Optimisation of antihypertensive treatment by crossover rotation of four major classes

Dickerson, JE Claire; Hingorani, Aroon D.; Ashby, Michael; Palmer, C.; Brown, Morris J.

doi:10.1016/s0140-6736(98)07614-4

Cited by 306 publications

(209 citation statements)

References 26 publications

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“…Ideally, observations including 24-hour ambulatory records of BP would have been more robust and added weight to the conclusions drawn from clinic readings. Nevertheless, in a broadly similar rotational crossover study of Dickerson and colleagues, 14 using clinic measurements, a high degree of concordance was observed when patients were treated with the same drug during two different observation periods, suggesting that in the present study, the discordance observed in BP changes between treatment periods with the ACE-I and the ARB was a real phenomenon and not simply a reflection of intrinsic variability in individual BP values obtained during clinic measurements.…”

Section: Discussionsupporting

confidence: 71%

“…However, marked heterogeneity in antihypertensive responses to the ACE-I and the ARB were observed, in keeping with previous observations on BP responses to monotherapy. 14,15 The most likely explanation for this finding is the multifactorial nature of hypertension with regard to aetiology and pathogenesis, reflecting a complex interaction of a variety of environmental and genetic factors responsible for BP elevation in hypertensive populations. 12 This multifactorial nature of hypertension is paralleled by heterogeneity in responses to single drugs which act on particular physiological systems and pathophysio- Most studies comparing antihypertensive drugs and antihypertensive drug classes are of a parallel-group nature, preferred by drug regulatory bodies for the purpose of drug registration.…”

Section: Discussionmentioning

confidence: 99%

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Discordant responses to two classes of drugs acting on the renin-angiotensin system

Sever

Chang

2001

J Renin Angiotensin Aldosterone Syst

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IntroductionMarked heterogeneity characterises blood pressure (BP) responses to antihypertensive drugs. The efficacy of drugs acting on the renin-angiotensin-aldosterone system (RAAS) is predicted (albeit weakly) by plasma renin activity (PRA) and it has been assumed that, within individuals, there would be concordance in efficacy between drugs acting at different sites to block the RAAS. DesignThe present study was a randomised, double-blind, two-way, crossover study designed to evaluate intra-individual BP responses to an angiotensin II AT 1 -receptor blocker (ARB), candesartan cilexetil, and an angiotensin-converting enzyme inhibitor (ACE-I), lisinopril, and to identify potential phenotypic characteristics of patients' responses to the drugs. Methods92 patients with essential hypertension, (mean systolic/diastolic BP 160/101 mmHg) entered the trial, of whom 76 patients completed both treatments. ResultsThere was marked heterogeneity in response to the two drugs. 50% of patients responded (fall in diastolic BP of >10 mmHg or achieved diastolic pressure <90 mmHg) to both drugs; 16% were non-responders to both drugs; 20% responded to the ACE-I but not the ARB and 15% responded to the ARB but not to the ACE-I. Individual responses to the two drugs were poorly correlated (for diastolic pressure: r=0.19, p=0.11; for systolic pressure: r=-0.01, p=0.92). For the ACE-I, the fall in both systolic and diastolic BP was related to pretreatment PRA (for diastolic pressure: r=0.31, p=0.008; for systolic pressure: r=0.24, p=0.04). In the case of the ARB, no relationship between the fall in BP and PRA was observed.These observations suggest that more complex mechanisms may be involved in BP reduction with ARBs than with ACE-I.

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Section: Discussionsupporting

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Discordant responses to two classes of drugs acting on the renin-angiotensin system

Sever

Chang

2001

J Renin Angiotensin Aldosterone Syst

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“…The advantage of switching treatments after a monotherapy has been well documented by Dickerson et al, 26 who demonstrated in a crossover study that patients who responded to diuretics and calcium channel blockers were little or not at all responsive to ACEI and beta-blockers, and vice versa. This concept has now been incorporated into the BHS guidelines.…”

Section: Management Of Resistance To Combined Therapymentioning

confidence: 92%

Management in general practice of hypertensive patients poorly controlled with a fixed-dose renin–angiotensin system inhibitor and diuretic combination: results from a French national survey

et al. 2006

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High rates of uncontrolled hypertensives have been reported in France as well as in other countries, partly owing to an inadequate management of hypertension by clinicians. The objectives of the study were (1) to describe the therapeutic decisions faced by general practitioners (GP) in hypertensives not controlled by fixed-dose combination antihypertensive therapy with a renin-angiotensin system (RAS) inhibitor and a diuretic (D) and (2) to evaluate the frequency with which ambulatory blood pressure monitoring (ABPM) is used in these patients. Each GP had to include five uncontrolled hypertensives on fixed-dose RAS inhibitor and D combination. A total of 2118 GPs included 9551 patients; 8643 patients were receiving at least one of the two drugs at a low dose (group 1) and the remaining 908 patients were receiving high doses of both drugs (group 2). The most common therapeutic choice was that of a new combination, either a fixed-dose in one pill or with separate preparations: 65% (n ¼ 5621) in group 1 and 56% (n ¼ 505) in group 2. An increase in dose was chosen in 28% of patients in group 1 (n ¼ 2467) and continuation of treatment without modification in 27% of patients in group 2 (n ¼ 242). A third active principle was only added in 2.5% of patients in group 1 (n ¼ 219) and 11% in group 2 (n ¼ 103). Ambulatory blood pressure monitoring was employed in 25% of patients (n ¼ 2413). An improvement in hypertension management should be expected from the implementation of the 2005 French guidelines.

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“…7,9-14 The antihypertensive response to RAS blockade is more obvious in high renin forms of hypertension whether renal or essential. 11 When combined with diuretics, RAS inhibitors can achieve an effective antihypertensive response in up to 85% of patients with mild hypertension. 9 Limited effects of RAS inhibition is present in black patients, 12 some low-renin forms of hypertension, intake of diet rich in sodium chloride and after NSAIDs intake.…”

Section: Antihypertensive Responsementioning

confidence: 99%

RAS inhibition in hypertension

Ibrahim

2006

J Hum Hypertens

100

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Optimisation of antihypertensive treatment by crossover rotation of four major classes

Cited by 306 publications

References 26 publications

Discordant responses to two classes of drugs acting on the renin-angiotensin system

Discordant responses to two classes of drugs acting on the renin-angiotensin system

Management in general practice of hypertensive patients poorly controlled with a fixed-dose renin–angiotensin system inhibitor and diuretic combination: results from a French national survey

RAS inhibition in hypertension

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