Ronald G. Marks

Effects of treatment on outcome in mildly symptomatic patients with ischemia during daily life. The Atenolol Silent Ischemia Study (ASIST)

BackgroundDetection of asymptomatic ischemia in patients with coronary artery disease has been associated with increased risk for adverse outcome, but treatment of patients with asymptomatic ischemia remains controversial. Accordingly, the purpose of this study was to determine if treatment reduces adverse outcome in patients with daily life ischemia. Methods and ResultsA multicenter, randomized, double-blind, placebo- controlled study of asymptomatic or minimally symptomatic outpatients with daily life silent ischemia due to coronary artery disease was conducted. The primary outcome measure was event- free survival at 1 year by Kaplan-Meier analysis. Events were death, resuscitated ventricular tachycardia/ fibrillation, myocardial infarction, hospitalization for unstable angina, aggravation of angina, or revascularization. The secondary outcome was ischemia during ambulatory ECG monitoring at 4 weeks. Three hundred six outpatients with mild or no angina (Canadian Cardiovascular Society class I or II), abnormal exercise tests, and ischemia on ambulatory monitoring were randomized to receive either atenolol (100 mg/d) or placebo. After 4 weeks of treatment, the number (mean±SD, 3.6±4.2 versus 1.7±4.6 episodes, P<.001) and average duration (30±3.3 versus 16.4+6.7 minutes, P<.001) of ischemic episodes per 48 hours of ambulatory monitoring decreased in atenolol- compared with placebo-assigned patients (4.4±4.6 to 3.1±6.0 episodes and 36.6±4.1 to 30±5.5 minutes). Event-free survival improved in atenolol-treated patients (P<.0066), who had an increased time to onset of first adverse event (120 versus 79 days) and fewer total first events compared with placebo (relative risk, 0.44; 95% confidence intervals, 0.26 to 0.75; P=.001). There was a nonsignificant trend for fewer serious events (death, resuscitation from ventricular tachycardia/fibrillation, nonfatal myocardial infarction, or hospitalization for unstable angina) in atenolol-treated patients (relative risk, 0.55; 95% confidence intervals, 0.22 to 1.33; P=.175). The most powerful univariate and multivariate correlate of event-free survival was absence of ischemia on ambulatory monitoring at 4 weeks. Side effects were mild and generally similar comparing atenolol- and placebo-treated patients, although bradycardia was more frequent with atenolol. ConclusionsAtenolol treatment reduced daily life ischemia and was associated with reduced risk for adverse outcome in asymptomatic and mildly symptomatic patients compared with placebo.

Nocturia: A Risk Factor for Falls in the Elderly

Objective: To determine if nocturia is a risk factor for reported falls and bone fractures in older persons.

Symptom prevalence in the elderly. An evaluation of age, sex, disease, and medication use.

Prevalence of reported symptoms was studied in 1927 women and 1140 men over 65 years of age in an ambulatory health screening program. Reports of 28 common symptoms were obtained from a standardized questionnaire completed by participants at the time of their fourth annual visit to the program. A comparison was made of the prevalence of specific symptoms by sex, age, disease states, and drug use patterns. The most common symptoms reported by women were nocturia (80.4%), swollen feet or ankles (30.5%), cold feet and/or legs (28.6%), and irregular heartbeat (23.2%), whereas men complained most often of nocturia (79.8%), irregular heartbeat (24.8%), cold feet and/or legs (23.6%), and tinnitus (23.1%). Women reported a mean of 3.99 symptoms compared with 3.22 reported by men (P < .0001). In women there was a statistically significant association for most symptoms in subjects reporting the use of medication compared with a group who did not use medication. In men the use of medication was less highly correlated with reports of symptoms. Nearly 100% of participants reported having at least one disease state. The number of symptoms reported was strongly related to the number of disease states, and after adjusting for diseases, women reported more symptoms than men. The best predictor of symptom prevalence was the number of disease states followed by the number of drugs used and then age.

Characteristics of a Contemporary Population with Angina Pectoris

To characterize a contemporary, nonhospitalized population with angina pectoris, data were obtained from a geographically diverse cohort of 5,125 outpatients with chronic stable angina cared for by 1,266 primary care physicians between September and November of 1990. Diagnosis was based on history supported by evidence for coronary artery disease (coronary angiography, old myocardial infarction, or an abnormal stress test, either alone or in combination). The mean age of the patients was 69 years and 53% were women. Seventy percent had > 1 associated illness and 64% took > 1 cardiovascular drug. Median angina frequency was approximately 2 episodes/week and increased angina frequency (p < 0.0001) was associated with decreased overall feeling of well-being. Although effort angina was present in 90% of patients, 47% also had rest angina and 35% had mental stress-evoked angina. Female gender (relative risk [RR] 1.09; 95% confidence interval [CI] 1.02 to 1.16), concomitant illness (RR 1.17; CI 1.09 to 1.25), and pharmacotherapy (RR 1.14; CI 1.07 to 1.22) were associated with excess risk for rest angina. Younger age (RR 1.30; CI 1.20 to 1.41), female gender (RR 1.16; CI 1.07 to 1.26), concomitant illness (RR 1.13; CI 1.03 to 1.24), and pharmacotherapy (RR 1.28; CI 1.15 to 1.93) were associated with excess risk for mental stress angina. These data suggest that contemporary outpatients with angina are frequently women and elderly patients with high rates of associated illness, rest, and mental stress-related angina.

Effect of Thromboxane A2 Blockade on Clinical Outcome and Restenosis After Successful Coronary Angioplasty Multi-Hospital Eastern Atlantic Restenosis Trial (M-HEART II)

BACKGROUND Antithromboxane therapy with aspirin reduces acute procedural complications of coronary angioplasty (PTCA) but has not been shown to prevent restenosis. The effect of chronic aspirin therapy on long-term clinical events after PTCA is unknown, and the utility of more specific antithromboxane agents is uncertain. The goal of this study was to assess the effects of aspirin (a nonselective inhibitor of thromboxane A2 synthesis) and sulotroban (a selective blocker of the thromboxane A2 receptor) on late clinical events and restenosis after PTCA. METHODS AND RESULTS Patients (n = 752) were randomly assigned to aspirin (325 mg daily), sulotroban (800 mg QID), or placebo, started within 6 hours before PTCA and continued for 6 months. The primary outcome was clinical failure at 6 months after successful PTCA, defined as (1) death, (2) myocardial infarction, or (3) restenosis associated with recurrent angina or need for repeat revascularization. Neither active treatment differed significantly from placebo in the rate of angiographic restenosis: 39% (73 of 188) in the aspirin-assigned group, 53% (100 of 189) in the sulotroban group, and 43% (85 of 196) in the placebo group. In contrast, aspirin therapy significantly improved clinical outcome in comparison to placebo (P = .046) and sulotroban (P = .006). Clinical failure occurred in 30% (49 of 162) of the aspirin group, 44% (73 of 166) of the sulotroban group, and 41% (71 of 175) of the placebo group. Myocardial infarction was significantly reduced by antithromboxane therapy: 1.2% in the aspirin group, 1.8% in the sulotroban group, and 5.7% in the placebo group (P = .030). CONCLUSIONS Thromboxane A2 blockade protects against late ischemic events after angioplasty even though angiographic restenosis is not significantly reduced. While both aspirin and sulotroban prevent the occurrence of myocardial infarction, overall clinical outcome appears superior for aspirin compared with sulotroban. Therefore, aspirin should be continued for at least 6 months after coronary angioplasty.

Drug use in an ambulatory elderly population: a five-year update.

Drug usage was studied in an ambulatory elderly population in Dunedin, Florida. Prescription and nonprescription drug use in these 2834 participants was compared with use during a period five years earlier. The average number of medications increased from 3.2 in 1978–80 to 3.7 in 1983–85. The most commonly prescribed medications in this population were hydrochlorothiazide-triamterene (13.5 percent), digoxin (9.6 percent), and hydrochlorothiazide (8.4 percent). There was a large increase in the use of nutritional supplements in the past five years, with 18.0 percent of these subjects reporting the use of vitamin E and 15.7 percent taking vitamin C. The general philosophy in geriatrics is to use the fewest drugs possible; however, it appears that the elderly are, in fact, receiving an increasing number of medications.

Mortality, Morbidity, and Cost-Accounting Related to Coronary Artery Bypass Graft Surgery in the Elderly

The purpose of this study was to document early mortality, perioperative complication rate, duration of hospitalization, and costs related to coronary artery bypass graft (CABG) surgery in the elderly. Arbitrarily, elderly patients were defined by age greater than or equal to 65 years; younger patients were less than or equal to 60 years old. A detailed list of specific perioperative complications was analyzed. Early (30-day) mortality was similar between groups, while 120-day mortality was higher among elderly compared with younger patients (7.6% versus 1.3%; p = 0.05). The number of elderly patients with 1 or more complications was also higher than among the younger patients (62% versus 43%; p = 0.05). When the incidences of atrial arrhythmias and transient psychoses were considered minor complications and excluded from consideration, the incidence of major complications was higher in the elderly: 41 major events among 76 younger surviving patients compared with 89 major complications in 61 older surviving patients (p = 0.001). Time spent in the intensive care unit and the duration of postoperative hospitalization were also greater in the elderly (p = 0.01 and p = 0.001, respectively). Finally, the elderly group incurred greater costs than the younger patients (p = 0.03). The likelihood of increased perioperative morbidity in elderly patients is documented in this study. Also, it appears that the increased frequency of complications in elderly patients is associated with a longer hospital stay and greater financial expense. Consequently, the careful preoperative evaluation of these patients, including cautious patient selection, assumes greater importance. After CABG procedures, the highly symptomatic elderly patient may experience dramatic relief of symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

A longitudinal evaluation of drug use in an ambulatory elderly population

Participants in a geriatric health screening program were studied longitudinally to determine the patterns of drug use over a 10 year period. There were 314 (34.0%) men and 610 (66.0%) women who completed 10 yearly health screening evaluations. The mean number of prescribed and non-prescribed drugs used per participant increased from 2.90 in 1978-79 to 4.08 in 1987-88 (p less than 0.0001). There was no significant difference between men and women in the rate of increased drug use. There was no significant increase in the mean number of drug ingredients per participant used over the 10 year period. The most frequently reported therapeutic categories for 1978-79 were antihypertensives, analgesic-antipyretics, antirheumatics, multiple vitamins, cathartics and vitamin E, which represented 10.2, 7.2, 6.5, 4.9, 4.8 and 3.8% of all categories used. There was a decline in all of these categories between interval 1 and 10. Increased use of drugs, particularly prescribed medications, by the elderly population may present problems of adverse drug reactions, drug interactions and medication compliance in the future. Changing patterns of drug use may have resulted, in part, from introduction of new therapeutic classes and from new treatment concepts over the 10 year study period.

Headache in the Elderly: An Evaluation of Risk Factors

SYNOPSIS

Central nervous system symptoms of elderly subjects using antihypertensive drugs.

The effects of antihypertensive agents on the frequencies of reported fainting, dizziness, losses of consciousness, and bone fractures were studied in a large, ambulatory elderly population. The frequencies of these symptoms were compared for subjects who used one or more of nine different antihypertensive agents and for subjects who were not using these medications and who served as a control group. Over 40 per cent of the total population were using at least one of the nine drug groups. Women who used antihypertensive medications reported significantly more fainting (P < 0.001), dizziness (P < 0.005) and “blacking‐out spells” (P < 0.002) but significantly fewer bone fractures (P < 0.02) compared with women who were not using such medication in the control group. For men, the use of only one drug group, propranolol, was associated with a significant increase in fainting and dizziness but not blacking‐out spells compared with men in the control. These results suggest that elderly persons may be subject to a variety of central nervous system side effects induced by antihypertensive drugs.