Abstract
Abstract Background Observational studies have reported a J-shaped relationship between blood pressure (BP) and all-cause and cardiovascular mortality in patients with heart failure (HF). Although decreasing BP significantly reduces the risk of fatal and non-fatal cardiovascular outcomes in the general population across a range of baseline BP categories, the extent to which those findings are applicable to HF patients and whether the relationship holds true when baseline BP is very low remain unclear. Therefore, it is yet to be established whether the observed J-shaped relationship between BP and clinical outcomes in patients with HF is causal and/or modified by antihypertensive treatment. Purpose We aimed to combine evidence from all HF trials that have investigated the effects of drugs with BP-lowering properties to assess (1) the extent to which such drugs reduce BP in HF, (2) the association between the net change in BP between treatment arms and cause-specific outcomes, and (3) whether treatment effects (including benefits and potential harms) vary according to baseline BP. Methods We conducted a systematic review and meta-analysis including randomised clinical trials of drugs with BP-lowering properties conducted in patients with chronic HF with at least 300 patient-years follow-up. Results We included a total of 37 trials (91,950 patients) and showed that treatment with drugs with BP-lowering properties significantly reduced SBP by 2.0 mmHg in all trials and by 2.4 mmHg in placebo-controlled trials (Figure 1). There was no evidence that BP reduction in placebo-controlled trials varied across strata of baseline BP, but there was suggestive evidence for differential effects by drug class, with renin-angiotensin-aldosterone system inhibitors reducing SBP by 3.2 mmHg (95% CI [−4.0, −2.4]), whilst BB appeared to have a neutral effect on BP. There was no evidence that the relative risk reduction afforded by treatment with BP-lowering drugs on all-cause mortality, cardiovascular mortality and HF hospitalisation was significantly different across categories of baseline BP. There was also no strong evidence for heterogeneity of treatment effect on adverse events leading to treatment discontinuation by baseline BP. Meta-regression did not show significant associations between the magnitude of BP reduction achieved in each trial and risk of those clinical outcomes. Figure 1 Conclusions Treatment with drugs with BP-lowering properties resulted in a small but significant decrease in SBP in patients with HF irrespective of baseline BP. There was no evidence that the effects of those drugs differed across the range of baseline SBP, thus supporting the efficacy and safety of those drugs in patients with low baseline BP. Data from published reports was insufficient to adequately investigate whether BP-dependent mechanisms contribute to the effect of BP-lowering drugs on clinical outcomes in patients with HF. Acknowledgement/Funding None
Published Version
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