Summary
Background
The
benefits of blood pressure lowering treatment for prevention of
cardiovascular disease are well established. However, the extent to
which these effects differ by baseline blood pressure, presence of
comorbidities, or drug class is less clear. We therefore performed a
systematic review and meta-analysis to clarify these differences.
Method
For
this systematic review and meta-analysis, we searched MEDLINE for
large-scale blood pressure lowering trials, published between Jan 1,
1966, and July 7, 2015, and we searched the medical literature to
identify trials up to Nov 9, 2015. All randomised controlled trials of
blood pressure lowering treatment were eligible for inclusion if they
included a minimum of 1000 patient-years of follow-up in each study arm.
No trials were excluded because of presence of baseline comorbidities,
and trials of antihypertensive drugs for indications other than
hypertension were eligible. We extracted summary-level data about study
characteristics and the outcomes of major cardiovascular disease events,
coronary heart disease, stroke, heart failure, renal failure, and
all-cause mortality. We used inverse variance weighted fixed-effects
meta-analyses to pool the estimates.
Results
We
identified 123 studies with 613 815 participants for the tabular
meta-analysis. Meta-regression analyses showed relative risk reductions
proportional to the magnitude of the blood pressure reductions achieved.
Every 10 mm Hg reduction in systolic blood pressure significantly
reduced the risk of major cardiovascular disease events (relative risk
[RR] 0·80, 95% CI 0·77–0·83), coronary heart disease (0·83, 0·78–0·88),
stroke (0·73, 0·68–0·77), and heart failure (0·72, 0·67–0·78), which, in
the populations studied, led to a significant 13% reduction in
all-cause mortality (0·87, 0·84–0·91). However, the effect on renal
failure was not significant (0·95, 0·84–1·07). Similar proportional risk
reductions (per 10 mm Hg lower systolic blood pressure) were noted in
trials with higher mean baseline systolic blood pressure and trials with
lower mean baseline systolic blood pressure (all p
trend>0·05).
There was no clear evidence that proportional risk reductions in major
cardiovascular disease differed by baseline disease history, except for
diabetes and chronic kidney disease, for which smaller, but significant,
risk reductions were detected. β blockers were inferior to other drugs
for the prevention of major cardiovascular disease events, stroke, and
renal failure. Calcium channel blockers were superior to other drugs for
the prevention of stroke. For the prevention of heart failure, calcium
channel blockers were inferior and diuretics were superior to other drug
classes. Risk of bias was judged to be low for 113 trials and unclear
for 10 trials. Heterogeneity for outcomes was low to moderate; the
I2
statistic for heterogeneity for major cardiovascular disease events was
41%, for coronary heart disease 25%, for stroke 26%, for heart failure
37%, for renal failure 28%, and for all-cause mortality 35%.
Interpretation
Blood
pressure lowering significantly reduces vascular risk across various
baseline blood pressure levels and comorbidities. Our results provide
strong support for lowering blood pressure to systolic blood pressures
less than 130 mm Hg and providing blood pressure lowering treatment to
individuals with a history of cardiovascular disease, coronary heart
disease, stroke, diabetes, heart failure, and chronic kidney disease.
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