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      Impact of baseline blood pressure on the magnitude of blood pressure lowering by nifedipine gastrointestinal therapeutic system: refreshing the Wilder’s principle

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          The objective of the study was to investigate the relationship between baseline blood pressure (BP) and the magnitude of BP reduction in patients with essential hypertension treated with nifedipine gastrointestinal therapeutic system (NGTS).

          Methods and patients

          One hundred and thirty-eight patients with essential hypertension were enrolled in this prospective, single-arm, open-label study. NGTS was administered for 24 weeks to achieve target BP of 140/90 mmHg. The dose could be uptitrated to 60 mg/d in case of unsatisfactory BP reduction after 4-week treatment. Home blood pressure measurement was recorded through the initial 1–14 days, and office BP and heart rate were evaluated at 2, 4, 8, 12, and 24 weeks.


          One hundred and seventeen patients (84.8%) completed the study, and their average BP decreased by 19.0/11.3 mmHg after 24 weeks. The reduction of either systolic or diastolic BP was positively correlated with baseline BP at weeks 2, 4, or 24 after treatment ( r=0.603–0.762, all p<0.05). The maximal BP reduction was observed in 83% of patients at 4 weeks of treatment even though the dose of nifedipine remained unchanged (30 mg/day).


          These findings show that BP reduction is greatly influenced by the baseline level. Patients with high baseline BP had maximum reduction after treatment with NGTS, and the maximal antihypertensive efficacy of NGTS could appear even at 4 weeks after treatment initiation.

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          Most cited references 21

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          An effective approach to high blood pressure control: a science advisory from the American Heart Association, the American College of Cardiology, and the Centers for Disease Control and Prevention.

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            MRC trial of treatment of mild hypertension: principal results. Medical Research Council Working Party.

            The main aim of the trial was to determine whether drug treatment of mild hypertension (phase V diastolic pressure 90-109 mm Hg) reduced the rates of stroke, of death due to hypertension, and of coronary events in men and women aged 35-64 years. Subsidiary aims were: to compare the course of blood pressure in two groups, one taking bendrofluazide and one taking propranolol, and to compare the incidence of suspected adverse reactions to these two drugs. The study was single blind and based almost entirely in general practices; 17 354 patients were recruited, and 85 572 patient years of observation have accrued. Patients were randomly allocated at entry to take bendrofluazide or propranolol or placebo tablets. The primary results were as follows. The stroke rate was reduced on active treatment: 60 strokes occurred in the treated group and 109 in the placebo group, giving rates of 1.4 and 2.6 per 1000 patient years of observation respectively (p less than 0.01 on sequential analysis). Treatment made no difference, however, to the overall rates of coronary events: 222 events occurred on active treatment and 234 in the placebo group (5.2 and 5.5 per 1000 patient years respectively). The incidence of all cardiovascular events was reduced on active treatment: 286 events occurred in the treated group and 352 in the placebo group, giving rates of 6.7 and 8.2 per 1000 patient years respectively (p less than 0.05 on sequential analysis). For mortality from all causes treatment made no difference to the rates. There were 248 deaths in the treated group and 253 in the placebo group (rates 5.8 and 5.9 per 1000 patient years respectively). Several post hoc analyses of subgroup results were also performed but they require very cautious interpretation. The all cause mortality was reduced in men on active treatment (157 deaths versus 181 in the placebo group; 7.1 and 8.2 per 1000 patient years respectively) but increased in women on active treatment (91 deaths versus 72; 4.4 and 3.5 per 1000 patient years respectively). The difference between the sexes in their response to treatment was significant (p = 0.05). Comparison of the two active drugs showed that the reduction in stroke rate on bendrofluazide was greater than that on propranolol (p = 0.002). The stroke rate was reduced in both smokers and non-smokers taking bendrofluazide but only in non-smokers taking propranolol. This difference between the responses to the two drugs was significant (p = 0.03).(ABSTRACT TRUNCATED AT 400 WORDS)
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              Relation between initial blood pressure and its fall with treatment.

              The relation between pre-treatment blood-pressure and the fall in pressure after treatment was examined for most classes of antihypertensive drugs. Positive correlations were demonstrated for all drugs, for placebo, and for bed rest. This suggests that for all manoeuvres response is related to the height of the pretreatment pressure. Substitution of the pre-treatment and achieved pressures by random numbers reveals that positive correlations are mathematically inevitable and do not indicate any action on a basic mechanism of essential hypertension. After statistical correction for mathematical associations between the variables the apparent effects were generally lost. A correlation between the pre-treatment value of any variable and its change after a therapeutic intervention thus may not be valid.

                Author and article information

                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Drug Design, Development and Therapy
                Dove Medical Press
                06 November 2017
                : 11
                : 3179-3186
                Department of Cardiology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China
                Author notes
                Correspondence: Wei Cui, Department of Cardiology, The Second Hospital of Hebei Medical University, No. 215 Hepingxi Road, Shijiazhuang, Hebei, People’s Republic of China, Tel/fax +86 311 6600 2115, Email cuiwei@
                © 2017 Hu et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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