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Biomedical subjects

D Waters

Publications and source records attributed to D Waters.

At least 73 records · Page 4Linked to original sources
PubMed1996

Review of cholesterol-lowering therapy: coronary angiographic and events trials.

Coronary angiographic trials have demonstrated that the lowering of cholesterol slows the progression of atherosclerosis, enhances atherosclerotic regression, limits the formation of new lesions, and reduces the incidence of coronary events. Atherosclerotic progression has been shown to be associated with an increased risk of cardiac death, cardiac death plus nonfatal myocardial infarction (MI), and all coronary events. Most of the atherosclerotic regression trials were too small and of too short duration to demonstrate a significant difference in hard coronary events between patients receiving cholesterol-lowering intervention and controls. However, when data from these studies were pooled, total mortality was found to be reduced by 26% and the rate of nonfatal MI by 39% in actively treated patients. The first events trial to demonstrate clearly a reduction in overall mortality was the Scandinavian Simvastatin Survival Study (4S), in which lowering of serum cholesterol in patients with coronary artery disease (CAD) and hypercholesterolemia also reduced coronary mortality, fatal and nonfatal MI, sudden cardiac death, and the need for revascularization. Reductions in major coronary events were seen consistently in all subgroups of patients studied and regardless of concomitant therapy with aspirin, beta blockers, or calcium antagonists. Further evidence of the benefit of cholesterol-lowering therapy was provided by the West of Scotland Coronary Prevention Study (WOSCOPS), which evaluated men with hypercholesterolemia but no history of CAD. Those receiving active treatment had less overall mortality, lower risk of definite nonfatal MI or death from definite or suspected CAD, and less need for revascularization. The Cholesterol and Recurrent Events (CARE) Study recently showed that lipid-lowering therapy is also beneficial in CAD patients with less severe dyslipidemia.

Anticholesteremic Agents↗
PubMed1996

Effects of cigarette smoking on the angiographic evolution of coronary atherosclerosis. A Canadian Coronary Atherosclerosis Intervention Trial (CCAIT) Substudy. CCAIT Study Group.

BACKGROUND: Although smoking increases both the risk of developing coronary disease and the risk of coronary events in patients with known coronary atherosclerosis, the effect of smoking on the evolution of coronary atherosclerosis as assessed by serial angiography is poorly defined. METHODS AND RESULTS: Ninety smokers with coronary atherosclerosis shown on a recent angiogram and with fasting cholesterol levels between 220 and 300 mg/dL were enrolled in a randomized, double-blind, placebo-controlled trial of cholesterol-lowering therapy, along with 241 nonsmokers and exsmokers. Lovastatin at a mean dose of 36 mg/d lowered total and LDL cholesterol by 21 +/- 11% and 29 +/- 11%, respectively, but these levels changed by < 2% in placebo-treated patients. Coronary arteriography was repeated after 2 years in 72 smokers and their 557 lesions were measured blindly with an automated quantitative system, along with 1752 lesions in 227 nonsmokers. Coronary change score, the per-patient mean of the minimal lumen diameter changes for all qualifying lesions, worsened by 0.16 +/- 0.16 mm in smokers and by 0.07 +/- 0.15 mm in nonsmokers in the placebo group (P < .001). Lovastatin-treated smokers had less worsening (0.07 +/- 0.15 mm) than placebo-treated smokers (P = .024). One or more coronary lesions progressed in 16 of 34 lovastatin-treated smokers and in 28 of 38 placebo-treated smokers (47% versus 74%, P < .001). In the placebo group, new coronary lesions developed in 21 of 38 smokers and in 28 of 115 nonsmokers (55% versus 24%, P < .001); fewer lovastatin-treated smokers developed new lesions (15% versus 55%, P < .001). CONCLUSIONS: Smoking accelerates coronary progression and new lesion formation as assessed by serial quantitative coronary arteriography. Lovastatin slows the progression of coronary atherosclerosis and prevents the development of new coronary lesions in smokers.

Adult↗
PubMed1996

Serum HIV-1 RNA levels and time to development of AIDS in the Multicenter Hemophilia Cohort Study.

OBJECTIVE: To determine if the long-term incidence of the acquired immunodeficiency syndrome (AIDS) is related to human immunodeficiency virus type 1 (HIV-1) RNA levels measured early in HIV-1 infection. DESIGN: Epidemiologic cohort study. SETTING: Five hemophilia treatment centers in the United States. SUBJECTS: A total of 165 subjects with hemophilia and HIV-1 infection (age at HIV-1 seroconversion, 1-66 years) followed from 1979 to 1995. METHODS: The HIV-1 RNA level was measured by polymerase chain reaction over a range of 200 to 1 million or more HIV-1 RNA copies/mL in archived serum specimens collected 12 to 36 months (median, 27 months) after the estimated date of HIV-1 seroconversion. Kaplan-Meier methods were used to examine the risk of AIDS and proportional hazards models were used to estimate relative hazards. RESULTS: The HIV-1 RNA values were similar in subjects younger than 17 years at seroconversion (median, 5214 copies/mL) and those 18 to 34 years old (median, 4693 copies/mL), but higher in those 35 years or older (median, 12069 copies/mL) (P = .02 compared with each younger group). At 10 years after seroconversion, the proportions of subjects with AIDS were 72% among subjects with 100,000 or more HIV-1 RNA copies/mL measured 12 to 36 months after HIV-1 seroconversion (n = 9), 52% among subjects with 10,000 to 99,999 copies/mL (n = 55), 22% among subjects with 1000 to 9,999 copies/mL (n = 82), and 0% among subjects with fewer than 1000 copies/mL (n = 19) (P < .001). The age-adjusted relative hazard for AIDS for subjects with 10,000 or more copies/mL was 14.3 (95% confidence interval, 1.9-105.6) compared with subjects with fewer than 1000 copies/mL. CONCLUSIONS: The HIV-1 RNA level during early chronic HIV-1 infection is a strong, age-independent predictor of clinical outcome; low levels define persons with a high probability of long-term AIDS-free survival.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Perinatal intervention trial in Africa: effect of a birth canal cleansing intervention to prevent HIV transmission.

BACKGROUND: Perinatal transmission of human immunodeficiency virus (HIV) type 1 contributes significantly to infant mortality. Exposure in the birth canal may account for some transmission. We examined the efficacy of a birth canal washing procedure in reducing perinatal transmission in Malawi. METHODS: The infection status of infants of 3327 control women (conventional delivery procedures) was compared with that of 3637 infants of intervention-delivered women. The infants' HIV status was determined by polymerase chain reaction on dried blood spots collected at 6 and 12 weeks of age. The intervention consisted of manual cleansing of the birth canal with a cotton pad soaked in 0.25% chlorhexidine, which was done on admission in labour and every 4 h until delivery. FINDINGS: No adverse reactions to the intervention procedure were seen. 2094 (30%) of the enrolled women were HIV-infected, and 59% of their infants were seen in follow-up. Among 982 vaginal vertex singleton deliveries to HIV-infected women, 269 (27%) infants were infected. The intervention had no significant impact on HIV transmission rates (27% in 505 intervention women compared with 28% in 477 control women), except when membranes were ruptured more than 4 h before delivery (transmission 25% in the intervention group vs 39% in the control group). INTERPRETATION: If birth canal exposure is an important risk factor, different or additional methods to reduce the risk of perinatal HIV transmission should be tested. Alternatively, perhaps birth canal exposure is not a major contributor to perinatal infection risk.

Adult↗
PubMed1996

Examining the molecular genetics of HTLV-I with an infectious molecular clone of the virus and permissive cell culture systems.

Infectious molecular clones of HTLV-I proviruses have only recently been reported. The long wait for such provirus clones reflects the difficulties inherent in propagating HTLV-I in vitro, and thus a rigorous demonstration of infectivity has awaited improved cell culture systems and sensitive detection techniques for HTLV-I. An intact HTLV-I provirus, originating from an American ATL patient, was subcloned into a plasmid vector and was designated pCS-HTLV. Transient transfections of mammalian cells with pCS-HTLV resulted in the synthesis of viral proteins and mRNAs which were assembled into virions that had physical and morphological characteristics typical of HTLV-I particles. The ability of these virus particles to infect cells, replicate, and produce infectious progeny was demonstrated initially in short term, cell-free infection assays by monitoring the expression of specific viral mRNAs. These studies have been extended in cell culture systems that support continuous virus production. Primary T-lymphocytes have been infected either with cell-free supernatant fluids from, or by coculture with, cells transiently transfected with pCS-HTLV, giving rise to continuous, IL-2-dependent cell lines that have been in culture for >1 year. Furthermore, fetal rhesus lung cells (FRhL) were shown to be permissive for HTLV-I replication and sustained virus expression after infection with pCS-HTLV. Continuous FRhL cell lines now have been established that express various HTLV-I proviruses and mutants. These provirus clones and cell lines provide us with the means to address long-standing questions dealing with the biology of HTLV-I.

Animals↗
PubMed1996

Lessons from coronary atherosclerosis "regression" trials.

This article describes the background and methodology of the published studies assessing the effects of cholesterol-lowering therapy and of treatment of multiple risk factors on the progression of coronary atherosclerosis. The results are then presented, followed by a discussion of the lessons that can be learned from this large series of similar trials.

Clinical Trials as Topic↗
PubMed1996

Effects of beta-blockade and atropine on ischemic responses in left ventricular regions subtending coronary stenosis during dobutamine stress echocardiography.

OBJECTIVES: This study was designed to examine the effects of a beta-adrenergic blocking agent on the ischemic response to dobutamine stress and to determine the degree to which these effects can be abolished by the addition of atropine. BACKGROUND: Whether beta-blockade affects the sensitivity of dobutamine stress echocardiography for the diagnosis of coronary artery disease has been controversial. METHODS: In nine pigs, a left anterior descending coronary artery stenosis was created to reduce flow reserve (maximal/rest flow) to 1.1 to 1.9 without baseline regional wall motion abnormalities. This corresponded to a 50% to 90% diameter stenosis. Wall thickening was measured using epicardial echocardiography. Regional lactate production and coronary venous pH were monitored from an adjacent cardiac vein. A standard protocol of dobutamine stress echocardiography was first performed. After normalization of the ischemic abnormalities elicited with this infusion, esmolol was infused at 50 micrograms/kg body weight per min and the dobutamine test was repeated, with 1.0 mg of atropine added at the maximal dobutamine dose. RESULTS: Without esmolol, dobutamine stress induced myocardial ischemia with a reduction in regional wall thickening and lactate production in all nine pigs. Multiple regression analysis revealed that coronary flow per heartbeat (p < 0.01) and lactate production (p < 0.05) independently correlated with regional wall thickening during dobutamine stress. The beta-blocker significantly reduced heart rate and regional oxygen consumption and altered the relation between coronary flow per heartbeat and regional wall thickening (p < 0.05) during dobutamine stress. Esmolol prevented dobutamine-induced ischemia (lactate production and wall motion abnormalities) in seven of nine pigs. The addition of atropine induced lactate production and a reduction in wall thickening in five of seven pigs in which ischemia had been prevented by beta-blockade. However, lactate production was higher and regional venous pH was lower with the baseline dobutamine infusion than with that performed after esmolol with atropine added at the maximal dobutamine dose (p < 0.05). CONCLUSIONS: A correlation between regional wall thickening and coronary flow per heartbeat was demonstrated during baseline dobutamine stress. Beta-blockade shifted this relation so that dobutamine stress-induced myocardial ischemia was attenuated. The mechanisms by which beta-blockade prevents dobutamine-induced ischemia appeared to be mainly through decreases in heart rate and rate of rise in left ventricular pressure, improvement of regional coronary flow per heartbeat and attenuation of regional ischemic lactate production. Adding atropine in conventional doses enhanced the ability of dobutamine stress to induce myocardial ischemia but did not completely abolish the effects of beta-blockade on either the severity of dobutamine-induced wall thickening abnormalities or regional metabolic disturbances.

Adrenergic beta-Antagonists↗
PubMed1996

The peripheral auditory characteristics of noctuid moths: responses to the search-phase echolocation calls of bats

The noctuid moths Agrotis segetum and Noctua pronuba show peak auditory sensitivity between 15 and 25 kHz, and a maximum sensitivity of 35 dB SPL. A. segetum shows a temporal integration time of 69 ms. It is predicted that bats using high-frequency and short-duration calls will be acoustically less apparent to these moths. Short-duration frequency-modulated (FM) calls of Plecotus auritus are not significantly less acoustically apparent than those of other FM bats with slightly longer call durations, based on their combined frequency and temporal structure alone. Long-duration, high-frequency, constant-frequency (CF) calls of Rhinolophus hipposideros at 113 kHz are significantly less apparent than those of the FM bats tested. The predicted low call apparency of the 83 kHz CF calls of R. ferrumequinum appears to be counteracted by their long duration. It is proposed that two separate mechanisms are exploited by bats to reduce their call apparency, low intensity in FM bats and high frequency in CF bats. Within the FM bats tested, shorter-duration calls do not significantly reduce the apparency of the call at the peripheral level, though they may limit the amount of information available to the central nervous system.

Journal Article↗
PubMed1996

The peripheral auditory characteristics of noctuid moths: information encoding and endogenous noise

The ability of the noctuid A1 cell acoustic receptor to encode biologically relevant information from bat echolocation calls is examined. Short-duration stimuli (less than approximately 6 ms) reduce the dynamic resolution of the receptor, making intensity, and hence range, estimates of foraging bats unreliable. This low dynamic range is further reduced by inaccurate encoding of stimulus intensity, reducing the real dynamic range of the A1 cell to 1 bit at stimulus durations below 3.1 ms. Interspike interval is also an unreliable measure of stimulus intensity at low stimulus levels and/or for short-duration stimuli. The quantity of information encoded per stimulus is reduced as the presentation rate of stimuli is increased. The spontaneous generation of A1 cell action potentials may reduce the ability of the moth to discriminate bat from non-bat signals. Even with a recognition criterion of three A1 cell spikes per call, the moth would regularly make wrong decisions about a bat being present in the immediate environment. Removing this noise would necessitate a considerable loss of information through filtering at the interneurone level. It is proposed that, for bats using short-duration calls, the moth would only be able to recognise an approaching bat from the repetitious nature of the incoming signal.

Journal Article↗
PubMed1996

The small aortic root and the Medtronic Hall valve: ultrafast computed tomography assessment of left ventricular mass following aortic valve replacement.

BACKGROUND AND AIMS OF THE STUDY: The selection of an appropriate size aortic valve substitute with respect to patient size and life-style, in the presence of a small aortic root, is problematic, and a decision to enlarge the aortic annulus is often arbitrary. An aortic valve substitute-patient mismatch may place an excessive load on the left ventricle resulting in residual left ventricular mass with attendant patient morbidity and mortality. The aim of this study was to assess the adequacy of the Medtronic Hall valve in the small aortic root using ultrafast computed tomography analysis of left ventricular mass. MATERIALS AND METHODS: In 13 patients the smallest Medtronic Hall valves (size 20 and 21; measured internal orifice area of 2.01 cm2 for both) were used to replace the native aortic valve. All patients had aortic stenosis, and left ventricular hypertrophy was established by echocardiography. The mean body surface area was 1.8 +/- 0.2 m2 (range 1.50-2.06 m2) and the mean weight was 75 +/- 15 Kg (range 50-97 Kg). The mean preoperative New York Heart Association functional class was 3.54 +/- 0.5. RESULTS: There was no operative or late mortality. At a mean follow up of 22 months after aortic valve replacement, the mean left ventricular mass index was 89 +/- 11.4 g/m2 (normal left ventricular mass index by ultrafast computed tomography = 97 +/- 14 g/m2) and mean New York Heart Association functional class was 1.6 +/- 0.8 (p (Binomial) = 0.0001 compared to preoperative). Doppler echocardiogram demonstrated a mean gradient across the prosthetic valve of 17 +/- 7 mmHg. There was no trend towards greater left ventricular mass index in patients with greater body surface area or weight. In no patient was the aortic annulus enlarged. CONCLUSIONS: Trends from this preliminary data suggest that implanting the smallest Medtronic-Hall aortic valves (sizes 20 and 21) results in normal left ventricular mass following aortic valve replacement in patients up to a body surface area of 2.06 m2 and provides support for the notion that an aortic annulus enlarging procedure was not necessary in this group of patients.

Adult↗
PubMed1995

Hyperlipidemia and coronary disease. Correction of the increased thrombogenic potential with cholesterol reduction.

BACKGROUND: Hypercholesterolemia is a risk factor for coronary disease, and platelet reactivity is increased with hypercholesterolemia, suggesting a prethrombotic risk. The aim of this study was to measure mural platelet thrombus formation on an injured arterial wall in a model simulating vessel stenosis and plaque rupture in hypercholesterolemic coronary disease patients before and after cholesterol reduction. METHODS AND RESULTS: Thirty-two patients with stable coronary disease were studied. Platelet thrombus formation and serum lipids were measured in 16 hypercholesterolemic patients (cholesterol > 5.2 mmol/L) before and after a mean of 2.5 months of pravastatin therapy (40 mg/d) and in 16 normocholesterolemic control patients. Thrombus formation was assessed by exposing porcine aortic media to the patient's flowing venous blood for 3 minutes at a shear rate of 754 or 2546 s-1 at 37 degrees C in an ex vivo superfusion chamber. Quantitative morphometric platelet thrombus formation at baseline was higher in the hypercholesterolemic patients at both the high and low shear rates: 4.8 +/- 1.0 and 3.3 +/- 0.7 micron 2/mm, respectively, compared with normocholesterolemic patients: 2.1 +/- 0.5 and 1.6 +/- 0.4 micron 2/mm (both P < .05). In the hypercholesterolemic patients, pravastatin decreased total cholesterol from 6.5 +/- 0.2 to 4.5 +/- 0.2 mmol/L and LDL cholesterol from 4.5 +/- 0.2 to 2.8 +/- 0.1 mmol/L (both P < .05). Platelet thrombus formation at high and low shear rates decreased to 2.0 +/- 0.3 and 1.3 +/- 0.3 micron 2/mm, respectively (both P < .05). CONCLUSIONS: Thus, hypercholesterolemia is associated with an enhanced platelet thrombus formation on an injured artery, increasing the propensity for acute thrombosis. Platelet thrombus formation at both high and low shear rates decreased as total and LDL cholesterol levels were reduced with pravastatin. Cholesterol lowering may therefore reduce the risk of acute coronary events in part by reducing the thrombogenic risk.

Animals↗
PubMed1995

Effects of cholesterol lowering on the progression of coronary atherosclerosis in women. A Canadian Coronary Atherosclerosis Intervention Trial (CCAIT) substudy.

BACKGROUND: Although coronary disease is the leading cause of death in women and its clinical features differ from those in men, very few women have been included in angiographic trials of cholesterol lowering. METHODS AND RESULTS: Sixty-two women with diffuse but not necessarily severe coronary atherosclerosis documented on a recent angiogram and with fasting serum cholesterol between 220 and 300 mg/dL were enrolled in a double-blind, placebo-controlled trial. More than one half had a history of hypertension, approximately one quarter were diabetics, and one third were current smokers. All women received dietary counseling. Lovastatin or placebo was begun at 20 mg/d and was titrated if necessary to 40 and then to 80 mg during the first 16 weeks to attain a fasting LDL cholesterol < or = 130 mg/dL. The mean lovastatin dose was 34 mg/d. Total and LDL cholesterol decreased by 24% and 32%, respectively, in lovastatin-treated women but by < 3% in women receiving placebo. Coronary arteriography was repeated after 2 years in 54 women (87%), and their 394 lesions were measured "blindly" on pairs of film with an automated computerized quantitative system. Progression, defined as a worsening in minimum diameter of one or more stenoses by > or = 0.4 mm, occurred in 7 of 25 lovastatin-treated women and 17 of 29 placebo-treated women (28% versus 59%, P = .031). New coronary lesions developed in 1 lovastatin-treated woman and 13 placebo-treated women (4% versus 45%, P < .001). The outcome for each of the angiographic end points was not significantly different between the women and the 245 men who completed the trial. CONCLUSIONS: Lovastatin slows the progression of coronary atherosclerosis and prevents the development of new coronary lesions in women.

Adult↗
PubMed1995

Incremental doses of dobutamine induce a biphasic response in dysfunctional left ventricular regions subtending coronary stenoses.

BACKGROUND: Dobutamine stress echocardiography has been proposed as a diagnostic tool to identify viable myocardium. How regional wall thickening responds to dobutamine in the ischemic or short-term hibernating myocardium has not been adequately defined. We hypothesized that regional wall thickening would improve initially and subsequently deteriorate with incremental doses of dobutamine in viable myocardial regions supplied by a stenotic coronary artery. This study was undertaken to determine whether this biphasic pattern of regional function characterizes the response of ischemic or hibernating myocardium to dobutamine and to explore the factors and mechanisms that determine this response. METHODS AND RESULTS: Twenty-six pigs in four groups were studied: a control group (n = 5) to assess the response of myocardium perfused by nonstenotic coronary artery to incremental doses of dobutamine, and three experimental groups with a left anterior descending coronary artery stenosis producing acute myocardial ischemia (n = 7), short-term myocardial hibernation for 90 minutes (n = 7), and short-term hibernation for 24 hours (n = 7) to determine the functional and metabolic response to dobutamine under these conditions. Regional coronary flow was reduced to 40% to 60% of baseline, with significant reductions of regional wall thickening as measured by two-dimensional echocardiography and sonomicrometers. An incremental dobutamine infusion from 2.5 to 25 micrograms.kg-1.min-1 increased wall thickening and coronary flow without lactate production in the control group. In the other three groups, during the incremental dobutamine infusion, regional wall thickening improved initially, from 11.4 +/- 7.5% to 19.8 +/- 11.4%, P < .01, at dobutamine doses of 2.5 to 10 (4.5 +/- 2.2) micrograms.min-1.kg-1 but deteriorated subsequently to 5.0 +/- 5.8% at the maximal dose of dobutamine of 12.6 +/- 4.1 micrograms.min-1.kg-1. The initial improvement of regional wall thickening was associated with a small increase in regional coronary flow (from 0.53 +/- 0.18 to 0.68 +/- 0.25 mL.min-1.g-1 myocardium, P < .05) and with regional lactate production. High doses of dobutamine did not further increase regional coronary flow but markedly increased lactate production and induced regional myocardial acidosis (pH 7.26 +/- 0.07). The biphasic pattern of response to dobutamine was observed in each of the three experimental groups. Both peak improvement and peak deterioration occurred earlier and at lower dobutamine dose levels in the group with acute ischemia compared with the group with short-term hibernation for 24 hours (P < .05). CONCLUSIONS: A biphasic response of wall thickening to incremental dobutamine with initial improvement and subsequent deterioration is characteristic of ischemic or short-term hibernating myocardium. The initial low-dose dobutamine infusion improved wall thickening in the ischemic or hibernating myocardial region to a modest level. This initial modest improvement was transient and at the expense of metabolic deterioration of myocardial ischemia, so that at higher doses during prolonged dobutamine infusion, wall thickening deteriorated, lactate accumulated, and myocardial acidosis developed.

Animals↗
PubMed1995

Randomized double-blind comparison of two doses of Hirulog with heparin as adjunctive therapy to streptokinase to promote early patency of the infarct-related artery in acute myocardial infarction.

BACKGROUND: An improved survival rate is a consequence of successful reperfusion of the infarct-related artery. This double-blind, randomized trial investigated the potential of Hirulog, a direct thrombin inhibitor, to improve the early patency rates obtained with streptokinase and aspirin. METHODS AND RESULTS: Angiographic patency of the culprit coronary artery lesion was assessed 90 and 120 minutes after the initiation of streptokinase and aspirin and again after 4 +/- 2 days in 68 patients with acute myocardial infarction. Patients were randomized to Hirulog 0.5 mg/kg per hour for 12 hours followed by 0.1 mg/kg per hour (low dose), Hirulog 1.0 mg/kg per hour for 12 hours followed by placebo (high dose), or to heparin 5000 U bolus followed by 1000 U/h titrated to an activated partial thromboplastin time (aPTT) 2 to 2.5 times control after 12 hours. At 90 minutes, TIMI flow grade 2 or 3 was observed in 96% of patients treated with the low dose of Hirulog, in 79% with the high dose, and in 46% with heparin (P = .006) and TIMI flow grade 3 was observed in 85%, 61%, and 31% of patients, respectively (P = .008). At 120 minutes, these figures were 100%, 82%, and 62% for TIMI flow grades 2 and 3 (P = .046) and 92%, 68%, and 46% for TIMI flow grade 3 (P = .014). At 90 minutes, the relative risk for restoring TIMI flow grade 3 was 2.77 with Hirulog 0.5 mg/kg per hour compared with heparin (95% confidence limits, 1.21 to 6.35; P < .001) and 1.4 compared with Hirulog 1.0 mg/kg per minute (95% confidence limits, 1.00 to 1.51; P = .04). Patients who received a placebo infusion after 12 hours experienced more clinical events and reocclusion during the following 4 days than patients in the other two groups. CONCLUSION: Hirulog yields higher early patency rates in the culprit coronary artery than heparin when used as adjunctive therapy to streptokinase and aspirin in the early phase of acute myocardial infarction. High doses are not required and may be less effective than lower doses, which suggests that too much thrombin inhibition may be harmful.

Aspirin↗
PubMed1995

Antianginal efficacy and safety of controlled-delivery diltiazem QD versus an equivalent dose of immediate-release diltiazem TID.

Controlled-delivery once-daily diltiazem (qd), 180 mg and 360 mg, was assessed in two multicenter, randomized, double-blind, placebo-controlled trials using a 3 x 3 Latin square design. Both studies compared the controlled-delivery dosage form to the same total daily dose of immediate-release diltiazem administered three times daily (tid) and to placebo. The primary measure of efficacy was the time to termination of the exercise tolerance test (ETT) at 2, 8, and 24 hours after the morning dose. There were no significant differences in time to ETT termination between the qd and tid formulations at any time, except at 24 hours with 180 mg qd versus 60 mg tid. The comparison to placebo showed that diltiazem 180 mg qd, 360 mg qd, and 120 mg tid significantly lengthened the time to ETT termination (p < 0.05) at all time points, while diltiazem 60 mg tid did not differ from placebo at any time point. The qd formulation also increased the time to 1-mm ST-segment depression and reduced the number of angina attacks and the amount of nitroglycerin used when compared to placebo. No new or unusual adverse events were noted. Diltiazem controlled-release capsules administered once daily are safe and effective for the treatment of patients with chronic stable angina.

Aged↗