Blood Pressure Lowering and Major Cardiovascular Events in People With and Without Chronic Kidney Disease: Meta-Analysis of Randomised Controlled Trials

Study Questions:

What are the cardiovascular effects of lowering blood pressure in people with chronic kidney disease?

Methods:

This was a collaborative prospective meta-analysis of randomized trials. Participating randomized trials of drugs to lower blood pressure compared with placebo or each other or that compared different blood pressure targets, with at least 1,000 patient-years of follow-up per arm, were included. The main outcome measures were major cardiovascular events (stroke, myocardial infarction, heart failure, or cardiovascular death) in composite and individually, and all-cause death. Twenty-six 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 m2 were the study cohort. 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 one-sixth per 5 mm Hg reduction in systolic blood pressure in individuals with (hazard ratio, 0.83; 95% confidence interval, 0.76-0.90) and without reduced eGFR (hazard ratio, 0.83; 95% confidence interval, 0.79-0.88), 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/beta-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:

The authors concluded that blood pressure lowering is an effective strategy for preventing cardiovascular events among people with moderately reduced eGFR, but there is little evidence to support the preferential choice of particular drug classes for the prevention of cardiovascular events in chronic kidney disease.

Perspective:

This study provides compelling evidence for the cardiovascular benefits of reduction in blood pressure in people with stage 1-3 chronic kidney disease. While the proportional reductions in the risk of major cardiovascular events were similar in people with and without evidence of chronic kidney disease, individuals with chronic kidney disease had much larger absolute benefits because their baseline risk was much higher. Specifically, blood pressure lowering per se, not the effects of a particular drug class (such as renin-angiotensin system blockade), seems to be significantly associated with lower cardiovascular risk in early stage chronic kidney disease. The high prevalence of chronic kidney disease in the community means that strategies to increase the use of blood pressure lowering treatments among this group, along with other proven treatments such as lipid lowering, are likely to be highly effective at reducing the burden of cardiovascular mortality and morbidity in the chronic kidney disease population.

Clinical Topics: Heart Failure and Cardiomyopathies, Acute Heart Failure

Keywords: Stroke, Myocardial Infarction, Follow-Up Studies, Morbidity, Renin-Angiotensin System, Blood Pressure, Risk Factors, Calcium Channel Blockers, Renal Insufficiency, Heart Failure, Glomerular Filtration Rate


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