July 23, 2009 — A new review has found that lowering blood pressure below the "standard" target of 140/90 mm Hg is not beneficial in terms of reducing mortality or morbidity . Dr Jose Agustin Arguedas (Universidad de Costa Rica, San Pedro de Montes de Oca) and colleagues report their findings online July 8, 2009 in the Cochrane Database of Systematic Reviews.
They explain that over the past five years, a trend toward lower targets has been recommended by hypertension experts who set treatment guidelines, "based on the assumption that the use of drugs to bring the BP lower than 140/90 mm Hg will reduce heart attack and stroke." But this approach "is not proven," they point out.
Arguedas told heartwire that they reviewed seven trials with more than 22 000 subjects comparing lower or standard diastolic BP targets, but they were unable to identify any studies comparing different systolic BP targets. "We found there is no evidence that reaching a target of below 90 mm Hg diastolic BP will provide additional clinical benefit, but we can't say whether lowering systolic BP below 140 mm Hg will be beneficial or not; there are no data."
Dr Franz Messerli (St Luke Roosevelt Hospital, New York, NY), who was not involved with this review, told heartwire that there is no question that the 140/90-mm-Hg BP limit is "absolutely arbitrary, and the benefits of antihypertensive medications are most obvious in patients with the highest BP. The closer we get to 'normotension,' the more difficult it becomes to show benefits of BP lowering.
"The Lewington meta-analysis of one million patients has convincingly shown that people fare better—ie, have fewer strokes and heart attacks—when their 'usual' BP is 115/70 mm Hg compared with those with a 'usual' BP of 130/80," Messerli adds. "However there are no data and probably never will be that lowering BP from 130/80 mm Hg to 115/70 mm Hg confers any benefits," he says.
Further Review Required in at-Risk Patients
Attempting to achieve lower BP targets has several consequences, the researchers note; "the most obvious is the need for large doses and increased number of antihypertensive drugs. This has inconvenience and economic costs to patients. More drugs and higher doses will also increase adverse drug effects, which if serious could negate any potential benefit associated with lower BP." There is also the potential that lowering BP too much may cause adverse cardiovascular (CV) events, the so-called "J-curve" phenomenon, they observe.
In their review, they included: the Modification of Diet in Renal Disease (MDRD) trial; the Hypertension Optimal Treatment (HOT) study; the BP Control in Diabetes (ABCD) trials H and N; the African American Study of Kidney Disease and Hypertension (AASK), and the Renoprotection in Patients With Nondiabetic Chronic Renal Disease (REIN-2) study.
They found that, despite a 4/3-mm-Hg-greater achieved reduction in systolic/diastolic BP (p < 0.001), attempting to achieve "lower targets" instead of "standard targets" did not change: * Total mortality (relative risk 0.92). * Myocardial infarction (MI; RR 0.90). * Stroke (RR 0.99). * Congestive heart failure (RR 0.88). * Major cardiovascular events (RR 0.94). * End-stage renal disease (RR 1.01)."This strategy did not prolong survival or reduce stroke, heart attack, heart failure, or kidney failure," they note. "More trials are needed, but at present there is no evidence to support aiming for a blood-pressure target lower than 140/90 mm Hg in any hypertensive patient."The researchers say they were unable to fully assess the net health effect of lower targets due to lack of information regarding all total serious adverse events and withdrawals due to adverse effects in six of seven trials.
Trials Needed to Compare Lower With Standard Systolic Targets
Arguedas and his colleagues note that a lower BP target of 130/80 mm Hg is currently recommended for at-risk patients, and they did perform a sensitivity analysis in diabetic and kidney-disease patients, which did not show significant benefits for treating to targets of lower than 135/85 mm Hg. "However, in these two populations, the evidence for a lack of benefit is less robust," they note.
Arguedas told heartwire that properly conducted randomized controlled trials are needed comparing lower systolic BP targets with standard ones in the general population and also in specific subgroups of at-risk patients.
One such study is the ongoing Action to Control Cardiovascular Disease in Diabetes (ACCORD) blood-pressure trial—an unmasked, open-label, randomized trial with participants randomized to one of two groups with different treatment goals: systolic blood pressure < 120 mm Hg for the more intensive goal, and systolic blood pressure < 140 mm Hg for the less intensive goal .The primary outcome measure is the first occurrence of a major CVD event, specifically nonfatal MI or stroke, or cardiovascular death during a follow-up period ranging from four to eight years. The results should provide some of the first definitive clinical-trial data on the possible benefit of treating to a more aggressive systolic blood-pressure goal.In the meantime, says Arguedas, "We are doing another separate systematic review specifically in patients with diabetes and chronic kidney disease to see whether targets lower than 130/80 mm Hg change morbidity or mortality as compared with standard targets."References
1. Arguedas JA, Perez MI, Wright JM. Treatment blood pressure targets for hypertension. Cochrane Database Syst Rev 2009; 3:CD004349.
2. Cushman WC, Grimm RH Jr, Cutler JA, et al. Rationale and design for the blood pressure intervention of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Am J Cardiol 2007; 99(12A):44i-55i.
There is a continuous adverse relationship between BP and CV events, but despite practice guidelines recommending control of BP with a threshold of 140/90 mm Hg, it is unclear if lower thresholds are associated with improved outcomes. In recent practice guidelines, lower thresholds have been recommended for patients with comorbidities such as diabetes or renal disease, but data for patients without these comorbidities are scarce.
This is a systematic review to examine if lower targeted BP is achieved in trials with lower vs higher targets and if lower targets are associated with improved clinical outcomes.