The assessment of vascular risk in men with erectile dysfunction: the role of the cardiologist and general physician.

Erectile dysfunction (ED) and cardiovascular disease (CVD) share risk factors and frequently coexist, with endothelial dysfunction believed to be the pathophysiologic link. ED is common, affecting more than 70% of men with known CVD. In addition, clinical studies have demonstrated that ED in men with no known CVD often precedes a CVD event by 2-5 years. ED severity has been correlated with increasing plaque burden in patients with coronary artery disease. ED is an independent marker of increased CVD risk including all-cause and especially CVD mortality, particularly in men aged 30-60 years. Thus, ED identifies a window of opportunity for CVD risk mitigation. We recommend that a thorough history, physical exam (including visceral adiposity), assessment of ED severity and duration and evaluation including fasting plasma glucose, lipids, resting electrocardiogram, family history, lifestyle factors, serum creatinine (estimated glomerular filtration rate) and albumin:creatinine ratio, and determination of the presence or absence of the metabolic syndrome be performed to characterise cardiovascular risk in all men with ED. Assessment of testosterone levels should also be considered and biomarkers may help to further quantify risk, even though their roles in development of CVD have not been firmly established. Finally, we recommend that a question about ED be included in assessment of CVD risk in all men and be added to CVD risk assessment guidelines.

Effect of cutaneous nitroglycerin patches on coronary artery diameter: issues concerning development of tolerance.

The coronary dilative and systemic responses to graded doses of intracoronary nitroglycerin were studied in 53 patients undergoing diagnostic coronary arteriography, 43 of whom had received a cutaneous nitroglycerin patch. During coronary arteriography, graded doses of 50, 100 and 200 micrograms of intracoronary nitroglycerin were given 5 min apart. An arteriogram and hemodynamic measurements were obtained after each dose. In the control group (n = 10) cumulative intracoronary nitroglycerin doses of 50, 150 and 350 micrograms caused an increase in coronary diameter in the left anterior descending artery of 20 +/- 4%, 21 +/- 3% and 22 +/- 7%, respectively, and in the circumflex artery of 18 +/- 6%, 23 +/- 8% and 18 +/- 5% (p less than 0.01 versus values in untreated group). In Group 1 (15 patients given a 5 mg/24 h nitroglycerin patch 2 to 12 h before coronary arteriography), the same intracoronary nitroglycerin doses increased the left anterior descending artery diameter by 6 +/- 2%, 7 +/- 2% and 7 +/- 2%, respectively, and the circumflex artery diameter by 3 +/- 2%, 3 +/- 2% and 1 +/- 3%. All values were statistically different from control (p less than 0.05). An even more pronounced blunting (p less than 0.01) of the coronary dilative response was observed in Group 2 (14 patients given a 15 mg/24 h nitroglycerin patch 2 to 12 h before arteriography).(ABSTRACT TRUNCATED AT 250 WORDS)

Prognostic significance of ventricular ectopic activity in survivors of acute myocardial infarction.

Twenty-four hour ambulatory electrocardiography was performed on 3,290 survivors of acute myocardial infarction participating in the Beta-Blocker Heart Attack Trial (BHAT). History of myocardial infarction before the qualifying event, congestive heart failure and age were independently associated with the frequency and complexity of ventricular premature beats. Of the 1,640 patients randomized to placebo therapy, 163 died (76 suffered sudden death) during a 25 month average follow-up period. Ventricular ectopic activity was an independent predictor of total mortality after taking into consideration 16 other prognostic factors describing past history, risk factors, physical examination and laboratory investigations. Seven categoric definitions of ventricular ectopic activity predicted mortality, with similar odds ratios ranging from 2.27 to 2.69. A reciprocal relation of the sensitivity and specificity of each definition in predicting mortality was observed. Three clinical criteria (ST depression, cardiomegaly and prior infarction) allowed stratification of patients into four subsets with respective mortality rates of 35.5% (three criteria present), 19.0% (two criteria), 11.5% (one criterion) and 4.7% (none). Presence of ventricular ectopic activity (greater than or equal to 10 ventricular premature beats/h or pairs, ventricular tachycardia or multiform complexes) was associated with higher mortality rates in all four risk strata. The relative risk was higher (3.86) in the lowest risk stratum (mortality 2.4% without and 9.1% with ventricular ectopic activity). Thus, in survivors of acute myocardial infarction, ventricular ectopic activity was more pronounced in patients with prior myocardial infarction and congestive heart failure. It predicted mortality independently of other factors. Although mortality ratios were similar for all seven arrhythmia definitions, a reciprocal relation between sensitivity and specificity of the definitions in predicting mortality existed; ventricular ectopic activity was associated with increased mortality in all risk strata, but with a higher risk ratio in the numerically larger, low risk subset.

Cibenzoline for treatment of ventricular arrhythmias: a double-blind placebo-controlled study.

Cibenzoline, a new class I antiarrhythmic drug, was administered to 24 patients with frequent (greater than 30/h) premature ventricular complexes. Three patients discontinued the medication because of epigastric distress before repeat ambulatory electrocardiography. Of the remaining 21 patients, 13 responded to 130 mg twice daily by more than 75% suppression of premature ventricular complex frequency and 6 additional patients responded to 160 mg twice daily during an open-label titration phase. Events of ventricular tachycardia (greater than or equal to 3 beats) were totally suppressed in 9 of 10 patients and markedly diminished in the 1 remaining patient. During a double-blind placebo-controlled crossover phase in 16 patients (21 patients minus 2 nonresponders and 3 who developed side effects), cibenzoline suppressed the number of premature ventricular complexes per 24 hours (4,075 +/- 868 to 1,758 +/- 1,089, p = 0.02), the number of events of ventricular tachycardia (31 +/- 30 to 2 +/- 0, p = 0.01) and the number of premature ventricular complex pairs (61 +/- 28 to 25 +/- 21, p = 0.01). Cibenzoline plasma concentration was 59 to 421 ng/ml in responders and higher (387, 758 and 852 ng/ml, respectively) in the three subjects with side effects (right bundle branch block in one, hypotension in one, gastrointestinal upset and central nervous system complaints in one). Cibenzoline plasma concentration correlated with PR interval (r = 0.55, p = 0.0106) and corrected QT interval (r = 0.58, p = 0.0054). Further clinical investigation of this new antiarrhythmic agent is needed.

Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant meta-analysis.

CONTEXT: Plasma fibrinogen levels may be associated with the risk of coronary heart disease (CHD) and stroke. OBJECTIVE: To assess the relationships of fibrinogen levels with risk of major vascular and with risk of nonvascular outcomes based on individual participant data. DATA SOURCES: Relevant studies were identified by computer-assisted searches, hand searches of reference lists, and personal communication with relevant investigators. STUDY SELECTION: All identified prospective studies were included with information available on baseline fibrinogen levels and details of subsequent major vascular morbidity and/or cause-specific mortality during at least 1 year of follow-up. Studies were excluded if they recruited participants on the basis of having had a previous history of cardiovascular disease; participants with known preexisting CHD or stroke were excluded. DATA EXTRACTION: Individual records were provided on each of 154,211 participants in 31 prospective studies. During 1.38 million person-years of follow-up, there were 6944 first nonfatal myocardial infarctions or stroke events and 13,210 deaths. Cause-specific mortality was generally available. Analyses involved proportional hazards modeling with adjustment for confounding by known cardiovascular risk factors and for regression dilution bias. DATA SYNTHESIS: Within each age group considered (40-59, 60-69, and > or =70 years), there was an approximately log-linear association with usual fibrinogen level for the risk of any CHD, any stroke, other vascular (eg, non-CHD, nonstroke) mortality, and nonvascular mortality. There was no evidence of a threshold within the range of usual fibrinogen level studied at any age. The age- and sex- adjusted hazard ratio per 1-g/L increase in usual fibrinogen level for CHD was 2.42 (95% confidence interval [CI], 2.24-2.60); stroke, 2.06 (95% CI, 1.83-2.33); other vascular mortality, 2.76 (95% CI, 2.28-3.35); and nonvascular mortality, 2.03 (95% CI, 1.90-2.18). The hazard ratios for CHD and stroke were reduced to about 1.8 after further adjustment for measured values of several established vascular risk factors. In a subset of 7011 participants with available C-reactive protein values, the findings for CHD were essentially unchanged following additional adjustment for C-reactive protein. The associations of fibrinogen level with CHD or stroke did not differ substantially according to sex, smoking, blood pressure, blood lipid levels, or several features of study design. CONCLUSIONS: In this large individual participant meta-analysis, moderately strong associations were found between usual plasma fibrinogen level and the risks of CHD, stroke, other vascular mortality, and nonvascular mortality in a wide range of circumstances in healthy middle-aged adults. Assessment of any causal relevance of elevated fibrinogen levels to disease requires additional research.

Delay in presentation and evaluation for acute stroke: Stroke Time Registry for Outcomes Knowledge and Epidemiology (S.T.R.O.K.E.).

BACKGROUND AND PURPOSE: Early treatment is a critical determinant of successful intervention in acute stroke. The study was designed to find current patterns of stroke care by determining delays in time from onset of signs or symptoms to arrival at the emergency department and to initial evaluation by physicians and by identifying factors associated with these delays. METHODS: Data were prospectively collected by nurses and physicians from patients, patients' family members, and medical records from 10 hospitals of the Robert Wood Johnson Health System in New Jersey. RESULTS: A total of 553 patients who presented with signs or symptoms of acute stroke were studied. Thirty-two percent of patients arrived at the emergency department within 1.5 hours of stroke onset. Forty-six percent of patients arrived within 3 hours and 61% within 6 hours. Delays in arrival time were significantly associated with sex, race, transportation mode, and history of cardiovascular disease. Patients arriving by ambulance were more likely to present earlier (odds ratio [OR] 3.7 for arrival within 3 hours; OR 4.5 for arrival within 6 hours). Patients arriving by ambulance (OR 2.3 within 15 minutes; OR 1.7 within 30 minutes) and those requiring admission to intensive care units (OR 4.5 within 15 minutes and OR 5.2 within 30 minutes) were examined sooner by physicians. CONCLUSIONS: Despite national efforts to promote prompt stroke evaluation and treatment, significant delays still exist. The lack of improvement throughout the past decade underscores the need for implementation of effective public health programs designed to minimize the time to evaluation and treatment of stroke.

Fosinopril: pharmacokinetics and pharmacodynamics in congestive heart failure.

Fosinoprilat, the active product of fosinopril, is eliminated by a hepatic pathway, in addition to the renal pathway shared by other angiotensin converting enzyme inhibitors. Congestive heart failure (CHF) may elevate drug plasma concentrations caused by a reduction in steady-state volume of distribution (Vss) and/or an impairment of clearance. This study compared the pharmacokinetics and pharmacodynamics of fosinopril (intravenous and oral) in 10 patients with established CHF and 10 age-, sex-, and weight-matched normal control subjects. There were no statistically significant differences between the patients with CHF and the control patients with respect to maximum drug concentration (Cmax) or area under the plasma concentration-time curve from 0 to infinity. Absolute bioavailability was approximately 29%. Vss was similar, and protein binding was 99% in both groups. The oral half-life of fosinoprilat was significantly longer than the intravenous half-life for both the patients with CHF and normal subjects, without statistically significant differences between the study groups. Median time to reach Cmax occurred at 4 hours in each group and corresponded to maximum angiotensin converting enzyme inhibition, which was essentially complete through 12 hours and markedly reduced through 24 hours. Thus these data indicate that patients with CHF can receive fosinopril without undue increases in fosinoprilat concentrations. This probably is due to the dual excretory pathways.

Efficacy and safety of pravastatin in patients with primary hypercholesterolemia. II. Once-daily versus twice-daily dosing.

This 8-week multicenter, placebo-controlled trial compared the efficacy and safety of the HMG-CoA reductase inhibitor, pravastatin, when administered either as single doses of 40 mg in the morning (AM) or evening (PM) or 20 mg twice daily (bid) in 196 diet-stabilized outpatients with primary type II hypercholesterolemia. Mean reductions in total and low-density lipoprotein (LDL) cholesterol concentrations were observed in all pravastatin groups after 1 week and were sustained throughout the study (P less than or equal to 0.001 versus baseline and placebo). At week 8, mean reductions from baseline in the pravastatin treatment groups were 23-27% for total cholesterol and 30-34% for LDL cholesterol. LDL cholesterol was reduced greater than or equal to 15% by pravastatin in all patients in the group treated with 40 mg PM and in 88 and 96% in those receiving 20 mg bid and 40 mg AM, respectively. High density lipoprotein cholesterol was elevated (up to 8%) and triglycerides were reduced (up to 25%) by all pravastatin regimens (P less than or equal to 0.05). Pravastatin was well tolerated and was associated with a low incidence of adverse events. No patient withdrew from the study due to a pravastatin-related adverse event. Once-daily pravastatin is a safe and effective treatment for patients with primary hypercholesterolemia and has a favorable safety profile.

Isolated systolic hypertension in the elderly: results of a statewide survey of clinical practice in New Jersey.

UNLABELLED: PURPOSE AND SUBJECTS AND METHODS: The advisability of treating isolated systolic hypertension (ISH) in the elderly is a matter of debate. We therefore surveyed current clinical practices for ISH among members of the New Jersey Academy of Family Physicians and the American College of Physicians-New Jersey Chapter (n = 1,514). To our knowledge, no such survey focusing on ISH had previously been reported. Two rounds of questionnaires were mailed three weeks apart in April and May of 1985, followed by a phone survey of non-respondents in June and July. A third mailing was performed where appropriate. RESULTS: The response rate was 87 percent. For ISH in patients aged 60 and older, 89 percent of the 1,318 respondents reported using drug therapy. A diuretic was chosen as the first-line drug by 67.5 percent of respondents. The most common second-line drug choices were a beta blocker (28 percent), a central alpha agonist (19 percent), and a diuretic (18.5 percent). The patient's age entered strongly into decisions on drug use. Although 55 percent of respondents would use drug therapy at a systolic blood pressure of 160 mm Hg or less for persons aged 60 to 69, only 35 percent would do so for persons aged 70 to 79, and 26 percent for persons aged 80 and older. For all patient age groups, older physicians were more likely to consider drug therapy than were younger physicians. Among specialty groups, general practitioners were the most likely to consider drug therapy and cardiologists the least likely to do so for all patient age groups. Family physicians and general internists appeared to have very similar practice patterns regarding definition and treatment of ISH. CONCLUSION: The overall message of the survey results is that the majority of physicians questioned use drug therapy, usually a diuretic or a beta blocker, for some patients with ISH. However, no widely accepted standard practice on the definition and management of ISH in persons aged 60 and older was observed.

Nondominant right coronary artery occlusion presenting with isolated right ventricular infarction and ventricular fibrillation.

It is generally believed that serious complications are unlikely in a myocardial infarction resulting from occlusion of a nondominant right coronary artery. A case of isolated right ventricular infarction caused by total occlusion of a nondominant right coronary artery complicated by two episodes of ventricular fibrillation is presented.

Efficacy and safety of atenolol, enalapril, and isradipine in elderly hypertensive women.

PURPOSE: This trial was designed to evaluate the efficacy and safety of three different classes of antihypertensive agents in elderly women. PATIENTS AND METHODS: The trial had three phases: 4 to 8 weeks of placebo, 6 weeks of titration, and 16 weeks of maintenance. White women between 60 and 80 years old with sitting diastolic blood pressures (DBPs) from 95 through 114 mm Hg treated with placebo were evaluated by history, physical examination, laboratory studies, and quality-of-life interview. After double-blind randomization with low-dose atenolol, enalapril, or isradipine, the dose was increased stepwise and hydrochlorothiazide added as needed to achieve goal DBP (less than 90 mm Hg and greater than 10 mm Hg below baseline). During maintenance, patients not at goal were "stepped up," and patients with uncontrolled DBP at maximum dosage were removed from the study. The pretreatment (baseline) blood pressure of the 315 randomized participants averaged 161/100 mm Hg; 92% had been treated previously for hypertension, 15% had diabetes mellitus, 11% smoked, and 38% consumed alcohol. RESULTS: For 245 patients completing the trial, the average decrease in blood pressure during treatment was 18.2/15.6 mm Hg. Antihypertensive efficacy was similar for the monotherapy drug regimens, with 84%, 71%, and 80% of patients receiving atenolol, enalapril, and isradipine, respectively, achieving DBP goal. Of the 70 patients who did not complete the trial, 42 left because of symptoms and 19 because of uncontrolled DBP. No important, unexpected drug-induced changes in symptoms or blood chemistries were noted. Symptom frequency differed little among the three dosage levels, becoming maximal by the second visit at the same dosage level. CONCLUSION: All three drugs lowered DBP comparably, and none produced alarming effects. Thirteen percent of patients left the study because of symptoms.

Prognostic importance of cardiac arrhythmias in systemic sclerosis.

Ambulatory electrocardiography was performed in 183 patients with systemic sclerosis recruited from five centers who were selected to reflect a balanced population with respect to disease extent and duration. Ventricular ectopy occurred in 67 percent of patients and was strongly correlated by both univariate and multivariate analyses with total mortality and with sudden death. By multivariate analysis, ventricular ectopy was strongly associated with increasing patient age and with other evidence of cardiac and pulmonary involvement but not with clinical and laboratory measures of duration and extent of systemic sclerosis. Evidence of myocardial fibrosis thought to be secondary to microvascular alteration is common in systemic sclerosis, but the clinical implications of myocardial involvement are less well appreciated. The present data suggest the need for ambulatory electrocardiography in the clinical assessment of selected patients with systemic sclerosis, especially those with cardiac or pulmonary involvement, as well as for studies of the effects of antiarrhythmic therapy.

Comparison of the duration of action of atenolol and nadolol for treatment of angina pectoris.

In a randomized, double-blind, placebo-controlled cross-over study, 16 patients with angina on effort due to proven coronary artery disease were given atenolol 50 or 100 mg and nadolol 40 or 80 mg every morning. Compared with placebo control, both beta blockers equally decreased angina frequency, suppressed supine, standing, submaximum and maximum heart rates and double products (all p less than 0.0001) and increased exercise tolerance (p less than 0.01) when the exercise stress test was done 3 to 4 hours after the daily dose. When the exercise stress test was done 24 hours after the daily dose, the suppression of resting and maximum exercise heart rates and maximum double product was more pronounced by nadolol than atenolol (p less than 0.05). Ambulatory electrocardiography heart rates were also equally suppressed by both beta blockers in the afternoon, evening and nighttime hours. However, in the hours just before and just after the ingestion of the daily dose the effect of nadolol (elimination half-life 1,436 +/- 420 minutes) was more pronounced (p less than 0.05) than that of atenolol (half-life 537 +/- 62 minutes). Negative correlations (p less than 0.03) between beta-blocker blood levels and submaximal exercise heart rates and double products were observed.

Beta-blocker duration of action and implications for therapy.

Two studies were conducted to measure the effect of serum half-life on beta-blocker-related heart rate reduction throughout the 24-hour period. In the first study, nadolol, atenolol and pindolol were associated with significant (p less than 0.01) heart rate reduction even at 24 hours after dose. Nadolol, with a plasma half-life of 15.5 hours, had the most pronounced heart rate-lowering effect 24 hours after the daily dose compared to pindolol, which had a half-life of 5.5 hours. In a randomized, double-blind, crossover study, nadolol and atenolol had similar effects 3 to 4 hours after the daily dose. Nadolol, however, produced greater suppression of heart rate and double product (blood pressure x heart rate) than atenolol (compared to placebo) 24 hours after ingestion of the daily dose. On ambulatory electrocardiography 24 hours after medication administration, 80 to 100% of the heart rate-attenuating effect of nadolol was maintained versus only 20 to 45% of atenolol's effect. Statistically significant (p less than 0.05) reductions in heart rate were produced by nadolol, but not by atenolol, between 4 and 5 A.M., 6 and 7 A.M., 8 and 9 A.M. and 9 and 10 A.M. Furthermore, nadolol remained at 52% of peak blood level at 24 hours, whereas atenolol was at 20%. The data from these 2 studies indicate that significant differences in duration of action exist between beta blockers.

Association between leukocyte count and the presence and extent of coronary atherosclerosis as determined by coronary arteriography.

Angiographic evidence of coronary artery disease (CAD) was correlated with leukocyte count (WBC), red cell count (RBC), cigarette smoking, age, sex, and cholesterol and triglyceride concentrations in 573 patients who underwent coronary arteriography and who did not have evidence of infection or recent myocardial infarction. Smokers had a higher WBC (7,449 +/- 1,964 leukocytes/mm3 vs 6,533 +/- 1,557, p = 0.0001) and RBC (4.921 X 10(6) +/- 0.491 X 10(6) erythrocytes/mm3 vs 4.753 X 10(6) +/- 0.480 X 10(6) p = 0.0001) than nonsmokers. Patients with CAD had a higher WBC (7,280 +/- 1,926 vs 6,664 +/- 1,700, p = 0.0005) and RBC (4.903 X 10(6) +/- 0.488 vs 4.777 X 10(6) +/- 0.485 X 10(6), p = 0.0062) than those with normal coronary arteriograms. A positive correlation between WBC and the severity of CAD (sum of arterial diameter narrowing) was noted (r = 0.16, p = 0.0001). Multiple regression showed an independent contribution of WBC in predicting severity of CAD (F = 9.26, p = 0.0025), after accounting for the effects of age, sex, serum cholesterol and triglyceride levels. When smoking was entered into the equation, the contribution of WBC in predicting the severity of angiographic CAD became weaker (F = 4.46, p = 0.035). Similar relations were seen when only smokers were analyzed and when patients with history of remote myocardial infarction were excluded. In nonsmokers these associations became either insignificant or much weaker. Thus, the relation of WBC, and RBC with CAD is mainly due to the elevation of WBC and RBC and the increase of CAD risk induced by cigarette smoking.

Effect of niacin supplementation on fibrinogen levels in patients with peripheral vascular disease.

This study demonstrates that niacin supplementation decreases plasma fibrinogen and low-density lipoprotein cholesterol in subjects with peripheral vascular disease randomized to receive niacin, warfarin, antioxidants, or placebo. Changes in fibrinogen levels are highly correlated with changes in low-density lipoprotein cholesterol (r = 0.61; p < 0.009) in subjects taking niacin.

Prognostic significance of ventricular ectopic activity in survivors of acute myocardial infarction who receive propranolol.

Beta blockers are frequently prescribed for survivors of acute myocardial infarction (AMI). Although ventricular ectopic activity was found to be associated with mortality in several cohorts, there are no data on the relation of ventricular ectopic activity to mortality in patients with AMI who receive beta blockers. One thousand six hundred and fifty participants in the Beta-Blocker Heart Attack Trial who were randomized to receive propranolol (60 or 80 mg 3 times daily) had 24-hour ambulatory electrocardiography at baseline. By multivariate analysis considering 16 variables, ventricular ectopic activity was independently associated with sudden death (p = 0.02 to 0.001) and total mortality (p = 0.04 to 0.0001) for an average follow-up of 25 months. By univariate analysis, ventricular ectopic activity was associated with increased total mortality (odds ratios 2.13 to 3.54) and sudden death mortality (odds ratio 2.26 to 3.93). The association of ventricular ectopic activity with mortality was observed in both high- and low-risk patient subsets with odds ratios similar to the placebo group. Thus, treatment with propranolol does not alter the relation between ventricular ectopic activity and mortality.

Effects of combined probucol-colestipol treatment for familial hypercholesterolemia and coronary artery disease.

To evaluate the effect of hypercholesterolemic treatment on coronary artery disease in patients known to be susceptible to disease progression, 44 patients with familial hypercholesterolemia and coronary artery disease were started on a lipid-lowering diet and either probucol (1 g/day) or colestipol (30 g/day). After 5 months of monotherapy, all patients went on a regimen of diet and 2-drug therapy. To date, combination therapy has continued for 3.4 to 4.1 years, and has resulted in the following changes from baseline in mean serum lipid levels: -48.5% in total cholesterol, -53.3% in low density lipoprotein cholesterol, -30.0% in high density lipoprotein cholesterol and +14.5% in triglycerides. The reduction in low density lipoprotein cholesterol apparently improved the clinical status of these patients despite the associated drop in high density lipoprotein cholesterol. In the 19 patients who underwent coronary arteriography before admission to the study, follow-up arteriograms showed that combined treatment stabilized the progression of established lesions and prevented the formation of new ones. Side effects occurred mainly with monotherapy and during the early phase of combination therapy. Reactions included diarrhea, constipation, other vague abdominal symptoms, headache and joint stiffness. In all instances, the side effects gradually subsided after the institution of combination therapy. The combination of probucol and colestipol plus diet appears to be effective in treating most patients with familial hypercholesterolemia.

Comparison of atenolol and nifedipine in chronic stable angina pectoris.

The antiangina effects of atenolol, 50 to 200 mg once daily, or nifedipine, 10 to 30 mg 3 times daily, were evaluated in a multicenter, randomized, double-blind, parallel study of 39 patients with known symptomatic coronary artery disease. Treatment was titrated to produce at least a 30% increase in treadmill exercise duration over placebo baseline and then maintained at that dosage for an additional 3 weeks. Both treatments produced significant (p less than 0.001) increases in duration of exercise, total work and exercise capacity when compared with placebo baseline. These improvements in exercise performance were obtained with significant (p less than 0.001) reductions in both ST-segment depression and rate-pressure product for atenolol compared with nifedipine. Furthermore, the total angina attack rate and rate at rest were significantly (p less than 0.01) less frequent with atenolol than with nifedipine. Hence, the antiischemic effects of atenolol exceeded those of nifedipine, based on ST-segment depression and rate-pressure product at comparable workloads.

Does withdrawal of antihypertensive medication increase the risk of cardiovascular events? Trial of Nonpharmacologic Interventions in the Elderly (TONE) Cooperative Research Group.

The Fifth Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure recommends that attempts to discontinue antihypertensive drug therapy be considered after blood pressure (BP) has been controlled for 1 year. However, discontinuation of drug therapy could unmask underlying conditions and precipitate clinical cardiovascular events. The Trial of Nonpharmacologic Interventions in the Elderly (TONE) was a clinical trial of the efficacy of weight loss and/or sodium reduction in controlling BP after withdrawal of drug therapy in patients with a BP< 145/85 mm Hg on 1 antihypertensive medication. Of 975 participants, 886 entered the drug withdrawal phase of the trial and 774 were successfully withdrawn from their medications. Thirty-three events (stroke, transient ischemic attack, myocardial infarction, arrhythmia, congestive heart failure, angina, other) occurred between randomization and the onset of drug withdrawal (median time 3.6 months), 57 events occurred either during or after drug withdrawal (14.0 months), and 36 events occurred after resumption of antihypertensive therapy (15.9 months). Event rates per 100 person-years were 5.5, 5.5, and 6.8 for the 3 time periods (p=0.84) in the nonoverweight group and 7.2, 5.2, and 5.6 (p=0.08) in the overweight group. The study shows that antihypertensive medication can be safely withdrawn in older persons without clinical evidence of cardiovascular disease who do not have diastolic pressure > or = 150/90 mm Hg at withdrawal, providing that good BP control can be maintained with nonpharmacologic therapy.