QUALITY OF LIFE ON ANGINA THERAPY: A RANDOMISED CONTROLLED TRIAL OF TRANSDERMAL GLYCERYL TRINITRATE AGAINST PLACEBO

doi:10.1016/S0140-6736(88)92942-X

The Lancet

Volume 332, Issue 8601, 2 July 1988, Pages 4-8

https://doi.org/10.1016/S0140-6736(88)92942-X Get rights and content

Abstract

In a randomised controlled trial in 427 men with chronic stable angina continuous use of 5 mg transdermal glyceryl trinitrate (GTN) showed no advantage over placebo in terms of efficacy (anginal attack rates and sublingual GTN consumption) or quality of life (as measured with the sickness impact profile and a health index of disability). Patients on the active drug reported headaches more frequently than patients on placebo, and a higher proportion of them withdrew from the trial because of headache. Quality-of-life measurements showed a significant adverse effect of active treatment, principally in the social interaction dimension of the sickness impact profile. A similar effect was observed in placebo patients when crossed to active treatment in a 4-week single-blind period. The results suggest no benefit in the relief of chest pain from 5 mg transdermal GTN when used continuously.

References (25)

N. Reichek et al.
Antiaginal effects of nitroglycerin patches
Am J Cardiol
(1984)
Pa Crean et al.
Failure of transdermal nitroglycerin to improve chronic stable angina A randomised placebo controlled double blind crossover trial
Am Heart J
(1984)
N. Sharpe et al.
Hemodynamic effects of intermittent transdermal nitroglycerin in chronic congestive heart failure
Am J Cardiol
(1987)
G. Lee et al.
Effects of long-term oral administration of isosorbide dinitrate on the antianginal response to nitroglycerin: Absence of cross-tolerance and self-tolerance shown by exercise testing
Am J Cardiol
(1978)
H. Letzel et al.
Advances in nitrate therapy for ischaemic heart disease: Results of a multicentre study with Transiderm Nitro
Z Allg Med
(1983)
H. Letzel et al.
Treatment of angina pectoris with Nitroderm TTS. Results of a multicentre field study in 37,596 patients
Med Welt
(1984)
B. Garnier et al.
Treatment of patients with angina pectoris in general practice with a new transdermal therapeutic system containing nitroglycerin (Nitroderm TTS)
Schweiz Rundsch Med Prax
(1982)
Ga Rose et al.
(1986)
M. Bergner et al.
The Sickness Impact Profile Development and final revision of a health status measure
Med Care
(1981)
D. Patrick
Standardization of comparative health status measures Using scales developed in America in an English speaking community

S. Fanshel et al.

A health status index and its application to health-services outcomes

Oper Res

(1970)

Aj Georgopoulos et al.

Therapeutic efficacy of a new transdermal system containing nitroglycerin in patients with angina pectoris

Eur J Clin Pharmacol

(1982)

Cited by (91)

Nitrates for stable angina: A systematic review and meta-analysis of randomized clinical trials
2011, International Journal of Cardiology
Citation Excerpt :
When tolerance was prevented with intermittent regimen, increased dose of nitrates was associated with more improvement of exercise performance. Quality of life was not improved in patients receiving continuous GTN patches compared with placebo [29]. In the trial with 427 patients, angina attacks and nitroglycerin consumption were reduced in both active and placebo groups.
To assess the effect (harms and benefits) of nitrates for stable angina.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE. Randomized controlled trials with both parallel and crossover design were included. The following outcome measures were evaluated: number of angina attacks weekly and nitroglycerin consumption, quality of life, total exercise duration, time to onset of angina and time to 1 mm ST depression.
Fifty-one trials with 3595 patients meeting inclusion criteria were analyzed. Both intermittent and continuous regimens of nitrates lengthened exercise duration significantly by 31 and 53 s respectively. The number of angina attacks was significantly reduced by 2.89 episodes weekly for continuous administration and 1.5 episodes weekly for intermittent administration. With intermittent administration, increased dose provided with 21 s more length of exercise duration. With continuous administration, exercise duration was pronged more in low-dose group. Quality of life was not improved by continuous application of GTN patches and was similar between continuous and intermittent groups. In addition, 51.6% patients receiving nitrates complained with headache.
Long-term administration of nitrates was beneficial for angina prophylaxis and improved exercise performance but might be ineffective for improving quality of life. With continuous regimen, low-dose nitrates were more effective than high-dose ones for improving exercise performance. By contrast, with intermittent regimen, high-dose nitrates were more effective. In addition, intermittent administration could bring zero-hour effect.
The Argentine-Spanish SF-36 Health Survey was successfully validated for local outcome research
2008, Journal of Clinical Epidemiology
To evaluate psychometric properties of the Argentine–Spanish SF-36 and to validate the physical component summary (PCS) and mental component summary (MCS) measures.
A self-administration of the SF-36 with 1-year follow-up was performed in a University-based ambulatory center in Buenos Aires. Diagnoses were abstracted from the chart. Univariate analysis, psychometric methods, and confirmatory factor analyses were conducted.
Of 3,290 subjects, 2,638 had computable scores and were included: 1,938 at their initial contact and 700 from a random sample of other enrollees. Cronbach's alpha ranged from 0.79 to 0.92 in all subscales except for General Health. Age was related to PCS scores (lower in the elderly) but not to MCS scores. PCS and MCS provided good discrimination among mutually exclusive disease categories; minor medical (52.2 vs. 51.1), psychosocial (48.1 vs. 43.0), chronic medical (46.2 vs. 51.0) and both chronic and mental conditions (44.9 vs. 45.1) in PCS and MCS, respectively (P < 0.01). Mean annual doctor visits increased from 3.6 to 5.3 in subjects with PCS > 55 and PCS < 35, and from 4.4 to 6.0 in subjects with MCS > 55 and MCS < 35, respectively (P < 0.0001).
SF-36 is a valid tool for outcome research in Argentina although normative general population studies are needed.
Chiropractic maintenance care and quality of life of a patient presenting with chronic low back pain
2005, Journal of Manipulative and Physiological Therapeutics
Citation Excerpt :
It is recommended that the psychometric properties of the SF-36 questionnaire and QWBS receive further investigation among chiropractic patients in general, and chiropractic MC patients more specifically. A further problem with interpreting changes in quality of life scores is that improved scores have been observed in patients participating in other studies who have been receiving placebo treatments and in patients in the run-in phase of studies before receiving either active or placebo interventions.34 It will be important to ask whether the improvements are a result of chiropractic spinal adjustments or some other aspect of MC, should further prospective studies show that there is an association between ongoing chiropractic MC, the resolution of subluxation indicators, and improved quality of life.
To report on a 26-year-old female patient presenting with uncomplicated chronic low back pain who received chiropractic maintenance care using 2 quality of life outcome assessment instruments.
Short-form (SF-36) subscales, Quality of Well-Being Scale, Visual Analog Scale, and number of tender vetebral spinous processes.
After 9 months of care the SF-36 subscale scores showed improvement. The SF-36, although low before care, approached normal on 3 subscales and exceeded normal population values on 5 subscales after 9 months. The SF-36 physical and mental composite scores improved from mean baseline scores of 23.4 and 25.3 to 43.7 and 62.8, respectively, after 9 months of care. The Quality of Well-Being Scale scores improved from a mean pre-intervention score of 1.1 to a post-intervention score of 8.2. The Visual Analog Scale scores improved from a mean pre-intervention score of 8 to a post-intervention score of 1.5. The mean number of chiropractic vertebral subluxations, detected via palpation of spinous process tenderness, went from a pre-care mean of 6.5 to a post-care mean of 4.
The patient appeared to experience improvement in quality of life while showing signs suggestive of improved spinal function. The relationship between indicators of vertebral subluxation and quality of life deserves further investigation using a research design that allows for exploration of possible causal relationships.
Comparative responsiveness of generic and specific quality-of-life instruments
2003, Journal of Clinical Epidemiology
We assessed the relative responsiveness of generic and specific quality of life instruments in 43 randomized controlled trials that compared head-to-head 31 generic and 84 specific instruments. Using weighted effect size as the metric of responsiveness, we assessed the impact of instrument type, disease category, and magnitude of underlying therapeutic effect on responsiveness, and assessed the responsiveness of specific instruments relative to the corresponding domains of generic measures. In studies with a nonzero therapeutic effect, specific instruments (mean = 0.57) were significantly more responsive than generic instruments (mean = 0.39, P = .01), and than the corresponding domains of generic instruments (mean = 0.40, P = .03). Studies with low, medium, and high therapeutic effects showed a corresponding gradation in responsiveness differences between specific and generic instruments. We conclude that, overall, specific instruments are more responsive than generic tools, and that investigators may come to misleading conclusions about relative instrument responsiveness if they include studies in which the magnitude of the underlying therapeutic effect is zero.
Methods to explain the clinical significance of health status measures
2002, Mayo Clinic Proceedings
Citation Excerpt :
Mean scores of patients with a particular diagnosis have provided another anchor for adding meaning to health status measures. Investigators have reported Sickness Impact Profile mean scores (range, 0-100; higher scores indicate worse health status) for a number of diagnoses, including severe rheumatoid arthritis (15.620 and 25.821), chronic airflow limitation severe enough to require a home oxygen tank (2422), chronic, stable angina (approximately 11.523), and amyotrophic lateral sclerosis.20 These anchors may be particularly useful for clinicians who treat such patients.
One can classify ways to establish the interpretability of quality-of-life measures as anchor based or distribution based. Anchor-based measures require an independent standard or anchor that is itself interpretable and at least moderately correlated with the instrument being explored. One can further classify anchor-based approaches into population-focused and individual-focused measures. Population-focused approaches are analogous to construct validation and rely on multiple anchors that frame an individual's response in terms of the entire population (eg, a group of patients with a score of 40 has a mortality of 20%). Anchors for population-based approaches include status on a single item, diagnosis, symptoms, disease severity, and response to treatment. Individual-focused approaches are analogous to criterion validation. These methods, which rely on a single anchor and establish a minimum important difference in change in score, require 2 steps. The first step establishes the smallest change in score that patients consider, on average, to be important (the minimum important difference). The second step estimates the proportion of patients who have achieved that minimum important difference. Anchors for the individual-focused approach include global ratings of change within patients and global ratings of differences between patients. Distribution-based methods rely on expressing an effect in terms of the underlying distribution of results. Investigators may express effects in terms of betweenperson standard deviation units, within-person standard deviation units, and the standard error of measurement. No single approach to interpretability is perfect. Use of multiple strategies is likely to enhance the interpretability of any particular instrument.
Tolerability and efficiency of new transdermic nitroglycerin patch in outpatients with chronic stable angina. The PATRICH Trial
2002, Revista Clinica Espanola
Obtener datos sobre la tolerabilidad local y sistémica de tres dosis diferentes (5 mg/24 h, 10 mg/ 24 h y 15 mg/24 h) de un nuevo modelo de parche de nitroglicerina (Trinipatch®», Sanofi-Synthelabo, S. A.) en pacientes con angina crónica estable.
Se estudiaron 954 pacientes durante un período de seguimiento de 12 semanas. Se distribuyeron del siguiente modo: 132 pacientes con parches de 5 mg/24 h, 727 con parches de 10 mg/24 h y 95 con parches de 15 mg/24 h. La tolerabilidad local se evaluó usando la escala de Draize y la tolerabilidad sistémica registrando los acontecimientos adversos y valorando el efecto sobre la presión arterial. Adicionalmente se evaluó la eficacia del tratamiento mediante las variaciones observadas en el número y la severidad de las crisis anginosas, así como del consumo semanal de nitroglicerina sublingual.
Noventa y cuatro pacientes (9,8%) mostraron signos de irritación cutánea. Treinta y dos pacientes (3,3%) mostraron eritema y un paciente (0,1%) mostró eritema más endurecimiento. Treinta y nueve pacientes (4,1%) presentaron algún acontecimiento adverso sistémico durante el estudio. Se documentaron 44 acontecimientos adversos, siendo el más frecuente la cefalea (79,5%). Sólo se observó un acontecimiento adverso grave (insuficiencia cardíaca ligera), que en opinión del investigador no estaba relacionado con la medicación. No se observó ningún abandono del tratamiento por efectos adversos. El número de pacientes con crisis anginosas y el número de crisis anginosas semanales descendió significativamente con el tratamiento.
Los parches transdérmicos de nitroglicerina estudiados se mostraron como una terapia segura y bien tolerada en la angina de pecho crónica estable, tanto en términos de tolerancia local como sistémica. Se confirmó además su eficacia al reducir significativamente las crisis anginosas.
To obtain data on local and systemic tolerability of three different doses (5 mg/24 h, 10 mg/24 h, and 15 mg/24 h) of a new model of nitroglycerin patch (Trinipatch®, Sanofi-Synthelabo, S. A.) in patients with chronic stable angina.
A total of 954 patients were studied for a follow-up period of 12 weeks. Patients were distributed as follows: 132 to the 5 mg/24 h patch, 727 to the 10 mg/24 h patch, and 95 to the 15 mg/24 h patch. The local tolerability was evaluated by using the Draize scale and the systemic tolerability by recording the adverse reactions and assessing the effect on blood pressure. Furthermore, the efficiency of therapy was evaluated by means of the variations observed in the number and severity of angina crises, as well as the weekly use of sublingual nitroglycerine.
Ninety-four patients (9.8%) showed signs of cutaneous irritation. Thirty-two patients (3.3%) showed erythema, and one patient (0.1%) showed erythema and induration. Thrity-nine patients (4.1%) had some type of systemic adverse reaction during the study. A total of 44 adverse reactions were recorded, headache being the most common (79.5%). Only one severe adverse reaction was observed (mild heart failure), which in the opinion of the researcher was not related to the medication. No dropouts were recorded on account of adverse reactions. The number of patients with angina crises and the number of weekly angina crises decreased significantly with therapy.
The transdermic nitroglycerin patch was demonstrated to be a safe and well tolerated therapy for chronic stable angina, both in terms of local and systemic tolerability. Moreover, its efficiency was demonstrated as the number of angina crises decreased significantly.

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QUALITY OF LIFE ON ANGINA THERAPY: A RANDOMISED CONTROLLED TRIAL OF TRANSDERMAL GLYCERYL TRINITRATE AGAINST PLACEBO

Abstract

Am J Cardiol

Am Heart J

Am J Cardiol

Am J Cardiol

Advances in nitrate therapy for ischaemic heart disease: Results of a multicentre study with Transiderm Nitro

Z Allg Med

Treatment of angina pectoris with Nitroderm TTS. Results of a multicentre field study in 37,596 patients

Med Welt

Treatment of patients with angina pectoris in general practice with a new transdermal therapeutic system containing nitroglycerin (Nitroderm TTS)

Schweiz Rundsch Med Prax

The Sickness Impact Profile Development and final revision of a health status measure

Med Care

Standardization of comparative health status measures Using scales developed in America in an English speaking community

A health status index and its application to health-services outcomes

Oper Res

Therapeutic efficacy of a new transdermal system containing nitroglycerin in patients with angina pectoris

Eur J Clin Pharmacol