Meta-Analysis Gives More Support To Aggressive Blood Pressure Treatment

A large new meta-analysis offers fresh support to the growing movement in favor of more aggressive treatment to lower high blood pressure. The findings are consistent with and extend the results of the recently reported NIH SPRINT trial, which found substantial clinical benefits for a systolic blood pressure target of 120 mm Hg instead of 140 mm Hg. Along with SPRINT the new study represents an important reversal of a recent trend that sought to relax guidelines and that favored less aggressive treatment.

Kazem Rahimi (University of Oxford, UK) and colleagues analyzed data from 613,815 patients who participated in 123 large-scale trials testing antihypertensive therapy. The findings from this very large new meta-analysis have been published in the Lancet.

The main result of the study is that lowering blood pressure provides consistent relative reductions in major outcomes independent of baseline blood pressure down to 130 mm Hg. For every 10 mm Hg reduction in systolic blood pressure there was a statistically significant 20% reduction in cardiovascular events, a 17% reduction in coronary heart disease, a 27% reduction in stroke, a 28% reduction in heart failure, and a 13% reduction in all-cause mortality. The authors found no evidence to support a J-shaped curve indicating a harmful effect at lower blood pressure levels.

Further, the reductions in relative risk were “broadly similar” in patients both with and without other cardiovascular risk factors and conditions, including previous cardiovascular disease, coronary heart disease, and cerebrovascular disease. However, diabetics appeared to have a smaller reduction in relative risk than nondiabetics.

The investigators also found that most antihypertensive drugs had similar overall effects, though some drugs were more effective in specific clinical settings. Calcium channel blockers were more effective in the prevention of stroke while diuretics were more effective in preventing heart failure. Beta blockers were less effective than other drugs in preventing cardiovascular events, stroke, and renal failure.

The authors write that their “findings suggest that blood pressure lowering to levels below those recommended in current guidelines (ie, systolic blood pressure of less than 140 mm Hg) will reduce the risk of cardiovascular disease.” The findings also support broad application of the SPRINT results, since there was residual uncertainty whether the benefits observed in SPRINT would “hold for high-risk individuals excluded from the trial, especially those with diabetes or cerebrovascular disease.”

“Collectively,” they write, the data from SPRINT and their study “suggest that revision is urgently needed to recent blood pressure lowering guidelines that have relaxed the blood pressure lowering thresholds.” The results also “support the case to shift” the focus of guidelines “from rigid blood pressure targets to risk-based targets, even when starting systolic blood pressure is lower than 130 mm Hg. Rather than a decision based on an arbitrary threshold for a single risk factor, this approach needs individualised assessment of the balance of absolute risks and benefits.”

In an accompanying comment, Stéphane Laurent and Pierre Boutouyrie (The European Georges Pompidou Hospital, Paris, France) support the authors call “for an urgent revision of recent guidelines for blood pressure lowering” and the shift “from rigid blood pressure targets to risk-based targets, even when starting systolic blood pressure is lower than 130 mm Hg.”

Asked for a comment on the study, Franz Messerli (Mt Sinai Icahn School of Medicine) called the study “thorough” but pointed out that it doesn’t address a key question that still remains unanswered:

“The clinically pertinent question is not whether or not a 10 mmHg BP reduction or even a BP reduction proportional to baseline BP is safe and efficacious. In their thorough study the authors clearly show that indeed it is. However what clinicians want to know is whether a BP reduction to below 130 mmHg should be aimed for in a patient presenting with a baseline systolic BP of 160 or higher, and if so, how swiftly such a target should be achieved. The author`s meta regression analysis may give us some hints in this regard but basically these seminal questions remain unanswered in the present study”

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