UCSD Statin Study: Statins Reduce Blood Pressure in Randomized, Placebo-Controll

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From Heartwire — a professional news service of WebMD

April 17, 2008 — Results from a randomized, double blind, placebo-controlled clinical trial have confirmed earlier observations that statins lower blood pressure [1]. The modest reduction was observed in a largely normotensive patient population and occurred in patients taking relatively low doses of statins, report investigators.

Lead investigator Dr Beatrice Golomb (University of California, San Diego [uCSD]) told heartwire that the study provides confirmation that the effects of statins extend to reductions in a second primary cardiovascular risk factor. "The observed reduction in blood pressure, about 2.2 mm Hg, is modest but at the population level can contribute to significant reductions in the risk of stroke," she said.

The study, known as the University of California San Diego Statin Study, is published in the April 14, 2008 issue of the Archives of Internal Medicine. A recent meta-analysis of 20 statin trials suggested that, as well as lowering lipids, the drugs produce a small but clinically meaningful reduction in blood pressure, noted Golomb, but the largest study had a sample size of only 100 patients, raising concerns about publication bias. Other reviews and meta-analyses had similar shortcomings.

In the UCSD study, Golomb and colleagues randomized 973 individuals who did not have diabetes or cardiovascular disease to statin therapy or placebo for six months. Of these participants, 322 were assigned to simvastatin 20 mg, 323 to pravastatin 40 mg, and 328 to placebo. Blood pressure was measured at the beginning of the study, at one and six months during treatment, and two months after treatment ended. Patients were included in the trial based on their low-density lipoprotein (LDL)-cholesterol levels — between 115 mg/dL and 190 mg/dL — and not selected by baseline blood pressure. Mean systolic and diastolic blood pressures at baseline were 126 mm Hg and 75 mm Hg, respectively, across the three treatment groups.

Blood-pressure reductions in the statin arms vs placebo

Statin treatment

Reduction in systolic BP (mm Hg)

P

Reduction in diastolic BP (mm Hg)

P

Statins

2.2

0.02

2.4

< 0.001

Pravastatin

1.5

0.20

2.3

0.002

Simvastatin

2.9

0.009

3.0

< 0.001

Excluding those with high blood pressure or taking hypertensive medication at baseline

Statins

2.6

0.006

2.5

< 0.001

Pravastatin

2.2

0.048

2.3

0.006

Simvastatin

3.0

0.005

2.7

0.002

In the intention-to-treat analysis, significant, although modest, reductions in blood pressure were observed in the combined statin group compared with placebo. The reductions, however, were slightly larger when investigators excluded those with high blood pressure at baseline. Those without high blood pressure and those not taking blood-pressure-lowering medications also had their blood pressure lowered on statin therapy. After drug therapy was stopped, the effect on blood pressure was lost.

Golomb said the results help explain the reduction in cardiovascular events with statins that occur early, those within the first six months. It is too early at that stage for statins to have an effect on plaque accumulation in arteries, so the benefit is a reduction in stroke risk, she said. She noted that reductions in blood pressure occurred with both the hydrophilic and lipophilic statins.

In terms of mechanism, the investigators suggest that statins might lower blood pressure through upregulation and/or activation of endothelial nitric-oxide synthase as well as through improvements in endothelial function and flow-mediated vasodilation. The antioxidant effects of the lipid-lowering medications are believed to bring about the latter two improvements, write Golomb and colleagues.

The National Heart, Lung, and Blood Institute, National Institutes of Health, and The UCSD General Clinical Research Center funded the study. Dr. Golomb has obtained funding. The other study authors have disclosed no relevant financial relationships.

Source

Golomb BA, Dimsdale JE, White HL, et al. Reduction in blood pressure with statins.

Arch Intern Med. 2008;168:721-727.

The complete contents of Heartwire, a professional news service of WebMD, can be found at www.theheart.org, a Web site for cardiovascular healthcare professionals.

Learning Objectives for This Educational ActivityUpon completion of this activity, participants will be able to:

Describe previous research into the efficacy of statins to reduce blood pressure and rates of incident hypertension. Identify the effects of simvastatin and pravastatin on blood pressure among adults without a history of cardiovascular disease.

Clinical Context

Although small clinical trials have suggested that statins may reduce blood pressure, a secondary analysis of a large trial of pravastatin by Tonelli and colleagues suggests otherwise. In this trial, which was published in the August 2006 issue of the Journal of Human Hypertension, pravastatin was no more effective than placebo in reducing either systolic or diastolic blood pressure from baseline levels through 24 months of treatment. Moreover, pravastatin failed to reduce the risk for incident hypertension vs placebo.

Participants in the Tonelli trial all had a history of cardiovascular disease. The current study examines the effects of simvastatin and pravastatin on blood pressure levels among patients without cardiovascular disease or a history of diabetes mellitus.

Study Highlights

Study participants had an LDL cholesterol level between 115 and 190 mg/dL. Patients with a history of cardiovascular disease or diabetes mellitus were excluded from participation. There were no exclusion criteria based on blood pressure values. Subjects were randomized to receive simvastatin 20 mg, pravastatin 40 mg, or placebo. Participants underwent clinical examinations at baseline plus at 1 month and 6 months during treatment. Brachial blood pressure was a secondary outcome of the study design. The main outcome of the study was the relationship between statin treatment and blood pressure at baseline and at 6 months. 973 participants provided data for study analysis. Baseline data were similar between study groups, except that the mean diastolic blood pressure in the placebo group was 1.4 mm Hg lower vs the pravastatin group. The mean systolic and diastolic blood pressure values for the entire study cohort were 126 and 75 mm Hg, respectively. The mean age of the subjects was 57 years, 68% were men, and 81% were white. Compared with placebo, pravastatin reduced systolic blood pressure by 1.5 mm Hg at 6 months, and simvastatin was associated with a relative reduction of 2.9 mm Hg. Both of these values were statistically significant. Pravastatin (–2.3 mm Hg) and simvastatin (–3.0 mm Hg) also reduced diastolic blood pressure relative to placebo. An analysis that excluded subjects with higher baseline blood pressures strengthened the finding that statins reduced blood pressure. Elevated levels of high-density lipoprotein cholesterol also portended enhanced efficacy of statins in the reduction of systolic blood pressure. Statins began to reduce blood pressure values relative to placebo by 1 month of treatment and continued a more gradual effect on reducing these levels to achieve statistically significant results at 6 months. Blood pressure values rebounded to near-baseline levels within 2 months of cessation of statins.

Pearls for Practice

A secondary analysis of a previous study suggested that pravastatin did not reduce blood pressure or the rate of incident hypertension vs placebo among a cohort of patients with a history of cardiovascular disease. In the current study, both simvastatin and pravastatin reduced systolic and diastolic blood pressure levels modestly but significantly vs placebo among patients without cardiovascular disease or a history of diabetes mellitus.

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