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Meta-Analysis
. 2017 Aug 16;8(8):CD008276.
doi: 10.1002/14651858.CD008276.pub2.

Pharmacotherapy for hypertension in adults aged 18 to 59 years

Vijaya M Musini  1 , Francois Gueyffier, Lorri Puil, Douglas M Salzwedel, James M Wright
Affiliations
Meta-Analysis

Pharmacotherapy for hypertension in adults aged 18 to 59 years

Vijaya M Musini et al. Cochrane Database Syst Rev. .

Abstract

Background: Hypertension is an important risk factor for adverse cardiovascular events including stroke, myocardial infarction, heart failure and renal failure. The main goal of treatment is to reduce these events. Systematic reviews have shown proven benefit of antihypertensive drug therapy in reducing cardiovascular morbidity and mortality but most of the evidence is in people 60 years of age and older. We wanted to know what the effects of therapy are in people 18 to 59 years of age.

Objectives: To quantify antihypertensive drug effects on all-cause mortality in adults aged 18 to 59 years with mild to moderate primary hypertension. To quantify effects on cardiovascular mortality plus morbidity (including cerebrovascular and coronary heart disease mortality plus morbidity), withdrawal due adverse events and estimate magnitude of systolic blood pressure (SBP) and diastolic blood pressure (DBP) lowering at one year.

Search methods: The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials up to January 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 We contacted authors of relevant papers regarding further published and unpublished work.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 of at least one year' duration comparing antihypertensive pharmacotherapy with a placebo or no treatment in adults aged 18 to 59 years with mild to moderate primary hypertension defined as SBP 140 mmHg or greater or DBP 90 mmHg or greater at baseline, or both.

Data collection and analysis: The outcomes assessed were all-cause mortality, total cardiovascular (CVS) mortality plus morbidity, withdrawals due to adverse events, and decrease in SBP and DBP. For dichotomous outcomes, we used risk ratio (RR) with 95% confidence interval (CI) and a fixed-effect model to combine outcomes across trials. For continuous outcomes, we used mean difference (MD) with 95% CI and a random-effects model as there was significant heterogeneity.

Main results: The population in the seven included studies (17,327 participants) were predominantly healthy adults with mild to moderate primary hypertension. The Medical Research Council Trial of Mild Hypertension contributed 14,541 (84%) of total randomized participants, with mean age of 50 years and mean baseline blood pressure of 160/98 mmHg and a mean duration of follow-up of five years. Treatments used in this study were bendrofluazide 10 mg daily or propranolol 80 mg to 240 mg daily with addition of methyldopa if required. The risk of bias in the studies was high or unclear for a number of domains and led us to downgrade the quality of evidence for all outcomes.Based on five studies, antihypertensive drug therapy as compared to placebo or untreated control may have little or no effect on all-cause mortality (2.4% with control vs 2.3% with treatment; low quality evidence; RR 0.94, 95% CI 0.77 to 1.13). Based on 4 studies, the effects on coronary heart disease were uncertain due to low quality evidence (RR 0.99, 95% CI 0.82 to 1.19). Low quality evidence from six studies showed that drug therapy may reduce total cardiovascular mortality and morbidity from 4.1% to 3.2% over five years (RR 0.78, 95% CI 0.67 to 0.91) due to reduction in cerebrovascular mortality and morbidity (1.3% with control vs 0.6% with treatment; RR 0.46, 95% CI 0.34 to 0.64). Very low quality evidence from three studies showed that withdrawals due to adverse events were higher with drug therapy from 0.7% to 3.0% (RR 4.82, 95% CI 1.67 to 13.92). The effects on blood pressure varied between the studies and we are uncertain as to how much of a difference treatment makes on average.

Authors' conclusions: Antihypertensive drugs used to treat predominantly healthy adults aged 18 to 59 years with mild to moderate primary hypertension have a small absolute effect to reduce cardiovascular mortality and morbidity primarily due to reduction in cerebrovascular mortality and morbidity. All-cause mortality and coronary heart disease were not reduced. There is lack of good evidence on withdrawal due to adverse events. Future trials in this age group should be at least 10 years in duration and should compare different first-line drug classes and strategies.

PubMed Disclaimer

Conflict of interest statement

VM: none.

FG: none.

LP: none.

DS: none.

JMW: none.

Figures

1
1
This is a partial study flow diagram and shows search findings from 2008 until 2017. The search done from 1946 to 2008 was identical to the "First line drugs for hypertension" review in which 24 trials met the inclusion criteria of which 17 had to be excluded and only seven studies provided data for quantitative synthesis in 18‐ to 59‐year‐old participants.
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.
1.1
1.1. Analysis
Comparison 1 Antihypertensive drug therapy versus control, Outcome 1 All‐cause mortality.
1.2
1.2. Analysis
Comparison 1 Antihypertensive drug therapy versus control, Outcome 2 Cardiovascular mortality plus morbidity overall.
1.3
1.3. Analysis
Comparison 1 Antihypertensive drug therapy versus control, Outcome 3 Cerebrovascular mortality plus morbidity.
1.4
1.4. Analysis
Comparison 1 Antihypertensive drug therapy versus control, Outcome 4 Coronary heart disease mortality plus morbidity.
1.5
1.5. Analysis
Comparison 1 Antihypertensive drug therapy versus control, Outcome 5 Withdrawal due to adverse events.
1.6
1.6. Analysis
Comparison 1 Antihypertensive drug therapy versus control, Outcome 6 Decrease in systolic blood pressure.
1.7
1.7. Analysis
Comparison 1 Antihypertensive drug therapy versus control, Outcome 7 Decrease in diastolic blood pressure.
See this image and copyright information in PMC

Update of

  • doi: 10.1002/14651858.CD008276

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References to other published versions of this review

Musini 2010
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