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Meta-Analysis
. 2018 Apr 18;4(4):CD001841.
doi: 10.1002/14651858.CD001841.pub3.

First-line drugs for hypertension

James M Wright  1 , Vijaya M Musini, Rupam Gill
Affiliations
Meta-Analysis

First-line drugs for hypertension

James M Wright et al. Cochrane Database Syst Rev. .

Abstract

Background: This is the first update of a review published in 2009. Sustained moderate to severe elevations in resting blood pressure leads to a critically important clinical question: What class of drug to use first-line? This review attempted to answer that question.

Objectives: To quantify the mortality and morbidity effects from different first-line antihypertensive drug classes: thiazides (low-dose and high-dose), beta-blockers, calcium channel blockers, ACE inhibitors, angiotensin II receptor blockers (ARB), and alpha-blockers, compared to placebo or no treatment.Secondary objectives: when different antihypertensive drug classes are used as the first-line drug, to quantify the blood pressure lowering effect and the rate of withdrawal due to adverse drug effects, compared to placebo or no treatment.

Search methods: The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials up to November 2017: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We contacted authors of relevant papers regarding further published and unpublished work.

Selection criteria: Randomized trials (RCT) of at least one year duration, comparing one of six major drug classes with a placebo or no treatment, in adult patients with blood pressure over 140/90 mmHg at baseline. The majority (over 70%) of the patients in the treatment group were taking the drug class of interest after one year. We included trials with both hypertensive and normotensive patients in this review if the majority (over 70%) of patients had elevated blood pressure, or the trial separately reported outcome data on patients with elevated blood pressure.

Data collection and analysis: The outcomes assessed were mortality, stroke, coronary heart disease (CHD), total cardiovascular events (CVS), decrease in systolic and diastolic blood pressure, and withdrawals due to adverse drug effects. We used a fixed-effect model to to combine dichotomous outcomes across trials and calculate risk ratio (RR) with 95% confidence interval (CI). We presented blood pressure data as mean difference (MD) with 99% CI.

Main results: The 2017 updated search failed to identify any new trials. The original review identified 24 trials with 28 active treatment arms, including 58,040 patients. We found no RCTs for ARBs or alpha-blockers. These results are mostly applicable to adult patients with moderate to severe primary hypertension. The mean age of participants was 56 years, and mean duration of follow-up was three to five years.High-quality evidence showed that first-line low-dose thiazides reduced mortality (11.0% with control versus 9.8% with treatment; RR 0.89, 95% CI 0.82 to 0.97); total CVS (12.9% with control versus 9.0% with treatment; RR 0.70, 95% CI 0.64 to 0.76), stroke (6.2% with control versus 4.2% with treatment; RR 0.68, 95% CI 0.60 to 0.77), and coronary heart disease (3.9% with control versus 2.8% with treatment; RR 0.72, 95% CI 0.61 to 0.84).Low- to moderate-quality evidence showed that first-line high-dose thiazides reduced stroke (1.9% with control versus 0.9% with treatment; RR 0.47, 95% CI 0.37 to 0.61) and total CVS (5.1% with control versus 3.7% with treatment; RR 0.72, 95% CI 0.63 to 0.82), but did not reduce mortality (3.1% with control versus 2.8% with treatment; RR 0.90, 95% CI 0.76 to 1.05), or coronary heart disease (2.7% with control versus 2.7% with treatment; RR 1.01, 95% CI 0.85 to 1.20).Low- to moderate-quality evidence showed that first-line beta-blockers did not reduce mortality (6.2% with control versus 6.0% with treatment; RR 0.96, 95% CI 0.86 to 1.07) or coronary heart disease (4.4% with control versus 3.9% with treatment; RR 0.90, 95% CI 0.78 to 1.03), but reduced stroke (3.4% with control versus 2.8% with treatment; RR 0.83, 95% CI 0.72 to 0.97) and total CVS (7.6% with control versus 6.8% with treatment; RR 0.89, 95% CI 0.81 to 0.98).Low- to moderate-quality evidence showed that first-line ACE inhibitors reduced mortality (13.6% with control versus 11.3% with treatment; RR 0.83, 95% CI 0.72 to 0.95), stroke (6.0% with control versus 3.9% with treatment; RR 0.65, 95% CI 0.52 to 0.82), coronary heart disease (13.5% with control versus 11.0% with treatment; RR 0.81, 95% CI 0.70 to 0.94), and total CVS (20.1% with control versus 15.3% with treatment; RR 0.76, 95% CI 0.67 to 0.85).Low-quality evidence showed that first-line calcium channel blockers reduced stroke (3.4% with control versus 1.9% with treatment; RR 0.58, 95% CI 0.41 to 0.84) and total CVS (8.0% with control versus 5.7% with treatment; RR 0.71, 95% CI 0.57 to 0.87), but not coronary heart disease (3.1% with control versus 2.4% with treatment; RR 0.77, 95% CI 0.55 to 1.09), or mortality (6.0% with control versus 5.1% with treatment; RR 0.86, 95% CI 0.68 to 1.09).There was low-quality evidence that withdrawals due to adverse effects were increased with first-line low-dose thiazides (5.0% with control versus 11.3% with treatment; RR 2.38, 95% CI 2.06 to 2.75), high-dose thiazides (2.2% with control versus 9.8% with treatment; RR 4.48, 95% CI 3.83 to 5.24), and beta-blockers (3.1% with control versus 14.4% with treatment; RR 4.59, 95% CI 4.11 to 5.13). No data for these outcomes were available for first-line ACE inhibitors or calcium channel blockers. The blood pressure data were not used to assess the effect of the different classes of drugs as the data were heterogeneous, and the number of drugs used in the trials differed.

Authors' conclusions: First-line low-dose thiazides reduced all morbidity and mortality outcomes in adult patients with moderate to severe primary hypertension. First-line ACE inhibitors and calcium channel blockers may be similarly effective, but the evidence was of lower quality. First-line high-dose thiazides and first-line beta-blockers were inferior to first-line low-dose thiazides.

PubMed Disclaimer

Conflict of interest statement

JMW: none.

VM: none.

RG: none.

Figures

1
1
Study flow diagram
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

ATTMH 1980 {published data only}
    1. Abernethy JD. The Australian therapeutic trial in mild hypertension. Hypertension 1984;6(5):774‐6. [MEDLINE: ] - PubMed
    1. Abernethy JD. The need to treat mild hypertension. Misinterpretation of results from the Australian trial. JAMA 1986;256(22):3134‐7. [MEDLINE: ] - PubMed
    1. Doyle AE. Cardiovascular morbidity and mortality in mild hypertension: the Australian trial. Journal of Cardiovascular Pharmacology 1985;7(Suppl 2):S10‐3. [MEDLINE: ] - PubMed
    1. Doyle AE. The Australian therapeutic trial in mild hypertension. Nephron 1987;47(Suppl 1):115‐9. [MEDLINE: ] - PubMed
    1. Management Committee. Initial results of the Australian therapeutic trial in mild hypertension. Report by the Management Committee. Clinical Science 1979;57:449s‐52s. [MEDLINE: ] - PubMed
Barraclough 1973 {published data only}
    1. Barraclough M, Joy MD, MacGregor GA, Foley TH, Lee MR, Rosendorff C, et al. Control of moderately raised blood pressure. Report of a co‐operative randomized controlled trial. British Medical Journal 1973;III:434‐6. [MEDLINE: ] - PMC - PubMed
Carter 1970 {published data only}
    1. Carter A. Hypotensive therapy in stroke survivors. Lancet 1970;I:485‐9. [MEDLINE: ] - PubMed
Dutch TIA 1993 {published data only}
    1. Dutch TIA Trial Study Group. Trial of secondary prevention with atenolol after transient ischemic attack or non‐disabling ischemic stroke. Stroke 1993;24:543‐8. - PubMed
EWPHE 1985 {published data only}
    1. Amery A, Berthaux P, Birkenhäger W, Boel A, Brixko P, Bulpitt C, et al. Antihypertensive therapy in patients above age 60 years. Fourth interim report of the European Working Party on High Blood Pressure in the Elderly. Clinical Science and Molecular Medicine 1978;55:263s‐70s. [MEDLINE: ] - PubMed
    1. Amery A, Berthaux P, Birkenhäger W, Boel A, Brixko P, Bulpitt C, et al. Antihypertensive therapy in patients above age 60. Third interim report of the European Working Party on High Blood Pressure in the Elderly. Acta Cardiologica 1978;33(2):113‐34. [MEDLINE: ] - PubMed
    1. Amery A, Berthaux P, Birkenhäger W, Bulpitt C, Clement D, Schaepdryver A, et al. Antihypertensive therapy in elderly patients. Pilot trial of the European Working Party on High Blood Pressure in the Elderly. Gerontology 1977;23(6):426‐37. [MEDLINE: ] - PubMed
    1. Amery A, Birkenhäger W, Brixko P, Bulpitt C, Clement D, Deruyttere M, et al. Glucose intolerance during diuretic therapy in elderly hypertensive patients. A second report from the European Working Party on High Blood Pressure in the Elderly. Postgraduate Medical Journal 1986;62(732):919‐24. [MEDLINE: ] - PMC - PubMed
    1. Amery A, Birkenhäger W, Brixko P, Bulpitt C, Clement D, Deruyttere M, et al. Mortality and morbidity results from the European Working Party on High Blood Pressure in the Elderly trial. Lancet 1985;1(8442):1349‐54. [MEDLINE: ] - PubMed
HOPE HYP 2000 {published data only}
    1. The HOPE Study Investigators. The HOPE (Heart Outcomes Prevention Evaluation) Study: the design of a large, simple randomized trial of angiotensin‐converting enzyme inhibitor (ramipril) and vitamin E in patients at high risk of cardiovascular events. Canadian Journal of Cardiology 1996;12:127‐37. - PubMed
    1. Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G. Effects of an angiotensin‐converting‐enzyme inhibitor, ramipril, on cardiovascular events in high‐risk patients. The Heart Outcomes Prevention Evaluation Outcomes Study Investigators. New England Journal of Medicine 2000;342(3):145‐53. [MEDLINE: ] - PubMed
HSCSG 1974 {published data only}
    1. Hypertension‐Stroke Cooperative Study Group. Effect of antihypertensive treatment on stroke recurrence. JAMA 1974;229:409‐18. [MEDLINE: ] - PubMed
HYVET 2008 {published data only}
    1. Beckett NS, Peters R, Fletcher AE, Staessen JA, Liu L, Dumitrascu D, et al. HYVET Study Group. Treatment of hypertension in patients 80 years of age or older. New Egyptian Journal of Medicine 2008;358(18):1887‐98. [MEDLINE: ] - PubMed
    1. Bulpitt CJ, Fletcher AE, Amery A, Coope J, Evans JG, Lightowlers S, et al. The Hypertension in the Very Elderly Trial (HYVET). Journal of Human Hypertension 1994;8(8):631‐2. - PubMed
    1. Bulpitt CJ, Fletcher AE, Amery A, Coope J, Evans JG, Lightowlers S, et al. The Hypertension in the Very Elderly Trial (HYVET): rationale, methodology and comparison with previous trials. Drugs & Aging 1994;5(3):171‐83. - PubMed
    1. Peters R, Beckett N, Forette F, Tuomilehto J, Clarke R, Ritchie C, et al. HYVET investigators. Incident dementia and blood pressure lowering in the Hypertension in the Very Elderly Trial cognitive function assessment (HYVET‐COG): a double‐blind, placebo controlled trial. Lancet 2008;7(8):683‐9. - PubMed
HYVET pilot 2003 {published data only}
    1. Beckett NS, Connor M, Sadler JD, Fletcher AE, Bulpitt CJ. Orthostatic fall in blood pressure in the very elderly: results from the Hypertension in the Very Elderly trial (HYVET) ‐ pilot. Journal of Human Hypertension 1999;13(12):839‐40. [MEDLINE: ] - PubMed
    1. Bulpitt CJ, Beckett NS, Cooke J, Dumitrascu DL, Gil‐Extremera B, Nachev C, et al. Results of the pilot study for the Hypertension in the Very Elderly Trial. Journal of Hypertension 2003;21:2409‐17. - PubMed
Kuramoto 1981 {published data only}
    1. Kuramoto K, Matsushita S, Kuwajima I, Murakami M. Prospective study on the treatment of mild hypertension in the aged. Japanese Heart Journal 1981;22:75‐85. [MEDLINE: ] - PubMed
MRC‐O 1992 {published data only}
    1. MRC Working Party. Medical Research Council trial of treatment of hypertension in older adults: principal results. British Medical Journal 1992;304:405‐12. [MEDLINE: ] - PMC - PubMed
MRC‐TMH 1985 {published data only}
    1. Medical Research Council Working Party. Comparison of the antihypertensive efficacy and adverse reactions to two doses of bendrofluazide and hydrochlorothiazide and the effect of potassium supplementation on the hypotensive action of bendrofluazide: sub studies of the Medical Research Council's trials of treatment of hypertension: Medical Research Council Working Party. Journal of Clinical Pharmacology 1987;27(4):271‐7. [MEDLINE: ] - PubMed
    1. Medical Research Council Working Party. Randomised controlled trial of treatment of mild hypertension: design and pilot trial. Report of the Medical Research Council Working party on Mild to Moderate Hypertension. British Medical Journal 1977;1(6074):1437‐40. [MEDLINE: ] - PMC - PubMed
    1. Medical Research Council Working Party on Mild Hypertension. Adverse reactions to bendrofluazide and propanolol for the treatment of mild hypertension. Report of Medical Research Council Working Party on Mild to Moderate Hypertension. Lancet 1981;2(8246):539‐43. [MEDLINE: ] - PubMed
    1. Medical Research Council Working Party on Mild Hypertension. Comparison of the antihypertensive efficacy and adverse reactions of two doses of bendrofluazide and hydrochlorothiazide and the effect of potassium supplementation on the hypotensive action of bendrofluazide: sub studies of the Medical Research Council's trials of treatment of mild hypertension. Journal of Clinical Pharmacology 1987;27(4):271‐7. [MEDLINE: ] - PubMed
    1. Medical Research Council Working Party on Mild Hypertension. Coronary heart disease in Medical Research Council trial of mild hypertension. British Heart Journal 1988;59(3):364‐78. [MEDLINE: ] - PMC - PubMed
OSLO 1986 {published data only}
    1. Helgeland A. Treatment of mild hypertension: a five year controlled drug trial. The Oslo study. American Journal of Medicine 1980;69:725‐32. [MEDLINE: ] - PubMed
    1. Helgeland A, Baksaas IA, Leren P. Mild hypertension ‐ early drug treatment or follow‐up only? the Oslo study. Acta Medica Scandinavica. Supplementum 1979;626:34‐6. [MEDLINE: ] - PubMed
    1. Helgeland A, Hjermann I, Holme I, Liren P. Serum triglycerides and serum uric acid in untreated and thiazide‐treated patients with mild hypertension. American Journal of Medicine 1978;64:34‐8. [MEDLINE: ] - PubMed
    1. Helgeland A, Leren P. Oslo study: treatment of mild hypertension. A five‐year controlled drug study. Nephron 1987;47(Suppl 1):108‐10. [MEDLINE: ] - PubMed
    1. Helgeland A, Leren P, Foss OP, Hjermann I, Holme I, Lund‐Larsen PG. Serum glucose levels during long‐term observation of treated and untreated men with mild hypertension. American Journal of Medicine 1984;76:802‐5. [MEDLINE: ] - PubMed
PATS 1996 {published data only}
    1. PATS collaborating group. Post‐stroke antihypertensive treatment study. A preliminary result. Chinese Medical Journal 1995;108(9):710‐7. [MEDLINE: ] - PubMed
SHEP 1991 {published data only}
    1. Applegate WB, Davis BR, Black HR, et al. Prevalence of postural hypotension at baseline in the systolic hypertension in the elderly program (SHEP) cohort. Journal of American Geriatric Society 1991;39:1057‐64. [MEDLINE: ] - PubMed
    1. Bearden D. Allman R. McDonald R, et al. Age, race, and gender variation in the utilization of coronary artery bypass surgery and angioplasty in SHEP. Journal of the American Geriatric Society 1994;42:1143‐49. [MEDLINE: ] - PubMed
    1. Black HR. Unger D. Burlando A, et al. Part 6: Baseline physical examination findings. Hypertension 1991;17(3 (Suppl II)):II‐77‐II‐101. [MEDLINE: ] - PubMed
    1. Borhani NO. Applegate WB. Cutler JA, et al. Part 1: rationale and design. Hypertension 1991;17(3 (Suppl II)):II‐2‐II‐15. [MEDLINE: ] - PubMed
    1. Brittain E. Palensky J. Blood J and Wittes J. Blinded subjective rankings as a method of assessing treatment effect: a large sample example from the systolic hypertension in the elderly program (SHEP). Statistics in Medicine 1997;16:681‐693. [MEDLINE: ] - PubMed
SHEP‐P 1989 {published data only}
    1. Black DM. Brand RJ. Greenlick M, et al. Compliance to treatment for hypertension in elderly patients: The SHEP pilot study. Journal of Gerontology 1987;42(5):552‐57. [MEDLINE: ] - PubMed
    1. Furberg CD. Black DM. for the SHEP research group. The systolic hypertension in the elderly program: Methodological issues. European Heart Journal 1988;9:223‐227. [MEDLINE: ] - PubMed
    1. Hulley SB. Feigal D. Ireland C, et al. Systolic hypertension in the elderly program (SHEP). Journal of the American Geriatric Society 1986;34(2):101‐105. [MEDLINE: ] - PubMed
    1. Hulley SB. Furberg CD. Gurland B. McDonald R, et al. Systolic Hypertension in the Elderly (SHEP): antihypertensive efficacy of chlorthalidone. The American Journal of cardiology 1985;56(15):913‐20. [MEDLINE: ] - PubMed
    1. Perry HM, et al. Morbidity and mortality in the Systolic Hypertension in the Elderly Program (SHEP) Pilot study. Stroke 1989;20:4‐13. [MEDLINE: ] - PubMed
SYST‐EUR 1997 {published data only}
    1. Amery A. Birkenhager W. Bulpitt CJ, et al. Syst‐Eur. A multicenter trial on the treatment of isolated systolic hypertension in the elderly: objectives, protocol and organization. Aging 1991;3(3):287‐302. [MEDLINE: ] - PubMed
    1. Birkenhager WH. Staessen J. Gasowski J, Leeuw PW. Effects of antihypertensive treatment on endpoints in the diabetic patients randomized in the systolic hypertension in Europe (Syst‐Eur) trial. Journal of Nephrology 2000;13:232‐237. [Accession number 331TE‐ 0011] - PubMed
    1. Gasowski J. Birkenhager WH. Staessen J, Leeuw PW. Benefit of antihypertensive treatment in diabetic patients enrolled in the systolic hypertension in Europe (Sys‐Eur) trial. Cardiovascular Drugs and Therapy 2000;14:49‐53. [Accession number 281MJ‐ 0006] - PubMed
    1. Girerd X, Amery A, Birkenhager W, Bulpitt C, Cox J, Leeuw P. SYST‐EUR: a multicenter trial of treatment of systolic hypertension in aged subjects. An initial report (French). Archives des Maladies du Coeur et des Vaisseaux 1992;85(8):1243‐7. - PubMed
    1. Slovick D, Staessen J, Bert P, Bulpitt C, Cort P, Fagard R, et al. Nitrendipine in older patients with isolated systolic hypertension: second progress report on the Syst‐Eur trial. J Hum Hypertens 1993;7(4):411‐2. - PubMed
TEST 1995 {published data only}
    1. Eriksson S, Olofsson BO, Wesley PO, for the TEST study group. Atenolol for secondary prevention after stroke. Cerebrovasc Dis 1995;5:21‐25.
UKPDS 39 1998 {published data only}
    1. UK Prospective Diabetes Study Group. Efficacy of atenolol and captopril in reducing risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 39. Brit Med J 1998;317:713‐720. - PMC - PubMed
    1. UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. Brit Med J 1998;317:703‐713. - PMC - PubMed
    1. United Kingdom Prospective Diabetes Study Group. UK prospective diabetes study VIII: study design, progress and performance. Diabetologia 1991;34:877‐90. - PubMed
USPHSHCSG 1977 {published data only}
    1. Smith WM, Bouchard RJ, Bromer L, et al. Morbidity and mortality in mild essential hypertension. Circ Res 1972;30/31(Suppl II):110‐20. - PubMed
    1. Smith WM, Johnson WP, Bromer L. Intervention trial in mild hypertension,U.S. Public Health Service Hospitals Cooperative Study Group. Intervention trial in mild hypertension, U.S. Public Health Service Hospitals Cooperative Study Group. Miami, Symposia Specialists: In Epidemiology and Control of Hypertension, edited by OPaul, 1975:461‐83.
    1. US. public health service hospital cooperative study group (USPHSHCSG). Treatment of mild hypertension. Results of a ten‐year intervention trial. Circ Res 1977;40(Suppl 1):98‐105. [MEDLINE: ] - PubMed
VA‐I 1967 {published data only}
    1. Freis ED. Antihypertensive Therapy; Principles and Practice, an International Symposium. In: Gross F editor(s). Antihypertensive Therapy; Principles and Practice, an International Symposium. New York: Springer‐Verlag, 1966:345‐54.
    1. Veterans Administration Cooperative Study Group on Antihypertensive Agents. A double‐blind control study of antihypertensive agents. III. Chlorothiazide alone and in combination with other agents: preliminary results. Arch Intern Med 1962;110:230‐5. [No unique identifier]
    1. Veterans Administration Cooperative Study Group on Antihypertensive Agents. Effects of treatment on morbidity in hypertension. Results in patients with diastolic blood pressures averaging 115 through 129 mm Hg. JAMA 1967;202:1028‐1034. [MEDLINE: ] - PubMed
VA‐II 1970 {published data only}
    1. Veterans Administration Cooperative Study Group on Antihypertensive Agents. Effects of treatment on morbidity in hypertension II. Results in patients with diastolic blood pressure averaging 90 through 114 mm Hg. JAMA 1970;213:1143‐1152. [MEDLINE: ] - PubMed
VA‐NHLBI 1978 {published data only}
    1. Perry Jr HM, et al. Evaluation of drug treatment in mild hypertension: VA‐NHLBI feasibility trial. Ann N Y Acad Sci 1978;304:267‐288. [MEDLINE: ] - PubMed
    1. Perry Jr HM, et al. Treatment of mild hypertension. Preliminary results of a two year feasibility trial. Circ Res 1977;40 suppl:1180‐187. [MEDLINE: ] - PubMed
Wolff 1966 {published data only}
    1. Wolff FW, Lindeman RD. Effects of treatment in hypertension. Results of a controlled study. J Chron Dis 1966;19:227‐240. [MEDLINE: ] - PubMed

References to studies excluded from this review

ACTIVE I 2011 {published data only}
    1. The Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE I)Investigators. Irbesartan in patients ACTIVE 1 with atrial fibrillation. N Engl J Med 2011;364:928‐33.
ADVANCE 2007 {published data only}
    1. Patel A, ADVANCE Collaborative Group, MacMahon S, Chalmers J, Neal B, et al. Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial. Lancet 2007;370:829‐40. - PubMed
ALLHAT 2000 {published data only}
    1. ALLHAT Group. Major cardiovascular events in hypertensive patients randomized to doxazosin vs chlorthalidone: the antihypertensive and lipid lowering treatment to prevent heart attack trial (ALLHAT). JAMA 2000;283:1967‐75. [MEDLINE: ] - PubMed
    1. Davis BR. Cutler JA. Gordon DJ. et al for the ALLHAT Research Group. Rationale and design for the Antihypertensive and Lipid Lowering Treatment to prevent Heart Attack Trial (ALLHAT). Am J Hypertens 1996;9:342‐360. [MEDLINE: ] - PubMed
BENEDICT 2004 {published data only}
    1. Ruggenenti P, Fassi A, Ilieva AP, Bruno S, Iliev IP, Brusegan V, Rubis N, Gherardi G, Arnoldi F, Ganeva M, Ene‐Iordache B, Gaspari F, Perna A, et al. Preventing microalbuminuria in type 2 diabetes. N Engl J Med 2004;351:1941‐51. - PubMed
BENEDICT A 2006 {published data only}
    1. Parving H, Lehnert H, Brochner ‐ Mortensen J, Gomis R, et al. The effect of irbesartan on teh development of diabetic nephropathy in patients with type 2 diabetes. NEJM 2001;345:870‐8. - PubMed
Berglund 1981 {published data only}
    1. Berglund G. Andersson O. Beta‐blockers of diuretics in hypertension? A six year follow‐up of blood pressure and metabolic side effects. Lancet 1981;I:744‐747. [MEDLINE: ] - PubMed
CASTEL 1994 {published data only}
    1. Casigila E. Spolaore P. Mazza A. Ginocchio G, et al. Effect of two different therapeutic approaches on total and cardiovascular mortality in a Cardiovascular Study in the Elderly (CASTEL). Jpn Heart J 1994;35(5):589‐600. [MEDLINE: ] - PubMed
Coope 1986 {published data only}
    1. Coope J. Randomised trial of treatment of hypertension in elderly patients in primary care. Brit Med J 1986;293:1145‐1151. [MEDLINE: ] - PMC - PubMed
DIABHYCAR 2004 {published data only}
    1. Marre M, Lievre M, Chatellier G, Mann JF, Passa P, Ménard J, DIABHYCAR Study Investigators. Effects of low dose ramipril on cardiovascular and renal outcomes in patients with type 2 diabetes and raised excretion of urinary albumin: randomised, double blind, placebo controlled trial (the DIABHYCAR study). BMJ 2004;328:495‐502. - PMC - PubMed
DREAM 2006 {published data only}
    1. DREAM trial investigators. Effect of ramipril on the incidence of diabetes. The DREAM trial investigators. N Engl J Med 2006;355:1551‐62. - PubMed
EUROPA 2003 {published data only}
    1. Fox KM, for the EURopean trial On reduction of‐cardiac events with Perindopril in stable coronary Artery disease Investigators. Efficacy of perindopril in reduction of‐ cardiovascular events among patients with stable coronary artery disease: Randomised, double‐blind, placebo‐controlled, multicentre trial (the EUROPA study). Lancet 2003;362:782‐8. - PubMed
Fuchs 2011 {published data only}
    1. Fuchs FD, Fuchs SC, Moreira LB, Gus M, Nobrega AC, et al. Prevention of hypertension in patients with pre‐hypertension: protocol for the PREVER‐prevention trial. Trials 2011;12(65):1‐7. [DOI: 10.1186/1745‐6215‐12‐65] - PMC - PubMed
GENERIC 2010 {published data only}
    1. Punzi HA, Lewin AJ, Lukic T, Goodin T, Chen W. Efficacy and safety of nebivolol monotherapy in Hispanics with Stage I‐II Hypertension (Abstract). Journal of clinical hypertension 2010;12:536. - PubMed
GENRES 2007 {published data only}
    1. Hitunen TP, Suonsyrja T, Hannila‐Handelberg T, Paavonen KJ, et al. Predictors of antihypertensive drug responses: initial data from a placebo‐controlled , randomized, cross over study with four antihypertensive drugs. Journal of Hypertension 2009;27:2001‐9. - PubMed
GLANT 1995 {published data only}
    1. Study Group on Long‐term Antihypertensive Therapy. A 12‐month comparison of ACE inhibitor and CA antagonist therapy in mild to moderate essential hypertension‐ the GLANT study. Hypertens Res 1995;18:235‐244. [MEDLINE: ] - PubMed
HAPPHY 1987 {published data only}
    1. Wilhelmsen L. Berglund B. Elmfeldt D. Fitzsimons T, et al. Beta‐blockers versus diuretics in hypertensive men: Main results from the HAPPHY trial. J Hypertens 1987;5:561‐572. [MEDLINE: ] - PubMed
HDFP 1984 {published data only}
    1. HDFP. Effect of stepped care treatment on the incidence of myocardial infarction and angina pectoris. 5‐year findings of the hypertension detection and follow‐up program. Hypertension 1984;6(Suppl 1):198‐206. [MEDLINE: ] - PubMed
Hood 2007 {published data only}
    1. Hood SJ, Taylor KP, Ashby MJ, Brown MJ. The Spironolactone, Amiloride, Losartan, and Thiazide (SALT) Double‐Blind Crossover Trial in Patients With Low‐Renin Hypertension and Elevated Aldosterone‐Renin Ratio. Circulation 2007;116:268‐75. - PubMed
HOPE 3 2016 {published data only}
    1. Lonn EM, Bosch J, Lopez‐ Jaramillo P, Zhu J, et al. Blood‐Pressure Lowering in Intermediate‐Risk Persons without Cardiovascular Disease. N Engl J Med 2016;374:2009‐20. - PubMed
HOT 1995 {published data only}
    1. Hansson L, Zanchetti A. The Hypertension Optimal Treatment (HOT) Study: 12‐month Data on Blood Pressure and Tolerability. With Special Reference to Age and Gender. Blood Pressure 1995;4(5):313‐19. - PubMed
IDM 2001 {published data only}
    1. Parving HH, Lehnert H, Brochner‐Mortensen J, Gomis R, Andersen S, Arner P. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. NEJM 2001;345:870‐878. - PubMed
IDNT 2003 {published data only}
    1. Berl T, Hunsicker LG, Lewis JB, Pfeffer MA, Porush JG, Rouleau JL, Drury PL, Esmatjes E, Hricik D, Parikh CR, Raz I, Vanhille P, Wiegmann TB, Wolfe BM, Locatelli F, Goldhaber SZ, Lewis EJ, Irbesartan Diabetic Nephropathy Trial. Collaborative Study Group. Cardiovascular outcomes in the Irbesartan diabetic nephropathy trial of patients with type 2 diabetes and overt nephropathy. Ann Intern Med 2003;138:542‐9. - PubMed
IMAGINE 2008 {published data only}
    1. Rouleau JL, Warnica WJ, Baillot R, Block PJ, Chocron S, Johnstone D, Myers MG, Calciu CD, Dalle‐Ave S, Martineau P, Mormont C, Gilst WH, IMAGINE (Ischemia Management with Accupril post‐bypass Graft via Inhibition of the coNverting Enzyme) Investigators. Effects of angiotensin converting enzyme inhibition in low‐risk patients early after coronary artery bypass surgery. Circulation 2008;117:24‐31. - PubMed
Imai 2011 {published data only}
    1. Imai E, Chan J, Ito S, Yamasaki T, et al. Effects of olmesartan on renal and cardiovascular outcomes in type 2 diabetes with overt nephropathy: a multicentre, randomised, placebo‐controlled study. Diabetologia 2011;54:2978‐86. - PMC - PubMed
INSIGHT 1996 {published data only}
    1. Brown MJ. Castaigne A. De Leeuw PW. Mancia G, et al. INSIGHT: International Nifedipine GITS study: Intervention as a goal in hypertension treatment. J Hum Hypertens 1996;10((Suppl3)):S157‐160. [MEDLINE: ] - PubMed
IPPPSH 1985 {published data only}
    1. The IPPPSH Collaborative Group. Cardiovascular risk and risk factors in a randomized trial of treatment based on the beta‐blocker, oxprenolol: The international prospective primary prevention study in hypertension (IPPPSH). J Hypertens 1985;3:379‐392. [MEDLINE: ] - PubMed
Kondo 2003 {published data only}
    1. Kondo J, Sone T, Tsuboi H, Mukawa H, Morishima I, Uesugi M, Kono T, Kosaka T, Yoshida T, Numaguchi Y, Matsui H, Murohara T, Okumura K. Effects of low‐dose angiotensin II receptor blocker candesartan on cardiovascular events in patients with coronary artery disease. Am Heart J 2003;146:E20‐25. - PubMed
Kuramoto‐2 1994 {published data only}
    1. Kuramoto K. Treatment of the elderly hypertensives in Japan: National Intervention Cooperative Study in Elderly Hypertensives. The National Intervention Cooperative study Group. J Hypertens 1994;12(6):S35‐40. [MEDLINE: ] - PubMed
Lewis 1993 {published data only}
    1. Lewis EJ, Hunsicker LG, Bain RP, Rohde RD. The effect of angiotensin‐converting‐enzyme inhibition on diabetic nephropathy. N Engl J Med 1993;329:1456‐62. - PubMed
Lewis 2001 {published data only}
    1. Lewis EJ, Hunsicker LG, Clarke WR, Berl T, Pohl MA, Lewis JB, Ritz E, Atkins RC, Rohde R, Raz I. Renoprotective effect of the angiotensin‐receptor antagonist irbesartan in patients with nephropathy due to Type 2 Diabetes. NEJM 2001;345:851‐860. - PubMed
MacMahon 2000 {published data only}
    1. MacMahon S, Sharpe N, Gamble G, Clague A, Mhurchu CN, Clark T, et al. PART‐2 Collaborative Research Group. Randomized, placebo‐controlled trial of the angiotensin‐converting enzyme inhibitor, ramipril, in patients with coronary or other occlusive arterial disease. J Am Coll Cardiol 2000;36:438‐43. - PubMed
MAPHY 1988 {published data only}
    1. Wikstrand J. Warnold I. Olsson G, et al. Primary prevention with metoprolol in patients with hypertension: mortality results from the MAPHY study. JAMA 1988;259:1976‐1982. [MEDLINE: ] - PubMed
    1. Wikstrand J, et al. Metoprolol versus thiazide diuretics in hypertension. Morbidity results from the MAPHYstudy Hypertension 1991;17:579‐588. [MEDLINE: ] - PubMed
Materson 1997 {published data only}
    1. Materson BJ. Reda DJ. Cushman WC. Massie BM, et al. Single‐drug therapy for hypertension in men: a comparison of six antihypertensive agents with placebo. NEJM 1997;328:914‐921. [MEDLINE: ] - PubMed
MIDAS 1996 {published data only}
    1. Borhani NO. Mercuri M. Borhani PA. Buckalew VM. Canossa‐Terris M, et al. Final outcome results of the multicenter isradipine diuretic atherosclerosis study (MIDAS) A randomised controlled trial. JAMA 1996;276:785‐791. [MEDLINE: ] - PubMed
Morgan 1980 {published data only}
    1. Morgan TO. Adams WR. Hodgson M, Gibberd RW. Failure of therapy to improve prognosis in elderly males with hypertension. Med J Aust 1980;2(1):27‐31. [MEDLINE: ] - PubMed
NAVIGATOR 2010 {published data only}
    1. McMurray JJ, Holman RR, Haffner SM, Bethel MA, Holzhauer B, Hua TA, et al. Effect of valsartan on the incidence of diabetes and cardiovascular events. N Engl J Med 2010;362:1477‐90. - PubMed
NICOLE 2003 {published data only}
    1. Dens JA, Desmet WJ, Coussement P, Scheerder KD, et al. Long term effects of nisoldipine on the progression of coronary atherosclerosis and the occurrence of clinical events: the NICOLE study. Heart 2003;89:887‐92. - PMC - PubMed
NORDIL 2000 {published data only}
    1. Hansson L. Hedner T. Lund‐Johnson P. Kjeldsen SE, et al. Randomised trial of effects of calcium antagonists compared with diuretics and beta‐blockers on cardiovascular morbidity and mortality in hypertension: the Nordic Dilitazem (NORDIL) study. Lancet 2000;356(9227):359‐65. [MEDLINE: ] - PubMed
PEACE 2004 {published data only}
    1. Braunwald E, Domanski MJ, Fowler SE, Geller NL, Gersh BJ, Hsia J, Pfeffer MA, Rice MM, Rosenberg YD, Rouleau JL, PEACE Trial Investigators. Angiotensin converting‐ enzyme inhibition in stable coronary artery disease. N Engl J Med 2004;351:2058‐68. - PMC - PubMed
Pool 2007 {published data only}
    1. Pool JL, Glazer R, Weinberger M, et al. Comparison of valsartan/hydrochlorothiazide combination therapy at doses up to 320/25mg versus monotherapy: a double‐blind, placebo‐controlled study followed by long‐term combination therapy in hypertensive adults. Clin Ther 2007;29(1):61‐73. - PubMed
PRoFESS 2008 {published data only}
    1. Yusuf S, Diener HC, Sacco RL, Cotton D, Ounpuu S, Lawton WA, etal. PRoFESS Study Group. Telmisartan to prevent recurrent stroke and cardiovascular events. N Engl J Med 2008;359:1225‐37. - PMC - PubMed
PROGRESS 2001 {published data only}
    1. PROGRESS Collaborative Group. Randomised trial of a perindopril‐based blood‐pressure‐lowering regimen among 6105 individuals with previous stroke or transient ischemic attack.. Lancet 2001;358:1033‐41. - PubMed
QUIET 2001 {published data only}
    1. Pitt B, O'Neill B, Feldman R, Ferrari R, Schwartz L, Judra H, Bass T, et al. The QUinapril Ischemic Event Trial (QUIET): Evaluation of chronic ACE inhibitor therapy in patients with ischemic heart disease and preserved left ventricular function. Am J Cardiol 2001;87:1058‐1063. - PubMed
REIN 1997 {published data only}
    1. GISEN Group. Randomised placebo‐controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non‐diabetic nephropathy [Gruppo Italiano di Studi Epidemiologici in Nefrologia]. Lancet 1997;349:1857‐63. - PubMed
RENAAL 2001 {published data only}
    1. Brenner BM, Cooper ME, Zeeuw D, Keane WF, Mitch WE, Parving HH, Remuzzi G, Snapinn SM, Zhang Z, Shahinfar S, RENAAL Study Investigators. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 2001;345:861‐9. - PubMed
ROAD 2007 {published data only}
    1. Hou FF, Xie D, Zhang X, Chen PY, Zhang WR, Liang M, Guo ZJ, Jiang JP. Renoprotection of Optimal Antiproteinuric Doses (ROAD) Study: a randomized controlled study of benazepril and losartan in chronic renal insufficiency. J Am Soc Nephrol 2007;18:1889‐98. - PubMed
ROADMAP 2011 {published data only}
    1. Haller H, Ito S, Izzo JL Jr, Januszewicz A, Katayama S, et al. ROADMAP Trial Investigators. Olmesartan for the delay or prevention of microalbuminuria in type 2 diabetes. N Engl J Med 2011;364:907‐17. - PubMed
SCAST 2015 {published data only}
    1. Jusufovic M, Sandset EC, Bath PM, Karlson BW, Berge E. Scandinavian Candesartan Acute Stroke Trial Study Group. Effects of blood pressure lowering in patients with acute ischemic stroke and carotid artery stenosis. International Journal of Stroke 2015;10:354‐9. - PubMed
SCAT 2000 {published data only}
    1. Teo KK, Burton JR, Buller CE, Plante S, Catellier D, Tymchak W, Dzavik V, Taylor D, Yokoyama S, Montague TJ. Long‐term effects of cholesterol lowering and angiotensin converting enzyme inhibition on coronary atherosclerosis.. Circulation 2000;102:1748‐54. - PubMed
Schmieder 2012 {published data only}
    1. Schmieder RE, Philipp T, Guerediaga J, Gorostidi M, et al. Long‐term antihypertensive efficacy and safety of the oral direct renin Inhibitor aliskiren. A 12‐month randomized, double‐blind comparator trial with hydrochlorothiazide. Circulation 2009;119:417‐25. - PubMed
SCOPE 2003 {published data only}
    1. Lithell H, Hansson L, Skoog I, Elmfeldt D, Hofman A, Olofsson B, Trenkwalder P, Zanchetti A. The Study on Cognition and Prognosis in the Elderly (SCOPE): principal results of a randomized double‐blind intervention trial. J Hypertension 2003;21:875‐886. - PubMed
SHELL 1995 {published data only}
    1. Zanchetti A. Evaluating the benefits of an antihypertensive agent using trials based on event and organ damage: the systolic Hypertension in the Elderly Long‐term Lacidipine (SHELL) trial and European Lacidipine Study on Atherosclerosis (ELSA). J of Hypertension‐ supplement 1995;13(4):S35‐9. [MEDLINE: ] - PubMed
Sprackling 1981 {published data only}
    1. Sprackling ME, Mitchell JRA, Short AH, Watt G. Blood pressure reduction in the elderly: a randomised controlled trial of methyldopa. BMJ 1981;283:1151‐3. [MEDLINE: ] - PMC - PubMed
STONE 1996 {published data only}
    1. Gong L. Zwang W. Zhu Y, et al. Shanghai Trial of Nifedipine in the Elderly (STONE) Study. J Hypertens 1996;14:1237‐46. [MEDLINE: ] - PubMed
STOP 1991 {published data only}
    1. Dahlof B, et al. Morbidity and mortality in the Swedish Trial in Old Patients with Hypertension (STOPHypertension). Lancet 1991;338:1281‐1285. [MEDLINE: ] - PubMed
STOP‐2 1993 {published data only}
    1. Dahlof B. Hansson L. Lindholm LH, et al. STOP ‐ Hypertension 2: A prospective intervention trial of "newer" vs "older" treatment alternatives in old patients with hypertension. Blood Pressure 1993;2:136‐141. [MEDLINE: ] - PubMed
Strandberg 1991 {published data only}
    1. Strandberg E, et al. Long‐term mortality after 5‐year multifactorial primary prevention of cardiovascular diseases in middle‐aged men. JAMA 1991;266:1255‐1259. [MEDLINE: ] - PubMed
SYST‐CHINA 1993 {published data only}
    1. Anonymous. [Systolic hypertension in the elderly: Chinese trial (Syst‐China)‐‐second interim report]. [Chinese] Chung‐Hua Hsin Hsueh Kuan Ping Tsa Chih [Chinese Journal of Cardiology] 1993;21(3):135‐7,185. [Accession number 1993350344] - PubMed
TOMHS 1993 {published data only}
    1. Neaton JD. Brimm RH. Prineas RJ, et al. Treatment of mild hypertension study. Final results. JAMA 1993;270:713‐724. [MEDLINE: ] - PubMed
TRANSCEND 2008 {published data only}
    1. Telmisartan Randomised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease (TRANSCEND) Investigators, Yusuf S, Teo K, Anderson C, Pogue J, Dyal L, Copland I, Schumacher H, Dagenais G, Sleight P. Effects of the angiotensin‐receptor blocker telmisartan on cardiovascular events in high‐risk patients intolerant to angiotensin converting enzyme inhibitors: a randomised controlled trial. Lancet 2008;372:1174‐83. - PubMed
VACS 1982 {published data only}
    1. Veterans Administrative Cooperative Study Group on Antihypertensive Agents. Comparison of propanolol and hydrochlorothiazide for the initial treatment of hypertension. II Results of long term therapy. JAMA 1982;248:2004‐2011. [MEDLINE: ] - PubMed
VHAS 1997 {published data only}
    1. Agabiti RE, Dal Palu D, Leonetti G, Magnani G, Pessina A, Zanchetti A. Clinical results of the verapamil in hypertension and atherosclerosis study.. J Hypertens 1997;15:1337‐1344. - PubMed
White 1995 {published data only}
    1. White WB, Stimpel M. Long‐term safety and efficacy of moexipril alone and in combination with hydrochlorothiazide in elderly patients with hypertension. J Hum Hypertension 1995;9(11):879‐84. [MEDLINE: ] - PubMed

Additional references

BBLTTC 2005
    1. Turnbull F, Neal B, Albert C, Chalmers J, Chapman N, Cutler J, Woodward M, MacMahon S: Blood Pressure Lowering Treatment Trialists' Collaboration. Effects of different blood pressure‐lowering regimens on major cardiovascular events in individuals with and without diabetes mellitus: results of prospectively designed overviews of randomized trials.. Arch Intern Med 2005;165(12):1410‐1419. [MEDLINE: ] - PubMed
Boissel 2005
    1. Boissel JP, Gueyffier F, Boutitie F, Pocock S, Fagard R. Apparent effect on blood pressure is only partly responsible for the risk reduction due to antihypertensive treatments.. Fund Clin Pharmacol 2005;19:579‐584. - PubMed
BPLTTC 2000
    1. Blood Pressure Lowering Treatment Trialists’ Collaboration. Effects of ACE inhibitors, calcium antagonists, and other blood pressure‐lowering drugs: results of prospectively designed overviews of randomised trials. Lancet 2000;355:1955‐64. - PubMed
Chen 2010
    1. Chen N, Zhou M, Yang M, Guo J, Zhu C, Yang J, Wang Y, Yang X, He L. Calcium channel blocker versus other classes of drugs for hypertension. Cochrane Database of Systematic Reviews 2010, Issue 8. [DOI: 10.1002/14651858.CD003654.pub4] - DOI - PubMed
Collins 1990
    1. Collins, R, Peto, R, Macmahon, S, Hebert, P, Fiebach, N.H, Eberlein, k.A, Godwin, J, Qizilbash, N, Taylor, J.O, Hennekens, C.H. Blood pressure, stroke, and coronary heart disease‐ Part 2. Short‐term reductions in blood pressure: overview of randomised drug trials in their epidemiological context. Lancet 1990;335:827‐38. [MEDLINE: ] - PubMed
Diao 2012
    1. Diao D, Wright JM, Cundiff DK, Gueyffier F. Pharmacotherapy for mild hypertension. Cochrane Database of Systematic Reviews 2012, Issue 8. [DOI: 10.1002/14651858.CD006742.pub2] - DOI - PMC - PubMed
Duarte 2010
    1. Duarte JD, Cooper‐DeHoff RM. Mechanisms for blood pressure lowering and metabolic effects of thiazide and thiazide‐like diuretics. Expert Rev Cardiovasc Ther. 2010;8(6):793‐802. - PMC - PubMed
Frishman 2005
    1. Frishman W.H, Cheng‐Lai A, Nawarskas J. Current Cardiovascular Drugs. Fourth. Current Science Group, 2005:153.
Goeres 2014
    1. Goeres LM, Eckstrom E, Lee DS. Pharmacotherapy for Hypertension in Older Adults: A Systematic Review. Drugs Aging 2014;31:897‐910. - PubMed
GRADEpro GDT [Computer program]
    1. McMaster University (developed by Evidence Prime). GRADEpro GDT. Hamilton (ON): McMaster University (developed by Evidence Prime), 2015.
Gueyffier 1996
    1. Gueyffier F. Froment A, Gouton M. New meta‐analysis of treatment trials of hypertension: improving the estimate of therapeutic benefit. J Human Hyperten 1996;10:1‐8. [MEDLINE: ] - PubMed
Gueyffier 1999
    1. Gueyffier F, Bulpitt C, Boissel JP, Schron E, Ekbom T, et al. for the INDANA Group. Antihypertensive drugs in very old people: a subgroup meta‐analysis of randomised controlled trials. Lancet 1999;353:793‐96. - PubMed
Higgins 2011a
    1. Higgins JP, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration. Available from handbook.cochrane.org, 2011.
Higgins 2011b
    1. Higgins JPT, Altman DG, Sterne JAC. Chapter 8: Assessing risk of bias in included studies. In: Higgins JP, Green S editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration. Available from handbook.cochrane.org, 2011.
Hughes 2004
    1. Hughes AD. "How do thiazide and thiazide‐like diuretics lower blood pressure?". J Renin Angiotensin Aldosterone Syst 2004;5(4):155‐60. - PubMed
Insua 1994
    1. Insua JT. Sacks HS. Lau TS. Lau J, et al. Drug treatment of hypertension in the elderly: A meta‐analysis. Ann Intern Med 1994;121:355‐62. [MEDLINE: ] - PubMed
Kang 2004
    1. Kang S, Wu FY, An N, Ren M. A Systematic Review and Meta‐Analysis of the Efficacy and Safety of a Fixed,Low‐Dose Perindopril‐Indapamide Combination as First‐Line Treatment of Hypertension. Clinical Therapeutics 2004;26(2):257‐70. - PubMed
Kızılırmak 2017
    1. Kızılırmak P, Uresin Y, Ozdemir O, Kilickiran B, et al. Renin‐angiotensin‐aldosterone system blockers and cardiovascular outcomes: a meta‐analysis of randomized clinical trials [Renin‐anjiyotensin‐aldosteron sistemi blokerleri ve kardiyovasküler sonuçları: Randomize klinik çalışmaların meta‐analizi]. Turk Kardiyol Dern Ars 2017;45(1):49‐66. [DOI: 10.5543/tkda.2016.78006] - DOI - PubMed
Law 2009
    1. Law MR, Morris JK, Wald NJ. Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta‐analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies. BMJ 2009;338:b1665. - PMC - PubMed
MacMahon 1993
    1. MacMahon S, Rogers A. The effects of blood pressure reduction in older patients: an overview of five randomized controlled trials in elderly hypertensives. Clin Exper Hypertension 1993;15(6):967‐78. [Accession number 1993344587] - PubMed
Mulrow 1994
    1. Mulrow CD, Cornell JA, Herrera CR, Kadri A, et al. Hypertension in the elderly: Implications and generalizability of randomized trials. JAMA 1994;272:1932‐8. [MEDLINE: ] - PubMed
Mulrow 1998
    1. Mulrow C, Lau J, Cornell J, Brand M. Pharmacotherapy for hypertension in the elderly. Cochrane Database of Systematic Reviews 1998, Issue 2. [DOI: 10.1002/14651858.CD000028] - DOI - PubMed
Musini 2009
    1. Musini VM, Tejani AM, Bassett K, Wright JM. Pharmacotherapy of hypertension in the elderly. Cochrane Database of Systematic Reviews 2009, Issue 4. [DOI: 10.1002/14651858.CD000028.pub2] - DOI - PubMed
Musini 2017
    1. Musini VM, Gueyffier F, Puil L, Salzwedel DM, Wright JM. Pharmacotherapy for hypertension in adults aged 18 to 59 years. Cochrane Database of Systematic Reviews 2017, Issue 8. [DOI: 10.1002/14651858.CD008276.pub2] - DOI - PMC - PubMed
Nikolaus 2000
    1. Nikolaus T, Sommer N, Becker C. Treatment of arterial hypertension with diuretics, beta‐ and calcium channel blockers in old patients. Z Gerontol Geriat 2000;33:427‐32. - PubMed
Parsons 2016
    1. Parsons C, Murad MH, Andersen S, Mookadam F, Labonte H. The effect of antihypertensive treatment on teh incidence of stroke and cognitive decline in the elderly: a meta‐analysis. Future Cardiology 2016;12(2):237‐48. - PubMed
Pearce 1995
    1. Pearce KA, Furberg CD, Rushing J. Does Antihypertensive Treatment of the Elderly Prevent Cardiovascular Events or Prolong Life? A Meta‐analysis ofHypertension Treatment Trials. Archives of Family Medicine 1995;4:943‐50. - PubMed
Psaty 1997
    1. Psaty BM, Smith NL, Siscovick DS, Koepsell TD, et al. Health outcomes associated with antihypertensive therapies used as first‐line agents. A systematic review and meta‐analysis.. JAMA 1997;277:739‐745. [MEDLINE: ] - PubMed
Psaty 2003
    1. Psaty BM, Lumley T, Furberg CD, Schellenbaum G, Pahor M, Alderman MH, Weiss NS. Health outcomes associated with various antihypertensive therapies used as first‐line agents: A network meta‐analysis. JAMA 2003;289:2534‐2544. - PubMed
Puttnam 2017
    1. Puttnam J, Davis BR, Pressel SL, Whelton PK, Cushman WC, Louis GT, Margolis KL, Oparil S, Williamson J, Ghosh A, Einhorn PT and, Barzilay JI. Association of 3 different antihypertensive medications with hip and pelvic fracture risk in older adults. Secondary analysis of a randomized clinical trial. JAMA Internal Medicine 2017;177(1):67‐76. - PubMed
Quan 1999
    1. Quan A, Kerlikowske K, Gueyffier F, Boissel JP and INDANA investigators. Efficacy of Treating Hypertension in Women. J General Internal Medicine 1999;14:718‐29. - PMC - PubMed
Reinhart 2011
    1. Reinhart M, Musini VM, Salzwedel DM, Dormuth C, Wright JM. First‐line diuretics versus other classes of antihypertensive drugs for hypertension. Cochrane Database of Systematic Reviews 2011, Issue 6. [DOI: 10.1002/14651858.CD008161.pub2] - DOI - PMC - PubMed
RevMan 2014 [Computer program]
    1. Copenhagen: Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager. Version 5.3. Copenhagen: Nordic Cochrane Centre, The Cochrane Collaboration, 2014.
Sundstro¨m 2015
    1. Sundstro¨m J, Arima H, Jackson R, Turnbull F, et al. Effects of Blood Pressure Reduction in Mild Hypertension. A Systematic Review and Meta‐analysis. Annals of Internal Medicine 2015;162:184‐191. - PubMed
Tan 2016
    1. Tan Xue‐ Ying, Hu Jing‐Bo. ACEIs/ARBs for the prevention of type 2 diabetes in patients with cardiovascular diseases: a systematic review and meta‐analysis. Int J Clin Exp Med 2016;9(5):7624‐37.
Taverny 2016
    1. Taverny G, Mimouni Y, LeDigarcher A, Chevalier P, Thijs L, Wright JM, Gueyffier F. Antihypertensive pharmacotherapy for prevention of sudden cardiac death in hypertensive individuals. Cochrane Database of Systematic Reviews 2016, Issue 3. [DOI: 10.1002/14651858.CD011745.pub2] - DOI - PMC - PubMed
Thijs 1992
    1. Thijs L. Fagard R. Lijnen P. Staessen J, et al. A meta‐analysis of outcome trials in elderly hypertensives. Journal of Hypertension 1992;10:1103‐9. [MEDLINE: ] - PubMed
Thomopoulos 2014
    1. Thomopoulos C, Parati G, Zanchetti. A. Effects of blood pressure lowering on outcome incidence in hypertension. 1. Overview, meta‐analyses, and meta‐regression analyses of randomized trials. Journal of Hypertension 2014;32(12):2285‐95. - PubMed
Thomopoulos 2016
    1. Thomopoulos, C, Parati, G, Zanchetti, A. Effects of blood pressure‐lowering treatment. 6. Prevention of heart failure and new‐onset heart failure ‐ Meta‐analyses of randomized trials. Journal of Hypertension March 2016;34(3):373‐84. - PubMed
Turnbull 2003
    1. Turnbull F. Blood Pressure Lowering Treatment Trialists' Collaboration. Effects of different blood‐pressure‐lowering regimens on major cardiovascular events: results of prospectively‐designed overviews of randomised trials. Lancet 2003;362:1527‐35. - PubMed
Wiysonge 2017
    1. Wiysonge, Charles S. Bradley, Hazel A. Volmink, Jimmy. Mayosi, Bongani M. Opie, Lionel H. Beta‐blockers for hypertension. Cochrane Database of Systematic Reviews 2017, Issue 1. [DOI: 10.1002/14651858.CD002003.pub2] - DOI - PMC - PubMed
Xue 2015
    1. Xue H, Lu Z, Tang WL, Pang LW, Wang GM, Wong GWK, Wright JM. First‐line drugs inhibiting the renin angiotensin system versus other first‐line antihypertensive drug classes for hypertension. Cochrane Database of Systematic Reviews 2015, Issue 1. [DOI: 10.1002/14651858.CD008170.pub2] - DOI - PubMed
Zanchetti 2015
    1. Zanchetti, A, Thomopoulos, C, Parati, G. Randomized Controlled Trials of Blood Pressure Lowering in Hypertension: A Critical Reappraisal. Circulation Research 2015;116(6):1058‐73. - PubMed
Zhu 2005
    1. Zhu Z, Zhu S, Liu D, Cao T, Wang L, Tepel M. Thiazide‐like diuretics attenuate agonist‐induced vasoconstriction by calcium desensitisation linked to Rho kinase". Hypertension 2005;45(2):233‐9. - PubMed

References to other published versions of this review

Wright 1999
    1. Wright JM. Cheng‐Han Lee, Chambers KC. Systematic review of antihypertensive therapies: does the evidence assist in choosing a first‐line drug?. CMAJ 1999;161(1):25‐32. [MEDLINE: ] - PMC - PubMed

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