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Blood pressure targets in the treatment of patients with elevated blood pressure

University of British Columbia

Background In the management of patients with elevated blood pressure, the ideal blood pressure target to maximize the reduction in morbidity and mortality has not been established. The standard of clinical practice for many years has been a target of less than or equal to 90 mmHg for diastolic blood pressure. More recently the focus has been a target of less than or equal to 140 mmHg for systolic blood pressure. However, there has been a tendency during the last few years to recommend lower target blood pressures than those traditionally used. Objectives The specific aim of this systematic review was to identify all randomized controlled trials where participants were randomized to different BP targets and to determine if, in the treatment of patients with elevated blood pressure, "lower target" blood pressures (≤135/85 mmHg) are associated with reduction in mortality and morbidity as compared with "traditional target" blood pressures (≤140-160 mmHg systolic and ≤ 90-100 mmHg diastolic). Design Systematic review with meta-analysis. Search strategy Electronic search of MEDLINE (1966-2004), EMBASE (1980-2004), and CENTRAL (up to April 2004); references from review articles, clinical guidelines, and clinical trials. Selection criteria Randomized controlled trials in patients with elevated blood pressure randomized to "lower" or to "traditional" blood pressure targets and providing data on any of the primary outcomes. Analysis Two reviewers independently assessed and established the included trials. The primary outcomes were all-cause, cardiovascular and non-cardiovascular mortality; total serious adverse events; other cardiovascular serious adverse events; all other serious adverse events. The secondary outcomes were achieved mean systolic and diastolic blood pressure, percentage of patients achieving the target blood pressure levels, withdrawals due to adverse effects, and mean number of antihypertensive drugs per patient. Main results Six trials including 21,751 subjects were identified. Two trials included only patients with diabetes, and three trials included only patients with chronic renal disease. None of the trials compared different targets for systolic blood pressure. Therefore, at present we have no information regarding the benefits or harms of trying to achieve "lower targets" as compared with "traditional targets" for systolic blood pressure. In trials comparing diastolic blood pressure targets, despite a greater achieved reduction in blood pressure, trying to achieve the "lower targets" instead of the "traditional target" did not result in any change in total, cardiovascular or non-cardiovascular mortality, and did not result in any change in the incidence of myocardial infarction, stroke, congestive heart failure, the composite outcome of major cardiovascular events, or end-stage renal disease. The overall safety of the more intensive treatment cannot be assessed due to the lack of information regarding total serious adverse events and withdrawals due to adverse effects. A sensitivity analysis performed in diabetic patients demonstrated that despite achieving significantly lower mean systolic and diastolic blood pressures, the groups allocated to a target diastolic blood pressure ≤ 80 mmHg did not achieve a statistically significant benefit in any of the mortality and morbidity outcomes as compared with a target of ≤ 90 mmHg. However, there was a trend toward decreased total mortality, major cardiovascular events and stroke incidence in diabetics randomized to "lower target" as compared with the "traditional target". A sensitivity analysis in patients with chronic renal disease demonstrated that despite achieving a substantially lower systolic and diastolic BP, there was no statistically significant difference in mortality, total cardiovascular events or end stage renal disease with "lower" as compared with "traditional" targets. Reviewers' conclusions In the absence of evidence, systolic blood pressure targets must be those that have been demonstrated to be better than placebo or no treatment in randomized controlled trials: ≤ 150 to 160 mmHg. For the non-diabetic non-chronic renal disease patients with elevated blood pressure, the diastolic target should be ≤ 90 mmHg. Treating patients to lower targets is not associated with a mortality or morbidity benefit. For the subgroups of patients with diabetes mellitus or chronic renal disease the conclusions are the same, but data are limited and the possibility exists that a clinically significant benefit or harm for lower targets could have been missed. Guidelines recommending lower systolic and diastolic blood pressure targets require testing in randomized trials, especially for patients with diabetes mellitus and chronic renal disease.

Thesis/Dissertation

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2009-11-24

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http://hdl.handle.net/2429/15584

Pharmacology

University of British Columbia

UBCV

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