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C J Pepine

Publications and source records attributed to C J Pepine.

At least 73 records · Page 4Linked to original sources
PubMed1998

Design and baseline characteristics of the Veterans Affairs Non-Q-Wave Infarction Strategies In-Hospital (VANQWISH) trial. VANQWISH Trial Research Investigators.

OBJECTIVES: The Veterans Affairs Non-Q-Wave Infarction Strategies In-Hospital (VANQWISH) trial was designed to compare outcomes of patients with a non-Q wave myocardial infarction (NQMI) who were randomized prospectively to an early "invasive" strategy versus an early "conservative" strategy. The primary objective was to compare early and late outcomes between the two strategies using a combined trial end point (all-cause mortality or nonfatal infarction) during at least 1 year of follow-up. BACKGROUND: Because of the widely held view that survivors of NQMI are at high risk for subsequent cardiac events, management of these patients has become more aggressive during the last decade. There is a paucity of data from controlled trials to support such an approach, however. METHODS: Appropriate patients with a new NQMI were randomized to an early "invasive" strategy (routine coronary angiography followed by myocardial revascularization, if feasible) versus an early "conservative" strategy (noninvasive, predischarge stress testing with planar thallium scintigraphy and radionuclide ventriculography), where the use of coronary angiography and myocardial revascularization was guided by the development of ischemia (clinical course or results of noninvasive tests, or both). RESULTS: A total of 920 patients were randomized (mean follow-up 23 months, range 12 to 44). The mean patient age was 61 +/- 10 years; 97% were male; 38% had ST segment depression at study entry; 30% had an anterior NQMI; 54% were hypertensive; 26% had diabetes requiring insulin; 43% were current smokers; 43% had a previous acute myocardial infarction; and 45% had antecedent angina within 3 weeks of the index NQMI. CONCLUSIONS: Baseline characteristics were compatible with a moderate to high risk group of patients with an NQMI.

Angina Pectoris↗
PubMed1998

Myonecrosis after revascularization procedures.

The detection of elevated cardiac enzyme levels and the occurrence of electrocardiographic (ECG) abnormalities after revascularization procedures have been the subject of recent controversy. This report represents an effort to achieve a consensus among a group of researchers with data on this subject. Creatine kinase (CK) or CK-MB isoenzyme (CK-MB) elevations occur in 5% to 30% of patients after a percutaneous intervention and commonly during coronary artery bypass graft surgery (CABG). Although Q wave formation is rare, other ECG changes are common. The rate of detection is highly dependent on the intensity of enzyme and ECG measurement. Because most events occur without the development of a Q wave, the ECG will not definitively diagnose them; even the ECG criteria for Q wave formation signifying an important clinical event have been variable. At least 10 studies evaluating > 10,000 patients undergoing percutaneous intervention have demonstrated that elevation of CK or CK-MB is associated not only with a higher mortality, but also with a higher risk of subsequent cardiac events and higher cost. Efforts to identify a specific cutoff value below which the prognosis is not impaired have not been successful. Rather, the risk of adverse outcomes increases with any elevation of CK or CK-MB and increases further in proportion to the level of intervention. This information complements similar previous data on CABG. Obtaining preprocedural and postprocedural ECGs and measurement of serial cardiac enzymes after revascularization are recommended. Patients with enzyme levels elevated more than threefold above the upper limit of normal or with ECG changes diagnostic for Q wave myocardial infarction (MI) should be treated as patients with an MI. Patients with more modest elevations should be observed carefully. Clinical trials should ensure systematic evaluation for myocardial necrosis, with attention paid to multivariable analysis of risk factors for poor long-term outcome, to determine the extent to which enzyme elevation is an independent risk factor after considering clinical history, coronary anatomy, left ventricular function and clinical evidence of ischemia. In addition, tracking of enzyme levels in clinical trials is needed to determine whether interventions that reduce periprocedural enzyme elevation also improve mortality.

Angioplasty, Balloon, Coronary↗
PubMed1998

Aspirin and newer orally active antiplatelet agents in the treatment of the post-myocardial infarction patient.

The thienopyridine derivatives, ticlopidine and clopidogrel, provide alternatives to aspirin for use in the prevention of recurrent ischemic events in the post-myocardial infarction patient. These drugs act through a different mechanism than aspirin and, as a result, have potentially different profiles of safety and efficacy. The following discusses the clinical data collected supporting the use of these drugs for secondary prevention and the unanswered questions that remain regarding their use in subpopulations of individuals at risk. Based on the available data, it may be concluded that aspirin should remain the drug of choice for the prevention of recurrent ischemic events in the majority of patients who have suffered a recent myocardial infarction.

Administration, Oral↗
PubMed1998

Rationale and design of the International Verapamil SR/Trandolapril Study (INVEST): an Internet-based randomized trial in coronary artery disease patients with hypertension.

OBJECTIVES: The primary objective of the International Verapamil SR/Trandolapril Study (INVEST) is to compare the risk for adverse outcomes (all-cause mortality, nonfatal myocardial infarction [MI] or nonfatal stroke) in hypertensive patients with coronary artery disease (CAD) treated with either a calcium antagonist-based or a noncalcium antagonist-based strategy. BACKGROUND: Treatment recommendations for hypertension include initial therapy with a diuretic or beta-adrenergic blocking agent, for which reductions in morbidity and mortality are documented from randomized trials but are less than expected from epidemiologic data. For this reason, recent attention has focused on calcium antagonists or angiotensin-converting enzyme inhibitors. While these agents reduce blood pressure, outcome data from large randomized trials are lacking, but some case-control data, dominated by short-acting dihydropyridines, suggest an increased risk of cardiovascular events. These studies had methodologic limitations and did not differentiate among calcium antagonist types and formulations. Several studies differentiating among calcium antagonist types and an overview of published randomized trials show no increased risk with verapamil and suggestion for benefit in CAD patients. METHODS: A total of 27,000 CAD patients with hypertension will be randomized at 1,500 primary care sites to receive either a calcium antagonist-based (verapamil) or beta-blocker/diuretic-based (atenolol/hydrochlorothiazide) antihypertensive care strategy. The study uses a novel, electronic "paper-less" system for direct on-screen data entry, randomization and drug distribution from a mail pharmacy linked to the coordination center via the Internet. RESULTS: Contract negotiations with the United States and international sites are ongoing. Patients being enrolled are predominantly elderly (72% aged 60 years or older) men (54%), with either an abnormal coronary angiogram or prior MI (71%). In addition to hypertension, CAD and elderly age, most patients (89%) have one or more associated conditions (diabetes, dyslipidemia, smoking, cerebral or peripheral vascular disease, etc.) contributing to increased risk for adverse outcome. While 26% have diabetes, most of these are noninsulin dependent. Using the protocol strategies, target blood pressures (according to JNC VI) have been reached in 58% at the fourth visit, and as expected most (89%) are requiring multiple antihypertensive drugs. CONCLUSION: The design and baseline characteristics of the initial patients recruited for a prospective, randomized, international, multicenter study comparing two therapeutic strategies to control hypertension in CAD patients are described.

Aged↗
PubMed1998

Angina pectoris in a contemporary population: characteristics and therapeutic implications. TIDES Investigators.

We characterized a contemporary, nonhospitalized population with angina pectoris by obtaining data from a geographically diverse cohort of 5125 outpatients with chronic stable angina cared for by 1266 primary-care physicians. Diagnosis was based on history supported by evidence for coronary artery disease (coronary angiography, old myocardial infarction [MI], and/or an abnormal stress test). Their mean age was 69 years and 53% were women. Seventy percent had more than one associated illness, and 65% used more than one cardiovascular drug. Calcium antagonists (46%) and nitrates (61%) were used most frequently. Median angina frequency was approximately 2 episodes/week, and increased angina frequency was associated (P < 0.0001) with decreased overall feeling of well-being. Although effort angina was present in 90% of patients, 47% also had rest angina and 34% had mental stress-evoked angina. Female gender (odds ratio: 1.09; 95% CI: 1.02-1.16), concomitant illness (1.17, 1.09-1.25), and pharmacotherapy (1.14, 1.07-1.22) were associated with rest angina. Younger age (1.30, 1.20-1.41), female gender (1.16, 1.07-1.26), concomitant illness (1.13, 1.03-1.24), and pharmacotherapy (1.28, 1.15-1.93) were associated with mental stress angina. Calcium antagonists were used for rest-evoked (1.09, 1.03-1.16) and mental stress-evoked (1.12, 1.04-1.21) angina. These data suggest that contemporary outpatients with angina are most likely to be women and elderly patients with high frequencies of associated illness, calcium antagonist and nitrate use, as well as rest- and mental stress-related angina. These characteristics differ from previous perceptions.

Age Distribution↗
PubMed1998

Rationale for ACE inhibition as an anti-ischaemic therapy.

Research has established endothelial dysfunction as a pathophysiological mechanism underlying many cardiovascular disease processes. Tissue angiotensin-converting enzyme (ACE) plays a central role in regulating processes that contribute to endothelial function and cardiovascular disease. A number of large clinical studies have demonstrated conclusively the beneficial effects of ACE inhibition in patients with myocardial ischaemia and left ventricular dysfunction, including a significant reduction in the risk of recurrent myocardial infarction. Mechanistic findings from these studies indicated that the beneficial effects of ACE inhibition would extend to patients with preserved left ventricular function. Available results suggest that ACE inhibition with quinapril improves endothelial function in large and small vessels in patients with coronary artery disease and preserved left ventricular function. Quinapril also inhibits progression of coronary atherosclerosis in patients with high levels of low-density lipoprotein cholesterol (> or = 130 mg.dl-1) and reverses the toxic effects of smoking on endothelial function. Endothelial dysfunction also may be an important mechanism in episodes of angina and silent ischaemia. The central role of tissue ACE in endothelial function suggests that ACE inhibition has antiischaemic effects. A study in progress, the QUinapril Antiischaemia and Symptoms of Angina Reduction trial, addresses shortcomings in earlier studies of ACE inhibition for ischaemia and is expected to define the role of quinapril in ischaemia.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Effects of quinapril on coronary blood flow in coronary artery disease patients with endothelial dysfunction. TREND Investigators. Trial on Reversing Endothelial Dysfunction.

This pilot study evaluates the effects of quinapril, an angiotensin-converting enzyme inhibitor with high tissue-binding affinity, on microvascular endothelial function in patients with mild (<40% narrowing) coronary artery disease and epicardial endothelial dysfunction. Patients randomized to quinapril had a trend suggesting an increase in endothelium-dependent coronary blood flow response.

Acetylcholine↗
PubMed1997

Prognostic significance of myocardial ischemia detected by ambulatory electrocardiography, exercise treadmill testing, and electrocardiogram at rest to predict cardiac events by one year (the Asymptomatic Cardiac Ischemia Pilot [ACIP] study)

Myocardial ischemia identified by ambulatory electrocardiography (AECG), exercising treadmill testing, (ETT), or 12-lead electrocardiogram at rest is associated with an adverse prognosis, but the effect of improving these ischemic manifestations by treatment on outcome is unknown. The Asymptomatic Cardiac Ischemia Pilot (ACIP) study was a National Heart, Lung, and Blood Institute funded study to determine the feasibility of conducting a large-scale prognosis study and to assess the effect of 3 treatment strategies (angina-guided strategy, AECG ischemia-guided strategy, and revascularization strategy) in reducing the manifestations of ischemia as indicated by AECG and ETT. The study cohort for this database study consisted of 496 randomized patients who performed the AECG, ETT, and 12-lead electrocardiogram at rest at both the qualifying and week 12 visits. The effect of modifying ischemia by treatment on the incidence of cardiac events (death, myocardial infarction, coronary revascularization procedure, or hospitalization for an ischemic event) at 1 year was examined. In the 2 medical treatment groups (n = 328) there was an association between the number of ambulatory electrocardiographic ischemic episodes at the qualifying visit and combined cardiac events at 1 year (p = 0.003). In the AECG ischemia-guided patients there was a trend associating greater reduction in the number of ambulatory electrocardiographic ischemia episodes with a reduced incidence of combined cardiac events (r = -0.15, p = 0.06). In the revascularization strategy patients this association was absent. In the medical treatment patients the exercise duration on the baseline ETT was inversely associated with an adverse prognosis (p = 0.02). The medical treatment strategies only slightly improved the exercise time and the exercise duration remained of prognostic significance. In the revascularization group strategy patients this association was absent. Thus, myocardial ischemia detected by AECG and an abnormal ETT are each independently associated with an adverse cardiac outcome in patients subsequently treated medically.

Electrocardiography↗
PubMed1997

Stent placement compared with balloon angioplasty for obstructed coronary bypass grafts. Saphenous Vein De Novo Trial Investigators.

BACKGROUND: Treatment of stenosis in saphenous-vein grafts after coronary-artery bypass surgery is a difficult challenge. The purpose of this study was to compare the effects of stent placement with those of balloon angioplasty on clinical and angiographic outcomes in patients with obstructive disease of saphenous-vein grafts. METHODS: A total of 220 patients with new lesions in aortocoronary-venous bypass grafts were randomly assigned to placement of Palmaz-Schatz stents or standard balloon angioplasty. Coronary angiography was performed during the index procedure and six months later. RESULTS: As compared with the patients assigned to angioplasty, those assigned to stenting had a higher rate of procedural efficacy, defined as a reduction in stenosis to less than 50 percent of the vessel diameter without a major cardiac complication (92 percent vs. 69 percent, P<0.001), but they had more frequent hemorrhagic complications (17 percent vs. 5 percent, P<0.01). Patients in the stent group had a larger mean (+/-SD) increase in luminal diameter immediately after the procedure (1.92+/-0.30 mm, as compared with 1.21+/-0.37 mm in the angioplasty group; P<0.001) and a greater mean net gain in luminal diameter at six months (0.85+/-0.96 vs. 0.54+/-0.91 mm, P=0.002). Restenosis occurred in 37 percent of the patients in the stent group and in 46 percent of the patients in the angioplasty group (P=0.24). The outcome in terms of freedom from death, myocardial infarction, repeated bypass surgery, or revascularization of the target lesion was significantly better in the stent group (73 percent vs. 58 percent, P = 0.03). CONCLUSIONS: As compared with balloon angioplasty, stenting of selected venous bypass-graft lesions resulted in superior procedural outcomes, a larger gain in luminal diameter, and a reduction in major cardiac events. However, there was no significant benefit in the rate of angiographic restenosis, which was the primary end point of the study.

Aged↗
PubMed1997

Asymptomatic Cardiac Ischemia Pilot (ACIP) study two-year follow-up: outcomes of patients randomized to initial strategies of medical therapy versus revascularization.

BACKGROUND: Patients with ischemia during stress testing and ambulatory ECG monitoring have an increased risk of cardiac events, but it is not known whether their prognosis is improved by more aggressive treatment with anti-ischemic drugs or revascularization. METHODS AND RESULTS: The Asymptomatic Cardiac Ischemia Pilot study randomized 558 such patients who had coronary anatomy suitable for revascularization to three treatment strategies: angina-guided drug therapy (n=183), angina plus ischemia-guided drug therapy (n=183), or revascularization by angioplasty or bypass surgery (n=192). Two years after randomization, the total mortality was 6.6% in the angina-guided strategy, 4.4% in the ischemia-guided strategy, and 1.1% in the revascularization strategy (P<.02). The rate of death or myocardial infarction was 12.1% in the angina-guided strategy, 8.8% in the ischemia-guided strategy, and 4.7% in the revascularization strategy (P<.04). The rate of death, myocardial infarction, or recurrent cardiac hospitalization was 41.8% in the angina-guided strategy, 38.5% in the ischemia-guided strategy, and 23.1% in the revascularization strategy (P<.001). Pairwise testing revealed significant differences between the revascularization and angina-guided strategies for each comparison. CONCLUSIONS: A strategy of initial revascularization appears to improve the prognosis of this population compared with angina-guided medical therapy. A larger long-term study is needed to confirm this benefit and to adequately test the potential of more aggressive drug therapy.

Adrenergic beta-Antagonists↗
PubMed1997

Anginal status and prediction of cardiac events in patients enrolled in the asymptomatic cardiac ischemia pilot (ACIP) study. ACIP investigators.

We hypothesized that among the patients enrolled in the Asymptomatic Cardiac Ischemia Pilot (ACIP) trial, those who reported angina either within the previous 6 weeks or experienced angina during ambulatory electrocardiographic (ECG) monitoring during activities of daily life or during stress testing would be more likely to experience an adverse cardiac event within a year than those who did not experience angina. Of the 558 patients enrolled in ACIP, 325 (58.2%) reported angina in the previous 6 weeks, 300 (53.8%) had stress-induced angina, and 63 (11.3%) reported angina during activities of daily life associated with ST-segment changes on the 48-hour ambulatory electrocardiogram. Some patients had > 1 of these angina symptoms and thus 8 angina status categories were identified. Adverse cardiac events were defined as death, nonfatal myocardial infarction (MI), or hospitalization for ischemic events, which included revascularization not specified by the ACIP protocol. One hundred and sixty-seven patients (29.9%) were asymptomatic (i.e., they never had angina) by our defined criteria. Three hundred ninety-one patients (70.1%) were symptomatic. Symptomatic patients had a higher incidence of death, MI, or hospitalization for ischemic events (15.3% symptomatic vs 7.8% asymptomatic, p = 0.016). History of angina within 6 weeks before randomization was predictive of death, MI, or hospitalization for ischemic event (p = 0.007). This finding was due to a large difference in the need for hospitalizations which would be expected to be driven by the presence of angina. By contrast, angina during ambulatory electrocardiogram or stress test was not predictive of an adverse cardiac event. The asymptomatic status of coronary disease patients who have objective documentation of ischemia is not uniformly defined and many different categories can be identified. In this population of patients with proven coronary artery disease and myocardial ischemia, a history of angina in the previous 6 weeks was a good predictor of an adverse event occurring in the next year.

Angina Pectoris↗
PubMed1997

Relation between ambulatory electrocardiographic monitoring and myocardial perfusion imaging to detect coronary artery disease and myocardial ischemia: an ACIP ancillary study. The Asymptomatic Cardiac Ischemia Pilot (ACIP) Investigators.

OBJECTIVES: This study sought to explore the relation between markers of ischemia detected by ambulatory electrocardiographic (AECG) monitoring and stress myocardial perfusion single-photon emission computed tomography (SPECT). BACKGROUND: Stress myocardial SPECT and AECG monitoring are both utilized in evaluating patients with coronary artery disease. However, information is limited regarding the relation between the presence and extent of ischemia as detected by these two modalities. METHODS: This was an ancillary study of the Asymptomatic Cardiac Ischemia Pilot (ACIP) trial. One hundred six patients with previous coronary angiography underwent AECG monitoring and stress SPECT within a close temporal time period. The frequency and duration of ischemia as assessed by AECG monitoring and the total and ischemic stress-induced myocardial perfusion defect sizes as assessed by SPECT were quantified in separate core laboratories. Multivariate logistic regression and linear regression analysis were used to determine associations between AECG and SPECT abnormalities with regard to angiographic, demographic and treadmill exercise variables. RESULTS: Seventy-four percent of patients with significant (> or = 50%) coronary artery stenosis had SPECT abnormalities, whereas 61% had ischemia by AECG monitoring. The most important predictors of SPECT abnormalities were severity (p < 0.001) of coronary artery stenosis, followed by total exercise duration (p = 0.016) and patient age (p = 0.04). The only predictor of AECG abnormalities was the presence of ST segment depression on the initial exercise treadmill test (p = 0.021). Only a 50% concordance for normalcy or abnormalcy was observed between the SPECT and AECG results, and no relation was observed between the frequency or duration of AECG ischemia and the quantified total or ischemic myocardial perfusion defect size as assessed by SPECT. CONCLUSIONS: Ischemia as detected by AECG monitoring does not correlate with the presence and extent of ischemia as quantified by stress SPECT. Because these techniques appear to detect different pathophysiologic manifestations of ischemia, they may be complementary in more fully defining the functional significance of coronary artery disease and, in particular, which patients are at highest risk for adverse cardiac events.

Adult↗
PubMed1997

Improved endothelial function with angiotensin-converting enzyme inhibitors.

Associations between coronary events and plasma renin activity, and between coronary risk reduction and angiotensin-converting enzyme (ACE) inhibitors, are now well recognized. Improvement in endothelial function may explain, in part, some of the effects of ACE inhibitors in reducing the rates of adverse cardiovascular outcomes observed in clinical trials. ACE inhibitors have been shown to restore the endothelium-mediated vascular relaxation response in animal models of severe atherosclerosis. Clinical trials are now under way to examine the effect of ACE inhibitors on surrogate outcomes that allow assessment of endothelial function in the progression of carotid and coronary atherosclerosis. The recently completed Trial on Reversing ENdothelial Dysfunction (TREND) demonstrated improved coronary endothelium-dependent vasomotor function after 6 months of treatment with quinapril. In addition, quinapril treatment was associated with a trend toward an increase in microvascular blood flow response. Other studies in progress will assess the effect of ACE inhibitors on clinical coronary risk and plaque progression.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

A detailed angiographic analysis of patients with ambulatory electrocardiographic ischemia: results from the Asymptomatic Cardiac Ischemia Pilot (ACIP) study angiographic core laboratory.

OBJECTIVES: The purpose of this Asymptomatic Cardiac Ischemia Pilot (ACIP) data bank study was to characterize angiographic features of coronary pathology of patients enrolled in the ACIP study. BACKGROUND: Ischemia during ambulatory electrocardiographic (AECG) monitoring is associated with increased morbidity and mortality. Reports relating AECG ischemia to severity or complexity of coronary artery disease are few in number and small in size and have produced conflicting results. METHODS: Coronary angiograms from patients with asymptomatic AECG ischemia enrolled in the ACIP study were reviewed at a central core laboratory. Quantitative measurement of percent stenosis and Thrombolysis in Myocardial Infarction flow grades were used to assess the severity of coronary artery disease. Lesions were also evaluated for the presence of intracoronary thrombus, ulceration and lumen contour as indicators of stenosis complexity. In addition, comparisons were made with 27 patients screened for the ACIP study, but who were found ineligible because they did not have AECG ischemia on 48-h Holter monitoring. RESULTS: A total of 329 (75%) of 439 patients with AECG ischemia had multivessel coronary artery disease. Proximal stenoses > or = 50% diameter reduction were common in patients with AECG ischemia (62.2%), as were proximal stenoses > or = 70% (38.7%). Features suggesting complex plaque were found in 50.1% of patients with AECG ischemia. CONCLUSIONS: Multivessel coronary artery disease, severe proximal stenoses and features of complex plaque were observed frequently in patients who exhibited AECG ischemia. The presence of severe and complex coronary artery disease may explain, in part, the increased risk for adverse outcome associated with ischemia during activities of daily life.

Coronary Angiography↗
PubMed1997

Relation between clinical, angiographic and ischemic findings at baseline and ischemia-related adverse outcomes at 1 year in the Asymptomatic Cardiac Ischemia Pilot study. ACIP Study Group.

OBJECTIVES: We attempted to investigate the relation between patient characteristics and adverse outcome in patients with ischemia and clinically stable coronary artery disease (CAD). BACKGROUND: Evidence suggests that cardiac ischemia, detected by exercise stress testing (ETT) and ambulatory electrocardiographic (AECG) monitoring during daily living, identifies a subgroup of patients at increased risk for adverse outcome, but the relation between these ischemia findings and clinical and angiographic characteristics is largely unknown. METHODS: We examined the relation between clinical, angiographic and ischemia characteristics at entry with adverse outcome observed at 1 year in the 558 patients enrolled in the Asymptomatic Cardiac Ischemia Pilot (ACIP) study. RESULTS: By the 12-month visit 13.1% of patients had an ischemia-related adverse clinical outcome that included death, nonfatal myocardial infarction or an ischemia-related hospital admission. Multivariate analysis identified only the number of AECG ischemic episodes at entry (odds ratio [OR] 1.06, 99% confidence interval [CI] 1.01 to 1.12, p = 0.002) as an independent predictor of outcome. Assignment to revascularization (as opposed to an initial medical treatment strategy) showed a trend (OR 0.56, 99% CI 0.26 to 1.2, p = 0.05). None of the other baseline clinical, exercise or angiographic variables examined provided additional information relative to adverse outcome. CONCLUSIONS: Determinants of adverse outcome, among clinically stable patients with CAD and ischemia induced by stress and daily life were magnitude of AECG ischemia before treatment and, possibly, initial treatment assignment. Among the many other characteristics examined, including age, symptom status and angiographic and exercise variables, none contributed additional independent prognostic information. These two simple variables, which may be modifiable, need further study in a larger trial.

Aged↗
PubMed1997

Effects of intermittent transdermal nitroglycerin on occurrence of ischemia after patch removal: results of the second transdermal intermittent dosing evaluation study (TIDES-II).

OBJECTIVES: We sought to evaluate the effects of intermittent transdermal nitroglycerin (TD-NTG) on the occurrence of ischemia during patch-off hours in patients with stable angina pectoris receiving a beta-adrenergic blocking agent or calcium antagonist, or both. BACKGROUND: The current recommendations for the use of intermittent TD-NTG may be associated with the occurrence of rebound ischemia. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled, crossover trial with three study periods. Tolerability to TD-NTG was assessed in Period I. Seventy-two patients were assigned to receive either double-blind transdermal placebo or maximally tolerated TD-NTG for 2 weeks (Period II) and were then crossed over to the alternative treatment for another 2 weeks (Period III). The patients were instructed to apply medication daily at 8 AM, to remove it at 10 PM and to note symptoms and sublingual nitroglycerin (SL-NTG) use in a diary. The occurrence of ischemia was assessed from patient-perceived angina, symptom-limited exercise treadmill test (ETT) and 48-h ambulatory electrocardiographic (AECG) monitoring. RESULTS: Transdermal NTG (0.2 to 0.4 mg/h) significantly reduced the magnitude of ST segment depression at angina onset during ETT compared with placebo. Total angina frequency was not significantly different between TD-NTG (mean [+/-SD] 3.2 +/- 4.2) and placebo (3.3 +/- 5.2). During patch-off hours, angina frequency increased with TD-NTG (1.1 +/- 2.1) compared with placebo (0.7 +/- 1.6) (p = 0.03). Similar trends for an increase in ischemia after TD-NTG were also observed from AECG analyses. Specifically, ischemia frequency tended to be lower during patch-off hours for placebo than with TD-NTG (0.05 +/- 0.09 vs. 0.08 +/- 0.20 episodes/h, respectively, p = 0.08), even though frequency of ischemia tended to be higher during patch-on hours for placebo than with TD-NTG (0.12 +/- 0.19 vs. 0.07 +/- 0.15 episodes/h, respectively, p = 0.11). During placebo, ischemia frequency decreased 58% (patch-on to patch-off, p = 0.01) compared with a 14% increase with TD-NTG. These changes attenuate the usual circadian variation in ischemia. CONCLUSIONS: An increase in ischemia frequency during patch-off hours after use of intermittent TD-NTG was perceived by patients, and this subjective finding was supported by a corresponding trend for AECG ischemia to increase during these same hours.

Administration, Cutaneous↗
PubMed1997

How european cardiologists perceive the role of calcium antagonists in the treatment of unstable angina.

Physicians in the United States have recently published a guide to the definition and management of unstable angina pectoris. The guideline divides this condition into three main groups: 'rest', 'new onset' and 'increasing' angina. For the great majority of patients, medication involves heparin, acetylsalicylic acid, nitrates and beta-blockers. In some patient groups, calcium antagonists are appropriate treatment. These recommendations seem to be broadly supported by European cardiologists. Study of individual cases, however, reveals a continuing diversity of opinion.

Angina, Unstable↗