Biomedical subjects

Bridget-Anne Kirwan

Publications and source records attributed to Bridget-Anne Kirwan.

8 recordsLinked to original sources

PubMed2006

The development of heart failure in patients with stable angina pectoris.

BACKGROUND: To describe the clinical characteristics of patients with stable angina pectoris who develop heart failure and the events preceding its onset. METHODS AND RESULTS: Of 7665 patients with stable angina in the ACTION trial, which compared long-acting nifedipine to placebo, 207 (2.7%) developed heart failure (HF) during a mean follow-up of 4.9 years. Those who developed HF were significantly (P<0.05) older, more often had diabetes, had a more extensive history of cardiovascular disease, lower ejection fractions, a higher serum creatinine and glucose, a lower haemoglobin, and were more often on blood pressure lowering drugs. A cardiac event or an intervention (n=155), a significant non-cardiac infection (n=19) or poor control of hypertension (n=12) preceded the development of HF in 186/207 cases (90%). There was no obvious precipitating factor in the remaining 21 patients (10%). Myocardial infarction increased the risk of the development of new HF within one week more than 100-fold. Nifedipine reduced the incidence of HF by 29% (P=0.015). CONCLUSIONS: The development of heart failure is uncommon in patients with stable angina, and even less so in the absence of an obvious precipitating factor.

Aged↗

PubMed2006

Tracking coronary calcification and atherosclerotic lesions in patients with stable angina pectoris undergoing nifedipine therapy.

AIMS: The objective of the Coronary Calcification (CC) study was to determine in patients with chronic symptomatic coronary artery disease, if, in addition to standard therapy, nifedipine GITS, relative to placebo, would arrest or slow down the progression of calcium or the development of new atherosclerotic lesions in the coronary arteries. METHODS AND RESULTS: The CC study was part of the ACTION trial. Multi-slice computerized tomography was used to measure and track the progression of CC. Five hundred and eighteen patients were included in this study. The changes in calcium score from baseline every 24 months, over a period of between 4.5 and 6 years, were similar in the nifedipine and placebo treatment groups (p = 0.8). Compared to placebo, more patients in the nifedipine group (71 vs. 60%) were free of new calcified atherosclerotic lesions during follow-up(p = 0.095). CONCLUSION: Nifedipine GITS was not effective in slowing down the progression of calcium in advanced atherosclerotic plaques in patients with stable angina pectoris. Although statistically not significant, Nifedipine demonstrated a trend in slowing down the development of new atherosclerotic lesions.

Aged↗

PubMed2006

Safety of nifedipine GITS in stable angina: the ACTION trial.

AIM: We describe the safety profile of nifedipine GITS as assessed from adverse events reported in the ACTION trial in which 7,665 patients with stable, symptomatic coronary artery disease were randomly assigned nifedipine GITS or placebo and followed for a mean of 4.9 years. METHODS: All adverse events were coded using the COSTART coding dictionary. The incidence rate for each event was calculated as the number of patients with the event concerned divided by the total time 'at risk'. Hazard ratios comparing nifedipine with placebo and their 95% confidence intervals were obtained by Cox proportional-hazards analysis. RESULTS: As reported previously, nifedipine significantly reduced the incidence of cardiovascular events and procedures [hazard ratio (HR) 0.89, 95% confidence interval (CI) 0.83-0.95]. Apart from the known side effects of nifedipine, which include peripheral oedema, vasodilatation, hypotension, asthenia, constipation, leg cramps, non-specific respiratory complaints, impotence and polyuria, and which were reported more frequently in patients assigned nifedipine, the incidence rates of most other adverse events were similar. There were no differences in the occurrence of gastrointestinal haemorrhage, myocardial infarction and suicide. The rate of occurrence of death or new cancer excluding non-melanoma skin cancer for patients with no history of cancer at baseline was 2.53/100 patient years for patients assigned nifedipine and 2.37/100 patient years for patients assigned placebo (HR 1.06, 95% CI 0.93-1.22). CONCLUSION: Overall nifedipine GITS was well tolerated by patients with stable symptomatic angina.

Adverse Drug Reaction Reporting Systems↗

PubMed2006

Incidence and outcome of atrial fibrillation in stable symptomatic coronary disease.

OBJECTIVES: Evaluate the prevalence, incidence and impact on prognosis of existing and new onset atrial fibrillation (AF) in patients with stable, symptomatic coronary artery disease. DESIGN: Data from the 7 665 participants included in the ACTION (A Coronary disease Trial Investigating Outcome with Nifedipine GITS) trial was used. RESULTS: Over a mean follow-up of 4.9 years, the incidence of recurrent AF in patients with AF at baseline (4.1%) was 13.5/100 patient-years and 1.64/100 patient-years for patients without baseline AF. Patients with AF at baseline had increased mortality and new overt heart failure. New onset AF was associated with increased morbidity and mortality and in particular soon after onset. [adjusted 30-day relative risk for mortality 23, 95% CI 14-36; for debilitating stroke 37, 95% CI 18-77; and for heart failure 54, 95% CI 32-93]. The incidence of AF was not affected by treatment with nifedipine GITS. CONCLUSION: The presence of AF in patients with stable symptomatic CAD is an independent risk factor and in particular in the first 30 days for subsequent mortality and morbidity.

Aged↗

PubMed2005

Risk score for predicting death, myocardial infarction, and stroke in patients with stable angina, based on a large randomised trial cohort of patients.

OBJECTIVE: To derive a risk score for the combination of death from all causes, myocardial infarction, and disabling stroke in patients with stable symptomatic angina who require treatment for angina and have preserved left ventricular function. DESIGN: Multivariate Cox regression analysis of data from a large multicentre trial. SETTING: Outpatient cardiology clinics in western Europe, Israel, Canada, Australia, and New Zealand. PARTICIPANTS: 7311 patients with all required data available. MAIN OUTCOME MEASURE: Death from any cause or myocardial infarction or disabling stroke during a mean follow-up of 4.9 years. RESULTS: 1063 patients either died from any cause or sustained myocardial infarction or disabling stroke. The five year risk of this composite ranged from 4% for patients in the lowest tenth of risk to 35% for patients in the highest tenth. The risk score combines 16 routinely available clinical variables (in order of decreasing contribution): age, left ventricular ejection fraction, smoking, white blood cell count, diabetes, casual blood glucose concentration, creatinine concentration, previous stroke, at least one angina attack a week, coronary angiographic findings (if available), lipid lowering treatment, QT interval, systolic blood pressure > or = 155 mm Hg, number of drugs used for angina, previous myocardial infarction, and sex. Fitting the same model separately to all cause death, myocardial infarction, and stroke gave similar results. The risk score did not seem to predict the nature of the event (death in 39%, myocardial infarction in 46%, and disabling stroke in 15%) or the incidence of angiography or revascularisation, which occurred in 29% of patients. CONCLUSION: This risk score is an objective aid in deciding on further management of patients with stable angina with the aim of reducing serious outcome events. The score can also be used in planning future trials.

Adult↗

PubMed2005

Effect of long-acting nifedipine on mortality and cardiovascular morbidity in patients with symptomatic stable angina and hypertension: the ACTION trial.

OBJECTIVE: To examine the effects of nifedipine GITS on clinical outcome in patients with concurrent stable angina and hypertension. METHODS: Data from the double-blind placebo-controlled ACTION trial was stratified for hypertension (blood pressure > or = 140/90 mmHg), at baseline. RESULTS: A total of 52% of 7665 ACTION patients were hypertensive. Some 80% were on a beta blocker; hypertensives were more often treated with other blood pressure-lowering drugs. Mean baseline blood pressure was 122/74 mmHg among normotensives and 151/85 mmHg among hypertensives. Follow-up blood pressures were reduced by nifedipine (P < 0.001) on the average by 3.9/2.4 and 6.6/3.5 mmHg among normotensives and hypertensives, respectively. Nifedipine GITS significantly (P < 0.05) reduced the combined incidence of all-cause mortality, myocardial infarction, refractory angina, heart failure, stroke and peripheral revascularization by 13% in hypertensives only. Nifedipine significantly reduced the incidence of any stroke or transient ischemic attack by almost 30% in both subgroups and the need for coronary angiography by 21% in normotensives and 16% in hypertensives. Among hypertensives, the incidence of new overt heart failure was significantly reduced by 38% and of debilitating stroke by 33%. Among normotensives, the need for coronary bypass grafting was significantly reduced by 32%. Nifedipine did not affect all-cause death, cardiovascular death and myocardial infarction in either normo- or hypertensives, but increased the need for peripheral revascularization. CONCLUSION: The salutary effects of the addition of nifedipine GITS to the basic regimen of patients with concurrent stable symptomatic coronary artery disease and hypertension emphasize the need for blood pressure control.

Adrenergic beta-Antagonists↗

PubMed2002

Combined endpoints: can we use them?

Analysing specific non-fatal events in isolation may lead to spurious conclusions about efficacy unless the events considered are combined with all-cause mortality. The use of combined endpoints has therefore become widespread, at least in cardiovascular disease trials. Combining all-cause mortality with selected non-fatal events is useful because event-free survival, an important criterion in therapy evaluation, is addressed in this manner. In many clinical trials, symptoms, signs or paraclinical measures (for example, blood pressure, exercise duration, quality of life scores) are used as endpoints. If the patient died before the endpoint was measured, or it was otherwise not possible to perform follow-up assessments as planned, the effect of treatment on these endpoints may be distorted if the patients concerned are ignored in the analysis. Examples are given of how distortion can be avoided by including all patients randomized in an analysis that uses a ranked combined endpoint based both on clinical events and on paraclinical measures. A distinction is made between a pseudo intention-to-treat analysis that disregards study medication status at the time of endpoint assessment but is confined to patients with data, and a true intention-to-treat analysis that takes into account all patients randomized based on a ranked combined endpoint.

Adrenergic beta-Antagonists↗

PubMedDate not supplied

Effect of long-acting nifedipine on mortality and cardiovascular morbidity in patients with stable angina requiring treatment (ACTION trial): randomised controlled trial.

BACKGROUND: Calcium antagonists are widely prescribed for angina pectoris but their effect on clinical outcome is controversial. We aimed to investigate the effect of the calcium antagonist nifedipine on long-term outcome in patients with stable angina pectoris. METHODS: We randomly assigned 3825 patients with treated stable symptomatic coronary disease to double-blind addition of nifedipine GITS (gastrointestinal therapeutic system) 60 mg once daily and 3840 to placebo. The primary endpoint was the combination of death, acute myocardial infarction, refractory angina, new overt heart failure, debilitating stroke, and peripheral revascularisation. Mean follow-up was 4.9 years (SD 1.1). Analysis was by intention to treat. FINDINGS: 310 patients allocated nifedipine died (1.64 per 100 patient-years) compared with 291 people allocated placebo (1.53 per 100 patient-years; hazard ratio 1.07 [95% CI 0.91-1.25], p=0.41). Primary endpoint rates were 4.60 per 100 patient-years for nifedipine and 4.75 per 100 patient-years for placebo (0.97 [0.88-1.07], p=0.54). With nifedipine, rate of death and any cardiovascular event or procedure was 9.32 per 100 patient-years versus 10.50 per 100 patient-years for placebo (0.89 [0.83-0.95], p=0.0012). The difference was mainly attributable to a reduction in the need for coronary angiography and interventions in patients assigned nifedipine, despite an increase in peripheral revascularisation. Nifedipine had no effect on the rate of myocardial infarction. INTERPRETATION: Addition of nifedipine GITS to conventional treatment of angina pectoris has no effect on major cardiovascular event-free survival. Nifedipine GITS is safe and reduces the need for coronary angiography and interventions.

Angina Pectoris↗