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Antihypertensive Treatment and Secondary Prevention of Cardiovascular Disease Events Among Persons Without Hypertension A Meta-analysis

Angela M. Thompson, MSPH; Tian Hu, MS, BM; Carrie L. Eshelbrenner, MD; Kristi Reynolds, PhD; Jiang He, MD, PhD; Lydia A. Bazzano, MD, PhD
JAMA. 2011;305(9):913-922. doi:10.1001/jama.2011.250.
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Context Cardiovascular disease (CVD) risk increases beginning at systolic blood pressure levels of 115 mm Hg. Use of antihypertensive medications among patients with a history of CVD or diabetes and without hypertension has been debated.

Objective To evaluate the effect of antihypertensive treatment on secondary prevention of CVD events and all-cause mortality among persons without clinically defined hypertension.

Data Sources Meta-analysis with systematic search of MEDLINE (1950 to week 3 of January 2011), EMBASE, and the Cochrane Collaboration Central Register of Controlled Clinical Trials and manual examination of references in selected articles and studies.

Study Selection From 874 potentially relevant publications, 25 trials that fulfilled the predetermined inclusion and exclusion criteria were included in the meta-analysis.

Data Extraction Information on participant characteristics, trial design and duration, treatment drug, dose, control, and clinical events were extracted using a standardized protocol. Outcomes included stroke, myocardial infarction (MI), congestive heart failure (CHF), composite CVD outcomes, CVD mortality, and all-cause mortality.

Results Compared with controls, participants receiving antihypertensive medications had a pooled relative risk of 0.77 (95% confidence interval [CI], 0.61 to 0.98) for stroke, 0.80 (95% CI, 0.69 to 0.93) for MI, 0.71 (95% CI, 0.65 to 0.77) for CHF, 0.85 (95% CI, 0.80 to 0.90) for composite CVD events, 0.83 (95% CI, 0.69 to 0.99) for CVD mortality, and 0.87 (95% CI, 0.80 to 0.95) for all-cause mortality from random-effects models. The corresponding absolute risk reductions per 1000 persons were −7.7 (95% CI, −15.2 to −0.3) for stroke, −13.3 (95% CI, −28.4 to 1.7) for MI, −43.6 (95% CI, −65.2 to −22.0) for CHF events, −27.1 (95% CI, −40.3 to −13.9) for composite CVD events, −15.4 (95% CI, −32.5 to 1.7) for CVD mortality, and −13.7 (95% CI, −24.6 to −2.8) for all-cause mortality. Results did not differ according to trial characteristics or subgroups defined by clinical history.

Conclusions Among patients with clinical history of CVD but without hypertension, antihypertensive treatment was associated with decreased risk of stroke, CHF, composite CVD events, and all-cause mortality. Additional randomized trial data are necessary to assess these outcomes in patients without CVD clinical recommendations.

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Figure 1. Selection Process for Studies Included in the Meta-analysis.
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Figure 2. Pooled Relative Risks and Absolute Risk Reductions for Fatal or Nonfatal Stroke, Myocardial Infarction, and Congestive Heart Failure and Composite Cardiovascular Disease Outcomes
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CI indicates confidence interval; CVD, cardiovascular disease; NA, not applicable; NR, not reported. Sizes of data markers indicate the weight of each study in the analysis. For expansions of study names, see Table 1 footnote.
aNumber of events could not be calculated from information provided.
bNumber of events was estimated from information provided.

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Figure 3. Pooled Relative Risks and Absolute Risk Reductions for Cardiovascular and All-Cause Mortality
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CI indicates confidence interval; CVD, cardiovascular disease; NA, not applicable; NR, not reported. Sizes of data markers indicate the weight of each study in the analysis. For expansions of study names, see Table 1 footnote.

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