Ischaemic threshold and haemodynamic changes during angina at rest in patients with unstable angina

To examine whether increases in heart rate might be a commontrigger of angina at rest, changes in heart rate, blood pressureand rate-pressure product during pain were compared with theischaemic threshold (heart rate with ST segment shift >=1 mm), determined by atrial pacing, in 272 patients with unstableangina. During an average of 5.9±5.2 episodes of angina,heart rate was comparable to control values (77.0±14.5vs 75.2±11.5, beats. min^–1, ns) and significantlylower than the ischaemic threshold (147.9±22.9, P <0.00001).The rate-pressure product was also lower (955±183 vs2033±369, x 10, P <0.00001). Heart rate during restangina was lower than the ischaemic threshold even when we consideredonly patients with ST depression during pain (n: 71, 81.4±16.0 vs 132.8±21.4, P<0.00001), those with three-vesseldisease (n: 43, 79.9±15.9 vs 136.9±22.0, P <0.00001), or those with a low ischaemic threshold (= <130beats. min, n: 78, 77.0±14.9 vs 118.3±10.7, P<0.00001).In 154 patients in whom a second pacing test was performed theresponse was reproducible in 137 cases (89%). Thus, heart rate barely changes during angina at rest in patientswith unstable angina and is consistently much lower than theischaemic threshold. These findings support the concept thatincreases in heart rate are an unlikely trigger of ischaemiaat rest, even in patients with markedly reduced coronary reserve.     

Coronary arterial spasm in angina at rest associated with transient ST-segment changes

In order to clarify the role of coronary arterial spasm in the pathogenesis of angina at rest, coronary arteriography was performed during spontaneous chest pain or following intravenous administration of ergonovine maleate in 40 patients with angina at rest. Coronary vasospasm was demonstrated in 23 patients with ST-segment elevation during chest pain (group I), in 7 with ST-segment depression (group II), and in 4 with both ST-segment depression and elevation (group III). Complete spastic occlusion of the proximal or of the midportion of the left anterior descending artery was always associated with ST-segment elevation in anterior leads. In contrast, transient ST-segment depression in anterior leads was associated with diffuse narrowing of the left anterior descending artery with slow progression of the contrast medium, or complete occlusion of a small branch or of the distal segment of the left anterior descending artery. ST-Segment elevation in inferior leads was associated with complete spastic occlusion or with significant spastic narrowing of the right coronary artery or of the circumflex artery. We conclude that coronary spasm can be demonstrated in a selected cohort of patients with angina at rest associated with transient ST-segment changes. In some cases the site and the severity of the spasm may produce varying degrees of ischemia, thus determining the direction of the ST-segment shift.     

单硝异山梨醇酯和硝酸甘油治疗不稳定型心绞痛效果比较

目的比较口服单硝异山梨醇酯和静脉持续滴注硝酸甘油治疗不稳定型心绞痛（UAP）的治疗效果。方法UAP患者200例随机分为口服单硝异山梨醇酯（ISMN）组和持续静脉滴注硝酸甘油（NTG）组,治疗48 h。NTG组起始剂量10μg/min,最大用量80100μg/min;ISMN组起始剂量20 mg Q6h,最大用量2040 mg Q6h。比较两组患者治疗后48 h临床症状和心电图改善情况。结果①ISMN组和NTG组对UAP患者的临床症状和心电图改善情况无显著差异。②用药后ISMN组较NTG组难治性心绞痛发生率无显著差异（12%比11%）。③用药后发生低血压:ISMN组0例,NTG组6例（6%）,两组差异显著（P<0.01）。结论口服ISMN与持续静脉滴注NTG治疗不稳定型心绞痛同样安全、有效,均可降低难治性心绞痛发生的风险,但口服ISMN方便、经济、临床易掌握。     

Circadian rhythm of angina in patients with unstable angina: relationship with extent of coronary disease, coronary reserve and ECG changes during pain

A circadian distribution of ischaemic events has been identifiedin ambulatory patients with stable angina. However, whethera similar distribution occurs in patients with unstable anginawho remain at bed rest is still uncertain. Therefore, we analysedthe possible circadian presentation of episodes of angina atrest (n=1222) in 193 patients hospitalized consecutively. Theinfluence of extent of coronary disease (number of vessels with>70% stenosis, 0, 1 and 2–3), type of ECG changes duringpain on a 12-lead ECG, and coronary reserve, as assessed byischaemic threshold (atrial pacing), were also evaluated. Therewere two peaks of highest incidence: at 0700–1000h andat 1900–2200h (P<0.0001) which were unrelated to theextent of coronary disease, coronary reserve or type of ECGchange. Patients with 1 or 2-3 vessel disease with a reducedischaemic threshold (=<150 beats. min ^–1), however,had a higher incidence of midnight angina (2300–0200h)than those with a normal threshold or with no vessel disease(P<0001). It is concluded that, in spite of being at bed rest, patientswith unstable angina present a definite circadian distributionof angina, with peaks in the early morning and late evening.Patients with a low coronary reserve seem to have a higher incidenceof midnight angina than others.     

Prospective evaluation of a prostacyclin-sparing aspiring formulation and heparin/warfarin in aspirin users with unstable angina or non-Q wave myocardial infarction at rest

The aim of this trial was to compare the efficacy of combinationantithrombotic therapy with a prostacyclin-sparing aspirin plusanticoagulation versus conventional aspirin plus anticoagulation,when added to antianginal therapy, in patients with unstableangina or non-Q wave myocardial infarction already being treatedwith aspirin. In a double-blind (for the aspirin) study, 144prior aspirin users were randomized; 72 patients received controiled-release,prostacyclin-sparing aspirin 75 mg daily plus anticoagulation(intravenous heparin followed by warfarin to maintain the internationalnormalized ratio at 2–3), and 72 patients received conventionalaspirin 75 mg daily plus the same anticoagulation. Controlled-releaseaspirin was formulated to preserve endothelial cell prostacyclinsynthesis. Trial therapy was begun by 13.2 ± 12.3 h ofqualifying pain, and continued for 12 weeks. The frequency of recurrent angina with electrocardiographicchanges, myocardial infarction, or death, was analysed by intentionto treat. At 12 weeks, events were     

Prognostic implications of transient -- predominantly silent -- ischaemia in patients with unstable angina pectoris

The occurrence of unstable angina pectoris, despite medicaltreatment, is generally regarded as an ominous prognostic signand an indication for invasive diagnosis and revascularization.We investigated 38 consecutive patients with severe unstableangina with a mean of 2.5 days of continuous two-channel, frequencymodulated Holter monitoring for ST segment analysis. In 16 patients,transient ischaemic episodes (more than 0.1 mV lasting morethan 1 min) occurred despite maximal medical treatment: 82%of the episodes were silent. Compared to the 22 patients withoutischaemic episodes there were no significant differences inprevalence of risk factors, numbers of vessels diseased (69%vs. 74% triple-vessel disease) or ejection fraction (54±15%vs. 53±16%). The 30-day prognosis, however, varied: of16 patients with ischaemic episodes, 14 (88%) had a subsequentcardiac event (death, AMI, PTCA or CABG) compared to only 10of 22 patients (45%) without ischaemic episodes (P < 0.02for all events, P <0.1 for death/ AMI only). Transient ischaemic episodes, predominantly silent, are frequentin patients with severe unstable angina. Objective evidenceof ongoing ischaemia despite medical treatment has a guardedshort-term prognosis. ‘Stabilization’ of unstableangina may be incomplete as long as transient ischaemia at restcan still be detected.     

Long-term follow-up after early intervention with intravenous diltiazem or intravenous nitroglycerin for unstable angina pectoris

Aims In a double-blind randomized trial in unstable angina itwas shown that intravenous diltiazem reduced ischaemic eventsin the first 48h after inclusion better than intra-venous nitroglycerin.The present study was performed to establish the long-term prognosisof the randomized patients, with respect to their initial treatmentassignment. Methods and results One year follow-up data on ischaemic end-pointsand anti-ischaemic medication were recorded. Results were availablefor all of the 121 randomized patients. One hundred and sixty-sevenprimary end-point events were recorded, of which 54 occurredin the first 48h and 113 during the follow-up. Survival analysisshowed that event-free survival was significantly better inthe diltiazem group (45·0%) than in the nitroglyceringroup (34·4%),P=0·04. The incidence rate after48h and one year for cardiac death are, respectively, 0% and4·1%. The trend in anti-ischaemic medication was higherin the nitroglycerin group. For beta-blockers, this trend becamesignificant after 12 months (P=0·03). Conclusion These results show that the initial benefit obtainedby early treatment with intravenous diltiazem was preservedduring the first year after the initial hospitalization, andthat, despite the high risk of cardiac events in our population,the overall mortality 12 months after inclusion was low.     

Intravenous nitroglycerin reduces ischaemia in unstable angina pectoris: a double-blind placebo-controlled study

Karlberg K-E, Saldeen T, Wallin R, Henriksson P, Nyquist O, Sylvén C (Huddinge Hospital, Huddinge; University of Uppsala, Uppsala; and Södertälje; Sweden). Intravenous nitroglycerin reduces ischaemia in unstable angina pectoris: a double-blind placebo-controlled study. J Intern Med 1998; 243 : 25–31

Objectives

To study whether intravenous nitroglycerin (NTG) reduces the incidence of ischaemic events and leucocyte activation, as well as inhibiting platelet aggregation in patients with unstable angina pectoris.

Design

Randomized double-blind placebo-controlled study.

Subjects

One hundred and sixty-two patients with a history and electrocardiographic changes suggesting unstable angina pectoris.

Interventions

A 48-hour titrated intravenous infusion of NTG or placebo.

Results

Of the 162 randomized patients, 19 were excluded because of an acute myocardial infarction on randomization (11 patients) or proven presence of a non-ischaemic cause of the pain (6 patients). Other causes (2 patients). No differences in the clinical findings were detected between the groups on randomization. In the comparison of NTG and placebo, fewer patients in the former group had more than two new attacks of chest pain lasting for <20 min or one new attack of chest pain lasting >20 min, despite sublingual NTG (13/25, P < 0.03). In addition, the attacks of pain lasting >20 min in the NTG group were delayed compared to those in the placebo group (P < 0.05), suggesting a beneficial effect on these more servere episodes. Fewer patients in the NTG group required more than two sublingual NTG tablets (P < 0.005). NTG also reduced the rate-pressure product (P < 0.05), compared to placebo after 2 h but not after 24 h. Compared to baseline, platelet aggregation was inhibited in the patients who had received an NTG infusion for 2 h (P < 0.05). In both groups, leucocytes were activated at baseline, but remained unchanged thereafter.

Conclusions

Intravenous NTG seems to reduce myocardial ischaemia in patients with unstable angina pectoris more than the placebo.

     

Very early risk stratification by electrocardiogram at rest in men with suspected unstable coronary heart disease

Abstract. Objectives. To determine the possibility of very early prognostic stratification based on electrocardiograms (ECGs) at rest and/or cardiac enzyme levels after an episode of suspected unstable coronary heart disease. Design and setting. Men with suspected unstable angina or non-Q-wave myocardial infarction were studied in the coronary care units of eight hospitals. The ECGs at rest and creatinine kinase were followed. Subjects. In total 911 men were followed for 12 months. Of 8136 consecutively admitted, 3365 fulfilled the inclusion criteria. Excluded were 2454 patients, mainly because of a larger myocardial damage, signs of myocardial dysfunction, other serious cardiac or non-cardiac disease or an ECG not possible to interprete regarding ST-T-segment changes in the precordial leads. Main outcome measures. End-points at follow-up were cardiac death, myocardial infarction and severe (class III or IV) angina. Results. Compared to patients with normal a ECG who had an 8% 1-year risk of myocardial infarction or death, the risk with isolated negative T waves was 14% (P < 0.05), ST elevation 16% (P < 0.05), ST depression 18% (P < 0.01) and the combination of ST elevation and ST depression 26% (P < 0.001). The only finding related to future severe angina was ST depression. The risk of cardiac events was comparably elevated in patients with anterior or inferior site of ECG changes. Cardiac enzyme levels had no predictive value regarding future events. Conclusions. Electrocardiograms at rest obtained during the initial days of hospitalization provide very early and valuble prognostic information in men admitted with suspected unstable coronary heart disease.     

Transient ischaemia refractory to conventional medical treatment in unstable angina: angiographic correlates and prognostic implications.

Complex stenosis morphology is frequently seen in patients with unstable angina. However, its relation to transient myocardial ischaemia and clinical outcome has not been adequately elucidated. We studied 86 patients admitted to the Coronary Care Unit for unstable angina; all patients underwent ECG Holter monitoring during the first 2-4 days, while receiving intensive triple drug treatment. Coronary angiography and subsequent analysis of the ischaemia-related artery were performed within 12 days of admission. Patients were grouped according to their angiographic features: 45 showed complex coronary morphology (CM: 29 eccentric stenosis with irregular borders or overhanging edges; 16 intracoronary thrombus), 11 had documented coronary spasm as well as moderate atherosclerosis (CS), seven had left main coronary artery disease, and the remaining 23 patients showed regular and smooth morphology of coronary stenosis (RM). At admission, transient myocardial ischaemia (TMI) was greater in patients with CM (85 +/- 60 min .24 h-1) than in those with RM or CS (33 +/- 26 min .24 h-1; P less than 0.005). After 3 days of full medical treatment TMI decreased in all groups, but 34/45 patients with CM and 9/34 with RM or CS still showed residual ischaemia (greater than 0 min .24 h-1): 76% vs 26%, P less than 0.02. Follow-up was obtained at hospital discharge and after 1 year in all patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

The contribution of ventricular tachy arrhythmias to the genesis of cardiac pain during transient myocardial ischaemia in patients with variant angina

The 24-h ambulatory electrocardiograms of 15 patients with bothvariant angina and ischaemia-related arrhythmias were analyzedto correlate cardiac pain with the following variables: site,type, duration and magnitude of ECG changes, presence and typeof arrhythmias and time of occurrence of ischaemic attacks duringthe 24-h. Apart from sublingual nitrate therapy, Holter monitoringwas performed in the Coronary Care Unit (CCU), in the drugfreestate in all patients. During a total of 79 days of monitoring,patients had 1385 ischaemic episodes, of which only 30% werepainful. The site of ischaemia did not predict the occurrenceof pain. Pain was more frequently associated with ST-segmentelevation, longer ischaemic duration, increased time to peakECG change, and greater ST-segment shift and arrhythmias. Whenthe 259 attacks in association with ventricular arrhythmiaswere compared to the arrhythmia-free episodes, they were morefrequently painful for the same duration and magnitude of ECGischaemic changes. Furthermore, the complexity of arrhythmiasincreased the probability of cardiac pain. Most ischaemic episodesoccurred at night and a decrease in the frequency of painfulepisodes (apart from those associated with arrhythmias) wasapparent. Thus, in addition to electrocardiographic severityand duration of ischaemia, the presence of ventricular arrhythmiasand the time of occurrence seem to influence pain perceptionduring ischaemia.     

Platelet activation in angina at rest. Evidence by paired measurement of plasma beta-thromboglobulin and platelet factor 4

Indexes of in vivo platelet activation, beta-thromboglobulinand platelet factor 4 were measured in triplicate in plasmafrom venous blood of 69 patients with proven ischaemic heartdisease (IHD), discarding samples with a ratio of the plasmaconcentrations of the two proteins <2.6, in order to ruleout sampling artifacts. Compared with 60 control volunteers,differences were not significant [for beta-thromboglobulin controls(ng ml^–1, mean±SD) 27.8–8.6, ischaemic patients32.3±17.1; for platelet factor 4 controls 4.3±1.4,ischaemic patients 5.9±5.7]. However, when patients werestratified according to disease activity (Group I—;patientswithout spontaneous ischaemic episodes at rest during 4 daysof continuous electrocardiographic monitoring; Group II—patientswith <l ischaemic episode/day; Group III—patients with>l episode/day), these indexes were increased in ‘active’patients (for beta-thromboglobulin, in Group II—32.4±10.5ng ml^–1, P<0.05 vs. Group I; in Group III—42.6±14.6ng ml^–1, P<0.01 vs. Group I, P<0.05 vs. control.Platelet factor 4 was increased only in Group III—8.9±7.2ngml^–1, P<0.05 vs. control). Beta-thromboglobulin andplatelet factor 4 were 25.0±6.7 ng ml^–1 and 4.9±4.8ng ml^–1, respectively, in Group I (P=NS vs. control).A relationship with the number of spontaenous ischaemic episodesat rest was confirmed by linear regression analysis (in GroupIII patients for beta-thromboglobulin: r=0.76, P<0.01, andfor platelet factor 4 r=0.62, P<0.01). Levles were not elevatedin patients with pervious myocardial infarction without ischaemiaat rest and/or patients with stable angina, and were not influencedby the occurrence of a positive exercise stress test. Coronaryangiograms of ischaemic patients were analyzed to assess theextent and severity of atherosclerotic involvement; for bothextent and severity, involvement was similar in the three groups.These data support the hypothesis of the occurrence of plateletactivation in patients with spontaneous angina at rest, butnot in other subsets of IHD patients, and establish the possibilityof detecting in vivo platelet activation in IHD by means ofsuch circulating markers.     

Effect of magnesium sulphate in patients with unstable angina: A double blind, randomized, placebo-controlled study

AIM: Administration of intravenous magnesium sulphate has been shownto be protective during acute myocardial ischaemia and it maytherefore have beneficial effects in unstable angina. The purposeof this study was to assess the effects of a 24-h infusion ofmagnesium in patients with unstable angina. METHODS AND RESULTS: Patients who presented with unstable angina with electrocardiographicchanges were randomized to receive a 24-h intravenous infusionof magnesium or placebo within 12 h of admission. The primaryendpoint was myocardial ischaemia, as assessed by 48 h Holtermonitoring. Resting 12-lead ECGs, creatine kinase-MB releaseand urinary catecholamines were also assessed. Patients werefollowed for 1 month. Thirty-one patients received magnesiumsulphate and 31 placebo. Baseline characteristics and extentof coronary disease were similar in both groups. On 48 h Holtermonitoring, 14 patients (50%) had transient ST segment shiftsin the magnesium group vs 12 patients (46%) in the placebo group.However, there were fewer ischaemic episodes in the magnesiumgroup (51 vs 101, P<0·001) and there was a trend towardsan increase in the total duration of ischaemia in the placebogroup compared to the magnesium group in the second 24 h (2176min vs 719 min respectively, P=0·08). Regression of Twave changes on the 24 h ECG occurred more frequently in patientswho received magnesium compared to those treated with placebo(11 patients vs 0 patients respectively, P<0·005).Creatine kinase-MB release was significantly less at 6 and 24h in patients who received magnesium compared to those treatedwith placebo. Catecholamine excretion was lower in patientstreated with magnesium than in those treated with placebo (adrenaline:1·05±0·16 vs 1·61±0·32ng . mmol^–1 creatinine; noradrenaline: 9·99±1·82vs 18·48±2·41 ng.mmol^–1 creatininerespectively in the first 12 h sample, P<0·05). CONCLUSION: Intravenous magnesium reduces ischaemic ECG changes, creatinekinase-MB release and urinary catecholamine excretion in theacute phase of unstable angina. Thus, magnesium may be a beneficialadditional therapy for these patients. Further studies are requiredto confirm these findings.     

Lack of indication of myocardial cell damage after myocardial ischaemia in patients with severe stable angina.

To evaluate myocardial cell damage in relation to spontaneous and exercise-induced ischaemia, release of myoglobin, creatine kinase (CK) and its isoenzyme MB (CK-MB) into the serum was estimated in 10 patients with severe stable angina. All patients had a positive exercise test, significant stenosis of one or more of the main coronary arteries and more than five ischaemic attacks per week. ST-segment monitoring was performed for 36 h. During the last 24 h of that period (period A) serial blood samples were analysed for myoglobin, CK and CK-MB using sensitive assays. Three days later (period B) the patients performed an exercise test at 0815 h, with ST-segment monitoring and blood sampling carried out as described for period A. During period A, 47 ischaemic episodes (100% silent) with a total duration of 599 min were noted in four patients. Forty-seven ischaemic episodes (94% silent) with a total duration of 804 min, were observed in seven patients during period B. Release of myoglobin, CK, and CK-MB did not increase in relation either to spontaneous or exercise-induced ischaemia. Thus even frequent and prolonged episodes of transient myocardial ischaemia (symptomatic or asymptomatic) in patients with severe stable angina pectoris does not seem to cause irreversible myocardial damage.     

Characterization and long-term prognosis of patients with effort-induced silent myocardial ischaemia.

The aim of this study was to evaluate the anatomo-clinical correlations and the prognostic significance of silent myocardial ischaemia (SI) during exercise testing (ET). Four hundred and six patients with angiographically proven CAD and positive ET were studied. Patients were divided into two groups: 309 patients (Group A) with positive ET for both electrocardiographical findings and angina, and 97 patients (Group B) with positive ET for electrocardiographical findings but not for angina (SI). In Group A the following clinical characteristics differed significantly from Group B: incidence of diabetes mellitus (15.8% vs 27.8%, P less than 0.04); duration of disease (less than 1 month from its first manifestation) (30.4% vs 54.6%, P less than 0.001) and a positive ET at low work-load (41.7% vs 50.5%, P less than 0.05). Mortality during follow-up (mean 72 +/- 11 months) was 8.6% in Group A and 8.2% in Group B (NS). Incidence of sudden death was similar in the two groups (2.9% vs 2.06%; NS). The multivariate analysis shown as independent variables, related significantly with a poor prognosis in both groups: left ventricular function (P less than 0.0001); prior myocardial infarction (P less than 0.0001); and multivessel disease (P less than 0.001). In conclusion, patients with a recent onset of symptoms, a positive ET at low workload and diabetes mellitus are more likely to present SI during ET. The long-term prognosis and the incidence of sudden death are similar in patients with painful and painless myocardial ischaemia during ET.     

Double-blind randomized trial of alteplase versus placebo in patients with chest pain at rest

Patients who have chest pain occurring at rest are at a significantrisk of myocardial infarction and or sudden death. Most trialsenter patients with anginal rest pain after an initial screeningperiod. Thus, the clinical efficacy of early thrombolytic treatmentfor patients with rest pain remains unproven. Eighty patients with chest pain at rest and with ECG changesof ST depression of at least 1 mm in any ECG lead, were randomizedto alteplase 100 mg infused over 3 h, or placebo. Concomitantly,all patients received intravenous heparin and 300 mg of aspirindaily (unless contra-indicated). Seventy-four patients had coronaryangiography (the majority within 72 h of admission) of which73 were assessable. The patency of the ischaemia-related vesselwas not significantly greater in the alteplase treated group(81% vs 78%, P =0.82). The culprit lesion morphology tendedto be more concentric in the alteplase treated group (84% vs56%, P = 0.06) although alteplase treatment was not associatedwith a significant reduction in the severity of the culpritlesion stenosis. Intra-coronary thrombi were detected in 7%of patients (3% placebo, 11% alteplase, P =0.35). The mean leftventricular ejection fraction for the alteplase-treated groupwas 49 ± 3% and for the placebo-treated patients 56 ±3% (P=0.05). There was no difference in the total in-hospitalcardiac event rate i.e. cardiac death, myocardial infarctionand coronary revascularization between patients receiving alteplase(10%, 63%, and 38%) and those receiving placebo (8%, 65%, and30%) respectively. At 6-month follow-up, 17 patients were readmitted to hospitalwith cardiac causes (eight in the alteplase-treated group andnine in the placebo-treated group). A further two patients diedbefore 6-month review, one in the alteplase group and one inthe placebo group. Alteplase treatment for patients with chest pain at rest doesnot significantly improve culprit vessel patency or reduce in-hospitalor long-term cardiac event rates. Thus, alteplase cannot berecommended as an adjuvant to conventional therapy in patientspresenting with rest pain and EGG changes of ST segment depression.     

Detection of ambulatory ischaemia is not of practical clinical value in the routine management of patients with stable angina: A long-term follow-up study

It has been reported that medically treated patients with stableangina and positive exercise test for ischaemia have an adverse1–2 year outlook if they are shown also to have transient,and predominantly silent, ischaemic episodes detected by ambulatoryST segment monitoring during their daily activities: it hasbeen suggested that this investigation could be used to identifypatients more likely to benefit from early investigation andtreatment. We assessed the long-term (up to 65 months) prognosticsignificance of transient iscliaemic episodes during daily activitiesin 172 patients routinely attending cardiac outpatients withmedically treated stable angina who had undergone exercise testingand 48 h of ambulatory ST segment monitoring between February1988 and August 1989 for this purpose. A positive exercise testfor ischaemia was not a prerequisite for inclusion. One hundred and four patients (60.5%) had a positive exercisetest for iscliaemia and 72 (42%) had transient ischaemia duringdaily activities (63 had both tests positive). Over a median50-month follow-up period 54 patients suffered at least onecardiac event (primary event: cardiac death n=7; non-fatal myocardialinfarction n=11; unstable angina n=18; elective CABGIPTCA n=18).Two further patients suffered non-cardiac death. Cardiac events,either objective (cardiac death or non-fatal myocardial infarction)or subjective (unstable angina or revascularisation) were nomore likely to occur in those with transient ischaemia duringdaily life when compared with those without, at follow-up timesup to 65 months. The detection of transient ischaemia during daily life is oflimited practical clinical value in the management of ‘lowrisk’ medically treated patients with stable angina, anddoes not appear to help identify subgroups at increased riskof an adverse outcome at follow-up to more than 5 years.     

Transdermal nitroglycerin efficacy in patients with chronic stable angina pectoris as related to sympathetic and renin-angiotensin-aldosterone activity.

The aim of this study was to evaluate the acute effects of transdermal nitroglycerin on the sympathetic and renin-angiotensin-aldosterone systems activity, in a group of patients with stable exercise induced angina pectoris. Eighteen outpatients (15M, 3F, age range 47-65 years) were included in this double-blind, randomized, crossover trial comparing the antianginal effects of a transdermal system delivering 20 mg.day-1 of nitroglycerin to an identical placebo. Plasma renin activity, plasma aldosterone and catecholamine concentrations were measured in resting basal conditions and at 4, 8, 24, and 32 h post-dosing. Patients were subdivided in two groups according to the increase in exercise duration after patch application greater than 30% (responders, n = 8) and less or equal to 30% (non-responders, n = 10) in respect to placebo. In responders plasma norepinephrine was slightly increased during transdermal nitroglycerin administration in comparison to placebo while no change was observed in plasma adrenaline and aldosterone concentrations and in plasma renin activity. In non-responders plasma norepinephrine levels significantly increased during nitroglycerin treatment in comparison with placebo. Multiple comparisons showed that this increase was significant at 4, 8 and 24 h post-dosing. Plasma epinephrine and aldosterone concentrations and plasma renin activity were also increased after nitroglycerin administration. In the population as a whole, a significant inverse correlation was found between the percent increase in exercise duration (active drug vs placebo) and the absolute values of plasma norepinephrine and aldosterone, 4 h post-dosing.(ABSTRACT TRUNCATED AT 250 WORDS)