Controversies in COX-2 selective inhibition.
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Anti-Inflammatory Agents, Non-Steroidal↗
Biomedical subjects
W Frishman
Publications and source records attributed to W Frishman.
Circadian heart rate response to chronotherapy versus conventional therapy in patients with hypertension and myocardial ischemia.
BACKGROUND: Changes in heart rate (HR) may contribute to the higher incidence of cardiovascular events in the morning. HYPOTHESIS: The objectives of this analysis were to assess HR patterns in two populations (patients with chronic stable angina or stage I to III hypertension) and to compare the effects of various antianginal and antihypertensive treatments on HR. METHODS: This was a retrospective analysis of HR data from two clinical trials evaluating the efficacy of controlled-onset, extended-release (COER)-verapamil. The effects of COER-verapamil were compared with placebo, nifedipine gastrointestinal therapeutic system (GITS), amlodipine, and the combination of amlodipine and atenolol. RESULTS: In patients with angina (n = 498), the change from baseline in HR following 4 weeks of treatment was -6.7 +/- 10.5 beats/min in the COER-verapamil group, -10.8 +/- 10.8 beats/min in the amlodipine/atenolol group, + 2.5 +/- 9.1 beats/ min in the amlodipine monotherapy group, and -1.3 +/- 10.5 beats/min in the placebo group (p<0.001). Data were stratified based on whether patients experienced asymptomatic ischemia during baseline ambulatory electrocardiographic monitoring. The circadian HR pattern was morphologically similar in all groups; however, differences in the magnitude of HR response were evident. In the subset of patients with asymptomatic ischemia (n = 101), treatment with amlodipine monotherapy increased HR compared with placebo. In this same subset of patients, HR reductions were achieved with COER-verapamil and amlodipine/atenolol. In patients with hypertension (n = 557), the change in HR following 10 weeks of treatment was -3.3 beats/min for patients treated with COER-verapamil compared with + 2.0 beats/min for patients treated with nifedipine GITS (p < 0.0001, between-group differences). CONCLUSION: This analysis demonstrates that morphologically similar circadian patterns of HR occur in both hypertensive patients and those with angina. In addition, significant variation exists among antianginal and antihypertensive agents regarding HR effects.
Adrenergic beta-Antagonists↗
Results of therapy with carvedilol, a beta-blocker vasodilator with antioxidant properties, in hypertensive patients.
Carvedilol is a new beta-blocker antihypertensive agent with vasodilating properties secondary to alpha 1-blocking activity. Peripheral vascular resistance is reduced and cardiac output and renal function are not altered with carvedilol. The antihypertensive effects of this agent are equivalent to those of other beta-blockers, calcium channel blockers, angiotensin converting enzyme inhibitors, and diuretics. Carvedilol has a neutral effect on lipids and glucose metabolism. The percentage of responders is increased when carvedilol is combined with a diuretic. This agent has several unique properties. In addition to its antihypertensive effects, carvedilol in vitro and in vivo has been shown to have antiproliferative effects on smooth muscle cells and to inhibit the action of oxygen-free radicals. The antioxidant properties of this compound are significantly greater than those of vitamin E. In animal models, carvedilol may slow the process of atherogenesis, reduce infarct size, and improve postinfarction survival to a greater degree than other beta-blockers. Recent studies have demonstrated that carvedilol reduces morbidity and mortality in patients with congestive heart failure who are already receiving angiotensin converting enzyme inhibitors, diuretics, and digitalis. The antioxidant and antiproliferative activities of carvedilol may present an advantage over other available antihypertensive medications.
Adrenergic beta-Antagonists↗
Risk factors for stroke and type of stroke in persons with isolated systolic hypertension. Systolic Hypertension in the Elderly Program Cooperative Research Group.
BACKGROUND AND PURPOSE: We sought to determine risk factors for stroke and stroke type in persons with isolated systolic hypertension (ISH). METHODS: We performed proportional hazards analyses of data from the Systolic Hypertension in the Elderly Program, a double-blind, randomized, placebo-controlled trial of 4736 persons aged > or =60 years with ISH (systolic blood pressure, 160 to 219 mm Hg; diastolic blood pressure, <90 mm Hg). One treatment group received chlorthalidone (12.5 to 25 mg/d) with step-up to atenolol (25.0 to 50.0 mg/d) or reserpine (0.05 to 0.10 mg/d), if needed. The other treatment group received matching placebo. The main outcome measures were stroke, stroke or transient ischemic attack [TIA], and stroke types: ischemic (including lacunar, atherosclerotic, and embolic) and hemorrhagic. RESULTS: During an average follow-up of 4.5 years, 384 strokes or TIAs and 262 strokes (including 217 ischemic, 66 lacunar, 26 atherosclerotic, and 25 embolic strokes) were documented. In multivariate analyses, placebo treatment, older age, smoking, history of diabetes, higher systolic blood pressure, lower HDL cholesterol, and ECG abnormality were significantly associated (P<0.05) with increased incidence of stroke or TIA, stroke, or ischemic stroke. Greater lacunar stroke risk was significantly related to placebo treatment, older age, history of diabetes (relative risk [RR] = 3.03; 95% confidence interval [CI], 1.70 to 5.40), and smoking (RR = 3.04; 95% CI, 1.73 to 5.37). Greater atherosclerotic and embolic stroke risk were significantly related to presence of carotid bruit (RR = 5.75; 95% CI, 2.50 to 13.24) and older age (RR = 1.65 per 5 years; 95% CI, 1.25 to 2.18), respectively. CONCLUSIONS: In older persons with ISH, history of diabetes and smoking are important risk factors for lacunar stroke, whereas carotid bruit and age are important risk factors for atherosclerotic and embolic stroke, respectively.
Aged↗
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↗
Asymptomatic Cardiac Ischemia Pilot (ACIP) Study. Relationship between exercise-induced and ambulatory ischemia in patients with stable coronary disease.
BACKGROUND: We investigated whether the presence and frequency of asymptomatic ischemic episodes recorded during ambulatory ECG (AECG) monitoring could be predicted on the basis of clinical characteristics or exercise treadmill test (ETT) performance in patients with stable coronary disease and whether the estimate of ischemia severity was similar between the AECG and ETT. METHODS AND RESULTS: Patients screened for the Asymptomatic Cardiac Ischemia Pilot (ACIP) study were selected for the current analysis if data were available from 48-hour AECG monitoring as well as from an ETT during which the patient developed > or = 1-mm ST-segment depression. Exercise ECG data were available for 143 of the 910 patients without ischemic episodes and for 659 of the 910 patients with ischemic episodes during AECG monitoring. Angina was more frequent among patients with ambulatory ischemic episodes than among patients without such ischemia (P < .001). Patients with AECG ischemia had a consistently more marked ischemic response on the ETT than patients without AECG ischemia; patients likely to have AECG ischemia could be predicted on the basis of ETT performance characteristics. However, the correlation coefficients between the severity of ischemia estimated by ETT and by AECG were small. CONCLUSIONS: There are significant relations between ischemia detected by AECG monitoring and by ETT, but the relations are limited, indicating that the two tests are not redundant to characterize coronary patients. A larger study investigating the prognostic significance of the ischemia identified by each modality, with follow-up for clinical events, will be necessary to determine the most appropriate methods to evaluate patients with stable coronary disease.
Coronary Disease↗
Factors limiting the enrollment of women in a randomized coronary artery disease trial. The Asymptomatic Cardiac Ischemia Pilot Study (ACIP) Investigators.
BACKGROUND AND HYPOTHESIS: Although it is recognized that women have been underrepresented in clinical trials of cardiovascular disease, the reasons for their limited enrollment have not been elucidated. METHODS: A prospective tracking system was established in the Asymptomatic Cardiac Ischemia Pilot study (ACIP) to monitor recruitment and identify protocol issues that interfered with the recruitment of women. Patients with stress test evidence for ischemia during the course of routine clinical care were screened for asymptomatic ischemia with an ambulatory electrocardiogram (ECG). RESULTS: Those with at least one episode of asymptomatic ischemia and angiographic evidence of coronary artery disease suited for revascularization could be randomized. Women comprised only 17% of the 1,820 patients screened for asymptomatic ischemia, and only 14% of the 558 patients randomized. The limited number of women screened for ischemia was largely due to the limited number of women (25% of all patients) found to have test evidence for ischemia or coronary artery disease suited for revascularization during the course of routine clinical care. Once patients were identified as having ischemia on stress test and ambulatory ECG, the major difference in eligibility was the difference in disqualifying angiograms, occurring 21/2 times as frequently in women as in men (p < 0.001). CONCLUSION: The percentage of women recruited was lower than the prevalence of ischemic heart disease in the general population because at participating centers (1) women were found to have ischemia less often than men during the course of routine clinical care, and (2) screening tests for ischemia were less predictive of protocol-defined coronary disease in women than in men.
Analysis of Variance↗
The placebo effect in cardiovascular disease.
The effect of placebo on the clinical course of systemic hypertension, angina pectoris, silent myocardial ischemia, CHF, and ventricular tachyarrhythmias has been well described. In the prevention of myocardial infarction, there appears to be a direct relation between compliance with placebo treatment and favorable clinical outcomes. The safety of short-term placebo-controlled trials has now been well documented in studies of drug treatment of angina pectoris. Although the ethical basis of performing placebo-controlled trials continues to be challenged in the evaluation of drugs for treating cardiovascular disease, as long as a life-saving treatment is not being denied it remains prudent to perform placebo-controlled studies for obtaining scientific information.
Cardiovascular Diseases↗
Clinical pharmacology of estrogens: cardiovascular actions and cardioprotective benefits of replacement therapy in postmenopausal women.
The use of estrogens in postmenopausal women has been the subject of much controversy regarding hormone formulation, dosage, use in combination with progestins, duration of treatment, and contraindications. Estrogens have been prescribed to relieve menopausal symptoms for more than three decades. The hormones reduce the gynecologic and psychologic changes associated with menopause while inhibiting bone resorption and possibly reducing the risk of cardiovascular disease. Their use however has been complicated by an increased risk of endometrial cancer and possibly breast cancer. The use of estrogens as cardioprotective agents is discussed and the clinical experiences and the possible mechanisms of action are reviewed. The clinical pharmacology of estrogens and the various formulations that are available as monotherapy or in combination with progestins will also be reviewed.
Adult↗
Management of hypertensive urgencies and emergencies.
Hypertensive emergency is a condition in which there is elevation of both systolic and diastolic blood pressure with the presence of acute target organ disease. Hypertensive urgency is a condition where the blood pressure is elevated (diastolic > 120 mmHg) with the absence of acute target organ disease. Hypertensive emergencies are best managed with parenteral drugs and careful intraarterial blood pressure monitoring. Hydralazine has been widely used in treatment of hypertension in eclampsia and preeclampsia, and its safety has been demonstrated in these patients. Sodium nitroprusside (SNP) has the most reliable antihypertensive activity, which begins immediately after its administration and ends when the infusion is stopped. As with diazoxide, it should be used with caution in patients with impaired cerebral flow. SNP is the preferred drug in obtaining controlled hypotension in patients undergoing neurovascular surgery. Intravenous nitroglycerin is useful in patients prone to myocardial ischemia, but should be avoided in patients with increased intracranial pressure. Esmolol is effective in controlling both supraventricular tachyarrhythmias and severe hypertension. Its short onset of duration of action make it useful in the emergent setting, but because of its negative inotropic effect its use should be avoided in patients with low cardiac output. Verapamil should not be used in patients with preexisting conduction abnormalities. Nicardipine is a potent arteriolar vasodilator without a significant direct depressant effect on myocardium. As with other afterload reducing agents, it should not be used in patients with severe aortic stenosis. Because angiotensin-converting enzyme (ACE) inhibitors generally cause cerebral vasodilatation, enalaprilat may be particularly beneficial for patients who are at high risk of developing cerebral hypotensive episodes secondary to impaired cerebral circulation. Fenoldopam, a selective post-synaptic dopaminergic receptor (DA1) has been shown to be effective in treating severe hypertension with a lower incidence of side effects than SNP. Hypertensive urgencies can usually be managed with oral agents. Oral nifedipine, captopril, clonidine, labetalol, prazosin, and nimodipine have all been shown to be effective in these situations.
Administration, Oral↗
Clinical pharmacology of estrogens: cardiovascular actions and cardioprotective benefits of replacement therapy in postmenopausal women.
The use of estrogens in postmenopausal women has been the subject of much controversy regarding hormone formulation, dosage, use in combination with progestins, duration of treatment, and contraindications. Estrogens have been prescribed to relieve menopausal symptoms for more than three decades. The hormones reduce the gynecologic and psychologic changes associated with menopause while inhibiting bone resorption and possibly reducing the risk of cardiovascular disease. Their use however has been complicated by an increased risk of endometrial cancer and possibly breast cancer. The use of estrogens as cardioprotective agents is discussed and the clinical experiences and the possible mechanisms of action are reviewed. The clinical pharmacology of estrogens and the various formulations that are available as monotherapy or in combination with progestins will also be reviewed.
Adult↗
Adverse dermatologic reactions from antiarrhythmic drug therapy.
Undesirable cutaneous reactions to drugs may occur early or late in the course of treatment. The ingestion of drugs may also aggravate existing dermatologic conditions. The adverse dermatologic reactions from antiarrhythmic drug therapy are reviewed. The exact incidence of dermatologic side effects from cardiovascular drugs has been difficult to estimate because of sporadic reporting. In this review, the cutaneous side effects are discussed according to drug class and the type of dermatologic reaction.
Anti-Arrhythmia Agents↗
Toxic effects of diltiazem in a patient with chronic renal failure.
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Acidosis↗
Nisoldipine: a new dihydropyridine calcium-channel blocker.
Nisoldipine is a new calcium-channel blocker of the dihydropyridine subclass, with a chemical structure similar to nifedipine. It has been used in clinical trials to assess its efficacy and safety in patients with hypertension, angina pectoris, and congestive heart failure. Similar to other dihydropyridines, nisoldipine is a potent peripheral and coronary dilator. The most optimal dosage regimen has not been established in clinical trials. The drug appears to have a favorable side-effect profile.
Angina Pectoris↗
Report of the Task Force on the Availability of Cardiovascular Drugs to the Medically Indigent.
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Cardiology↗
Angina pectoris and silent ischemia in the elderly: a management update.
Coronary artery disease accompanied by symptomatic and asymptomatic myocardial ischemia is a common entity in older patients. The pathophysiology of myocardial ischemia is related to an imbalance in myocardial demand and coronary perfusion. Treatment strategies for symptomatic myocardial ischemia include correction of aggravating medical conditions (eg, anemia or hypertension) and the use of nitrates, beta-adrenergic blockers, salicylates, and calcium-entry blockers, alone or in combination. Silent myocardial ischemia is also a prevalent condition in older individuals, with and without angina pectoris. Treatment regimens are similar to those used in symptomatic patients.
Adrenergic beta-Antagonists↗
Dementia. Age-dependent incidence, prevalence, and mortality in the old old.
Age has been reported as a strong risk factor for dementia. Supporting data have been derived mainly from prevalence studies, which had varied criteria and sample compositions that precluded direct comparisons, especially among those aged 85 years and older. Data regarding rates of dementia are presented based on 85 incident cases in the Bronx (NY) Aging Study, a prospective study of 488 initially nondemented, old old persons (mean age on entry, 79 years). Overall, the incidence rate over 8 years of follow-up for all-cause dementia was 3.4 per 100 per year (43% Alzheimer's disease, 30% mixed Alzheimer's and vascular, and 27% other). Incidence rose significantly, irrespective of gender, as subjects were followed up through three age intervals--ages 75 to 79 years (1.3/100 per year), 80 to 84 years (3.5), and 85 years and older (6.0). The comparable age-associated prevalence rates of dementia were 3.7%, 12.2%, and 23.9%, respectively, with an overall period prevalence of 22.8%. Additionally, there was a threefold greater mortality associated with dementia. In conclusion, despite the shortened life expectancy of demented persons, dementia is a highly prevalent condition among those aged 85 years and older. Public policy attention is warranted, since this group is the fastest growing population subgroup.
Aged↗
Acute hemodynamic effects of terazosin in hypertensive and normotensive patients.
Terazosin, a selective alpha 1-adrenergic antagonist, was administered intravenously to 10 patients undergoing cardiac catheterization to determine its short-term hemodynamic effects. Hemodynamic measurements were performed before and 30 minutes after three doses of the drug: 1, 1, and 3 mg. One milligram of terazosin reduced the blood pressure (systolic/diastolic, mean) from a mean of 152.0/86.3, 110.7 mm Hg by -24.3/-9.4, -15.3 mm Hg (p less than 0.05). In the five patients who received 5 mg of the drug, blood pressure declined in a dose-dependent manner by -21.8/-3.8, -11.6 mm Hg after 1 mg, and by -35.8/-14.8, -22.8 mm Hg (p less than 0.05) after all 5 mg of the drug. The changes in blood pressure paralleled the terazosin-induced decrease in systemic resistance. Similar changes were recorded for pulmonary artery and capillary wedge pressures and pulmonary vascular resistance. The greatest hemodynamic response was noted with the first drug dose; succeeding doses had a progressively diminished incremental effect. Cardiac output, heart rate, and maximum left ventricular dp/dt demonstrated little change, whereas left ventricular end-diastolic pressure decreased after all three doses, reaching significance after 2 mg (-3.4 +/- 0.9 mm Hg, p less than 0.05), and left ventricular ejection fraction tended to increase (+5.6% +/- 2.4%, p less than 0.05 after 1 mg) and showed a dose dependence analogous to that of systemic resistance. Although not generally reaching statistical significance, indexes of aortic stiffness and compliance displayed a favorable effect. These data are consistent with terazosin's specific alpha 1-antagonism. Left ventricular performance is improved by afterload reduction, since terazosin demonstrated no direct effect on cardiac contractility.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenergic alpha-Antagonists↗