Statins, antihypertensive treatment, and blood pressure control in clinic and over 24 hours: evidence from PHYLLIS randomised double blind trial

Abstract

Objective: To investigate the possibility that statins reduce blood pressure as well as cholesterol concentrations through clinic and 24 hour ambulatory blood pressure monitoring.

Design: Randomised placebo controlled double blind trial.

Setting: 13 hospitals in Italy

Participants: 508 patients with mild hypertension and hypercholesterolaemia, aged 45 to 70 years.

Intervention: Participants were randomised to antihypertensive treatment (hydrochlorothiazide 25 mg once daily or fosinopril 20 mg once daily) with or without the addition of a statin (pravastatin 40 mg once daily). Main outcome measures Clinic and ambulatory blood pressure measured every year throughout an average 2.6 year treatment period.

Results: Both the group receiving antihypertensive treatment without pravastatin (n=254) (with little change in total cholesterol) and the group receiving antihypertensive treatment with pravastatin (n=253) (with marked and sustained reduction in total cholesterol and low density lipoprotein cholesterol) had a clear cut sustained reduction in clinic measured systolic and diastolic blood pressure as well as in 24 hour, and day and night, systolic and diastolic blood pressure. Pravastatin performed slightly worse than placebo, and between group differences did not exceed 1.9 (95% confidence interval -0.6 to 4.3, P=0.13) mm Hg throughout the treatment period. This was also the case when participants who remained on monotherapy with hydrochlorothiazide or fosinopril throughout the study were considered separately.

Conclusions: Administration of a statin in hypertensive patients in whom blood pressure is effectively reduced by concomitant antihypertensive treatment does not have an additional blood pressure lowering effect. Trial registration BRISQUI_*IV_2004_001 (registered at Osservatorio Nazionale sulla Sperimentazione Clinica dei Medicinali-National Monitoring Centre on Clinical Research with Medicines).

Fig 1 Flow of participants in study (for purposes of analysis reported here, only randomisation to pravastatin or corresponding placebo is considered)

Fig 2 Clinic, 24 hour, daytime, and night-time systolic and diastolic blood pressure, showing mean values at baseline, throughout treatment period, and at study end in patients taking pravastatin or corresponding placebo. All values during treatment were always significantly different from those at baseline (P<0.001). Baseline and on-treatment values were not significantly different between treatment groups

Fig 3 Average serum lipid concentrations in patients taking pravastatin or corresponding placebo at baseline and throughout treatment period. Data are means and standard deviations; P values refer to overall treatment effect in analysis of covariance. In groups randomised to receive pravastatin in combination with either hydrochlorothiazide or fosinopril, total cholesterol and low density lipoprotein cholesterol during treatment were always significantly lower than at baseline (P<0.001)