Database : MEDLINE
Search on : Chlorthalidone [Words]
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Clinical Trials Registry
Clinical Trials Registry
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[PMID]: 29523524
[Au] Autor:Singh S; McDonough CW; Gong Y; Alghamdi WA; Arwood MJ; Bargal SA; Dumeny L; Li WY; Mehanna M; Stockard B; Yang G; de Oliveira FA; Fredette NC; Shahin MH; Bailey KR; Beitelshees AL; Boerwinkle E; Chapman AB; Gums JG; Turner ST; Cooper-DeHoff RM; Johnson JA
[Ad] Address:Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, University of Florida, Gainesville, FL.
[Ti] Title:Genome Wide Association Study Identifies the Locus to be Associated With Chlorthalidone Induced Glucose Increase in Hypertensive Patients.
[So] Source:J Am Heart Assoc;7(6), 2018 Mar 09.
[Is] ISSN:2047-9980
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:BACKGROUND: Thiazide and thiazide-like diuretics are first-line medications for treating uncomplicated hypertension. However, their use has been associated with adverse metabolic events, including hyperglycemia and incident diabetes mellitus, with incompletely understood mechanisms. Our goal was to identify genomic variants associated with thiazide-like diuretic/chlorthalidone-induced glucose change. METHODS AND RESULTS: Genome-wide analysis of glucose change after treatment with chlorthalidone was performed by race among the white (n=175) and black (n=135) participants from the PEAR-2 (Pharmacogenomic Evaluation of Antihypertensive Responses-2). Single-nucleotide polymorphisms with <5×10 were further prioritized using in silico analysis based on their expression quantitative trait loci function. Among blacks, an intronic single-nucleotide polymorphism (rs9943291) in the was associated with increase in glucose levels following chlorthalidone treatment (ß=12.5; =4.17×10 ). G-allele carriers of had higher glucose levels (glucose change=+16.29 mg/dL) post chlorthalidone treatment compared with noncarriers of G allele (glucose change=+2.80 mg/dL). This association was successfully replicated in an independent replication cohort of hydrochlorothiazide-treated participants from the PEAR study (ß=5.54; =0.023). A meta-analysis of the 2 studies was performed by race in Meta-Analysis Helper, where this single-nucleotide polymorphism, rs9943291, was genome-wide significant with a meta-analysis value of 3.71×10 . , a part of the HMG-CoA synthase family, is important for ketogenesis and cholesterol synthesis pathways that are essential in glucose homeostasis. CONCLUSIONS: These results suggest that is a promising candidate gene involved in chlorthalidone and Hydrochlorothiazide (HCTZ)-induced glucose change. This may provide insights into the mechanisms involved in thiazide-induced hyperglycemia that may ultimately facilitate personalized approaches to antihypertensive selection for hypertension treatment. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00246519 and NCT01203852.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[Cl] Clinical Trial:ClinicalTrial
[St] Status:In-Data-Review

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[PMID]: 29360915
[Au] Autor:Barzilay JI; Davis BR; Pressel SL; Ghosh A; Rahman M; Einhorn PT; Cushman WC; Whelton PK; Wright JT
[Ad] Address:Division of Endocrinology, Kaiser Permanente of Georgia, and the Division of Endocrinology, Emory University School of Medicine, Atlanta, Georgia, USA.
[Ti] Title:The Effects of eGFR Change on CVD, Renal, and Mortality Outcomes in a Hypertensive Cohort Treated With 3 Different Antihypertensive Medications.
[So] Source:Am J Hypertens;, 2018 Jan 19.
[Is] ISSN:1941-7225
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:BACKGROUND: Impaired renal function is a risk factor for cardiovascular disease, end-stage renal disease (ESRD), and mortality. The impact of short-term renal function decline on outcomes is less well studied. The association of antihypertensive medications with the impact of short-term estimated glomerular filtration rate (eGFR) decline is not known. METHODS: We examined 20,207 hypertensive participants with baseline and 2-year creatinine levels from which eGFR changes were estimated. The associations between eGFR change with incident coronary heart disease (CHD), stroke, heart failure (HF), all-cause mortality, and ESRD during 2.9 years of in-trial follow up, and with mortality during in-trial and post-trial follow-up (7.6 years), were studied. Results were assessed by primary hypertension (HTN) treatment (chlorthalidone, lisinopril, and amlodipine) and adjusted for baseline eGFR levels. RESULTS: In the short run, an eGFR decline below the cohort median (-1.28 ml/minute/1.73 m2/2 years) vs. above the median, or a 5 ml/min/1.73 m2/year decline vs. no decline, was associated with significant hazard risk for CHD (1.06-1.28), HF (1.24-1.91), ESRD (2.84-6.01), and mortality (1.08-1.19), but not with stroke risk. In the long term, there was a significant association with mortality (1.11-1.34). Interaction terms for outcomes by antihypertensive treatments were not statistically significant except for ESRD between amlodipine vs. chlorthalidone (hazard ratio: 3.17 [2.59, 3.88] vs. 2.41 [1.98, 2.97]; P interaction = 0.005) for a 5 ml/min/1.73 m2/year eGFR decline. CONCLUSION: Decline in eGFR over 2 years is associated with increased risk of clinical outcomes beyond the effects of baseline eGFR. These risks were the same irrespective of the primary medication used to treat HTN.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1801
[Cu] Class update date: 180308
[Lr] Last revision date:180308
[St] Status:Publisher
[do] DOI:10.1093/ajh/hpx223

  3 / 1549 MEDLINE  
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[PMID]: 29504252
[Au] Autor:Bakris GL; Zhao L; Kupfer S; Juhasz A; Hisada M; Lloyd E; Oparil S
[Ad] Address:University of Chicago Medicine, Chicago, IL, USA.
[Ti] Title:Long-term efficacy and tolerability of azilsartan medoxomil/chlorthalidone vs olmesartan medoxomil/hydrochlorothiazide in chronic kidney disease.
[So] Source:J Clin Hypertens (Greenwich);, 2018 Mar 04.
[Is] ISSN:1751-7176
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:An open-label, long-term study evaluated safety and tolerability of azilsartan medoxomil/chlorthalidone (AZL-M/CLD) vs olmesartan/hydrochlorothiazide (OLM/HCTZ) in hypertensive participants with stage 3 chronic kidney disease. Initial therapy was AZL-M/CLD 20/12.5 mg (n = 77) or OLM/HCTZ 20/12.5 mg (n = 76), but could be up-titrated (AZL-M/CLD to 40/25 mg; OLM/HCTZ to 40/25 mg [US] or 20/25 mg [Europe]) with other agents added during weeks 4-52. Primary endpoint was proportion of participants with ≥ 1 adverse event (AE) through week 52. Baseline demographics were similar. AEs did not differ between groups (88.3%, AZL-M/CLD vs 76.3%, OLM/HCTZ; P = .058). AZL-M/CLD showed greater systolic BP reductions after initial dosing (P = .037) but not during long-term follow-up (P = .588). A greater proportion of participants up-titrated to the highest dose with OLM/HCTZ (48.7%) vs AZL-M/CLD (29.9%) (P = .021) and were taking additional antihypertensive medications (26.3% vs 16.9%). Both AZL-M/CLD and OLM/HCTZ showed similar efficacy and tolerability.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180305
[Lr] Last revision date:180305
[St] Status:Publisher
[do] DOI:10.1111/jch.13230

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[PMID]: 29504233
[Au] Autor:van der Merwe WM
[Ad] Address:Hypertension Clinic, Auckland, New Zealand.
[Ti] Title:Treatment of hypertension in CKD patients with azilsartan/chlorthalidone vs olmesartan/hydrochlorothiazide.
[So] Source:J Clin Hypertens (Greenwich);, 2018 Mar 04.
[Is] ISSN:1751-7176
[Cp] Country of publication:United States
[La] Language:eng
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180305
[Lr] Last revision date:180305
[St] Status:Publisher
[do] DOI:10.1111/jch.13233

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[PMID]: 29498881
[Au] Autor:Slíva J
[Ti] Title:Postavení hydrochlorothiazidu mezi thiazidovými a thiazidum podobnými diuretiky. [The current position of hydrochlorothiazide among thiazide and thiazide-like diuretics].
[So] Source:Vnitr Lek;64(1):83-85, 2018.
[Is] ISSN:0042-773X
[Cp] Country of publication:Czech Republic
[La] Language:cze
[Ab] Abstract:Thiazide and thiazide-like diuretics are an important group of drugs used in the treatment of essential arterial hyper-tension. While their beneficial therapeutic effect in monotherapy is evident, they are increasingly used in fixed combinations, particularly with ACE inhibitors or sartans. The aim of this article was to summarize the current status of hydrochlorothiazide and compare its effects with other substances in this subgroup of diuretics.Key words: diuretics - HCTZ - hydrochlorothiazide - hypertension - chlorthalidone - indapamide - thiazide.
[Pt] Publication type:ENGLISH ABSTRACT; JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180302
[Lr] Last revision date:180302
[St] Status:In-Data-Review

  6 / 1549 MEDLINE  
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[PMID]: 29334491
[Au] Autor:Cushman WC; Bakris GL; White WB; Weber MA; Sica D; Roberts A; Lloyd E; Kupfer S
[Ad] Address:Veterans Affairs Medical Center, University of Tennessee Health Science Center, Memphis, Tennessee.
[Ti] Title:A randomized titrate-to-target study comparing fixed-dose combinations of azilsartan medoxomil and chlorthalidone with olmesartan and hydrochlorothiazide in stage-2 systolic hypertension.
[So] Source:J Hypertens;36(4):947-956, 2018 Apr.
[Is] ISSN:1473-5598
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:BACKGROUND: Azilsartan medoxomil (AZL-M), an angiotensin II receptor blocker, has been developed in fixed-dose combinations (FDCs) with chlorthalidone (CTD). OBJECTIVE/METHODS: We compared FDCs of AZL-M/CTD 20/12.5 mg once daily titrated to 40/25 mg if needed or AZL-M/CTD 40/12.5 mg once daily titrated to 80/25 mg if needed with an olmesartan medoxomil (OLM)-hydrochlorothiazide (HCTZ) 20/12.5 mg FDC once daily titrated to 40/25 mg if needed in a randomized, double-blind, 8-week study of 1085 participants with clinic SBP 160-190 mmHg and DBP 119 mmHg or less. Titration to higher doses occurred at week 4 if BP was at least 140/90 mmHg (≥130/80 mmHg if diabetes or chronic kidney disease). The primary endpoint was change from baseline in clinic SBP; 24-h ambulatory BP monitoring was also measured. RESULTS: Greater reductions in clinic SBP from a baseline of 165 mmHg were observed (P < 0.001) in both AZL-M/CTD arms (-37.6 and -38.2 mmHg) versus OLM/HCTZ (-31.5 mmHg), despite greater dose titration in the OLM/HCTZ group. At 8 weeks, both AZL-M/CTD FDCs reduced 24-h SBP more than OLM/HCTZ (-26.4 and -27.9 versus -20.7 mmHg; both P < 0.001), and higher proportions in both AZL-M/CTD groups achieved target BP compared with the OLM/HCTZ group (69.4 and 68.9 versus 54.7%, both P < 0.001). Adverse events leading to drug discontinuation occurred in 6.2, 9.5, and 3.1% with the AZL-M/CTD lower and higher doses, and OLM/HCTZ, respectively. CONCLUSION: This large, titration-to-target BP study demonstrated AZL-M/CTD FDCs to have superior antihypertensive efficacy compared with the maximum approved dose of OLM/HCTZ.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1801
[Cu] Class update date: 180228
[Lr] Last revision date:180228
[St] Status:In-Data-Review
[do] DOI:10.1097/HJH.0000000000001647

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Castro, Iran
Cesarino, Evandro José
Sousa, Ana Luiza Lima
Afiune Neto, Abrahao
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[PMID]: 29227377
[Au] Autor:Fuchs FD; Fuchs SC; Poli-de-Figueiredo CE; Figueiredo Neto JA; Scala LCN; Vilela-Martin JF; Moreira LB; Chaves H; Mota Gomes M; de Sousa MR; Silva RPE; Castro I; Cesarino EJ; Sousa ALL; Alves JG; Steffens AA; Brandão AA; Bortolotto LA; Afiune Neto A; Nóbrega AC; Franco RS; Sobral Filho DC; Nobre F; Schlatter R; Gus M; De David CN; Rafaelli L; Sesin GP; Berwanger O; Whelton PK
[Ad] Address:Division of Cardiology, Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul.
[Ti] Title:Effectiveness of low-dose diuretics for blood pressure reduction to optimal values in prehypertension: a randomized clinical trial.
[So] Source:J Hypertens;36(4):933-938, 2018 Apr.
[Is] ISSN:1473-5598
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:BACKGROUND: To determine the effectiveness of low-dose diuretic therapy to achieve an optimal level of blood pressure (BP) in adults with prehypertension. METHODS: The PREVER-prevention trial was a randomized, parallel, double-blinded, placebo-controlled trial, with 18 months of follow-up, conducted at 21 academic medical centers in Brazil. Of 1772 individuals evaluated for eligibility, 730 volunteers with prehypertension who were aged 30-70 years, and who did not reach optimal blood pressure after 3 months of lifestyle intervention, were randomized to a fixed association of chlorthalidone 12.5 mg and amiloride 2.5 mg or placebo once a day. The main outcomes were the percentage of participants who achieved an optimal level of BP. RESULTS: A total of 372 participants were randomly allocated to diuretics and 358 to placebo. After 18 months of treatment, optimal BP was noted in 25.6% of the diuretic group and 19.3% in the placebo group (P < 0.05). The mean net reduction in SBP and DBP for the diuretic group compared with placebo was 2.8 mmHg (95% CI 1.1 to 4.5) and 1.1 mmHg (95% CI -0.09 to 2.4), respectively. Most participants in the active treatment group (74.5%) and in the placebo group (80.7%) continued to have BP in the prehypertension range or progressed to hypertension. CONCLUSION: Low-dose diuretic therapy increased the probability of individuals with prehypertension to achieve optimal BP but most of those treated continued to have a BP in the prehypertension range or progressed to having overt hypertension.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1712
[Cu] Class update date: 180228
[Lr] Last revision date:180228
[St] Status:In-Data-Review
[do] DOI:10.1097/HJH.0000000000001624

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[PMID]: 29465713
[Au] Autor:Roush GC; Abdelfattah R; Song S; Kostis JB; Ernst ME; Sica DA
[Ad] Address:Department of Medicine, NYC Health and Hospitals/Woodhull.
[Ti] Title:Hydrochlorothiazide and alternative diuretics versus renin-angiotensin system inhibitors for the regression of left ventricular hypertrophy: a head-to-head meta-analysis.
[So] Source:J Hypertens;, 2018 Feb 20.
[Is] ISSN:1473-5598
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:BACKGROUND: Found in 36-41% of hypertension, elevated left ventricular mass (LVM) independently predicts cardiovascular events and total mortality. Conversely, drug-induced regression of LVM predicts improved outcomes. Previous studies have favored renin-angiotensin system inhibitors (RASIs) over other antihypertensives for reducing LVM but ignored differences among thiazide-type diuretics. From evidence regarding potency, cardiovascular events, and electrolytes, we hypothesized a priori that 'CHIP' diuretics [CHlorthalidone, Indapamide and Potassium-sparing Diuretic/hydrochlorothiazide (PSD/HCTZ)] would rival RASIs for reducing LVM. METHOD AND RESULTS: Systematic review yielded 12 relevant double-blind randomized trials. CHIPs were more closely associated with reduced LVM than HCTZ (P = 0.004), indicating that RASIs must be compared with each diuretic separately. Publication bias favoring RASIs was corrected by cumulative analysis. For reducing LVM, HCTZ tended to be less effective than RASIs. However, the following surpassed RASIs: chlorthalidone Hedge's G: -0.37 (95% CI -0.72 to -0.02), P = 0.036; indapamide -0.20 (-0.39 to -0.01), P = 0.035; all CHIPs combined (with 61% of patients in one trial) -0.25 (-0.41to -0.09), P = 0.002. Statistical significance (P < 0.05) did not depend on any one trial. CHIPs reduction in LVM was 37% greater than that from RASIs. CHIPs superiority tended to increase with trial duration, from a negligible effect at 0.5 year to a maximal effect at 0.9-1.0 years: -0.26 (-0.43 to -0.09), P = 0.003. Fifty-eight percent of patients had information on echocardiographic components of LVM: relative to RASIs, CHIPs significantly reduced end-diastolic LV internal dimension (EDLVID): -0.18 (-0.36 to -0.00), P = 0.046. Strength of evidence favoring CHIPs over RASIs was at least moderate. CONCLUSION: In these novel results in patients with hypertension, CHIPs surpassed RASIs for reducing LVM and EDLVID.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180221
[Lr] Last revision date:180221
[St] Status:Publisher
[do] DOI:10.1097/HJH.0000000000001691

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[PMID]: 29399724
[Au] Autor:Scheen AJ
[Ad] Address:Division of Diabetes, Nutrition and Metabolic Disorders, Department of Medicine, CHU Liège, University of Liège, CHU Sart Tilman (B35), B-4000, Liege, Belgium. andre.scheen@chu.ulg.ac.be.
[Ti] Title:Type 2 Diabetes and Thiazide Diuretics.
[So] Source:Curr Diab Rep;18(2):6, 2018 Feb 05.
[Is] ISSN:1539-0829
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:PURPOSE OF REVIEW: In patients with prediabetes or type 2 diabetes, the use of thiazides as antihypertensive agents has been challenged because associated metabolic adverse events, including new-onset diabetes. RECENT FINDINGS: These metabolic disturbances are less marked with low-dose thiazides and, in most but not all studies, with thiazide-like diuretics (chlorthalidone, indapamide) than with thiazide-type diuretics (hydrochlorothiazide). In post hoc analyses of subgroups of patients with hypertension and type 2 diabetes, thiazides resulted in a significant reduction in cardiovascular events, all-cause mortality, and hospitalization for heart failure compared to placebo and generally were shown to be non-inferior to other antihypertensive agents. Benefits attributed to thiazide diuretics in terms of cardiovascular event reduction outweigh the risk of worsening glucose control in type 2 diabetes and of new-onset diabetes in non-diabetic patients. Thiazides still play a key role in the management of patients with type 2 diabetes and hypertension.
[Pt] Publication type:JOURNAL ARTICLE; REVIEW
[Em] Entry month:1802
[Cu] Class update date: 180209
[Lr] Last revision date:180209
[St] Status:In-Data-Review
[do] DOI:10.1007/s11892-018-0976-6

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Clinical Trials Registry
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[PMID]: 29212812
[Au] Autor:Dewland TA; Soliman EZ; Yamal JM; Davis BR; Alonso A; Albert CM; Simpson LM; Haywood LJ; Marcus GM
[Ad] Address:From the Knight Cardiovascular Institute, Oregon Health & Science University, Portland (T.A.D.); Cardiology Section, Department of Internal Medicine, Wake Forest School of Medicine, Winston Salem, NC (E.Z.S.); University of Texas School of Public Health, Houston (J.-M.Y., B.R.D., L.M.S.); Depart
[Ti] Title:Pharmacologic Prevention of Incident Atrial Fibrillation: Long-Term Results From the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial).
[So] Source:Circ Arrhythm Electrophysiol;10(12), 2017 Dec.
[Is] ISSN:1941-3084
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:BACKGROUND: Although atrial fibrillation (AF) guidelines indicate that pharmacological blockade of the renin-angiotensin system may be considered for primary AF prevention in hypertensive patients, previous studies have yielded conflicting results. We sought to determine whether randomization to lisinopril reduces incident AF or atrial flutter (AFL) compared with chlorthalidone in a large clinical trial cohort with extended post-trial surveillance. METHODS AND RESULTS: We performed a secondary analysis of the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial), a randomized, double-blind, active-controlled clinical trial that enrolled hypertensive individuals ≥55 years of age with at least one other cardiovascular risk factor. Participants were randomly assigned to receive amlodipine, lisinopril, or chlorthalidone. Individuals with elevated fasting low-density lipoprotein cholesterol levels were also randomized to pravastatin versus usual care. The primary outcome was the development of either AF or AFL as diagnosed by serial study ECGs or by Medicare claims data. Among 14 837 participants without prevalent AF or AFL, 2514 developed AF/AFL during a mean 7.5±3.2 years of follow-up. Compared with chlorthalidone, randomization to either lisinopril (hazard ratio, 1.04; 95% confidence interval, 0.94-1.15; =0.46) or amlodipine (hazard ratio, 0.93; 95% confidence interval, 0.84-1.03; =0.16) was not associated with a significant reduction in incident AF/AFL. CONCLUSIONS: Compared with chlorthalidone, treatment with lisinopril is not associated with a meaningful reduction in incident AF or AFL among older adults with a history of hypertension. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000542.
[Mh] MeSH terms primary: Amlodipine/therapeutic use
Antihypertensive Agents/therapeutic use
Atrial Fibrillation/prevention & control
Atrial Flutter/prevention & control
Chlorthalidone/therapeutic use
Hypertension/drug therapy
Lisinopril/therapeutic use
Myocardial Infarction/prevention & control
Primary Prevention/methods
[Mh] MeSH terms secundary: Amlodipine/adverse effects
Antihypertensive Agents/adverse effects
Atrial Fibrillation/diagnosis
Atrial Fibrillation/epidemiology
Atrial Fibrillation/physiopathology
Atrial Flutter/diagnosis
Atrial Flutter/epidemiology
Atrial Flutter/physiopathology
Chlorthalidone/adverse effects
Double-Blind Method
Female
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use
Hypertension/diagnosis
Hypertension/epidemiology
Hypertension/physiopathology
Incidence
Lisinopril/adverse effects
Male
Middle Aged
Myocardial Infarction/diagnosis
Myocardial Infarction/epidemiology
Myocardial Infarction/physiopathology
Risk Factors
Time Factors
Treatment Outcome
United States/epidemiology
[Pt] Publication type:JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL
[Nm] Name of substance:0 (Antihypertensive Agents); 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors); 1J444QC288 (Amlodipine); E7199S1YWR (Lisinopril); Q0MQD1073Q (Chlorthalidone)
[Em] Entry month:1712
[Cu] Class update date: 180207
[Lr] Last revision date:180207
[Js] Journal subset:IM
[Da] Date of entry for processing:171208
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE


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