalapril increased mortality to the same extent as enalapril alone. This study confirms that Ang II contributes to protective mechanisms against acute cerebral ischaemia through non AT1-receptor-mediated, BP-independent effects.

Topics: Acute Disease; Angiotensin Receptor Antagonists; Animals; Antihypertensive Agents; Benzimidazoles; Biphenyl Compounds; Brain Ischemia; Disease Models, Animal; Enalapril; Gerbillinae; Lisinopril; Losartan; Male; Receptor, Angiotensin, Type 1; Receptors, Angiotensin; Reproducibility of Results; Stroke; Tetrazoles