Biomedical subjects

D Mulcahy

Publications and source records attributed to D Mulcahy.

At least 19 recordsLinked to original sources

PubMed1999

Percutaneous catheter and guidewire fragmentation with local administration of recombinant tissue plasminogen activator as a treatment for massive pulmonary embolism.

The purpose of this article is to report four patients with massive pulmonary embolism treated with percutaneous catheter and guidewire fragmentation and local administration of recombinant tissue plasminogen activator (r-TPA). Four patients with massive pulmonary embolism initially underwent pulmonary angiography. Thrombus fragmentation was performed with both standard angiographic guidewires and catheters followed by local infusion of 41-200 mg of r-TPA. Pulmonary angiography was repeated after treatment. All patients survived with improvement in their clinical status and eventual discharge from hospital. Angiography in all patients post treatment demonstrated improvement in pulmonary perfusion (mean Miller score before treatment 22.5; mean Miller score after treatment 5.75). No patient had a significant complication. Mechanical fragmentation of the thrombus followed by local infusion of r-TPA was an effective treatment for massive pulmonary embolism in these four patients with no significant complications.

Aged↗

PubMed1999

"Circadian" variation in cardiovascular events and implications for therapy?

For many years, it was thought that acute cardiovascular events occurred in a random fashion. However, over the past 13 years or so, a significant amount of research, both retrospective and prospective, has shown that there is an excess of ischaemic activity, arrhythmic activity and acute cardiovascular events in the first few hours after waking and commencing activity. This excess may well be at least partly linked to the known physiological changes which occur after waking, including a surge in heart rate, blood pressure and catecholamine release, activation of the renin-angiotensin system, an increase in platelet aggregability on assuming the upright posture, and the final trough in the fibrinolytic system. Because of the relatively short half-life and duration of the therapeutic effect (<24 h) of many anti-ischaemic and anti-arrhythmic agents, it is likely that single day agents taken in the morning will have reached subtherapeutic levels at the time of waking and commencing activity the following morning. As many patients do not take their daily (morning) medication immediately on rising, and allowing for time for adsorption, it is likely that, despite our knowledge of "circadian variations" in both physiological responses and pathophysiological events in the morning waking hours, patients are in fact at least protection at this particular high-risk time of the 24 h day. With our knowledge about when events are more likely to happen, we should consider carefully the timing of administration of medications, having factored in the likely length of therapeutic effect in each instance. It is likely that the almost universal inability to demonstrate prognostic benefit with many anti-ischaemic and anti-arrhythmic agents to date relates at least in part to a lack of appropriate "protection" at the time of apparent greatest risk in the patient with cardiovascular disease. Intelligent prescribing might indeed improve outcome, and even in the absence of proof on this regard, it would seem appropriate that we at least strive to achieve such an outcome.

Acute Disease↗

PubMed1998

Aspirin improves endothelial dysfunction in atherosclerosis.

BACKGROUND: The beneficial effects of aspirin in atherosclerosis are generally attributed to its antiplatelet activities, but its influence on endothelial function remains uncertain. We hypothesized that a cyclooxygenase-dependent constricting factor contributes to the endothelial dysfunction in atherosclerosis and that its action can be reversed by aspirin. METHODS AND RESULTS: In 14 patients with coronary atherosclerosis and 5 with risk factors, we tested femoral vascular endothelial function with acetylcholine and substance P and endothelium-independent function with sodium nitroprusside before and after intravenous aspirin. Drugs were infused into the femoral artery, and Doppler flow velocity was measured. Acetylcholine-induced but not substance P-or sodium nitroprusside-induced vasodilation was lower in patients with atherosclerosis than in those with only risk factors. Aspirin had no baseline effect but improved acetylcholine-mediated vasodilation only in patients with atherosclerosis; at the peak dose, acetylcholine-mediated femoral vascular resistance index was 19 +/- 5%, P=.002 lower. There was a correlation between the baseline response to acetylcholine and the magnitude of improvement with aspirin (r=.5, P=.05). Thus, patients with a depressed response to acetylcholine had greater improvement with aspirin, and vice versa. The presence of atherosclerosis was an independent determinant of improvement with aspirin. Aspirin had no effect on the responses to either substance P or sodium nitroprusside. CONCLUSIONS: Cyclooxygenase-dependent, endothelium-derived vasoconstrictor release modulates acetylcholine-induced peripheral vasodilation in patients with atherosclerosis. Improvement of endothelial dysfunction with aspirin may improve vasodilation, reduce thrombosis, and inhibit progression of atherosclerosis and provides a pathophysiological basis for the beneficial effects of aspirin in atherosclerosis.

Acetylcholine↗

PubMed1998

Patellofemoral contact forces and pressures during intramedullary tibial nailing.

Patellofemoral joint forces and pressures were measured in a cadaver model during intramedullary nailing of the tibia. A significant increase in contact pressures was found at the lateral facet of the patellofemoral articulation using the medial paratendinous approach (P = 0.01) and at the medial facet when using the trans-patellar tendon approach (P = 0.001) to the proximal tibia. Increased contact pressures at the patello-femoral joint may result in chondral injury, which in turn may cause anterior knee pain, a common complication of tibial nailing.

Arthralgia↗

PubMed1998

Long-term prognosis in unstable angina. The importance of early risk stratification using continuous ST segment monitoring.

AIMS: To assess the ability of clinical characteristics, admission ECG and continuous ST segment monitoring in determining long-term prognosis in unstable angina. METHODS: Two hundred and twelve patients with unstable angina (mean age 59 years), presenting within 24 h of an acute episode of angina were recruited at three hospitals and treated with standardized medical therapy. All patients kept chest pain charts and underwent ST segment monitoring for 48 h. The occurrence of death, myocardial infarction, and need for revascularization was assessed over a median follow-up of 2.6 years. RESULTS: The risk of death of myocardial infarction was greatest in the first 6-8 weeks after admission. Admission ECG ST depression and the presence of transient ischaemia predicted increased risk of subsequent death or myocardial infarction, whereas a normal ECG predicted a good prognosis. In 14 patients, ST segment monitoring provided the only evidence of recurrent ischaemia, and 72% of this group suffered an adverse event. Transient ischaemia and a history of hypertension were the most powerful independent predictors of death or myocardial infarction. CONCLUSIONS: Adverse events in unstable angina occur early after admission and can be predicted by clinical and ECG characteristics, and by the presence of transient ischaemia during ST segment monitoring. Risk stratification by these simple assessments can identify patients with unstable angina at high risk.

Adult↗

PubMed1998

Long-term (5 year) effects of transient (silent) ischaemia on left ventricular systolic function in stable angina. Clinical and radionuclide study.

AIMS: (a) to assess short (1 year) and long-term (5 year) changes in left ventricular ejection fraction in patients with stable coronary disease with or without ECG evidence of transient ischaemia during daily life on routine therapy, and (b) to assess whether patients with recurrent transient ischaemic episodes have a particular propensity to gradual deterioration in left ventricular ejection fraction in the absence of infarction. METHODS AND RESULTS: One hundred and forty eight patients (127 males; mean age 59 years), part of a natural history cohort of 172 patients who had undergone exercise testing, 48 h ambulatory ST monitoring, and resting radionuclide ventriculography at baseline, and who had not suffered any intervening cardiac event, underwent repeat radionuclide ventriculography at 1 year follow-up on identical or very similar medications. Furthermore, 56 patients (50 males; mean age 65 years) of this cohort, who had ischaemia both on exercise testing and ambulatory monitoring at baseline (n=33), or no ischaemia on either test at baseline (n=23), and who had suffered no intervening event, underwent repeat exercise testing, ambulatory monitoring and radionuclide ventriculography at a mean of 61.8 months follow-up. In 38 of these 56 cases, long-term testing mirrored baseline testing in terms of presence or absence of ischaemia (both tests +, n=25; both tests -, n=13). At one year there was no change in left ventricular ejection fraction, either for the whole group (n=148; left ventricular ejection fraction 47=11.6% - 47.13+11.07%, P=ns) or for subgroups with (n=62; left ventricular ejection fraction 48+12.1%-48.5+10.5%, P=ns) and without (n=86; left ventricular ejection fraction 46.2+10.4%-46.2+11.3%, P=ns) evidence of transient ischaemia at baseline. At 61 months, there was a small fall in mean left ventricular ejection fraction for the total study group (n=56; left ventricular ejection fraction 45.8+9.3%-42.1+8.8%, P<0.05); however, this fall was not significant for those patients with both baseline and 5 year evidence of transient ischaemia (n=25; left ventricular ejection fraction 44.9+8.7%-41.3+7.5%, P=0.056). CONCLUSION: In medically treated stable coronary patients who do not suffer any intervening cardiac event, recurrent transient (silent) ischaemic episodes do not, in themselves, lead to gradual deterioration in left ventricular systolic function over a 1-5 year period.

Adult↗

PubMed1998

Contribution of nitric oxide to reactive hyperemia: impact of endothelial dysfunction.

Our objectives were to (1) test the hypothesis that nitric oxide (NO) contributes to peak reactive hyperemia (RH) in the human peripheral vasculature, (2) examine the impact of atherosclerosis and its risk factors on RH, and (3) investigate whether L-arginine will improve RH in patients with endothelial dysfunction. The endothelium contributes to shear stress-mediated vasomotion by releasing a variety of dilating factors, including NO, but the contribution of NO to peak RH in patients with and without endothelial dysfunction is unknown. Endothelium-dependent and endothelium-independent function was assessed with intrafemoral arterial acetylcholine (ACh) and sodium nitroprusside. RH was produced by occlusion of blood flow to the leg for 3 minutes. The study was repeated after NG-monomethyl-L-arginine (L-NMMA) in 44 subjects and L-arginine in 9 patients with atherosclerosis. There were 15 normal control subjects without risk factors for atherosclerosis and 29 patients with risk factors or angiographic atherosclerosis. Microvascular vasodilation in response to ACh, but not to sodium nitroprusside, was lower in the patients with risk factors or atherosclerosis compared with normal control subjects, P=0.048, and the inhibition of ACh-induced microvascular dilation by L-NMMA was also greater in normal control subjects (P=0.045). Similarly, RH, including the peak response, was inhibited by L-NMMA in normal control subjects (P=0.0011) but not in patients with risk factors or atherosclerosis, suggesting that the contribution of NO to both ACh-induced dilation and RH was diminished in patients with risk factors or atherosclerosis. L-Arginine did not affect vasodilation in response to ACh, sodium nitroprusside, or RH. We concluded that (1) NO contributes to all phases of RH in the normal human peripheral vasculature, (2) patients with atherosclerosis or its risks have abnormal NO bioactivity in response to pharmacological and physiological stimulation, and (3) L-arginine does not improve RH in atherosclerosis. Reduced physiological vasodilation in atherosclerosis may contribute to or exacerbate hypertension and ischemia.

Acetylcholine↗

PubMed1998

Circadian variation in cardiovascular events.

Prospective studies have shown not only that there is a greater incidence of acute myocardial infarction during the morning waking hours but also that transient myocardial ischemia, unstable angina, sudden cardiac death, complex ventricular arrhythmieas, and strokes have a greater incidence at a similar time. Studies of the physiologic responses that occur throughout the day have shed much light on why such a pattern in the timing of cardiovascular events is seen. It has been shown, for example, that blood pressure and heart rate surge on waking and at the start of daily activities, as does release of catecholamine. It appears that delaying the time of arising and of commencing activities simply shifts the risk of cardiovascular events rather than negating it. The most important clinical message obtained from the study of circadian variation in cardiovascular disease is that protection should be offered to cover the morning waking hours in addition to other times of the day. This need is being addressed with the increasing use of long-acting therapeutic agents.

Journal Article↗

PubMed1998

Chymopapain chemonucleolysis: a review of 105 cases.

A review of 105 consecutive cases of chymopapain chemonucleolysis for single level lumbar disc herniation was undertaken. Mean follow-up was 12.2 years (range 10-15.3). Patients were assessed using the Oswestry Disability Questionnaire. Eighty-seven patients were available for follow-up. An excellent or good response occurred in 58 patients (67%); four patients (4.5%) had a moderate response but were only minimally disabled. The treatment failed in 25 patients (28.5%) and 21 of these went on to surgery within a mean of 5.2 months (range 3 weeks-12 months). In 15 patients (71%) disc sequestration or lateral recess stenosis was found. Five of the remaining six cases had a large disc herniation at surgery. Surgery resulted in a significant improvement in nine cases. Discitis following chemonucleolysis occurred in six patients (5.7%). Chymopapain chemonucleolysis has a useful role in the management of lumbar intervertebral disc prolapse. However, its efficacy is dependent on careful clinical and radiological patient selection.

Adult↗

PubMed1997

Blood pressure changes during transient myocardial ischemia: insights into mechanisms.

OBJECTIVES: We investigated the contribution of changes in systemic blood pressure to the genesis of spontaneous myocardial ischemia. BACKGROUND: Although increases in heart rate often precede the development of spontaneous myocardial ischemia, it remains a subject of controversy whether these are accompanied by simultaneous changes in blood pressure. METHODS: Using an ambulatory monitoring device that triggered blood pressure recordings from the level of the ST segment, we documented systolic and diastolic blood pressure and heart rate changes related to episodes of ST segment depression in 17 patients with stable coronary artery disease. RESULTS: Systolic blood pressure and heart rate, but not diastolic pressure, increased significantly before the onset of ST segment depression and persisted throughout the ischemic episode. There was a significant correlation between the changes in heart rate and systolic blood pressure during episodes of myocardial ischemia (r = 0.5, p = 0.0005) and between heart rate and systolic blood pressure changes at 1-mm ST segment depression during treadmill exercise testing and ambulatory monitoring (r = 0.73, p = 0.0005 for heart rate; r = 0.77, p = 0.0008 for systolic blood pressure), indicating that patients with a low heart rate threshold during ischemic episodes also had a lower systolic blood pressure threshold before ischemia during both tests. Circadian changes in systolic blood pressure paralleled the variations in heart rate and ischemic episodes, with the lowest values at night. CONCLUSIONS: Significant increases in myocardial oxygen demand, including systolic blood pressure, occur during episodes of spontaneous myocardial ischemia. Patients with a lower heart rate threshold during ischemic episodes had a lower systolic blood pressure threshold during both ambulatory monitoring and treadmill exercise. The effects of antianginal therapy on blood pressure changes during ischemia need to be explored further.

Aged↗

PubMed1997

Pathophysiology of transient myocardial ischemia in acute coronary syndromes. Characterization by continuous ST-segment monitoring.

BACKGROUND: Transient ischemia in stable coronary disease peaks in the morning, reflecting increased myocardial oxygen demand and coronary vasomotor tone after walking. In acute coronary syndromes, however, ischemia may result from transient thrombus formation or coronary spasm at the site of a ruptured plaque. We report on the pathophysiological mechanisms underlying transient ischemia in acute coronary syndromes despite optimal therapy, on the basis of analysis of heart rate changes preceding ischemia and its circadian variation. METHODS AND RESULTS: Two hundred fifty-six patients with unstable angina or non-Q-wave myocardial infarction underwent continuous ST-segment monitoring for 48 hours while receiving maximal medical therapy. All ischemic episodes were characterized by their timing, duration, association with pain, and heart rate changes before the onset of ischemia. During 10,629 hours of monitoring, 44 patients (17.2%) had 176 episodes of transient ischemia. The mean heart rate at onset of ischemia was 68 +/- 12.8 bpm, and > 55% of ischemic episodes were not preceded by a significant increase in heart rate. Ischemic activity had a single nocturnal peak, with 64% of all episodes occurring between 10 PM and 8 AM, this nocturnal preponderance being evident for episodes with or without a preceding increase in heart rate. The characteristics and timing of transient ischemia were similar in unstable angina and non-Q-wave myocardial infarction, but transient ischemia was more frequent (27.3% versus 15.1%; P < .05) and prolonged (median, 20 versus 13.5 minutes; P < .01) in non-Q-wave myocardial infarction. CONCLUSIONS: In acute coronary syndromes, transient ischemia has a low threshold, occurs predominantly without an increase in myocardial oxygen demand, and is present mainly at night rather than in the morning. These findings in patients receiving maximal medical therapy suggest significant pathophysiological differences underlying transient ischemia compared with stable coronary disease.

Acute Disease↗

PubMed1997

Coronary vascular nitric oxide activity in hypertension and hypercholesterolemia. Comparison of acetylcholine and substance P.

BACKGROUND: Whether the abnormal responses of the human coronary circulation to acetylcholine in patients with hypertension and hypercholesterolemia extend to other, nonmuscarinic stimulators of the endothelium and whether this signifies a specific abnormality of NO is not known. METHODS AND RESULTS: We studied 26 patients with angiographically normal coronary arteries, 10 without risk factors, and 16 with either hypertension (n = 9) and/or hypercholesterolemia (n = 10). Dose-response curves were performed with acetylcholine, substance P, and sodium nitroprusside before and after NG-monomethyl-L-arginine (L-NMMA). Substance P produced predominantly epicardial coronary dilation, whereas the dilating effect of acetylcholine was mainly microvascular. There was no correlation between the responses to the two drugs. L-NMMA did not affect the response to sodium nitroprusside, but it suppressed dilation in response to both substance P and acetylcholine, suggesting that the latter promote bioavailability of NO from the coronary vascular endothelium. Compared with patients without risks, those with hypercholesterolemia and hypertension had significantly reduced vasodilation with substance P: 21% versus 12.6% (P = .004) increase in epicardial coronary diameter and 35% versus 19% (P < .05) decrease in vascular resistance. Similar differences were noted with acetylcholine but not with sodium nitroprusside or adenosine. Epicardial and microvascular dilations with substance P or acetylcholine after L-NMMA were similar in patients with and without risk factors, indicating that the reduced effect of endothelium-dependent vasodilators in those with hypertension and hypercholesterolemia is due to diminished NO activity. CONCLUSIONS: (1) Substance P- and acetylcholine-induced coronary vasodilation, like that to acetylcholine, is at least partly due to stimulation of NO activity, indicating that the dysfunction of the coronary vascular endothelial cell layer is not restricted to muscarinic receptors. (2) Hypertension and hypercholesterolemia are associated with depression of both basal and pharmacologically stimulated bioavailability of NO.

Acetylcholine↗

PubMed1997

Nitric oxide activity in the atherosclerotic human coronary circulation.

OBJECTIVES: We determined the activity of nitric oxide at rest and after acetylcholine in the atherosclerotic human coronary circulation. BACKGROUND: Although responses to acetylcholine, an endothelium-dependent vasodilator, are abnormal in patients with coronary atherosclerosis, whether this reflects abnormal nitric oxide activity in humans in vivo has not been investigated previously. METHODS: We investigated the effects of intracoronary L-NG-monomethyl arginine (L-NMMA), a specific antagonist of nitric oxide synthesis, on coronary vascular resistance and epicardial coronary artery diameter at rest and after acetylcholine in 24 patients with coronary artery disease and in 12 subjects with angiographically normal coronary arteries who were free from atherosclerotic risk factors. RESULTS: With L-NMMA, the 13 +/- 4% (mean +/- SEM) increase in coronary vascular resistance and the 4 +/- 1% lumen diameter narrowing in atherosclerotic patients were lower than the 38 +/- 9% increase in resistance and the 15 +/- 2% decrease in diameter (both p < 0.01) observed in normal control subjects, indicating reduced basal nitric oxide activity in atherosclerosis. The degree of angiographic atherosclerotic narrowing did not correlate with the magnitude of diameter reduction. Acetylcholine-induced coronary epicardial and microvascular dilation was also depressed in atherosclerotic patients (32.2 +/- 9% reduction in coronary vascular resistance with 10(-6) mol/liter acetylcholine) compared with normal control subjects (65.5 +/- 2% decrease, p < 0.01). L-NMMA inhibited acetylcholine-induced epicardial and microvascular vasodilation in both patient groups, but the inhibition was greater in normal control subjects than in atherosclerotic patients, indicating that stimulation of nitric oxide activity by acetylcholine is reduced in atherosclerotic patients compared with normal control subjects. Coronary vascular dilation with sodium nitroprusside was similar in both groups and was not suppressed by L-NMMA. Furthermore, L-arginine reversed the constrictor effects of L-NMMA, indicating that the action of L-NMMA is specifically caused by inhibition of nitric oxide production from L-arginine. CONCLUSIONS: These findings indicate that 1) there is a reduced basal activity of nitric oxide in the human atherosclerotic epicardial and microvascular coronary circulation; and 2) acetylcholine-induced coronary vascular dilation is at least partly due to stimulation of the activity of nitric oxide, and the reduced response to acetylcholine is due to attenuation in the stimulated activity of nitric oxide in patients with atherosclerosis.

Acetylcholine↗

PubMed1997

An evaluation of patients comprehension of orthopaedic terminology: implications for informed consent.

We conducted a prospective study into patient comprehension of orthopaedic terminology that commonly appears on consent forms. The majority of patients questioned were unsure of the meaning of simple terms such as 'fracture reduction' or 'internal fixation'. All the patients questioned had signed consent forms recently for such procedures in an acute orthopaedic unit. We conclude that many patients willingly consent to procedures that they do not fully understand. This implies that there is an element of trust involved in the process of giving consent. We believe that this aspect of the doctor-patient relationship should be legally respected.

Adult↗

PubMed1997

Informed consent from whom?

To obtain legally safe informed consent requires that the patient has a 'substantial understanding' of the proposed procedure and that the doctor obtaining the informed consent has sufficient knowledge to explain the nature of the procedure to the patient. In this paper we have shown that significant misunderstanding exists among non-specialist junior doctors of certain common orthopaedic procedures and conditions. Junior doctors often lack sufficient technical training to fully inform their patients and thus meet legal requirements. The implications of this are that the onus falls even more on specialists to ensure that their patients receive a more detailed explanation of the proposed intervention.

Arthroscopy↗

PubMed1996

Tenuous link between ischaemic threshold and both ambulatory ischaemia and symptom status over time in stable angina: a 5-year follow-up study.

This study evaluates changes in ischaemic threshold over a 5-year period in patients with stable angina pectoris, who did not suffer any intervening cardiac event. Changes in ischaemic threshold are related to alterations in symptomatic status and ambulatory ischaemia. Over long-term follow-up, there is a significant fall in ischaemic threshold in such patients (mean heart rate at onset of ischaemia fell from 104 +/- 17.8 to 97 +/- 17.4 bpm: P < 0.001), but this is not matched by a worsening of either symptoms or ischaemia during daily life. In the 68% of patients that had a reduction in ischaemic threshold of > or = 5 bpm, 68% had either definite reduction or no change in symptoms and 84% had either reduction, abolition or no change in transient ischaemic activity. The dissociation between ischaemic threshold, ambulatory ischaemia and symptoms has implications for long-term monitoring and management of the patient with stable angina.

Adult↗

PubMed1996

Patterns and behavior of transient myocardial ischemia in stable coronary disease are the same in both men and women: a comparative study.

OBJECTIVES: This study sought to compare the circadian variations in transient ischemic activity, mean heart rate and ischemic threshold between women and men with coronary artery disease. BACKGROUND: There is a circadian variation in ischemic activity, onset of myocardial infarction and sudden cardiac death in patients with coronary artery disease, but studies assessing ischemia have incorporated predominantly male subjects. METHODS: Thirty-one women and 45 men underwent at least 48 h of ambulatory ST segment monitoring. RESULTS: There was a similar and significant circadian variation in ischemic activity in both women and men (p < 0.0001 and p < 0.0001, respectively), with a trough at night, a surge in the morning and a peak between 1 and 2 PM, corresponding to a similar circadian variation in mean hourly heart rate (p < 0.0001) that was not different between men and women (p = 0.28, power to detect a shift 99.9%). Mean heart rate at onset of ischemia (ischemic threshold) had similar variability in women and men (p = 0.96), and harmonic regression analysis confirmed a significant circadian variation (p < 0.0001), with a trough at night and a peak during activity hours. Heart rate increased significantly in the 5 min before ischemia throughout the 24 h (p < 0.0001), with no gender differences in the pattern of preonset to onset heart rate changes over time (p = 0.52); the smallest differences were recorded in the middle of the night. The majority of ischemic episodes (80%) had a heart rate increase > 5 beats/min in the 5 min before ischemia, but there were no gender differences. CONCLUSIONS: Women with coronary artery disease have a pattern of ischemic activity and underlying pathophysiologic mechanisms very similar to men. The importance of increase in myocardial oxygen demand in the genesis of ischemia in both men and women is reflected by similar magnitude of heart rate increases before ischemia. The lower ischemic threshold during the nocturnal hours, when blood pressure is also lower, is consistent with a circadian variation in underlying coronary vascular tone.

Acute Disease↗

PubMed1996

The Total Ischaemic Burden European Trial (TIBET). Effects of atenolol, nifedipine SR and their combination on the exercise test and the total ischaemic burden in 608 patients with stable angina. The TIBET Study Group.

OBJECTIVES: To determine the effects of atenolol, nifedipine and their combination on exercise parameters and ambulatory ischaemic activity in patients with mild chronic stable angina. SETTING: Multicentre, multinational study involving 608 patients from 69 centres in nine countries. DESIGN: Placebo washout followed by double-blind parallel-group study comparing atenolol 50 mg bd, nifedipine SR 20 mg bd, and their combination. Patients underwent maximal exercise testing using either a bicycle (n = 289) or treadmill (n = 319) and 48 h of ambulatory ST segment monitoring outside the hospital environment at the end of the placebo washout period and after 6 weeks of active therapy. RESULTS: Both medications alone and in combination caused significant improvements in exercise parameters and significant reductions in ischaemic activity during daily activities, when compared with placebo. There were, however, no significant differences between groups, for any of the measured ischaemic parameters although combination therapy resulted in a greater fall in resting systolic and diastolic blood pressure than either treatment alone. CONCLUSIONS: In the management of mild chronic stable angina there appears to be little advantage gained from using combination therapy for ischaemia reduction.

Adrenergic beta-Antagonists↗