The effects of thromboxane A2 inhibition (Picotamide) and angiotensin II receptor blockade (Losartan) in primary Raynaud's phenomenon

Pancera, P; Sansone, Stefano; Secchi, S; Covi, G; Lechi, Alessandro

doi:10.1046/j.1365-2796.1997.00219.x

Cited by 41 publications

(15 citation statements)

References 11 publications

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“…By contrast, in a subsequent clinical trial performed with dazoxiben, there was no reduction in the number of vasospasm episodes 83 and a similar finding was made in a different trial when a specific TXA 2 receptor antagonist was used. 84 The results of these clinical trials do not necessarily overturn the proposal, simply because TXA 2 may not be the only COX product that contributes to the vasospasm and because factors other than COX products may also be involved.…”

Section: The Nature Of the Vasoconstrictor Cox Productsmentioning

confidence: 96%

Mechanisms of Raynaud’s disease

2005

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Raynaud's phenomenon is due to transient cessation of blood flow to the digits of the hands or feet. An attack of Raynaud’s phenomenon is classically manifested as triphasic color changes. The white phase is due to excessive vasoconstriction and cessation of regional blood flow. This phase is followed by a cyanotic phase, as the residual blood in the finger desaturates. The red phase is due to hyperemia as the attack subsides and blood flow is restored. An attack is frequently associated with pain and/or paresthesia due to sensory nerve ischemia. Variants of Raynaud’s phenomenon include acrocyanosis and primary livedo reticularis, each of which is associated with reduced skin blood flow, exacerbated by cold or emotional upset. Raynaud’s phenomenon in the absence of other disorders is primary Raynaud’s phenomenon, or Raynaud’s disease. The mechanisms of Raynaud’s disease include increased activation of the sympathetic nerves, in response to cold or emotion; an impaired habituation of the cardiovascular response to stress may contribute. In addition, there appears to be a local fault, which is likely multifactorial. This local fault is due to an alteration in vascular function rather than vascular structure. The alteration in vascular function may be related to increased sensitivity to cold of the adrenergic receptors on the digital artery vascular smooth muscle. In some cases, locally released or systemically circulating vasoconstrictors may participate, including endothelin, 5-hydroxytryptamine and thromboxane. A deficiency or increased degradation of nitric oxide, possibly due to increased oxidative stress, may be involved in some cases. These recent pathophysiological insights may lead to new therapeutic options.

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Section: The Nature Of the Vasoconstrictor Cox Productsmentioning

confidence: 96%

Mechanisms of Raynaud’s disease

2005

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“…It does not exhibit the adverse respiratory side effects, such as cough, that are common to angiotensin-converting enzyme (ACE) inhibitors (13), which have also been shown to be of controversial benefit in RP (14). A small number of patients with primary RP have been treated with low doses of losartan, and a significant improvement in RP episodes was demonstrated in that study (15). The efficacy of losartan in secondary RP has not been studied, although 1 case report did not demonstrate its benefit in the treatment of established scleroderma renal crisis (16).…”

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confidence: 99%

Losartan therapy for Raynaud's phenomenon and scleroderma: Clinical and biochemical findings in a fifteen-week, randomized, parallel-group, controlled trial

Dziadzio

Denton

Smith

et al. 1999

Arthritis & Rheumatism

277

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Objective. To compare the efficacy and tolerability of losartan, an antagonist of angiotensin II receptor type 1, with nifedipine for the treatment of primary and secondary Raynaud's phenomenon (RP) in a pilot study.Methods. In a randomized, parallel-group, controlled trial, patients with primary RP (n ‫؍‬ 25) or RP secondary to systemic sclerosis (SSc [scleroderma]; n ‫؍‬ 27) were allocated to receive 12 weeks' treatment with either losartan (50 mg/day) or nifedipine (40 mg/day). Primary outcome variables were the severity and frequency of RP episodes and findings on vascular measurements, including thermography and laser Doppler flowmetry. Serum levels of soluble adhesion molecules, endothelin 1, fibrinogen, von Willebrand factor, and procollagen type I N-terminal propeptide (PINP) were also measured.Results. There was a reduction in the severity of RP episodes following treatment with losartan and with nifedipine, but this effect was greater in the losartan arm of the study (P < 0.05): episode frequency was reduced only in the losartan group (P < 0.01 versus baseline). Symptomatic improvement was associated with a significant reduction in soluble vascular cell adhesion molecule 1 and PINP (P < 0.01). Subgroup analysis suggested that although these biochemical changes occurred mainly in SSc patients, the clinical benefit was greater in the primary RP group.Conclusion. This study confirms the tolerability of short-term treatment of RP with losartan, and our data suggest its clinical benefit. Further evaluation of this drug as a long-term treatment for SSc-associated RP should be considered, since it may have additional disease-modifying potential.Episodic digital ischemia provoked by cold and emotion was first described by Maurice Raynaud over 130 years ago (1). When it occurs in isolation, it is designated primary Raynaud's phenomenon (RP) to distinguish it from those cases in which there is an underlying or associated pathology. It affects ϳ10% of the adult population, with a predilection for females, and up to 5% of patients presenting with this condition later develop an autoimmune rheumatic disorder, such as systemic sclerosis (SSc; scleroderma) (2). Successful treatment is often difficult, and although clinical trials suggest that vasodilators can be effective, the responses of individual patients to a particular agent are often idiosyncratic.The pathogenesis of the vascular dysfunction underlying RP is incompletely understood, and relatively few well-controlled clinical trials with vasoactive drugs have been undertaken. Lack of distinction between primary and secondary RP in some of these studies makes their interpretation difficult. Calcium channel antagonists such as nifedipine have been shown to be effective (3-6), although striking differences in individual responses have been described (3,7). Moreover, efficacy is often particularly limited in patients with RP

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“…Other drugs that appear to be effective include captopril, losartan, guanethidine, prazosin, and sustainedrelease transdermal glyceryl trinitrate patches and slidenafil. [39][40][41] Selective serotonin reuptake inhibitors (SSRIs) have been studied recently as well and may be helpful in the treatment of Raynaud's syndrome. 42 Behavioral modification with biofeedback has helped many patients, and acupuncture has even proved beneficial in one small study.…”

Section: Treatment and Outcomementioning

confidence: 99%