Blood pressure lowering and major cardiovascular events in people with and without chronic kidney disease: meta-analysis of randomised controlled trials

Abstract

Objective: To define the cardiovascular effects of lowering blood pressure in people with chronic kidney disease.

Design: Collaborative prospective meta-analysis of randomised trials.

Data sources and eligibility: Participating randomised trials of drugs to lower blood pressure compared with placebo or each other or that compare different blood pressure targets, with at least 1000 patient years of follow-up per arm.

Main outcome measures: Major cardiovascular events (stroke, myocardial infarction, heart failure, or cardiovascular death) in composite and individually and all cause death.

Participants: 26 trials (152,290 participants), including 30,295 individuals with reduced estimated glomerular filtration rate (eGFR), which was defined as eGFR <60 mL/min/1.73 m(2).

Data extraction: Individual participant data were available for 23 trials, with summary data from another three. Meta-analysis according to baseline kidney function was performed. Pooled hazard ratios per 5 mm Hg lower blood pressure were estimated with a random effects model.

Results: Compared with placebo, blood pressure lowering regimens reduced the risk of major cardiovascular events by about a sixth per 5 mm Hg reduction in systolic blood pressure in individuals with (hazard ratio 0.83, 95% confidence interval 0.76 to 0.90) and without reduced eGFR (0.83, 0.79 to 0.88), with no evidence for any difference in effect (P=1.00 for homogeneity). The results were similar irrespective of whether blood pressure was reduced by regimens based on angiotensin converting enzyme inhibitors, calcium antagonists, or diuretics/β blockers. There was no evidence that the effects of different drug classes on major cardiovascular events varied between patients with different eGFR (all P>0.60 for homogeneity).

Conclusions: Blood pressure lowering is an effective strategy for preventing cardiovascular events among people with moderately reduced eGFR. There is little evidence from these overviews to support the preferential choice of particular drug classes for the prevention of cardiovascular events in chronic kidney disease.

Fig 1 Effects of angiotensin converting enzyme inhibitor or calcium antagonist based regimens v placebo for risk of major cardiovascular events according to kidney function status. P value for homogeneity indicates consistency of effect of treatment regimen among subgroup. Overall mean difference in systolic and diastolic blood pressure during follow-up in actively treated/first listed regimens v control/second listed regimens, calculated by weighting difference observed in each contributing trial by number of patients in trial. Negative values indicate lower mean systolic and diastolic blood pressure during follow-up in actively treated/first listed groups than in control/second listed groups

Fig 2 Effects of angiotensin converting enzyme inhibitor or calcium antagonist based regimens v placebo per 5 mm Hg reduction in systolic blood pressure over time on risk of major cardiovascular events according to kidney function status. Pooled estimates estimated with relative risk model weighted for blood pressure reduction. Values show relative risk per 5 mm Hg reduction in systolic blood pressure over time. *Data from HOPE trial not available for analysis of three GFR categories

Fig 3 Effects of more intensive v less intensive blood pressure lowering regimens for risk of major cardiovascular events according to kidney function status

Fig 4 Effects of blood pressure lowering regimens based on different drug classes for risk of major cardiovascular events according to kidney function status

Fig 5 Proportional increase in risk ratio of treatment effect on major cardiovascular events for every 10 mL/min/1.73 m² decrement in eGFR

Fig 6 Associations between systolic blood pressure reduction and risk reduction for major vascular events according to kidney function status. Centre of each circle is placed at estimates of risk ratio for each trial. Area of each circle is proportional to variance of log odds ratio. Fitted lines represent summary meta-regressions for total major cardiovascular events. Intercepts were 0.96 (0.93 to 1.01) for eGFR ≥60 mL/min/1.73 m² and 0.97 (0.89 to 1.04) for eGFR <60 mL/min/1.73 m²

Fig 7 Effects of angiotensin converting enzyme inhibitor or calcium antagonist based regimens v placebo per 5 mm Hg reduction in systolic blood pressure over time on risk of major cardiovascular events according to proteinuria status