Effects of Intensive Blood Pressure Lowering on Cardiovascular and Renal Outcomes

Study Questions:

Are more intensive blood pressure (BP)-lowering strategies associated with greater reductions in risk of major cardiovascular (CV) and renal events in persons at high risk, including those with CV disease, diabetes, and renal disease?

Methods:

An updated systematic review and meta-analysis was conducted for trials published between January 1, 1950, and November 3, 2015. Inclusion criteria included controlled trials with at least 6 months of follow-up that randomly assigned participants to more versus less intensive BP-lowering treatment, with different BP targets or different BP changes from baseline. The authors did a meta-analysis of BP reductions on relative risk (RR) of major CV events (myocardial infarction, stroke, heart failure, or CV death, separately and combined), and nonvascular and all-cause mortality, end-stage kidney disease, and adverse events, as well as albuminuria and progression of retinopathy in trials done in patients with diabetes.

Results:

There were 19 trials including 44,989 participants, in whom 2,496 major CV events were recorded during a mean 3.8 years of follow-up (range 1.0–8.4 years). After randomization, patients in the more intensive BP-lowering treatment group had mean BP levels of 133/76 mm Hg, compared with 140/81 mm Hg in the less intensive treatment group. Intensive BP-lowering treatment achieved RR reductions (95% confidence interval [CI]) for major CV events (14% [4–22]), myocardial infarction (13% [0–24]), stroke (22% [10–32]), albuminuria (10% [3–16]), and retinopathy progression (19% [0–34]). However, more intensive treatment had no clear effects on heart failure (15% [95% CI, –11 to 34]), CV death (9% [–11 to 26]), total mortality (9% [–3 to 19]), or end-stage kidney disease (10% [–6 to 23]). The reduction in major CV events was consistent across patient groups, and additional BP lowering had a clear benefit even in patients with systolic BP <140 mm Hg. The absolute benefits were greatest in trials in which all enrolled patients had vascular disease, renal disease, or diabetes. Serious adverse events associated with BP lowering were only reported by six trials and had an event rate of 1.2% per year in intensive BP-lowering group participants, compared with 0.9% in the less intensive treatment group (RR, 1.35; 95% CI, 0.93–1.97). Severe hypotension was more frequent in the more intensive treatment regimen (RR, 2.68; 95% CI, 1.21–5.89; p = 0.015), but the absolute excess was small (0.3% vs. 0.1% per person-year for the duration of follow-up).

Conclusions:

Intensive BP lowering provided greater vascular protection than standard regimens. In high-risk patients, there are additional benefits from more intensive BP lowering, including for those with systolic BP <140 mm Hg. The net absolute benefits of intensive BP lowering in high-risk individuals are large.

Perspective:

The approximate mean difference of 7/4 mm Hg from more intensive compared to less intensive BP-lowering treatment produced remarkable results, particularly in strokes. Most importantly, the results are at odds with the recent recommendations by the Eighth Joint National Committee (JNC8) to raise target level for those >60 years of age to 150/90 mm Hg. Much of the JNC8’s recommendations were based on the ACCORD trial in diabetes, in which there was no additional benefit of decreasing from <140 to <120 mm Hg despite a mean difference in systolic BP of 14 mm Hg. Support of the systematic review conclusions is provided by the recent publication of SPRINT (Systolic Pressure Interventional Trial), which was stopped after 3 years because of surprisingly robust results (available at NEJM.org). SPRINT was designed to answer the question: ‘Does a lower blood pressure level further reduce CV events and all-cause mortality in people with very high CV risk?’ A systolic BP target of <120 mm Hg compared to <140 mm Hg was associated with a 25% reduction in composite endpoints, which was driven primarily by reduction in heart failure, and death from CV and all-cause mortality. The latter was a surprise considering there was no reduction in stroke rate or myocardial infarctions.

Clinical Topics: Diabetes and Cardiometabolic Disease, Heart Failure and Cardiomyopathies, Prevention, Acute Heart Failure, Hypertension

Keywords: Albuminuria, Blood Pressure, Cardiovascular Diseases, Diabetes Mellitus, Heart Failure, Hypertension, Hypotension, Kidney Failure, Chronic, Metabolic Syndrome X, Myocardial Infarction, Primary Prevention, Renal Insufficiency, Chronic, Risk, Stroke


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